Technology situation

Technical situation

Summary

In this page we review the proximate technology situation. 

Technology has been a key driver of consumer interest in health care since the 1940s.  Significant current developments are reviewed.
Health Information Technology policy is discussed. 

Introduction

Heath care markets are deeply affected by technology developments and constraints.  Since the 1940s deployment of penicillin Americans have been convinced that their health issues have technological solutions.  The health care VDS has formed around this view, supporting and leveraging it. 


Expected technological advances, some discussed by NIH is the National Institute of Health, Bethesda Maryland.  It is the primary federal agency for the support and conduct of biomedical and behavioral research.  It is also one of the four US special containment units of the CDC.   director Francis Collins, suggest major transformations & powerful justification of health care:







Technology contents
  • AI & Robotics
  • Application development
  • Biotechnology research
  • Circuits
  • Epidemiology studies patterns, causes and effects of health and disease in populations.  It identifies risk factors for disease and focuses on preventative health care.  Being observational it suffers from a core limitation.  It can only show association, not causation.  It can suggest hypothesis but it can not disprove them.  
  • Epigenetics
  • Financial services
  • Obitiary of emergent force in venture capital (Jun 2016)
  • Distributed ledgers: bitcoin is a set of open-source software, used to provide infrastructure that supports a distributed cryptocurrency and payment system, based on the blockchain.   All transaction inputs are unspent outputs from previous transactions.  All transaction inputs are signed.  Change is provided in an additional output to the transaction. 
    's blockchain is a bitcoin distributed database technology that allows several bitcoin operators to keep a shared, cryptographically verified, ledger and consensus mechanism to allow agreement on what transactions have happened and in what order.  It implements a Merkle tree.  Six times an hour on average, a new group of validated transactions, a block, is created, added to the local block chain and published to all nodes.  Paraphrasing breadwallet's Aaron Voisine, publishing is robust because: Each operator has connected via references from its initial peers to a random subset of all the other operators; and the new block is offered to the connected peers who can both ask for it if they have not seen it previously from some other source and pass it on to their other peers in a cascade (a gossip network).  To build new blocks an operator must have all the prior blocks in the chain.  All unspent bitcoins are represented [only] in the blockchain.  Miners keep the blockchain consistent by verifying that a new block has a proof-of-work.  This requires that miners find a nonce that multiplied by the block hash is smaller than the network's difficulty target.   (Oct 2016)
  • Genomics
  • Microbiology
  • Modeling
  • Neuroscience
  • Payments
  • Process engines
    • Business process management
  • Proteomics
  • Quality
  • Robotics
  • Scientific method
  • Screening
  • Search
  • Servers
  • 200 prescription drugs including: beta blockers stop the action of beta-adrenergic signals and hence slow the heart.  , P.P.I. is proton pump inhibitor, which irreversibly block operation of gastric parietal cells' hydrogen/potassium ATPase, used as a medication: esomeprazole; to treat GERD.  They are among the most widely prescribed drugs in the world. 
    s, birth control pills, corticosteroids, anticonvulsants, prescription-strength ibuprofen, interferon; have depression is a debilitating state which is facilitated by genetic predisposition - for example genes coding for relatively low serotonin levels; and an accumulation of traumatic events.  There is evidence of shifts in the sleep/wake cycle in affected individuals (Dec 2015).  The affected person will experience a pathological sense of loss of control, prolonged sadness, irritability, sleep disturbances, loss of appetite, and inability to experience pleasure.  It affects 12% of men and 20% of women.  It appears to be associated with androgen deprivation therapy treatment for prostate cancer (Apr 2016).  Chronic stress depletes the nucleus accumbens of dopamine, biasing humans towards depression.  Depression easily leads to following unhealthy pathways: drinking, overeating; which increase the risk of heart disease.   It has been associated with an aging related B12 deficiency (Sep 2016).  During depression, stress mediates inhibition of dopamine signalling.  There is an association between depression and particular brain regions: Hippocampal dendrite and spine number reductions, Dorsal raphe nucleus linked to loneliness, Abnormalities of the ACC.  Childhood adversity can increase depression risk by linking recollections of uncontrollable situations to overgeneralizations that life will always be terrible and uncontrollable.  Treatments include: CBT, UMHS depression management.  As of 2010 drug treatments take weeks to facilitate a response & many patients do not respond to the first drug applied, often prolonging the agony.   Genomic predictions of which treatment will be effective have not been possible because: Not all clinical depressions are the same, a standard definition of drug response is difficult; as a side effect, drugs which one-third of American's take (Jun 2018)


  • Neuroscience reveals how we develop and operate.  It is highlighting changes in health care practice that can optimize treatments.



    Neuroscience

  • Alzheimer's is a dementia which correlates with deposition of amyloid plaques in the neurons.  As of 2015 there are 5 million Alzheimer's patients in the USA.  It was originally defined as starting in middle age which is rare, so it was a rare dementia.  But in 1980s it was redefined as any dementia without another known cause. Early indications include mood and behavioral changes (MBI) and memory and thinking problems (MCI).  Variants include: late-onset sporadic; with risk factors - ApoE4, presenilin, androgen deprivation therapy (Dec 2015).  There are multiple theories of the mechanism of Alzheimer's during aging: Allen Roses argues that it is due to gene alleles that limit the capacity of mitochondria to support neuron operation; It may be initiated by: stress induced HHV-6a, HHV7 herpes activation (Jun 2018) and or an increasingly leaky blood-brain barrier; and a subsequent innate immune response to the infections (May 2016).  The Alzheimer's pathway follows:
    • Plaques form and set off the formation of tangled thread-like tau protein.
      • Solanezumab aimed to inhibit plaque formation but clinical trials failed (Nov 2016).  
      • BACE inhibitors block an enzyme needed to form amyloid. 
    • The Tau tangles kill nerve cells.  LMTX is a drug treatment targeted at these tangles. 
    • The brain becomes inflamed resulting in the killing of many more nerve cells. 
    as a behavioral disorder (Jul 2016)
  • Boston University SOM's Matthew Pase finds sugary drinks tied to rapid brain aging and Alzheimer's is a dementia which correlates with deposition of amyloid plaques in the neurons.  As of 2015 there are 5 million Alzheimer's patients in the USA.  It was originally defined as starting in middle age which is rare, so it was a rare dementia.  But in 1980s it was redefined as any dementia without another known cause. Early indications include mood and behavioral changes (MBI) and memory and thinking problems (MCI).  Variants include: late-onset sporadic; with risk factors - ApoE4, presenilin, androgen deprivation therapy (Dec 2015).  There are multiple theories of the mechanism of Alzheimer's during aging: Allen Roses argues that it is due to gene alleles that limit the capacity of mitochondria to support neuron operation; It may be initiated by: stress induced HHV-6a, HHV7 herpes activation (Jun 2018) and or an increasingly leaky blood-brain barrier; and a subsequent innate immune response to the infections (May 2016).  The Alzheimer's pathway follows:
    • Plaques form and set off the formation of tangled thread-like tau protein.
      • Solanezumab aimed to inhibit plaque formation but clinical trials failed (Nov 2016).  
      • BACE inhibitors block an enzyme needed to form amyloid. 
    • The Tau tangles kill nerve cells.  LMTX is a drug treatment targeted at these tangles. 
    • The brain becomes inflamed resulting in the killing of many more nerve cells. 
    markers (Apr 2017)
  • Mount Sinai Icahn SOM's Dr. Joel Dudley's precision medicine is the integration of molecular research and clinical data through a taxonomy based on a knowledge network overlaid on an information commons.  It aims to support treatment of disease and remove the organ and symptom based methodological flaws in the ICD.  Supporters of the D.S.M. note the aggressive shift to precision medicine at the NIMH under Dr. Insel, constrained useful clinical research (Nov 2015). 
    (Big Data encompasses the IT systems and processes necessary to do population based data collection, management and analysis.  For the analysis to be useful it requires a hierarchy of supporting BI infrastructure:
    • Analytics utilization and integration delivered via SaaS and the Cloud to cope with the silos and data intensive nature. 
    • Analytics tools (BI) for PHM will be hard to develop.  
      • Complex data models must include clinical aspects of the patient specific data, including disease state population wide.  
      • A key aspect is providing clear signals about the nature of the data using data visualization. 
    • Data communication with the ability to exchange and transact.  HIEs and EMPI alliance approaches are all struggling to provide effective exchange. 
    • Data labeling and secure access and retreival.  While HIPAA was initially drafted as a secure MPI the index was removed from the legislation leaving the US without such a tool.  Silos imply that the security architecture will need to be robust. 
    • Raw data scrubbing, restructuring and standardization.  Even financial data is having to be restandarized shifting from ICD-9 to -10.  The intent is to transform the unstructured data via OCR and NLP to structured records to support the analytics process. 
    • Raw data warehousing is distributed across silos including PCP, Hospital system and network, cloud and SaaS for process, clinical and financial data. 
    • Data collection from the patient's proximate environment as well as provider CPOE, EHRs, workflow and process infrastructure.  The integration of the EHR into a big data collection tool is key.  
    ) study associates Roseoloviruses is a subset: HHV6 (HHV-6A, HHV-6B), HHV7; of Herpes viruses.  HHV6 typically infects human infants before age two, with symptoms of fever, diarrhea, and a rash known as roseola. 
    : HHV-6A is a double stranded DNA Roseolovirus.  It infects all tested humans and is neuroinflammatory, being seen in diseases such as MS. 
    , HHV7 is a double stranded DNA Roseolovirus. 
    ; with Alzheimer's disease is a dementia which correlates with deposition of amyloid plaques in the neurons.  As of 2015 there are 5 million Alzheimer's patients in the USA.  It was originally defined as starting in middle age which is rare, so it was a rare dementia.  But in 1980s it was redefined as any dementia without another known cause. Early indications include mood and behavioral changes (MBI) and memory and thinking problems (MCI).  Variants include: late-onset sporadic; with risk factors - ApoE4, presenilin, androgen deprivation therapy (Dec 2015).  There are multiple theories of the mechanism of Alzheimer's during aging: Allen Roses argues that it is due to gene alleles that limit the capacity of mitochondria to support neuron operation; It may be initiated by: stress induced HHV-6a, HHV7 herpes activation (Jun 2018) and or an increasingly leaky blood-brain barrier; and a subsequent innate immune response to the infections (May 2016).  The Alzheimer's pathway follows:
    • Plaques form and set off the formation of tangled thread-like tau protein.
      • Solanezumab aimed to inhibit plaque formation but clinical trials failed (Nov 2016).  
      • BACE inhibitors block an enzyme needed to form amyloid. 
    • The Tau tangles kill nerve cells.  LMTX is a drug treatment targeted at these tangles. 
    • The brain becomes inflamed resulting in the killing of many more nerve cells. 
    , judged by changes in the entorinal cortex is a main limbic association area between the hippocampus and the neocortex, in the medial temporal lobe.  It is a hub for memory and navigation. 
    , hippocampus is a part of the brain involved in the temporary storage or coding of long-term episodic memory.  Memory formation in the cells of the hippocampus uses the MAP kinase signalling network which is impacted by sleep deprivation.  The hippocampus dependent memory system is directly affected by cholinergic changes throughout the wake-sleep cycle.  Increased acetylcholine during REM sleep promotes information attained during wakefulness to be stored in the hippocampus by suppressing previous excitatory connections while facilitating encoding without interference from previously stored information.  During slow-wave sleep low levels of acetylcholine cause the release of the suppression and allow for spontaneous recovery of hippocampal neurons resulting in memory consolidation.  It was initially associated with memory formation by McGill University's Dr. Brenda Milner, via studies of 'HM' Henry Molaison, whose medial temporal lobes had been surgically destroyed leaving him unable to create new memories.  The size of neurons' dendritic trees expands and contracts over a female rat's ovulatory cycle, with the peak in size and cognitive skills at the estrogen high point.  Adult neurogenesis occurs in the hippocampus (3% of neurons are replaced each month) where the new neurons integrate into preexisting circuits.  It is enhanced by learning, exercise, estrogen, antidepressants, environmental enrichment, and brain injury and inhibited by various stressors explains Sapolsky.  Prolonged stress makes the hippocampus atrophy.  He notes the new neurons are essential for integrating new information into preexisting schemas -- learning that two things you thought were the same are actually different. 
    , promoter enrichments for C2H2 zink finger is a large set of finger like binding domains in mammalian transcription factors with a Cys2-His2 (C2H2) fold group, which can bind in the major groove of DNA. 
    transcription factor are enzymes which associate with a transcription complex to bind to the DNA and control its transcription and hence translation into proteins.  The regulation of DNA transcription and protein synthesis are reviewed by Tsonis.  Transcription factors allow environmental state to become reflected in the control of DNA transcription.  Transcription factors can regulate multiple genes, allowing network effects & multiple transcription factors can regulate a gene allowing sophisticated control processes.  In AWF the transcription, translation and deployment infrastructure of the eukaryotic cell has been abstracted in a codelet based implementation. 
    binding motifs and signalling, is an emergent capability which is used by cooperating agents to support coordination & rival agents to support control and dominance.  In eukaryotic cells signalling is used extensively.  A signal interacts with the exposed region of a receptor molecule inducing it to change shape to an activated form.  Chains of enzymes interact with the activated receptor relaying, amplifying and responding to the signal to change the state of the cell.  Many of the signalling pathways pass through the nuclear membrane and interact with the DNA to change its state.  Enzymes sensitive to the changes induced in the DNA then start to operate generating actions including sending further signals.  Cell signalling is reviewed by Helmreich.  Signalling is a fundamental aspect of CAS theory and is discussed from the abstract CAS perspective in signals and sensors.  In AWF the eukaryotic signalling architecture has been abstracted in a codelet based implementation.  To be credible signals must be hard to fake.  To be effective they must be easily detected by the target recipient.  To be efficient they are low cost to produce and destroy. 
    links with ApoE4 is a gene variant which produces the E4 variant of APOE.  It is a risk-factor for late-onset sporadic Alzheimer's disease.  Being homozygote for E4 does not imply getting Alzheimer's but does increase the risk 20 fold.  ApoE2 may reduce the risk of Alzheimer's.  It appears that ApoE4 differentially affects women.  Apoe4 is known to be broken down into fragments which impare mitochondrial operation.  It also promotes amyloid plaque buildup.  Therapies are being developed based on small molecules which reshape ApoE4 to be more like ApoE3 reducing the breakdown.   
    . It seems likely that after remaining dormant for years the virus is a relatively small capsule containing genetic material which utilizes the cellular infrastructure of its target host to replicate its genetic material and operational proteins.  The relationship with the host is short term, relative to parasites, with the virus entering the host cell, leveraging the host infrastructure to replicate its self massively and then exiting the host cell by rupturing it. 
    activates (stressor is a multi-faceted condition reflecting high cortisol levels.  Dr. Robert Sapolsky's studies of baboons indicate that stress helps build readiness for fight or flight.  As these actions occur the levels of cortisol return to the baseline rate.  A stressor is anything that disrupts the regular homeostatic balance.  The stress response is the array of neural and endocrine changes that occur to respond effectively to the crisis and reestablish homeostasis. 
    • The short term response to the stressor
      • activates the amygdala which: Stimulates the brain stem resulting in inhibition of the parasympathetic nervous system and activation of the sympathetic nervous system with the hormones epinephrine and norepinephrine deployed around the body, Activates the PVN which generates a cascade resulting in glucocorticoid secretion to: get energy to the muscles with increased blood pressure for a powerful response.  The brain's acuity and cognition are stimulated.  The immune system is stimulated with beta-endorphin and repair activities curtail.  But when the stressor is
    • long term: loneliness, debt; and no action is necessary, or possible, long term damage ensues.  Damage from such stress may only occur in specific situations: Nuclear families coping with parents moving in.  Sustained stress provides an evolved amplifier of a position of dominance and status.  It is a strategy in female aggression used to limit reproductive competition.  Sustained stress:
      • Stops the frontal cortex from ensuring we do the harder thing, instead substituting amplification of the individual's propensity for risk-taking and impairing risk assessment! 
      • Activates the integration between the thalamus and amygdala. 
        • Acts differently on the amygdala in comparison to the frontal cortex and hippocampus: Stress strengthens the integration between the Amygdala and the hippocampus, making the hippocampus fearful. 
        • BLA & BNST respond with increased BDNF levels and expanded dendrites persistently increasing anxiety and fear conditioning. 
      • Makes it easier to learn a fear association and to consolidate it into long-term memory.  Sustained stress makes it harder to unlearn fear by making the prefrontal cortex inhibit the BLA from learning to break the fear association and weakening the prefrontal cortex's hold over the amygdala.  And glucocorticoids decrease activation of the medial prefrontal cortex during processing of emotional faces.  Accuracy of assessing emotions from faces suffers.  A terrified rat generating lots of glucocorticoids will cause dendrites in the hippocampus to atrophy but when it generates the same amount from excitement of running on a wheel the dendrites expand.  The activation of the amygdala seems to determine how the hippocampus responds. 
      • Depletes the nucleus accumbens of dopamine biasing rats toward social subordination and biasing humans toward depression. 
      • Disrupts working memory by amplifying norepinephrine signalling in the prefrontal cortex and amygdala to prefrontal cortex signalling until they become destructive.  It also desynchronizes activation in different frontal lobe regions impacting shifting of attention.  
      • Increases the risk of autoimmune disease (Jan 2017) 
    • During depression, stress inhibits dopamine signalling.  
    • Strategies for stress reduction include: Mindfulness. 
    ) & generates an immune has to support and protect an inventory of host cell types, detect and respond to invaders and maintain the symbiont equilibrium within the microbiome.  It detects microbes which have breached the secreted mucus barrier, driving them back and fortifying the barrier.  It culls species within the microbiome that are expanding beyond requirements.  It destroys invaders who make it into the internal transport networks.  As part of its initialization it has immune cells which suppress the main system to allow the microbiome to bootstrap.  The initial microbiome is tailored by the antibodies supplied from the mother's milk while breastfeeding.  The immune system consists of two main parts the older non-adaptive part and the newer adaptive part.  The adaptive part achieves this property by being schematically specified by DNA which is highly variable.  By rapid reproduction the system recombines the DNA variable regions in vast numbers of offspring cells which once they have been shown not to attack the host cell lines are used as templates for interacting with any foreign body (antigen).  When the immune cell's DNA hyper-variable regions are expressed as y-shaped antibody proteins they typically include some receptor like structures which match the surfaces of the typical antigen.  Once the antibody becomes bound to the antigen the immune system cells can destroy the invader. 
    response that stimulates plaques which kill neurons, specialized eukaryotic cells include channels which control flows of sodium and potassium ions across the massively extended cell membrane supporting an electro-chemical wave which is then converted into an outgoing chemical signal transmission from synapses which target nearby neuron or muscle cell receptors.  Neurons are supported by glial cells.  Neurons include a:
    • Receptive element - dendrites
    • Transmitting element - axon and synaptic terminals
    • Highly variable DNA schema using transposons. 
    (Jun 2018)
  • Alzheimer's is a dementia which correlates with deposition of amyloid plaques in the neurons.  As of 2015 there are 5 million Alzheimer's patients in the USA.  It was originally defined as starting in middle age which is rare, so it was a rare dementia.  But in 1980s it was redefined as any dementia without another known cause. Early indications include mood and behavioral changes (MBI) and memory and thinking problems (MCI).  Variants include: late-onset sporadic; with risk factors - ApoE4, presenilin, androgen deprivation therapy (Dec 2015).  There are multiple theories of the mechanism of Alzheimer's during aging: Allen Roses argues that it is due to gene alleles that limit the capacity of mitochondria to support neuron operation; It may be initiated by: stress induced HHV-6a, HHV7 herpes activation (Jun 2018) and or an increasingly leaky blood-brain barrier; and a subsequent innate immune response to the infections (May 2016).  The Alzheimer's pathway follows:
    • Plaques form and set off the formation of tangled thread-like tau protein.
      • Solanezumab aimed to inhibit plaque formation but clinical trials failed (Nov 2016).  
      • BACE inhibitors block an enzyme needed to form amyloid. 
    • The Tau tangles kill nerve cells.  LMTX is a drug treatment targeted at these tangles. 
    • The brain becomes inflamed resulting in the killing of many more nerve cells. 
    (May 2014May 2016)
  • Obama brain initiative (Sep 2015)
  • Brain maps (Connectome based Jul 2016)
  • Syngenta's Paraquat is NN-dimethyl-44-bipyridinium dichloride, a systemic weed killer, used on oranges, coffee and suger cane, manufactured and sold by the Swiss pesticide company Syngenta.  It is banned in the EU, but still allowed to be sold and used in the US.  Drinking even a sip can be lethal.  Recent research by the NIH links paraquat to Parkinson's disease.  The 2011 research found Iowa and North Carolina farmers and family members that handled paraquat or rotenone were 2.5 times more likely to develop Parkinson's disease.  A 2012 study found paraquat increased the likelihood 11 fold for people with certain genetic variations.  The link is disputed by Syngenta. 
    linked by N.I.H. is the National Institute of Health, Bethesda Maryland.  It is the primary federal agency for the support and conduct of biomedical and behavioral research.  It is also one of the four US special containment units of the CDC.   to Parkinson's disease corresponds to the breakdown of certain interneurons in the brain.  It is not fully understood why this occurs.  Dopamine system neuron breakdown generates the classical symptoms of tremors and rigidity.  In some instances an uncommon LRRK2 gene mutation confers a high risk of Parkinson's disease.  In rare cases Italian and Greek families are impacted in their early forties and fifties resulting from a single letter mutation in alpha-synuclein which alters the alpha-synuclein protein causing degeneration in the substantia nigra.  But poisoning from MPTP has also been shown to destroy dopamine system neurons.  Paraquat has also been linked to Parkinson's disease.  Parkinson's disease does not directly kill many sufferers.  But it impacts swallowing which encourages development of pneumonia through inhaling or aspirating food.  And it undermines balance which can increase the possibility of falls.  Dememtia can also develop. 
    E.P.A. is the Environmental Protection Agency of the Federal government. 
    considers restrictions in US is the United States of America.   (Dec 2016)
  • Temporal Interference is a technique for targeting electrical stimulation at neurons within a brain by superposing two very high frequency electronic fields which only interfere constructively at the target neuron and at a low enough frequency to have an effect on the neuron. 
    technique developed by MIT is Massachusetts Institute of Technology.   Picower Institute of Learning's Tsai shows promise in mice (Jun 2017)
  • Brigham & Women's finds mothers' sounds needed for babies' brains to grow (Feb 2015)
  • McGurk effect is an illusion, described by Harry McGurk and John MacDonald, where a video shows a person speaking, and saying 'da da da da'.  But on closing your eyes you hear what is being said as 'ba ba ba'.   The illusion is generated by setting up conflicting signals: The mouth is moving to say 'ga'; while the sound is 'ba'.  the brain resolves the conflict into a single intermediate percept 'da'.  The illusion demonstrates how late in the processing chain and reconstructed our conscious experience is.  Imaging indicates the illusion is constructud in the frontal lobes and or superior temporal sulcus and is then sent back to the early sensory regions. 
    (Feb 2017)
  • Memories in the brain includes functionally different types: Declarative (episodic and semantic), Implicit, Procedural, Spatial, Temporal, Verbal; Hebb noted that glutamate receptive neurons learn by (NMDA channel based) synaptic strengthening.  This strengthening is sustained by subsequent LTP.  The non-realtime learning and planning processes operate through consciousness using the working memory structures, and then via sleep, the salient ones are consolidated while the rest are destroyed and garbage collected.   actively destroyed in fruit flies using Rac is a class of small monomeric GTP-binding proteins including Rac1 and Rac2.  Rac GTPases are implicated in memory removal (Feb 2010) and control of cytoskeleton assembly. 
    (Feb 2010
  • Purpose of sleep facilitates salient memory formation and removal of non-salient memories.  The five different stages of the nightly sleep cycles support different aspects of memory formation.  The sleep stages follow Pre-sleep and include: Stage one characterized by light sleep and lasting 10 minutes, Stage two where theta waves and sleep spindles occur, Stage three and Stage four together represent deep slow-wave sleep (SWS) with delta waves, Stage five is REM sleep; sleep cycles last between 90-110 minutes each and as the night progresses SWS times reduce and REM times increase.   Sleep includes the operation of synapse synthesis and maintenance through DNA based activity including membrane trafficking, synaptic vesicle recycling, myelin structural protein formation and cholesterol and protein synthesis. 
    is to forget.  The mechanism includes removing synapses, a neuron structure which provides a junction with other neurons.  It generates signal molecules, either excitatory or inhibitory, which are kept in vesicles until the synapse is stimulated when the signal molecules are released across the synaptic cleft from the neuron.  The provisioning of synapses is under genetic control and is part of long term memory formation as identified by Eric Kandel.  Modulation signals (from slow receptors) initiate the synaptic strengthening which occurs in memory. 
    Wisconsin-Madison's de Vivo supports synaptic homeostasis is Tonini & Cirelli's hypothesis that proposes sleep-wake cycles cause generalized synaptic weakening which leads to down-selection of weak synapses.  Pruning does not strike every synapse.  They argue that well established memories are left intact. 
    Johns Hopkins's Diering shows Homer1A is the product of the Homer1 gene short form splice.  The HomeriA has an EVH1 domain which competes with the long splice forms such as Homer1B and Homer1C, uncoupling mGluR signalling and shrinking dendritic spline structures.  Homer1a is expressed by neuronal activity.   is shipped to synapses where in sleep it pairs back synapses (Feb 2017). 
  • Northeastern & Mass. General hospital psychologist Feldman Barrett's fMRI is functional magnetic resonance imaging.  Seiji Ogawa leveraged the coupling of neuronal circuit activity and blood flow through the associated glial cells to build a 3 dimensional picture of brain cell activity.  As haemoglobin gives up its oxygen to support the neural activity it becomes magnetic and acts as a signal detected by the fMRI.  fMRI easily visualizes the state of activity in the living human brain at millimeter resolution, up to several times a second but it cannot track the time course of neural firing so it is augmented with EEG. 
    studies found superagers' is a older person who remains as mentally agile: in terms of memory and attention; as a twenty year old according to neurologist Marsel Mesulam.  In fMRI analyses superagers are found to retain well developed 'emotional' brain regions: midcingulate cortex, anterior insula; which are major hubs for general communication throughout the brain.  In comparison in other older people these regions have thined and their mental responses are relatively poor.  The superagers maintain the communication networks by regularly performing hard tiring and taxing mental or physical work (Jan 2016). 
    hard mental work sustains their major neural communication networks (Jan 2017)
  • Cohen & Andersen's review common reference frames is a coordinate system (set of axis) centered on a particular aspect of the situation that describes the location of an object.  The brain supports many frames of reference including for vision (2009), hearing & movement planning (Jul 2002).  Auditory stimuli are initially coded in a head-centered reference frame.  The motor system codes actions in reference frames that depend on motor effectors.  Eye movements are codes in a reference frame that depends on the difference between current and desired arm position.  It is often necessary to transform the location representation of the sensory stimulus into a representation appropriate for the motor act.  An eye-centered reference frame depends on the location of the eye in the head.  A retinotopic reference frame depends on the retinal location that is activated by a visual stimulus.  Double-saccade tasks show how the location of the second visual target is coded relative to current and desired eye position (eye-centered).  
    for movement plans in the posterior parietal cortex of the cerebral cortex is at the back of the brain divided into two.  It associates sensory signals of various modalities with:
    • Details about the location of the body and
    • Models interpreting touch, visual signals, language and mathematics. 
    (Jul 2002)






  • Jul 2016 NYT A new Harbinger of Alzheimers

    Pam Belluck reports personality differs in at least five key ways:
    • Extroversion-introversion - whether the person gains energy from socializing or retiring
    • Neuroticism-stability - does a person worry or are they calm and self-satisfied
    • Agreeableness-antagonism - is a person courteous & trusting or rude and suspicious
    • Conscientiousness-un-directedness - is a person careful or careless
    • Openness-non-openness - are they daring or conforming
    changes could indicate the earliest stage of dementia is a classification of memory impairment, constrained feelings and enfeebled or extinct intellect.  The most common form for people under 60 is FTD.  Dementia has multiple causes including: vascular disease (inducing VCI) including strokes, head trauma, syphilis and mercury poisoning for treating syphilis, alcoholism, B12 deficiency (Sep 2016), privation, Androgen deprivation therapy (Oct 2016), stress, Parkinson's disease and prion infections such as Alzheimer's disease, CJD and kuru.  The condition is typically chronic and treatment long term (Laguna Honda ward) and is predicted by Stanley Prusiner to become a major burden on the health system.  It appears to develop faster in women than men.  

    Alzheimer is a dementia which correlates with deposition of amyloid plaques in the neurons.  As of 2015 there are 5 million Alzheimer's patients in the USA.  It was originally defined as starting in middle age which is rare, so it was a rare dementia.  But in 1980s it was redefined as any dementia without another known cause. Early indications include mood and behavioral changes (MBI) and memory and thinking problems (MCI).  Variants include: late-onset sporadic; with risk factors - ApoE4, presenilin, androgen deprivation therapy (Dec 2015).  There are multiple theories of the mechanism of Alzheimer's during aging: Allen Roses argues that it is due to gene alleles that limit the capacity of mitochondria to support neuron operation; It may be initiated by: stress induced HHV-6a, HHV7 herpes activation (Jun 2018) and or an increasingly leaky blood-brain barrier; and a subsequent innate immune response to the infections (May 2016).  The Alzheimer's pathway follows:
    • Plaques form and set off the formation of tangled thread-like tau protein.
      • Solanezumab aimed to inhibit plaque formation but clinical trials failed (Nov 2016).  
      • BACE inhibitors block an enzyme needed to form amyloid. 
    • The Tau tangles kill nerve cells.  LMTX is a drug treatment targeted at these tangles. 
    • The brain becomes inflamed resulting in the killing of many more nerve cells. 
    's experts want to recognize and measure sharp changes in mood and behavior that can precede the memory and thinking problems of dementia.  They are proposing a new diagnosis: MBI is mild behavioral impairment, a proposed early diagnosis for dementia.  It recognizes and measures something that some experts say is often overlooked: Sharp changes in mood and behavior can precede the memory and thinking problems of dementia.  But there is a risk of over diagnosis which could leave many people unnecessarily fearful about their futures and seeking more tests.  And the diagnosis could affect insurance premiums.  To imply MBI the symptoms must last for more than six months and be a fundamental change in behavior.  
    which would precede MCI is mild cognitive impairment, a sense of memory loss despite normal performance on memory tests.  It is often associated with Alzheimer's disease. 


    University of Calgary neuropsychiatrist Dr. Zahinoor Ismail notes that studies and anecdotes suggest emotional are low level agents distributed across the brain and body which associate, via the amygdala and rich club hubs, important environmental signals with encoded high speed sensors, and distributed programs of action to model: predict, prioritize guidance signals, select and respond effectively, coherently and rapidly to the initial signal.  The majority of emotion centered brain regions interface to the midbrain through the hypothalamus.  The most accessible signs of emotions are the hard to control and universal facial expressions.  Emotions provide prioritization for conscious access given that an animal has only one body, but possibly many cells, with which to achieve its highest level goals.  Because of this emotions clash with group goals and are disparaged by the powerful.  Evolutionary psychology argues evolution shaped human emotions during the long period of hunter-gatherer existence in the African savanna.  Human emotions are universal and include: Anger, Appreciation of natural beauty, Disgust, Fear, Gratitude, Grief, Guilt, Happiness, Honor, Jealousy, Liking, Love, Rage, Romantic love, Lust for revenge, Passion, Sadness, Self-control, Shame, Sympathy, Surprise; and the sham emotions and distrust induced by reciprocal altruism.   and behavioral changes are symptomatic of dementia, not seperate from it.  People with MCI that also have mood and behavior changes develop full-blown dementia faster and do much worse over time.  Autopsies show they had more brain damage. 


    Jun 2018 NYT A Common Virus May Play Role in Alzheimer's Disease, Study Finds

    Pam Belluck reports it has been a controversial theory about Alzheimer's disease is a dementia which correlates with deposition of amyloid plaques in the neurons.  As of 2015 there are 5 million Alzheimer's patients in the USA.  It was originally defined as starting in middle age which is rare, so it was a rare dementia.  But in 1980s it was redefined as any dementia without another known cause. Early indications include mood and behavioral changes (MBI) and memory and thinking problems (MCI).  Variants include: late-onset sporadic; with risk factors - ApoE4, presenilin, androgen deprivation therapy (Dec 2015).  There are multiple theories of the mechanism of Alzheimer's during aging: Allen Roses argues that it is due to gene alleles that limit the capacity of mitochondria to support neuron operation; It may be initiated by: stress induced HHV-6a, HHV7 herpes activation (Jun 2018) and or an increasingly leaky blood-brain barrier; and a subsequent innate immune response to the infections (May 2016).  The Alzheimer's pathway follows:
    • Plaques form and set off the formation of tangled thread-like tau protein.
      • Solanezumab aimed to inhibit plaque formation but clinical trials failed (Nov 2016).  
      • BACE inhibitors block an enzyme needed to form amyloid. 
    • The Tau tangles kill nerve cells.  LMTX is a drug treatment targeted at these tangles. 
    • The brain becomes inflamed resulting in the killing of many more nerve cells. 
    , often dismissed by experts as a sketchy cul-de-sac off the beaten path from mainstream research. 

    A new study, published in Neuron, associates Roseoloviruses is a subset: HHV6 (HHV-6A, HHV-6B), HHV7; of Herpes viruses.  HHV6 typically infects human infants before age two, with symptoms of fever, diarrhea, and a rash known as roseola. 
    : HHV-6A is a double stranded DNA Roseolovirus.  It infects all tested humans and is neuroinflammatory, being seen in diseases such as MS. 
    , HHV7 is a double stranded DNA Roseolovirus. 
    ; with Alzheimer's disease, judged by changes in the entorinal cortex is a main limbic association area between the hippocampus and the neocortex, in the medial temporal lobe.  It is a hub for memory and navigation. 
    , hippocampus is a part of the brain involved in the temporary storage or coding of long-term episodic memory.  Memory formation in the cells of the hippocampus uses the MAP kinase signalling network which is impacted by sleep deprivation.  The hippocampus dependent memory system is directly affected by cholinergic changes throughout the wake-sleep cycle.  Increased acetylcholine during REM sleep promotes information attained during wakefulness to be stored in the hippocampus by suppressing previous excitatory connections while facilitating encoding without interference from previously stored information.  During slow-wave sleep low levels of acetylcholine cause the release of the suppression and allow for spontaneous recovery of hippocampal neurons resulting in memory consolidation.  It was initially associated with memory formation by McGill University's Dr. Brenda Milner, via studies of 'HM' Henry Molaison, whose medial temporal lobes had been surgically destroyed leaving him unable to create new memories.  The size of neurons' dendritic trees expands and contracts over a female rat's ovulatory cycle, with the peak in size and cognitive skills at the estrogen high point.  Adult neurogenesis occurs in the hippocampus (3% of neurons are replaced each month) where the new neurons integrate into preexisting circuits.  It is enhanced by learning, exercise, estrogen, antidepressants, environmental enrichment, and brain injury and inhibited by various stressors explains Sapolsky.  Prolonged stress makes the hippocampus atrophy.  He notes the new neurons are essential for integrating new information into preexisting schemas -- learning that two things you thought were the same are actually different. 
    , and signalling, is an emergent capability which is used by cooperating agents to support coordination & rival agents to support control and dominance.  In eukaryotic cells signalling is used extensively.  A signal interacts with the exposed region of a receptor molecule inducing it to change shape to an activated form.  Chains of enzymes interact with the activated receptor relaying, amplifying and responding to the signal to change the state of the cell.  Many of the signalling pathways pass through the nuclear membrane and interact with the DNA to change its state.  Enzymes sensitive to the changes induced in the DNA then start to operate generating actions including sending further signals.  Cell signalling is reviewed by Helmreich.  Signalling is a fundamental aspect of CAS theory and is discussed from the abstract CAS perspective in signals and sensors.  In AWF the eukaryotic signalling architecture has been abstracted in a codelet based implementation.  To be credible signals must be hard to fake.  To be effective they must be easily detected by the target recipient.  To be efficient they are low cost to produce and destroy. 
    links with ApoE4 is a gene variant which produces the E4 variant of APOE.  It is a risk-factor for late-onset sporadic Alzheimer's disease.  Being homozygote for E4 does not imply getting Alzheimer's but does increase the risk 20 fold.  ApoE2 may reduce the risk of Alzheimer's.  It appears that ApoE4 differentially affects women.  Apoe4 is known to be broken down into fragments which impare mitochondrial operation.  It also promotes amyloid plaque buildup.  Therapies are being developed based on small molecules which reshape ApoE4 to be more like ApoE3 reducing the breakdown.   


    The findings imply new treatment strategies:
    • Vaccines & drugs to preempt infections
    • Screen people for the genes that increase vulnerability to these infections. 

    Lead Author Dr. Joel Dudley, is a Big Data encompasses the IT systems and processes necessary to do population based data collection, management and analysis.  For the analysis to be useful it requires a hierarchy of supporting BI infrastructure:
    • Analytics utilization and integration delivered via SaaS and the Cloud to cope with the silos and data intensive nature. 
    • Analytics tools (BI) for PHM will be hard to develop.  
      • Complex data models must include clinical aspects of the patient specific data, including disease state population wide.  
      • A key aspect is providing clear signals about the nature of the data using data visualization. 
    • Data communication with the ability to exchange and transact.  HIEs and EMPI alliance approaches are all struggling to provide effective exchange. 
    • Data labeling and secure access and retreival.  While HIPAA was initially drafted as a secure MPI the index was removed from the legislation leaving the US without such a tool.  Silos imply that the security architecture will need to be robust. 
    • Raw data scrubbing, restructuring and standardization.  Even financial data is having to be restandarized shifting from ICD-9 to -10.  The intent is to transform the unstructured data via OCR and NLP to structured records to support the analytics process. 
    • Raw data warehousing is distributed across silos including PCP, Hospital system and network, cloud and SaaS for process, clinical and financial data. 
    • Data collection from the patient's proximate environment as well as provider CPOE, EHRs, workflow and process infrastructure.  The integration of the EHR into a big data collection tool is key.  
    researcher, who was looking for drug associations within Alzheimer's disease studies.  But instead he kept finding associations with Roseoloviruses.  It is proposed that these viruses is a relatively small capsule containing genetic material which utilizes the cellular infrastructure of its target host to replicate its genetic material and operational proteins.  The relationship with the host is short term, relative to parasites, with the virus entering the host cell, leveraging the host infrastructure to replicate its self massively and then exiting the host cell by rupturing it. 
    , reactivated from a dormant state within neurons, specialized eukaryotic cells include channels which control flows of sodium and potassium ions across the massively extended cell membrane supporting an electro-chemical wave which is then converted into an outgoing chemical signal transmission from synapses which target nearby neuron or muscle cell receptors.  Neurons are supported by glial cells.  Neurons include a:
    • Receptive element - dendrites
    • Transmitting element - axon and synaptic terminals
    • Highly variable DNA schema using transposons. 
    by stress is a multi-faceted condition reflecting high cortisol levels.  Dr. Robert Sapolsky's studies of baboons indicate that stress helps build readiness for fight or flight.  As these actions occur the levels of cortisol return to the baseline rate.  A stressor is anything that disrupts the regular homeostatic balance.  The stress response is the array of neural and endocrine changes that occur to respond effectively to the crisis and reestablish homeostasis. 
    • The short term response to the stressor
      • activates the amygdala which: Stimulates the brain stem resulting in inhibition of the parasympathetic nervous system and activation of the sympathetic nervous system with the hormones epinephrine and norepinephrine deployed around the body, Activates the PVN which generates a cascade resulting in glucocorticoid secretion to: get energy to the muscles with increased blood pressure for a powerful response.  The brain's acuity and cognition are stimulated.  The immune system is stimulated with beta-endorphin and repair activities curtail.  But when the stressor is
    • long term: loneliness, debt; and no action is necessary, or possible, long term damage ensues.  Damage from such stress may only occur in specific situations: Nuclear families coping with parents moving in.  Sustained stress provides an evolved amplifier of a position of dominance and status.  It is a strategy in female aggression used to limit reproductive competition.  Sustained stress:
      • Stops the frontal cortex from ensuring we do the harder thing, instead substituting amplification of the individual's propensity for risk-taking and impairing risk assessment! 
      • Activates the integration between the thalamus and amygdala. 
        • Acts differently on the amygdala in comparison to the frontal cortex and hippocampus: Stress strengthens the integration between the Amygdala and the hippocampus, making the hippocampus fearful. 
        • BLA & BNST respond with increased BDNF levels and expanded dendrites persistently increasing anxiety and fear conditioning. 
      • Makes it easier to learn a fear association and to consolidate it into long-term memory.  Sustained stress makes it harder to unlearn fear by making the prefrontal cortex inhibit the BLA from learning to break the fear association and weakening the prefrontal cortex's hold over the amygdala.  And glucocorticoids decrease activation of the medial prefrontal cortex during processing of emotional faces.  Accuracy of assessing emotions from faces suffers.  A terrified rat generating lots of glucocorticoids will cause dendrites in the hippocampus to atrophy but when it generates the same amount from excitement of running on a wheel the dendrites expand.  The activation of the amygdala seems to determine how the hippocampus responds. 
      • Depletes the nucleus accumbens of dopamine biasing rats toward social subordination and biasing humans toward depression. 
      • Disrupts working memory by amplifying norepinephrine signalling in the prefrontal cortex and amygdala to prefrontal cortex signalling until they become destructive.  It also desynchronizes activation in different frontal lobe regions impacting shifting of attention.  
      • Increases the risk of autoimmune disease (Jan 2017) 
    • During depression, stress inhibits dopamine signalling.  
    • Strategies for stress reduction include: Mindfulness. 
    or illness, amplify a pathological immune system has to support and protect an inventory of host cell types, detect and respond to invaders and maintain the symbiont equilibrium within the microbiome.  It detects microbes which have breached the secreted mucus barrier, driving them back and fortifying the barrier.  It culls species within the microbiome that are expanding beyond requirements.  It destroys invaders who make it into the internal transport networks.  As part of its initialization it has immune cells which suppress the main system to allow the microbiome to bootstrap.  The initial microbiome is tailored by the antibodies supplied from the mother's milk while breastfeeding.  The immune system consists of two main parts the older non-adaptive part and the newer adaptive part.  The adaptive part achieves this property by being schematically specified by DNA which is highly variable.  By rapid reproduction the system recombines the DNA variable regions in vast numbers of offspring cells which once they have been shown not to attack the host cell lines are used as templates for interacting with any foreign body (antigen).  When the immune cell's DNA hyper-variable regions are expressed as y-shaped antibody proteins they typically include some receptor like structures which match the surfaces of the typical antigen.  Once the antibody becomes bound to the antigen the immune system cells can destroy the invader. 
    response, which leads to an accumulation of amyloid plaques.  It is likely that other pathogens may generate a similar response. 

    Many Alzheimer's researchers see no causal link from viruses to Alzheimer's, noting that the disease may increase the opportunity for infection. 

    The new study:
    A further set of experiments, in mice & invitro brain cells, to be published soon, found HHV-6A and HHV7 generated a protective response in amyloid, resulting in the virus being held in plaque nets. 





    Sep 2015 NYT Putting Her Mind to How the Brain Works

    Claudia Dreifus reports that Dr. Cori Bargmann's mission to help lead a president's initiative starts with a search for the needed tools. 
    Dr. Bargmann was an M.I.T. graduate student when she discovered a gene HER2 is a gene encoding the protein 'human epidermal growth factor receptor 2', which is similar in structure to the native receptor HER1. 
    in rats that mutated to generate a cancer is the out-of-control growth of cells, which have stopped obeying their cooperative schematic planning and signalling infrastructure.  It results from compounded: oncogene, tumor suppressor, DNA caretaker; mutations in the DNA.  In 2010 one third of Americans are likely to die of cancer.  Cell division rates did not predict likelihood of cancer.  Viral infections are associated.  Radiation and carcinogen exposure are associated.  Lifestyle impacts the likelihood of cancer occurring: Drinking alcohol to excess, lack of exercise, Obesity, Smoking, More sun than your evolved melanin protection level; all significantly increase the risk of cancer occurring (Jul 2016).  .  Later other researchers noted that the same gene is altered in humans for a breast cancer is a variety of different cancerous conditions of the breast tissue.  World wide it is the leading type of cancer in women and is 100 times more common in women than men.  260,000 new cases of breast cancer will occur in the US in 2018 causing 41,000 deaths.  The varieties include: Hormone sensitive tumors that test negative for her2 (the most common type affecting three quarters of breast cancers in the US, BRCA1/2 positive, ductal carcinomas including DCIS, lobular carcinomas including LCIS.  Receptor presence on the cancer cells is used as a classification: Her2+/-, estrogen (ER)+/-, progesterone (PR)+/-.  Metastasis classes the cancer as stage 4.  Genetic risk factors include: BRCA, p53, PTEN, STK11, CHEK2, ATM, GATA3, BRIP1 and PALB2.  Treatments include: Tamoxifen, Raloxifene; where worrying racial disparities have been found (Dec 2013).  International studies indicate early stage breast cancer typed by a genomic test: Oncotype DX, MammaPrint; can be treated without chemotherapy (Aug 2016, Jun 2018)
    .  Bargmann's work in the rat cancer showed the immune system could attack the product of the gene.  Genentech then developed Herceptin: breast tumors grow rapidly because they respond via the human EGF receptor (HER), coded for by the gene 'Her2', to cell growth signal epidermal growth factor (EGF).  Herceptin inhibits the growth of the Her-2+ tumors by inhibiting the EGFR.   to deploy the immune system against the cell surface receptor product of Bargmann's gene. 

    She then moved on to working on the nervous system using the simple system C. elegans because its genes had been completely sequenced and it was transparent.  It's brain has 7,000 connections and 300 neurons.  So Bargmann could observe and "know what any cell does.  I know what it's connected to.  I know what genes it expresses."  For a researcher she noted that's a lot. 

    Bargmann notes that her work provides details about human brains because the genes are not very different.  In 1993 Bargmann showed that C. Eligans could smell.  She then moved the gene that is the sensor for an attractant and moved it to a different neuron that senses things the worm finds dangerous. Now the worm ran away from the attractant.  Bargmann said "This said that the odor-sensing nerve cells form an innate map where each one knows whether something is good or bad about the environment.  There's a completely unlearned internal set of preferences, a set of instincts about what's good and bad. 

    Bargmann explained the problem facing the 'brain innitiative'.  We have $100 million for the first year.  They had to prioritize some aspects of brain research that the $100 million would really make a difference.  The team agreed on a basic outline: Use the money for mapping brain activity in circuits and networks. 

    Bargmann says to do this they will do two steps:
    1. Create new and improved technologies to study the brain.  With better tools, all the neuroscience will move forward. 
    2. Apply these technologies to make discoveries about how the brain functions. 
    The theme is understanding brain activity, the flows of information through millions of interconnected nerve cells. 

    The long term goal is to use that knowledge to help prevent and treat brain disorders.  That may be a decade or two away. 


    May 2018 NYT For Women With Early Breast Cancer, Herceptin Treatment Can Be Much Shorter

    Denise Grady reports over the past 20 years, hundreds of thousands of women with breast cancer is a variety of different cancerous conditions of the breast tissue.  World wide it is the leading type of cancer in women and is 100 times more common in women than men.  260,000 new cases of breast cancer will occur in the US in 2018 causing 41,000 deaths.  The varieties include: Hormone sensitive tumors that test negative for her2 (the most common type affecting three quarters of breast cancers in the US, BRCA1/2 positive, ductal carcinomas including DCIS, lobular carcinomas including LCIS.  Receptor presence on the cancer cells is used as a classification: Her2+/-, estrogen (ER)+/-, progesterone (PR)+/-.  Metastasis classes the cancer as stage 4.  Genetic risk factors include: BRCA, p53, PTEN, STK11, CHEK2, ATM, GATA3, BRIP1 and PALB2.  Treatments include: Tamoxifen, Raloxifene; where worrying racial disparities have been found (Dec 2013).  International studies indicate early stage breast cancer typed by a genomic test: Oncotype DX, MammaPrint; can be treated without chemotherapy (Aug 2016, Jun 2018)
      have taken the drug Herceptin: breast tumors grow rapidly because they respond via the human EGF receptor (HER), coded for by the gene 'Her2', to cell growth signal epidermal growth factor (EGF).  Herceptin inhibits the growth of the Her-2+ tumors by inhibiting the EGFR.  , typically for a year or more.  The medicine, used to treat an aggressive form of the disease, is credited with saving many lives, but it also has some tough side effects, particularly damage to the heart. 

    A Cambridge University UK Persephone study, by Dr. Helena Earl, following thousands of women with early-stage breast cancer for five years found those treated for 6 months with Herceptin did as well as those treated for a year, the treatment cost was less and they had less side effects.  The patients will be tracked for 10 years.  A year was used in initial trials and had become the norm. 

    Roche (Genentech), said prior studies did not concur with the new UK study.  They noted that the F.D.A. Food and Drug Administration. 
    has only approved the 12 month protocol. 

    The results are likely to change protocols for treatment and highlight a valuable research process that pharmaceutical companies don't do. 





    Jun 2017 NYT New Electrical Brain Stimulation Technique Shows Promise in Mice

    Pam Belluck reports pulses of electricity delivered to the brain can help patients with Parkinson's disease corresponds to the breakdown of certain interneurons in the brain.  It is not fully understood why this occurs.  Dopamine system neuron breakdown generates the classical symptoms of tremors and rigidity.  In some instances an uncommon LRRK2 gene mutation confers a high risk of Parkinson's disease.  In rare cases Italian and Greek families are impacted in their early forties and fifties resulting from a single letter mutation in alpha-synuclein which alters the alpha-synuclein protein causing degeneration in the substantia nigra.  But poisoning from MPTP has also been shown to destroy dopamine system neurons.  Paraquat has also been linked to Parkinson's disease.  Parkinson's disease does not directly kill many sufferers.  But it impacts swallowing which encourages development of pneumonia through inhaling or aspirating food.  And it undermines balance which can increase the possibility of falls.  Dememtia can also develop. 
    , depression is a debilitating state which is facilitated by genetic predisposition - for example genes coding for relatively low serotonin levels; and an accumulation of traumatic events.  There is evidence of shifts in the sleep/wake cycle in affected individuals (Dec 2015).  The affected person will experience a pathological sense of loss of control, prolonged sadness, irritability, sleep disturbances, loss of appetite, and inability to experience pleasure.  It affects 12% of men and 20% of women.  It appears to be associated with androgen deprivation therapy treatment for prostate cancer (Apr 2016).  Chronic stress depletes the nucleus accumbens of dopamine, biasing humans towards depression.  Depression easily leads to following unhealthy pathways: drinking, overeating; which increase the risk of heart disease.   It has been associated with an aging related B12 deficiency (Sep 2016).  During depression, stress mediates inhibition of dopamine signalling.  There is an association between depression and particular brain regions: Hippocampal dendrite and spine number reductions, Dorsal raphe nucleus linked to loneliness, Abnormalities of the ACC.  Childhood adversity can increase depression risk by linking recollections of uncontrollable situations to overgeneralizations that life will always be terrible and uncontrollable.  Treatments include: CBT, UMHS depression management.  As of 2010 drug treatments take weeks to facilitate a response & many patients do not respond to the first drug applied, often prolonging the agony.   Genomic predictions of which treatment will be effective have not been possible because: Not all clinical depressions are the same, a standard definition of drug response is difficult;, obsessive-compulsive disorder and possibly other conditions.  But the available methods all have shortcomings: They either involve the risks of surgery, from implanting electrodes deep within the brain, or they stimulate from the skull's surface, limiting the ability to target electricity to the right brain areas. 

    Research by the MIT is Massachusetts Institute of Technology.   Pickower institute of learning & memory's Li-Huei Tsui reported in Cell experiments demonstrating temporal interference is a technique for targeting electrical stimulation at neurons within a brain by superposing two very high frequency electronic fields which only interfere constructively at the target neuron and at a low enough frequency to have an effect on the neuron. 
    of target neurons, specialized eukaryotic cells include channels which control flows of sodium and potassium ions across the massively extended cell membrane supporting an electro-chemical wave which is then converted into an outgoing chemical signal transmission from synapses which target nearby neuron or muscle cell receptors.  Neurons are supported by glial cells.  Neurons include a:
    • Receptive element - dendrites
    • Transmitting element - axon and synaptic terminals
    • Highly variable DNA schema using transposons. 
    in mice. 

    Some researchers question if the technique can deliver 130 hertz frequencies.  Others wonder if the technique would be able to support treatment for Parkinson's disease where the stimulation would have to be continuous.  It is also questioned if the targeting can be precise and localized enough to be useful. 



    Jul 2016 NYT In Brain Map, Mind's Gears Get Rare Look

    Carl Zimmer reports the brain looks like a featureless expanse of folds and bulges, but it's actually carved up into invisible territories.  Each is specialized: Some groups of neurons become active when we recognize faces, others when we read, others when we raise our hands. 

    Neuroscience researchers at Washington University School of Medicine lead by Dr. Matthew Glasser, associated with the HumanConnectome published a new larger Brodmann type map of brain regions.  It includes: 97 unknown/forgotten regions, 84 familiar Brodmann's areas in additional detail. 

    A computer used the connectome data to recognize discrete regions of the cortex based on myelination is the fatty insulating material deployed by Schwann cells & oligodendrocytes, both types of glial cells, around axons to improve their conduction rate.  In humans it is still occurring 25 years after birth.  It has great impact on long axons, in neurons that project over long distances, where it helps brain inter-region signalling.  The long development time of myelination allows for the later myelinated brain regions to be particularly shaped by the proximate environment. 
    , activity, etc.  The software can map any new brain in about one hour. 

    New area 55b is now viewed as working in tandem with Broca's area is the inferior frontal cortex.  It is involved with spoken language.  Lesions have resulted in an inability to speak or write even though language is understood.   on language processing. 




    Feb 2017 NYT When Mismatched Voices and Lips Make Your Brain Play Tricks

    Joanna Klein reports the good news is, the human brain is flexible and efficient.  This helps us make sense of the world.  But the bad news is, the human brain is flexible and efficient.  This means the brain can sometimes make mistakes. 

    Klein notes that the McGurk effect is an illusion, described by Harry McGurk and John MacDonald, where a video shows a person speaking, and saying 'da da da da'.  But on closing your eyes you hear what is being said as 'ba ba ba'.   The illusion is generated by setting up conflicting signals: The mouth is moving to say 'ga'; while the sound is 'ba'.  the brain resolves the conflict into a single intermediate percept 'da'.  The illusion demonstrates how late in the processing chain and reconstructed our conscious experience is.  Imaging indicates the illusion is constructud in the frontal lobes and or superior temporal sulcus and is then sent back to the early sensory regions. 
    has become more visible day-to-day with the bad sound synchronization delivered with streaming video. 

    Research by Baylor College neuroscientist's John Magnotti, Michael Beuchamp and Lin Zhu published in PLOS computational biology, reports the brain:





    Feb 2010 NYT Forgetting, With a Purpose

    Science times notes just why the brain erases certain memories in the brain includes functionally different types: Declarative (episodic and semantic), Implicit, Procedural, Spatial, Temporal, Verbal; Hebb noted that glutamate receptive neurons learn by (NMDA channel based) synaptic strengthening.  This strengthening is sustained by subsequent LTP.  The non-realtime learning and planning processes operate through consciousness using the working memory structures, and then via sleep, the salient ones are consolidated while the rest are destroyed and garbage collected.   has long been a topic of interest to scientists. 

    In US is the United States of America.   and China Dr. Yi Zhong of Cold Spring Harbor Laboratory and Tsinghua University reported in Cell, that fruit flies short-term memory is erased by the brain on purpose, so that new, more relevant memories can be recorded.  Rac is a class of small monomeric GTP-binding proteins including Rac1 and Rac2.  Rac GTPases are implicated in memory removal (Feb 2010) and control of cytoskeleton assembly. 
    participates in the erosion of the memories. 

    The researchers varied Rac levels in fruit flies while subjecting the flies to two situations:
    1. Foul smelling odor
    2. A different Foul smelling odor associated with an electric shock.  Under normal Rac levels the flies usually pick situation 1. 
    Researchers then switched which odor was associated with the shock.  The flies soon learned to pick situation 2, unless Rac was blocked when the flies would zigzag back and forth.  The researchers conclude Rac is required for the earlier short-term memory to be erased so it does not interfere with the later memory. 



    Jan 2017 NYT How to Become a 'Superager'

    In professor Lisa Feldman Barrett's NYT opinion she writes -- think about the people in your life who are 65 and over:  Some of them are experiencing the usual mental difficutlies of old age, like forgetfulness or a dwindling attention span.  Yet others somehow manager to remain mentally sharp.  [Barrett notes] her father-in-law, a retired doctor, is 83 and he still edits books and  runs several medical websites. 

    Feldman Barrett compared 17 superagers is a older person who remains as mentally agile: in terms of memory and attention; as a twenty year old according to neurologist Marsel Mesulam.  In fMRI analyses superagers are found to retain well developed 'emotional' brain regions: midcingulate cortex, anterior insula; which are major hubs for general communication throughout the brain.  In comparison in other older people these regions have thined and their mental responses are relatively poor.  The superagers maintain the communication networks by regularly performing hard tiring and taxing mental or physical work (Jan 2016). 
    with other similarly aged regular people using fMRI is functional magnetic resonance imaging.  Seiji Ogawa leveraged the coupling of neuronal circuit activity and blood flow through the associated glial cells to build a 3 dimensional picture of brain cell activity.  As haemoglobin gives up its oxygen to support the neural activity it becomes magnetic and acts as a signal detected by the fMRI.  fMRI easily visualizes the state of activity in the living human brain at millimeter resolution, up to several times a second but it cannot track the time course of neural firing so it is augmented with EEG. 
    brain scans.  They found that superagers were using hard work to remain sharp.  They observed the hard work was exercising the major brain communication hubs with vigorous exercise and strenuous mental effort.  They found the work had to be hard enough to make you feel bad. 

    Feldman Barrett makes the point that the major communication hubs are participating in many aspects of executive control, highlighting the failure of Dr. Paul MacLean's 1940s triune brain is Dr. Paul MacLean's popular but discredited 1940s theory of the brain.  He proposed a three layer structure:
    1. Reptilian inner brain containing circuits for basic survival; which is interfaced to layer 2 through the hypothalamus and together with the brain stem, spine and projections into the body make up the autonomic nervous system. 
    2. Limbic middle brain containing emotional circuits which signal layer 1 through the hypothalamus. 
    3. Rational outer brain which is uniquely human.  
    model, which predicts their separation.  Feldman Barrett argues "The human brain didn't evolve like a piece of sedimentary rock, with layers of increasing cognitive sophistication slowly accruing over time.  Rather (in the words of the neuroscientist Georg Striedter), brains evolve like companies do: they reorganize as they expand." 


    Spring 2017 Kent State Magazine Attention, Please

    Adam Piore reports MIT is Massachusetts Institute of Technology.   neuroscientist Earl Miller, Kent State BA 1985, continues to break new ground in the understanding of cognition is the ability to orchestrate thought and action in accordance with internal goals according to Princeton's Jonathan Cohen. 
    -- and his research may help us move beyond the limits of the brain's working memory is a dominant function of the dorsolateral prefrontal cortex and the areas it connects with.  Prefrontal neurons implement an active memory continuing to fire after the signal is gone for potentially dozens of seconds from the inferior temporal cortex (multi-sensory integration area) and lower level sensory neurons characterized by Hubel & Weisel, while the short-term memory task continues.  If the prefrontal cortex gets distracted the memory is lost from consciousness.  Earl Miller argues the prefrontal cortex implements the rules that decide which working memory neurons will fire (Spring 2017). 


    Piore explains that in 1990 Miller worked at the NIMH is the National Institute of Mental Health. 
    for Bob Desimone looking for neurons, specialized eukaryotic cells include channels which control flows of sodium and potassium ions across the massively extended cell membrane supporting an electro-chemical wave which is then converted into an outgoing chemical signal transmission from synapses which target nearby neuron or muscle cell receptors.  Neurons are supported by glial cells.  Neurons include a:
    • Receptive element - dendrites
    • Transmitting element - axon and synaptic terminals
    • Highly variable DNA schema using transposons. 
    in the inferior temporal cortex of the cerebral cortex is involved in associating sensory input with comprehending language (TEO), storing new memories, visual memory, emotion and deriving meaning.  The temporal lobe is located bellow the parietal lobe, and between the frontal lobe and occipital lobe. 
    that only fired when an animal spotted an item it was storing in short-term memory.  Aiming to progress the work of Hubel & Wiesel recorded neuronal activity in the primary visual area of the cat in the 1960s.  They noted that these neurons signalled in response to simple bars of light.  This ground breaking insight induced researchers to explore the temporal cortex and eventually led to Tanaka's identification of neuronal alphabets.   into this sensory integration area Miller was interested to understand:
    • What happens in the inferior temporal cortex after a unified picture emerges?
    • How do our brains tell us what it means?
    During experiments using repetition, Desimone & Miller noticed certain parts of the brain were focused on repetition, regardless of what the current cognitive goal was.  They detected two firing patterns:
    1. Neurons firing when animals saw a second matching object
    2. When an animal spotted a picture it was actively holding in working memory different neurons fired and much more intensely. 
    Miller wondered what was applying the switch to change the volume.  Scientists were already implicating the prefrontal cortex (PFC) is
    • The front part of the frontal lobe of the cerebral cortex.  It evolved most recently.  During adolescence when the PFC is still deploying, older brain agents provide equivalent strategies: ventral striatum.  The PFC has been implicated in planning, working memory: dorsolateral; decision making: Orbitofrontal cortex; and social behavior.  Different PFC circuits track internal reward driven strategies and externally signalled advice.  The PFC chooses between conflicting options, letting go or restraint, especially between cognition and emotions.  It imposes an overarching strategy for managing working memory.  It is essential for thinking about multiple items with different labels.  It includes neurons that are interested in particular sub-categories: Dog, Cat.  Once it has made a decision it signals the rest of the frontal lobe just behind it.  Glucocorticoids decrease excitability of the PFC.  
    in high-level executive functions of cognition is the ability to orchestrate thought and action in accordance with internal goals according to Princeton's Jonathan Cohen. 
    including working memory so Miller focused his research there.  He wanted to explain how the executive functions could turn up the volume when a matching high level object was detected. 
    He asked his animals to wait for a second cue before deciding there was a match.  He hypothesized he would detect activity in multiple neurons in the prefrontal cortex every time he changed the rule about what matched.  These neurons, he asserted turned up or down the volume of the neurons he had studied previously.  As predicted a rule change caused twice as many neurons in the prefrontal cortex to fire.  Miller concluded the prefrontal cortex role was not short-term memory but to learn the rules of the situation.  It was controlling which lower level neurons should be actively firing and which should be taken offline. 

    This model suggests that neurons are multi-functional, rather than only performing the specialized functions demonstrated by Hubel & Weisel recorded neuronal activity in the primary visual area of the cat in the 1960s.  They noted that these neurons signalled in response to simple bars of light.  This ground breaking insight induced researchers to explore the temporal cortex and eventually led to Tanaka's identification of neuronal alphabets.  , and explains:

    Miller subsequently characterized the significance of neural oscillations are repetitive firing of sets of neurons.  They are seen throughout the central nervous system. 
    (brain waves).  Miller argues that when an item is held in working memory, neural oscillations allow the prefrontal cortex to act as the switch operator holding several items on the cusp of awareness.  He argues the oscillations aren't enough to make the neurons spike.  But the brain waves bind together all the neurons in a circuit with every crest, pushing the neurons so close to their firing point that they're primed to respond to just the slightest extra stimulus.  This might help answer a question that has long intrigued scientists: How can the human brain store a virtually unlimited number of long-term memories, yet remain severely limited in the information we can hold in our conscious minds at once?  There is a limit to how many oscillations can be supported per second so working memory ends up with a finite capacity nominally "7 +/- 2". 

    Miller hypothesizes that it should be possible to tailor the neural oscillations raising the capacity of working memory. 


    Memory and sleep


    Feb 2017 NYT The purpose of sleep? To Forget, Scientists Say

    Carl Zimmer reports Over the years, scientists have come up with a lot of ideas about why we sleep facilitates salient memory formation and removal of non-salient memories.  The five different stages of the nightly sleep cycles support different aspects of memory formation.  The sleep stages follow Pre-sleep and include: Stage one characterized by light sleep and lasting 10 minutes, Stage two where theta waves and sleep spindles occur, Stage three and Stage four together represent deep slow-wave sleep (SWS) with delta waves, Stage five is REM sleep; sleep cycles last between 90-110 minutes each and as the night progresses SWS times reduce and REM times increase.   Sleep includes the operation of synapse synthesis and maintenance through DNA based activity including membrane trafficking, synaptic vesicle recycling, myelin structural protein formation and cholesterol and protein synthesis. 


    Two papers published in Science support University of Wisconsin-Maddison scientists Tononi and Cirelli's synaptic homeostasis is Tonini & Cirelli's hypothesis that proposes sleep-wake cycles cause generalized synaptic weakening which leads to down-selection of weak synapses.  Pruning does not strike every synapse.  They argue that well established memories are left intact. 
    hypothesis:
    Other researchers remain to be convinced.  Some question if this is the main function of sleep.  And some argue it has not been shown if it is sleep or the biological clock that generates the pruning. 






    Jun 2017 NYT You Look Familiar.  Now Scientists Know Why.

    Nicholas Wade reports the brain has an amazing capacity for recognizing faces.  It can identify a face in a few thousandths of a second, from a first impression of its owner and retain the memory in the brain includes functionally different types: Declarative (episodic and semantic), Implicit, Procedural, Spatial, Temporal, Verbal; Hebb noted that glutamate receptive neurons learn by (NMDA channel based) synaptic strengthening.  This strengthening is sustained by subsequent LTP.  The non-realtime learning and planning processes operate through consciousness using the working memory structures, and then via sleep, the salient ones are consolidated while the rest are destroyed and garbage collected.   for decades. 

    Caltech's Le Chang & Doris Tsao reported in Cell they had deciphered how primate brains recognize specific faces. 

    They used fMRI is functional magnetic resonance imaging.  Seiji Ogawa leveraged the coupling of neuronal circuit activity and blood flow through the associated glial cells to build a 3 dimensional picture of brain cell activity.  As haemoglobin gives up its oxygen to support the neural activity it becomes magnetic and acts as a signal detected by the fMRI.  fMRI easily visualizes the state of activity in the living human brain at millimeter resolution, up to several times a second but it cannot track the time course of neural firing so it is augmented with EEG. 
    augmented with electrode monitoring of active face cell are neurons which respond when the features of a face are presented to the retina.  Faces are recognized by dedicated neural networks consisting of face cells grouped into 6 patches of 10,000 cells on each side of the brain in the cortex just behind the ear.  The face cells respond abstractly to the dimensions and features of faces.  Each face cell responds to a combination of facial dimensions, creating a holistic representation.  A single face cell represents a vector of about 6 dimensions.  Two hundred cells can together represent the 50 dimensions which are required to identify a face in a face space where an infinite number of faces can be represented.  Cal tech's Chang & Tsao argue there is an average face at the origin of the face space and each actual face is represented as differences from it in the face space (Jun 2017).   neurons, specialized eukaryotic cells include channels which control flows of sodium and potassium ions across the massively extended cell membrane supporting an electro-chemical wave which is then converted into an outgoing chemical signal transmission from synapses which target nearby neuron or muscle cell receptors.  Neurons are supported by glial cells.  Neurons include a:
    • Receptive element - dendrites
    • Transmitting element - axon and synaptic terminals
    • Highly variable DNA schema using transposons. 
    of macaque monkey brains, to detect neural activity as they presented the monkeys with a series of pictures of 2,000 human faces with subtly altered feature sets. 

    This allowed Le Chang and Tsao to identify which aspects of the faces triggered the cells and how the features of the faces were encoded. 

    They found:

    Jul 2017 NYT Study of How We Look at Faces May Offer Insight Into Autism

    Pam Belluck reports how we look at other people's faces is strongly influenced by our genes, scientists have found in new research that may be especially important for understanding autism is a major hereditary mental disorder that starts before age three.  Autistics do not attribute minds to other people.  They almost never pretend.  They can't explain the difference between an instance of an object and a memory of it.  Autism occurs in every country and social class.  It lasts a lifetime.  It has genetic and neurological causes.  The genes: SHANK3, CDH10; are involved but account for a very small percentage of the risk.  Facial gaze studies indicate a high genetic influence and an opportunity to identify more genes associated with autism (Jul 2017).  ASD is associated with a reduced fusiform face area response.  Tests [in development] for autism include: SynapDx's blood test. 
    because it suggests that people are born with neurological differences that affect how they develop socially

    A study by: Emory School of Medicine's pediatrician is a doctor who specializes in the treatment of infants, children and adolescents.  They are represented by the American Academy of Pediatrics. 
    Dr. Warren Jones, Washington School of Medicine's child psychiatrist Dr. John Constantino, & Children's Healthcare of Atlanta's psychologist Dr. Ami Klin; reported in Nature provides data on how children look at faces:
    The study tracked eye movements of 338 toddlers, 18 to 24 months, who were watching videos of motherly women and children playing at a day care.  There were:
    • 250 toddlers who were developing normally including 41 pairs of identical twins, 42 pairs of non-identical twins and 84 unrelated children. 
    • 88 children with autism. 
    The results showed:
    • Identical twins matched how much the other twin looked at the eyes [or mouths] of people on screen 91%.  The identical twins actually had matching movements of their eyes in terms of time and direction.  
    • Fraternal twins the match dropped to 35%
    • Unrelated children randomly paired had no matching.  
    • Children with autism spent significantly less time looking at faces and more time looking at objects.  Children with autism could be identified from their eye tracking data. 


    Dr. Jones noted: "When we started to get the results back, I thought that I had the wrong data because the match between identical twins was so strong.  I thought I might have mistakenly matched data from the same twin." 

    Researchers see an opportunity to use eye are major sensors in primates, based on opsins deployed in the retina & especially fovea, signalling the visual system: Superior colliculi, Thalamus (LGN), Primary visual cortex; and indirectly the amygdala.  They also signal [social] emotional state to other people.  And they have implicit censorious power with pictures of eyes encouraging people within their view to act more honorably.  Eyes are poor scanners and use a saccade to present detail slowly to the fovea.  The eye's optical structures and retina are supported by RPE.  Eyes do not connect to the brain through the brain stem and so still operate in locked-in syndrome.  Evo-devo shows eyes have deep homology.  High pressure within the eye can result in glaucoma.  Genetic inheritance can result in retinoblastoma.  Age is associated with AMD. 
    movements to identify genes for autism.  Dr. Jones explained: "How much Twin 1 looked at the eyes in a video that Twin 2 didn't get to see predicted how much Twin 2 would look at the eyes in a different video."  He asserts that indicates a genetically driven behavior of "seeking out" social information found in the eyes rather than "merely responding to" facial features.  He hopes to pinpoint "what is disrupted in children with autism as they develop and learn about the world." 







    Jul 2002 Nature Neuroscience Review Yale Cohen & Richard Andersen describe a common movement planning reference frame


    Dartmouth College's Cohen & Cal Tech's Andersen explain orchestrating a movement towards a sensory target requires many computational processes, including a transformation between reference frames is a coordinate system (set of axis) centered on a particular aspect of the situation that describes the location of an object.  The brain supports many frames of reference including for vision (2009), hearing & movement planning (Jul 2002).  Auditory stimuli are initially coded in a head-centered reference frame.  The motor system codes actions in reference frames that depend on motor effectors.  Eye movements are codes in a reference frame that depends on the difference between current and desired arm position.  It is often necessary to transform the location representation of the sensory stimulus into a representation appropriate for the motor act.  An eye-centered reference frame depends on the location of the eye in the head.  A retinotopic reference frame depends on the retinal location that is activated by a visual stimulus.  Double-saccade tasks show how the location of the second visual target is coded relative to current and desired eye position (eye-centered).  
    .  This transformation is important because the reference frames in which sensory stimuli are encoded often differ from those of motor effectors.  The posterior parietal cortex of the cerebral cortex is at the back of the brain divided into two.  It associates sensory signals of various modalities with:
    • Details about the location of the body and
    • Models interpreting touch, visual signals, language and mathematics. 
    (PPC) has an important role in these transformations.  Recent work indicates that a significant proportion of parietal neurons, specialized eukaryotic cells include channels which control flows of sodium and potassium ions across the massively extended cell membrane supporting an electro-chemical wave which is then converted into an outgoing chemical signal transmission from synapses which target nearby neuron or muscle cell receptors.  Neurons are supported by glial cells.  Neurons include a:
    • Receptive element - dendrites
    • Transmitting element - axon and synaptic terminals
    • Highly variable DNA schema using transposons. 
    in two cortical areas transforms the sensory signals that are used to guide movements into a common reference frame.  This common reference frame is an eye are major sensors in primates, based on opsins deployed in the retina & especially fovea, signalling the visual system: Superior colliculi, Thalamus (LGN), Primary visual cortex; and indirectly the amygdala.  They also signal [social] emotional state to other people.  And they have implicit censorious power with pictures of eyes encouraging people within their view to act more honorably.  Eyes are poor scanners and use a saccade to present detail slowly to the fovea.  The eye's optical structures and retina are supported by RPE.  Eyes do not connect to the brain through the brain stem and so still operate in locked-in syndrome.  Evo-devo shows eyes have deep homology.  High pressure within the eye can result in glaucoma.  Genetic inheritance can result in retinoblastoma.  Age is associated with AMD. 
    -centered representation that is modulated by eye-, head-, body-, or limb-position signals.  A common reference frame might facilitate communications between different areas that are involved in cooridinating the movements of different effectors.  It might also be an efficient way to represent the locations of different sensor targets in the world. 

    Cohen & Anderson argue goal directed behavior dynamically links sensory stimuli to motor acts.  Several intermediate processes must occur:
    • Change the locus of attention
    • Response selection
    • Coordinate transformations
    • Decision to act on sensory stimuli
    Cohen & Anderson note the neural correlates of these strategies occur in the PPC is
    • Posterior parietal cortex.  Its neurons receive visual, auditory and somatosensory inputs and are involved in:
      • Planning
      • Cognitive intermediaries (encoded as firing rates): Attention, Salience, Decision variables; of sensorimotor transformations.   PPC areas LIP and PRR are involved in transforming target locations into a common reference frame.  or
    • Potentially preventable complication 
    .  They review the coordinate transformations that occur during this movement planning. 

    Movement planning is a focus of the PPC.  Functional subdivisions of PPC cells: AIP is anterior intraparietal area of the intraparietal sulcus.  It is involved in grasp planning. 
    , LIP is either the
    • Medicaid supplemental 'low-income pool' hospital funding program which reimburses hospitals for the cost of care for the uninsured.  LIP is being wound down as the ACA Medicaid expansion occurs.  Or it is the
    • Lateral intraparietal area is involved in saccades of the eyes.  Some neurons in the LIP code the location of visual and auditary targets in an eye-centered reference frame.  Others code the location of a sound in reference frame intermediate between head-centered and eye-centered.  For many cells the magnitude of response is 'gain' modulated by eye, head, body or initial hand position. 
    , PRR is the parietal reach region of the intraparietal sulcus.  It is specialized for reaching.  It includes the MIP and dorsal aspect of the PO.  PRR neurons code visual targets in an eye-centered reference frame.  Some PRR neurons code auditory-target locations in eye-centered reference frames.  Others may code auditory-targets in a head-centered reference frame.  A third set encode auditory-target locations in an intermediate frame between eye- and head-centered.  For many cells the magnitude of response is 'gain' modulated by eye, head, body or initial hand position. 
    ; code for specific types of movement plan.  LIP and PPR both include neurons which use an eye-centered reference frame for auditory, visual, sensory and motor aspects suggesting eye-centered is being used as a common reference frame. 

    They conclude the PPC, and other cortical areas, in primates and humans, can 'read out' a stimulus-target location in different reference frames by using gain fields alters the responsiveness of neurons based on factors including: eye, head, body or initial hand position.  Gain modulation provides a mechanism for coordinate transformations.  While certain neurons code their auditory targets in a head-centered reference frame, their level of responsiveness is modulated by eye position.  The neuron responded robustly when the eye position was to the left but when the eye position was to the right the neuron hardly responded.  The neuron was not affected by changes in hand position.  
    as a selector in conjuction with common eye-centered representations of target locations.  Cohen & Anderson note that this architecture and representation provides great flexibility with simultaneous readout of many reference frames.  And they suggest evidence, neural network simulation including hidden layer analysis & midbrain and cortical auditory centers projecting directly to the PPC, implicates the PPC as the site of many coordinate transformations, such as:
    • Head-centered representations of auditory targets to eye-centered representations. 
    • Modelled body-centered representations of auditory targets had hidden layer neurons with gain effects for both eye and head position. 






    Feb 2015 NYT Mothers' Sounds required for Babies' Brains to Grow

    Douglas Quenqua writes that the sound of a mother's voice plays a critical role in a baby's early development is a phase during the operation of a CAS agent.  It allows for schematic strategies to be iteratively blended with environmental signals to solve the logistical issues of migrating newly built and transformed sub-agents.  That is needed to achieve the adult configuration of the agent and optimize it for the proximate environment.  Smiley includes examples of the developmental phase agents required in an emergent CAS.  In situations where parents invest in the growth and memetic learning of their offspring the schematic grab bag can support optimizations to develop models, structures and actions to construct an adept adult.  In humans, adolescence leverages neural plasticity, elder sibling advice and adult coaching to help prepare the deploying neuronal network and body to successfully compete. 
    .  Researchers recently demonstrated that the brain itself may rely on a mother's voice and heartbeat to grow. 

    Researchers at Brigham and Women's Hospital showed that premature babies without these signals had significantly less developed auditory cortex is part of the temporal lobe that processes auditory information.  It is present in both brain hemispheres.  Auditory sensations only reach consciousness once signalled by the auditory cortex.  Final sound processing is performed by the parietal and frontal lobes in humans. 


    The findings published in the Proceedings of the National Academy of Sciences can help guide doctors and parents caring for premature babies who often suffer from developmental and cognitive disabilities. 


    Aug 2015 NYT For Evolving Brains, a Diet of Carbs

    Carl Zimmer argues that the diet of our Pleistocene ancestors went through two big shifts:
    1. Addition of meat
    2. Addition of cooking released carbohydrates.  Campfires have been dated back to 1.8 million years ago. 
    Some evolutionary geneticists, such as Mark Thomas of University College London, argue that the addition of cooked carbohydrates provided the additional energy supply to enable the enlargement of our brains.  Today our brain consumes as much as a quarter of the calorie intake.  

    The assertion is based on the following logic: 
    • Our bodies convert starch into glucose using amylase.  But the reaction works better on pre-cooked starches.  That was a significant benefit to a hungry hunter gatherer. 
    • Chimpanzees have two copies of the amylase gene.  Humans have as many as 18 copies. 
      • Studies of pre-agricultural hunters from Europe reveal that people had extra copies long before they started farming.  
      • The survival value of the extra gene copies allowed them to spread through the population. 
    • Brain size increases started about 800,000 years ago. 

    Aug 2015 NYT Turn the Page, Spur the Brain

    Dr. Perri Klass reports that the year old AAP policy that all pediatric primary care should include literacy promotion starting at birth is of major significance. 
    Klass developed the policy based on extensive research associating growing up with books and reading aloud with language development is a phase during the operation of a CAS agent.  It allows for schematic strategies to be iteratively blended with environmental signals to solve the logistical issues of migrating newly built and transformed sub-agents.  That is needed to achieve the adult configuration of the agent and optimize it for the proximate environment.  Smiley includes examples of the developmental phase agents required in an emergent CAS.  In situations where parents invest in the growth and memetic learning of their offspring the schematic grab bag can support optimizations to develop models, structures and actions to construct an adept adult.  In humans, adolescence leverages neural plasticity, elder sibling advice and adult coaching to help prepare the deploying neuronal network and body to successfully compete. 
    and school success. 

    Pediatricians is a doctor who specializes in the treatment of infants, children and adolescents.  They are represented by the American Academy of Pediatrics. 
    in charge of infants and toddlers should stress the importance of reading to even the youngest children. 

    The mechanisms behind the benefits of early reading are complex.  fMRI is functional magnetic resonance imaging.  Seiji Ogawa leveraged the coupling of neuronal circuit activity and blood flow through the associated glial cells to build a 3 dimensional picture of brain cell activity.  As haemoglobin gives up its oxygen to support the neural activity it becomes magnetic and acts as a signal detected by the fMRI.  fMRI easily visualizes the state of activity in the living human brain at millimeter resolution, up to several times a second but it cannot track the time course of neural firing so it is augmented with EEG. 
    studies of children listening to age appropriate stories found differences in brain activation dependent on if children had been read to at home.  More books and reading corresponded to greater activity in the parietal-temporal-occipital association cortex is a multi-sensory integration area of the sensory signals from parietal, temporal and occipital lobes.  .  It is active in older children when they read to themselves and in younger children when they hear stories.  When children who have been read to hear stories they imagine what is being discussed in their mind's eye

    Researchers are questioning if videos and cartoons remove this 'mind's eye are major sensors in primates, based on opsins deployed in the retina & especially fovea, signalling the visual system: Superior colliculi, Thalamus (LGN), Primary visual cortex; and indirectly the amygdala.  They also signal [social] emotional state to other people.  And they have implicit censorious power with pictures of eyes encouraging people within their view to act more honorably.  Eyes are poor scanners and use a saccade to present detail slowly to the fovea.  The eye's optical structures and retina are supported by RPE.  Eyes do not connect to the brain through the brain stem and so still operate in locked-in syndrome.  Evo-devo shows eyes have deep homology.  High pressure within the eye can result in glaucoma.  Genetic inheritance can result in retinoblastoma.  Age is associated with AMD. 
    ' activity.  Already researchers have determined that children need to hear language spoken by people.  Screens do not work. 

    There are vast disparities between the amounts of language that different children hear.  And reading to and with young children appears to amplify the language they hear more than just talking. 
    One property of books is they include more vocabulary than parents typically use in talking with their children. 


    Oct 2015 NYT Anorexia May Be Habit, Not Resolve, Study Finds

    Erica Goode reports a new study in Nature Neuroscience, by Professor B. Timothy Walsh of Columbia and Dr. Joanna Steinglass at New York State Psychiatric Institute at Columbia University Medical Center, suggests anorexia nervosa is an eating disorder.  As of 2015, 50 percent of hospitalized anorexic patients who are discharged at a normal rate relapse within a year.  It has the highest mortality of any mental illness.  It involves brain circuits involved in habitual behavior.  The initial weightloss acts as a reward with compliments relieving anxiety and increasing self-esteem.  Diet gets paired with weight loss (the reward) in the ventral striatum and eventually dieting becomes the reward as the dorsal striatum gets involved in the patient's decision making making it a habit. 
    is a well-entrenched habit.  People with anorexia nervosa can't stop dieting. 

    The researchers used fMRI is functional magnetic resonance imaging.  Seiji Ogawa leveraged the coupling of neuronal circuit activity and blood flow through the associated glial cells to build a 3 dimensional picture of brain cell activity.  As haemoglobin gives up its oxygen to support the neural activity it becomes magnetic and acts as a signal detected by the fMRI.  fMRI easily visualizes the state of activity in the living human brain at millimeter resolution, up to several times a second but it cannot track the time course of neural firing so it is augmented with EEG. 
    to look at brain activity in 21 women with anorexia and 21 healthy women while they made decisions about what to eat. 
    The anorexic women were more likely to choose low-fat, low calorie foods, and didn't find high-fat, high-calorie foods as tasty as the controls. 

    All the subjects activated the ventral striatum is a region within the basal ganglia.   It is a target of the tegmentostriatal dopamine pathway.  It has been captured by brain imaging assigning values to subliminal symbols experimentally associated with winning (highly valued) and losing (low valuation) money.  During adolescence, prior to the deployment of the prefrontal cortex, the ventral striatum helps balance/control emotional decision making. 
    .  But the anorexic women showed more activity in the dorsal striatum is a region within the basal ganglia.   It has been associated with habitual behavior.  .  This suggests they were acting habitually based on past learning. 

    One treatment strategy that would be consistent with this study's conclusions would be to get the patient to look at entrees as well as at the salad bar, or to switch to eating with the left hand, to signal this is a new situation. 


    May 2016 NYT Opinion Never Diet Again - The problem isn't willpower.  It's neuroscience.  And you can't fight back. 

    In an opinion Sandra Aamodt writes six years after dropping an average of 129 pounds on the TV program "The Biggest Loser," a new study reports, the participants were burning about 500 fewer calories a day than other people their age and size.  This helps explain why they had regained 70 percent of their lost weight since the show's finale.  The diet industry reacted defensively, arguing that the participants had lost weight too fast or ate the wrong kinds of food -- that diets do work, if you pick the right one. 

    Aamodt argues this research just adds to a collection showing dieting is rarely effective. 
    Aamodt states neuroscience provides the constraint that undermines diet. The brain has a set of tools that aim to maintain its set point is a weight range that the brain of humans, and rats which have a similar diet, are evolved to maintain.  It varies by person, depending on genes and environmental signals.  The brain has various mechanisms to maintain the set point including: Metabolic suppression.  It is possible dieting may raise the set point May 2016. 
    :
    So Aamodt explains, when a person's weight drops below the set point they burn fewer calories, produce hunger inducing hormones are signalling molecules: ACTH, TRH, Melanocyte stimulating hormone, Testosterone, Oxytocin, Vasopressin, Insulin, Growth hormone, Estrogen, Progesterone, Angiotensin II, Asprosin, EPO, Irisin, Leptin, FGF21 hormone, Prostaglandins, TSH, Thyroxine, Glococorticoids; that are transported by the circulatory system to interact with target organs having appropriate receptors.  The levels of hormones can fluctuate massively, as in pregnancy. 
    , and find eating more rewarding and their weight rises.  So Aamodt notes a 2002 report that, only 1% of 231 million Europeans dieters achieved permanent weight loss. 

    Why does dieting lead to weight gain?  Aamodt suggests:


    May 2016 NYT Zika's Secret Assault

    Pam Belluck reports a graduate student's offhand remark led to a remarkable finding about how the virus has caused lasting brain damage in so many babies. 

    Researchers developing an organoid is a tiny ball of brain cells grown from stem cells and mimicking early brain development.  The stem cells have differentiated into most types of brain cells.  A 100-day-old organoid resembles a late second trimester foetus. 
    , have used it with Zika is a Flaviviridae family virus.  It came from the Zika Forest of Uganda isolated in 1947.  It is related to dengue, yellow fever, Japanese encephalitis and West Nile.  Zika is transmitted sexually or via a daytime mosquito vector such as the Aedes genus.  It has resulted in a pandemic in South America.  Zika fever has been associated with a number of troubling complications:
    • Guillain-Barre syndrome
    • Microcephaly.  The mechanism may have been identified (May 2016)
    to identify how the brain damage (Mar 2016) is caused. 

    They reported in Cell that Zika attacks and kills neural progenitor cells, much more than neurons, specialized eukaryotic cells include channels which control flows of sodium and potassium ions across the massively extended cell membrane supporting an electro-chemical wave which is then converted into an outgoing chemical signal transmission from synapses which target nearby neuron or muscle cell receptors.  Neurons are supported by glial cells.  Neurons include a:
    • Receptive element - dendrites
    • Transmitting element - axon and synaptic terminals
    • Highly variable DNA schema using transposons. 
    or stem cells is a biological cell which is partly or wholly undifferentiated.  A totipotent cell can generate a complete embryo and placenta.  Embryos include pluripotent cells which can generate any tissue in the body.  Adult humans' cells have turned off this ability but still include multipotent stem cells that differentiate into multiple cell types.   Typically a cell's local environment will have the signals required for it to obtain context and differentiate appropriately.  This will include both the external environment and the internal state of the cell which has replicated from a parent and obtained its epi-genetic state.   So introduction of undifferentiated stem cells into an injured area is not likely to have either aspect of the environment suitable.  Consequently development is aiming to encourage differentiation to progenitor cells for the damaged region.  This requires delivering the cells to the appropriate part of the body.  To avoid rejection by the immune system techniques aim to use cell lines developed from the patient's cells.  The techniques to generate these cell lines include: SCNT, iPS.  Possible mechanisms of stem cell therapy are: Generation of new differentiated cells, Stimulation of growth of new blood vessels to repopulate damaged regions, Secretion of growth factors, Treatment of diabetes (1 and 2) with addition of pancreatic cells, Assistance of other mechanisms;.  This resulted in fewer neurons leading to less brain volume.  It appears that Zika infection will be dangerous in both the first and second trimester of pregnancy.  Zika uses the neural progenitor cells as its reproductive factory.  It takes about three days to destroy them and it does not damage all of them.  Zika increases activity of the apoptotic, programmed cell death is a signal initiated DNA controlled process which results in eukaryotic cells self-destructing.   signalling enzyme caspase are mediators of apoptosis. 
    -3.  The researchers hope caspase inhibitors may reduce the effects of Zika.  One drug, of a set of 173 prevented the effects of Zika and is now in clinical trials with cancer is the out-of-control growth of cells, which have stopped obeying their cooperative schematic planning and signalling infrastructure.  It results from compounded: oncogene, tumor suppressor, DNA caretaker; mutations in the DNA.  In 2010 one third of Americans are likely to die of cancer.  Cell division rates did not predict likelihood of cancer.  Viral infections are associated.  Radiation and carcinogen exposure are associated.  Lifestyle impacts the likelihood of cancer occurring: Drinking alcohol to excess, lack of exercise, Obesity, Smoking, More sun than your evolved melanin protection level; all significantly increase the risk of cancer occurring (Jul 2016).   patients. 

    The model suggests the mechanism of association of Zika with Guillain-Barre syndrome (GBS) is a condition where peripheral neurons are attacked by the immune system.  Zika virus attacks the Glial cells protecting neurons and can be associated with GBS symptoms.  
    .  Zika attacks Glial cells support neurons: Creating the initial structural tracks along which the neurons travel, Insulating them by deploying the myelin sheath - an activity which is influenced by sleep, Storing energy for them and removing debris from damage to neurons.  Robert Sapolsky notes Glial cells outnumber neurons ten to one.  They include various subtypes.  They greatly influence how neurons speak to one another, and also form glial networks that communicate completely differently from neurons. 
    damaging the neural sheath of long living neurons. 





    Genomics highlights evolved changes and chemical mechanisms.  Discovery of historic samples is necessary: Cholera;




    Study of Genome Deltas

    One of the ten emerging technologies from Technology Review 2004. 


    Researchers include:

    Perlegen

    http://www.eurekalert.org/pub_releases/2003-03/nc-psp022703.php
    Perlegen scientists find genetic basis for difference between humans and non-human primates
    Genomic rearrangements discovered using DNA (DNA), a polymer composed of a chain of deoxy ribose sugars with purine or pyrimidine side chains.  DNA naturally forms into helical pairs with the side chains stacked in the center of the helix.  It is a natural form of schematic string.  The purines and pyrimidines couple so that AT and GC pairs make up the stackable items.  A code of triplets of base pairs (enabling 64 separate items to be named) has evolved which now redundantly represents each of the 20 amino-acids that are deployed into proteins, along with triplets representing the termination sequence.  Chemical modifications and histone binding (chromatin) allow cells to represent state directly on the DNA schema.  To cope with inconsistencies in the cell wide state second messenger and evolved amplification strategies are used. 
    microarrays is a 2D array on a solid substrate that assays large amounts of biological material using high-throughput screening.  It is the central technology of Bio-MEMS, LOC and MTAS.  They are used with tissues, cells, antibodies, DNA, RNA, protein, peptides and carbohydrates.  Once fed magnetic nanoparticles individual cells can be moved independently and simultaneously on a microarray of magnetic cells.  A microarray of NMR microcells is being developed.   are expected to reveal genetic regions important to human health
    Mountain View, CA ¾ March 3, 2003 ¾ Perlegen Sciences, Inc. today announced the publication of a scientific paper in the latest issue of the peer-reviewed journal Genome Research. The paper, “Genomic DNA insertions and deletions occur frequently between humans and nonhuman primates,” describes novel findings suggesting that genomic rearrangements, not single base pair changes in DNA, provide the genetic basis for the differences between humans and non-human primates such as the chimpanzee.
    “This is a very surprising and important discovery of the fundamental basis of structural genomic differences between humans and other primates,” said David Cox, M.D., Ph.D, Perlegen’s Chief Scientific Officer. “It provides a valuable starting point from which to improve our understanding of what makes human beings unique.”

    Analysis of the differences in sequence between human and chimpanzee DNA has previously established that the two species are approximately 98.5% identical. For this reason, it is widely accepted that qualitative and quantitative differences in gene expression are responsible for the major biological differences among humans, chimpanzees and other non-human primates. To date it has been commonly thought that single base pair changes in these genomes, not larger DNA rearrangements, would underlie the majority of these postulated genomic regulatory differences.

    “Comparative genome analysis of human and non-human primates is a useful technique for deciphering the function of specific genomic regions,” commented Kelly Frazer, Ph.D., Senior Director of Genomic Biology at Perlegen and the lead author on the paper. “This study illustrates the power and versatility of Perlegen’s high-density array technology in the detection of DNA rearrangements.”

    Comparison of human chromosome 21 with chimpanzee, orangutan, rhesus macaque, and woolly monkey DNA sequences identified a significant number of random genomic rearrangements between human and nonhuman primate DNA. This evidence shows, contrary to popular belief, that genomic rearrangements have occurred frequently during primate genome evolution and are a significant source of variation between humans and chimpanzees as well as other primates. These DNA rearrangements are commonly found in segments containing genes, suggesting possible functional consequences and therefore provide natural starting points for focused investigations of variations in gene expression between humans and other primates, including variations which may provide important clues in researching human health and disease.

    Perlegen conducts genetics research and develops products that impact and improve people’s lives through a proprietary, cost-effective method for rapidly analyzing and comparing entire genomes. This whole genome association study capability enables Perlegen to identify genes that work in concert to cause common diseases and affect the body’s response to drugs. Perlegen has ongoing research collaborations with partners including Bristol-Myers Squibb, Eli Lilly & Co., GlaxoSmithKline, Pfizer and Unilever.

    Jan 2014 NYT Aiming to push genomics forward in new study

    Having noted that gene sequencing's first wave of businesses have largely failed to generate a bonanza of new drugs NYT looks at the new approach being taken by Regeneron Pharmaceuticals. 

    Regeneron is partnering with Geisinger to sequence 100,000 of Geisinger's 3 million patients, seeking genetic variants lined to different diseases that may provide clues to developing new drugs.  Dr Leslie Biesecker of NHGRI is the NIH's national human genome research institute which aims to advance human health through genomics research. 
    argues that the study is significant.  "It's the largest clinical sequencing undertaking in this country.  The move of sequencing into general health care is going to change medicine.  " 

    George Yancopoulis, the chief scientific officer of Regeneron, said the plummeting cost of DNA (DNA), a polymer composed of a chain of deoxy ribose sugars with purine or pyrimidine side chains.  DNA naturally forms into helical pairs with the side chains stacked in the center of the helix.  It is a natural form of schematic string.  The purines and pyrimidines couple so that AT and GC pairs make up the stackable items.  A code of triplets of base pairs (enabling 64 separate items to be named) has evolved which now redundantly represents each of the 20 amino-acids that are deployed into proteins, along with triplets representing the termination sequence.  Chemical modifications and histone binding (chromatin) allow cells to represent state directly on the DNA schema.  To cope with inconsistencies in the cell wide state second messenger and evolved amplification strategies are used. 
    seqencing and Regeneron's capabilities point towards successful biotech leverage of genomics. 

    Geisinger already has collected 45,000 DNA samples from its population base.  The population's attributes are described in its EHR refers to electronic health records which are a synonym of EMR.  EHRs have strengths and weaknesses:
    • The EHR provides an integrated record of the health systems notes on a patient including: Diagnosis and Treatment plans and protocols followed, Prescribed drugs with doses, Adverse drug reactions;
    • The EHR does not necessarily reflect the patient's situation accurately. 
    • The EHR often acts as a catch-all.  There is often little time for a doctor, newly attending the patient, to review and validate the historic details. 
    • The meaningful use requirements of HITECH and Medicare/Medicaid specify compliance of an EHR system or EHR module for specific environments such as an ambulatory or hospital in-patent setting. 
    • As of 2016 interfacing with the EHR is cumbersome and undermines face-to-face time between doctor and patient.  Doctors are allocated 12 minutes to interact with a patient of which less than five minutes was used for recording hand written notes.  With the EHR 12 minutes may be required to update the record!
    .  It makes the data provided to Regeneron anonymous.  However, Geisinger will know the identities matched in the samples which it hope to use for clinical care.  David Ledbetter CSO of Geisinger commented "If the sequencing finds that a patient has a mutation indicating a high risk of getting breast cancer is a variety of different cancerous conditions of the breast tissue.  World wide it is the leading type of cancer in women and is 100 times more common in women than men.  260,000 new cases of breast cancer will occur in the US in 2018 causing 41,000 deaths.  The varieties include: Hormone sensitive tumors that test negative for her2 (the most common type affecting three quarters of breast cancers in the US, BRCA1/2 positive, ductal carcinomas including DCIS, lobular carcinomas including LCIS.  Receptor presence on the cancer cells is used as a classification: Her2+/-, estrogen (ER)+/-, progesterone (PR)+/-.  Metastasis classes the cancer as stage 4.  Genetic risk factors include: BRCA, p53, PTEN, STK11, CHEK2, ATM, GATA3, BRIP1 and PALB2.  Treatments include: Tamoxifen, Raloxifene; where worrying racial disparities have been found (Dec 2013).  International studies indicate early stage breast cancer typed by a genomic test: Oncotype DX, MammaPrint; can be treated without chemotherapy (Aug 2016, Jun 2018)
    , the person can be informed and steps can be taken to prevent the disease.  Certain mutations could also provide information helpful to choosing the best drug treatment for the patient". 

    Sequencing 100,000 genomes will probably cost $100 million over five years.  Regeneron is covering Geisinger's costs.  Geisinger will share in the proceeds of any drugs developed. 

    Regeneron said they might also collaborate with other academic centers and health systems. 

    Amgen paid $415 million in 2013 to acquire deCODE Genetics which had decoded the genomic sequences of 300,000 people in Iceland. 

    The previous generation of gene-hunting studies sampled the DNA of people at particular spots on the genome.  While this found many common genetic variations they did not correlate with a significant effect. 

    The new projects by sequencing the complete exomes is the 1 ot 2 percent of the genome which codes for the proteins. 
    or genomes of large populations are able to look for rarer variations that might have a bigger influence on disease risk. 


    May 2016 NYT Private Talks Are Conducted About a Synthetic Genome

    Andrew Pollack reports scientists are now contemplating the fabrication of a human genome, meaning they would use chemicals to manufacture the entire DNA (DNA), a polymer composed of a chain of deoxy ribose sugars with purine or pyrimidine side chains.  DNA naturally forms into helical pairs with the side chains stacked in the center of the helix.  It is a natural form of schematic string.  The purines and pyrimidines couple so that AT and GC pairs make up the stackable items.  A code of triplets of base pairs (enabling 64 separate items to be named) has evolved which now redundantly represents each of the 20 amino-acids that are deployed into proteins, along with triplets representing the termination sequence.  Chemical modifications and histone binding (chromatin) allow cells to represent state directly on the DNA schema.  To cope with inconsistencies in the cell wide state second messenger and evolved amplification strategies are used. 
    contained in human chromosomes.  They meet with George Church at Harvard.  The organizers included: Jef Boeke, Andrew Hessel.  A paper has been submitted to a journal. 

    The project called "HGP is the human genome project an international research project to determine the sequence of DNA base pairs of humans and identify and map physically and functionally all the genes in the human genome.  The HapMap project proved very helpful for discovering the SNPs. 
    2: The Human Genome Synthesis Project" is still being thought through.  The organizers argue there could be a big benefit.  They explain that the goal is to improve the synthesis of DNA encoded cells, not just human DNA (DNA), a polymer composed of a chain of deoxy ribose sugars with purine or pyrimidine side chains.  DNA naturally forms into helical pairs with the side chains stacked in the center of the helix.  It is a natural form of schematic string.  The purines and pyrimidines couple so that AT and GC pairs make up the stackable items.  A code of triplets of base pairs (enabling 64 separate items to be named) has evolved which now redundantly represents each of the 20 amino-acids that are deployed into proteins, along with triplets representing the termination sequence.  Chemical modifications and histone binding (chromatin) allow cells to represent state directly on the DNA schema.  To cope with inconsistencies in the cell wide state second messenger and evolved amplification strategies are used. 
    or to create whole people. 

    Synthesizing a gene or an entire genome would allow for many changes to be applied to the DNA.  Already chemical production networks developed to deploy in yeast require adding of multiple genes to the yeast DNA. 

    Currently DNA synthesis is difficult and error-prone.  Strands can be built reliably of length 200 base pairs.  And it still costs three cents to add a base pair so 8 million bases would cost $90 million. 


    Dr. J. Craig Venter has synthesized a full bacterial genome and deployed it successfully into a cell.  However, the initial synthesis was a near copy of an actual bacterium's DNA sequence.  Subsequently in 2016 he has developed a synthetic genome. 




    Dr. Boeke is leading an international consortium that is synthesizing the genome of yeast (12 million base pairs).  The scientists are deleting nonfunctional stretches of the DNA (DNA), a polymer composed of a chain of deoxy ribose sugars with purine or pyrimidine side chains.  DNA naturally forms into helical pairs with the side chains stacked in the center of the helix.  It is a natural form of schematic string.  The purines and pyrimidines couple so that AT and GC pairs make up the stackable items.  A code of triplets of base pairs (enabling 64 separate items to be named) has evolved which now redundantly represents each of the 20 amino-acids that are deployed into proteins, along with triplets representing the termination sequence.  Chemical modifications and histone binding (chromatin) allow cells to represent state directly on the DNA schema.  To cope with inconsistencies in the cell wide state second messenger and evolved amplification strategies are used. 
    !


    The human genome is 200 times larger than that of yeast so the process may not be feasible. 

    Implicit in the development is the possibility, through cloning, of producing human beings without parents.  This and other ethical issues such as making copies of particular people -- Einstein, or developing chromosomes selected to develop good soldiers worry ethicists.


    DNA2.0's Jeremy Minshull, commented "Our ability to understand what to build is so far behind what we can build, I just don't think that being able to make more and more and more and cheaper and cheaper and cheaper is going to get us the understanding we need." 





    Big Data



    Nov 2016 NYT Simons Foundation Looks to Enhance Computation Tools for Science

    Kenneth Chang reports a new private research institute financed by the billionaire James H. Simons in New York will develop software tools and apply cutting edge computing techniques to science often not possible in academia and industry. 


    Simons Foundation hopes the Flatiron Institute will fill an overlooked niche.  Simons concluded most programs developed for science research are written by graduate students.  Hence they suffer from:
    • Poor development techniques
    • Lack of maintenance
    • University departments not being able to hire professional programmers
    Flatiron Institute is the first in-house research program by the Simons Foundation. 




    Flatiron will deploy professional computer programmers, to produce software for the in-house scientists and anyone else that needs it. 

    Simon said the impetus for the institute developed from a brainstorming workshop about "what we might do to help move the needle in science."  A Belgian physicist and mathematician, Ingred Daubechies, suggested an effort to develop better computational tools.  Daubechies said there is a real need for analyzing big data encompasses the IT systems and processes necessary to do population based data collection, management and analysis.  For the analysis to be useful it requires a hierarchy of supporting BI infrastructure:
    • Analytics utilization and integration delivered via SaaS and the Cloud to cope with the silos and data intensive nature. 
    • Analytics tools (BI) for PHM will be hard to develop.  
      • Complex data models must include clinical aspects of the patient specific data, including disease state population wide.  
      • A key aspect is providing clear signals about the nature of the data using data visualization. 
    • Data communication with the ability to exchange and transact.  HIEs and EMPI alliance approaches are all struggling to provide effective exchange. 
    • Data labeling and secure access and retreival.  While HIPAA was initially drafted as a secure MPI the index was removed from the legislation leaving the US without such a tool.  Silos imply that the security architecture will need to be robust. 
    • Raw data scrubbing, restructuring and standardization.  Even financial data is having to be restandarized shifting from ICD-9 to -10.  The intent is to transform the unstructured data via OCR and NLP to structured records to support the analytics process. 
    • Raw data warehousing is distributed across silos including PCP, Hospital system and network, cloud and SaaS for process, clinical and financial data. 
    • Data collection from the patient's proximate environment as well as provider CPOE, EHRs, workflow and process infrastructure.  The integration of the EHR into a big data collection tool is key.  


    Flatiron Institutes first area of focus will be computational biology based on input from New York University's Dr. Leslie Greengard who outlined possibilities. 



    Jan 2017 NYT Data Could Be the Next Tech Hot Button

    Steve Lohr reports wealth is schematically useful information and its equivalent, schematically useful energy, to paraphrase Beinhocker.  It is useful because an agent has schematic strategies that can utilize the information or energy to extend or leverage control of the cognitive niche.    and influence in the technology business have always been about gaining the upper hand in software or the machines that software ran on. 
    Now data -- gathered in those immense pools of information that are at the heart of everything from artificial intelligence to online shopping recommendations -- is increasingly a focus of technology competition.  And academics and some policy makers, especially in Europe, are considering whether big internet companies like Google and Facebook might use their data resources as a barrier to new entrants and innovation is the economic realization of invention and combinatorial exaptation. 


    Lohr notes:
    Lohr argues the increasing importance of data is indicated by:
    • Artificial intelligence in mainstream business software makes certain data sets very valuable. 
    • Microsoft paid 26.2 billion for LinkedIn because of:
      • 467 million users
      • Profiles and maps of connections of