Study Of Various Normal Forms And Functional Dependency: Fill & Download for Free

Keeping in mind that this is my personal opinion & in no way reflects government or NIH policy:Of course we’re going to be closer to finding a cure for Alzheimer’s. We are going to learn some important things about AD in 2019; although, of course, I can’t predict what those advances will be. It’s unlikely that we’ll stumble upon a cure for AD in 2019, and even if we did, we probably wouldn’t recognize it for several more years.When you talk about finding a cure for AD, you have to give some thought to exactly what that means. In medicine, people often think of cures in terms of infectious disease - penicillin curing diplococcal pneumonia; or surgery - an appendectomy curing appendicitis. Someone is ill, a doctor makes an intervention, and the person returns to their previous state of physical health (financial health may be a different matter, at least in the US).The perspective changes, however, when you start talking about diseases associated with aging: surgery may replace a fractured hip, but it’s not going to completely restore function, nor will it prevent further osteoarthritis as you age. A coronary stent will relieve angina and improve quality of life, but arteriosclerotic plaques will continue to accumulate in your coronary arteries.Dementias, including Alzheimer’s, are diseases of aging. Age is the major risk factor. Not so many years ago, the expectation was that you were going to ‘lose your marbles’ if you lived long enough. Today’s expectation - more correctly, our hope - seems to be that healthy aging means minimal loss of cognitive abilities, as well as continued independence until the night we pass away in our sleep. However, half of American 90 year-olds have dementia.So what does it mean when we talk about a “cure” for Alzheimer’s? Some history, and an understanding of the current state of affairs is needed to frame that question.Loss of cognitive ability with age has always been recognized, indeed expected. It wasn’t much of a problem, historically, since few individuals lived long enough to experience dementia.AD was first described in the medical literature in 1906 by Alois Alzheimer, a German neuropathologist, who performed an autopsy on Mme D, Auguste Deter - Wikipedia, a woman who began to become demented in her 40’s, was institutionalized, and died at age 56. Alzheimer wrote a paper describing Mme D’s dementia and her brain: there was dramatic atrophy, and when examined microscopically, loss of neurons as well as large numbers of abnormal deposits, some looking like plaques while other appeared more tangle-like. What is most notable about Mme D, however, was the fact that she was only in her 40’s when her illness began. If she had been in her 70’s or 80’s, none of her symptoms or findings would have been considered remarkable.Mme D had presenile, early onset AD. Presenile dementia is clearly abnormal and a diagnosable illness. There is also senile dementia, late onset AD, which is neuropathologically identical to Mme D’s presenile AD - severe atrophy, neuron loss, plaques, and tangles. The brains look identical, with the only difference being age of onset. While dementia at age 55 is clearly abnormal, losing your memory and confusion after you turn 90… “well, what do you expect from Mom? Let’s see how you are when you’re her age.”Some time in the 1970’s, the acceptance of senile dementia as normal began to come into question. In the 70’s, 80’s, and 90’s, a series of important discoveries were made:The plaques and tangles Alzheimer described are amyloids: aggregates of mis-folded protein that clump together (rather like prion disease). The plaques are made up of aggregated β-amyloid protein, that is released when amyloid precursor protein (APP, a trans membrane protein that turns over very rapidly in neurons and glia) is cleaved. Tangles are amyloids made of mis-folded, hyper-phosphorylated Tau (a protein normally involved in stabilizing intracellular microtubules).Early onset, familial AD (FAD), which is probably what Mme D had, is a genetic disorder: autosomal dominant, meaning if you carry the mutation, you are going to become demented at the same age as your mother or father did. The causal mutations have been identified, and are in either the gene for APP (the precursor protein to β-amyloid) or the genes of either of 2 enzyme complexes (presenilin 1 & presenilin 2) involved in cleaving APP, releasing β-amyloidThere are other genetic risk factors for AD. People with Downs syndrome, trisomy 21 (3 copies of chromosome 21) also have a much higher risk of early onset AD. The APP gene is on chromosome 21, meaning that people with DS have an extra copy of the APP gene, presumably leading to more β-amyloid formation.People with 1 or 2 copies of the E4 allele (variant)of the ApoE gene have a 10 - 15 year earlier age of onset of AD (60’s or 70’s rather than 80’s or 90’s). People with the E4 allele also have earlier deposition of β-amyloid plaques in their brains. ApoE is a protein primarily involved in transport of cholesterol. The ApoE gene has 3 alleles: E2, E3, and E4. Homozygotes, with 2 copies of the E4 allele are at greater risk for AD than heterozygotes (1 copy) who are at greater risk than people with E2 or E3. People who have the E2 allele actually have a lower risk of AD. Some 25–30% of Asians and Caucasians have an E4 allele and are at increased risk for AD. However, unlike FAD, ApoE4, even in homozygotes, is not 100% penetrant.In other words, abnormal processing of APP and increased production of β-amyloid, that then gets deposited as extracellular plaques in the brain, causes early onset FAD, as well as, presumably, the more common late onset AD. This was the basis for the ‘amyloid cascade hypothesis’, which became & remains, the most widely accepted scientific model for AD pathogenesis. For more details, see: John K Hsiao's answer to What is the relationship between Alzheimer’s disease and the β-amyloid peptide?A slight detour is needed at this point: In the 90’s & 00’s, Pharma actually found several drugs that reverse cognitive decline in AD & LBD (Lewy Body Dementia). The cholinesterase inhibitors (AChE-I’s), which block breakdown of the neurotransmitter, acetylcholine in the brain (tacrine, Cognex; donepezil, Aricept; and rivastigmine, Exelon), and the NMDA receptor antagonist, memantine (Namenda) improve cognition in people with moderate AD. Unfortunately, the beneficial effects last for only a few months, and long term decline continues, unabated. These drugs probably work better in LBD than AD, although that’s not been rigorously proven, yet.The problem (or so we claim) is that AChE-I’s and memantine treat the symptoms of AD rather than its cause. We need “disease-modifying” treatments that attack AD’s root cause(s). If the amyloid cascade hypothesis is correct, then obviously, the way to cure AD is to get rid of excess β-amyloid (e.g, plaques). Not surprisingly, the last 25 years have seen a huge (& continuing) effort to develop drugs to remove or reduce β-amyloid in the brain.Pharma & academic investigators have identified vaccines or monoclonal antibodies (MAbs) that clear β-amyloid plaques & improve cognition in mouse models of AD. They’ve also found various drugs that inhibit enzymes involved in producing β-amyloid (gamma-secretase, the active moiety of presenilin 1 & 2; as well as β-amyloid cleaving enzyme, BACE). Unfortunately, these β-amyloid vaccines (AN 1792), MAbs (gantenerumab, solanezumab, bapineuzumab), gamma secretase inhibitors (semagacestat), and BACE inhibitors (verubecestat, lanabecestat LY2886721, JNJ-54861911) didn’t help patients with AD. The pivotal, FDA Phase 3 trials, costing many billions of $$, have either been stopped due to side effects (AN1792 caused encephalitis, while semagacestat actually worsened cognition) or failed to demonstrate any benefit versus placebo in people with AD.These very expensive failures have been disappointing, leading some large drug companies to abandon AD research. It’s important to examine why trials failed. In some of the earliest trials, there was actually no way to determine whether the anti-β-amyloid agent affected brain β-amyloid: how could a drug work if it doesn’t engage its putative target? It wasn’t until the end of the 2000’s that methods to measure brain β-amyloid (using CSF or PET neuroimaging) were developed. More recent (failed) trials have demonstrated changes in brain β-amyloid. However, even in patients whose β-amyloid plaques were entirely cleared by treatment, no cognitive benefit was evident.It turns out that β-amyloid plaques actually begin to appear 15–20 years before onset of dementia. Moreover, a third or more of people in their 70’s or 80’s have β-amyloid in their brains but don’t have cognitive impairment. The view of many AD investigators now, is that ‘the horse is already out of the barn’ if anti-β-amyloid therapies are delayed until AD is diagnosed. Academic investigators, supported by NIA have turned towards testing various anti-β-amyloid drugs in people at high risk for AD but not yet cognitively impaired, hoping to prevent onset of AD.Major trials of various anti-β-amyloid drugs are in progressIn Medellin, Columbia, there is a large family with a presenilin 1 mutation that leads to FAD. NIA is sponsoring a trial of crenezumab (Genentech), an anti-β-amyloid MAb, in people with the mutation but still cognitively normal, to see if this might prevent onset of AD. A Study of Crenezumab Versus Placebo in Preclinical Presenilin1 (PSEN1) E280A Mutation Carriers to Evaluate Efficacy and Safety in the Treatment of Autosomal-Dominant Alzheimer's Disease (AD), Including a Placebo-Treated Non-Carrier Cohort - Full Text View - ClinicalTrials.gov The trial should finish in 2022A multi-national, multi-site cohort of FAD families was started by NIA in 2008. The Dominantly Inherited Alzheimer’s Network (DIAN) has followed several hundred individuals - both with and without the causative mutations - from FAD families. DIAN has now begun treatment trials of anti-β-amyloid MAbs (solanezumab and gantenerumab) in mutation carriers who haven’t developed dementia, yet. The hope, again, is that reduction of β-amyloid will delay or prevent onset of AD (Dominantly Inherited Alzheimer Network Trial: An Opportunity to Prevent Dementia. A Study of Potential Disease Modifying Treatments in Individuals at Risk for or With a Type of Early Onset Alzheimer's Disease Caused by a Genetic Mutation. - Full Text View - ClinicalTrials.gov ) The trial should finish in 2023There is an NIA supported trial of an active β-amyloid vaccine and a BACE inhibitor in cognitively normal ApoE4 homozygotes (A Study of CAD106 and CNP520 Versus Placebo in Participants at Risk for the Onset of Clinical Symptoms of Alzheimer's Disease - Full Text View - ClinicalTrials.gov) The goal is to see if onset of disease can be delayed or prevented in ApoE4 carriers at genetic risk for AD. The trial should finish in 2025NIA supports the A4 trial, which is using solanezumab in people with documented brain β-amyloid plaques (based on β-amyloid PET scans), to see if reducing β-amyloid will prevent cognitive decline. Clinical Trial of Solanezumab for Older Individuals Who May be at Risk for Memory Loss - Full Text View - ClinicalTrials.gov. A4 should read out in 2022There are some industry sponsored, pivotal, FDA Phase 3, anti-β-amyloid in AD patients trials still in process. There was promising data on the anti-β-amyloid MAb - aducanumab (Biogen & Neuroimmune) - showing that it reduced brain β-amyloid and might slow progression of AD. Aducanumab is in the middle of two Phase 3 registration trials (221AD302 Phase 3 Study of Aducanumab (BIIB037) in Early Alzheimer's Disease - Full Text View - ClinicalTrials.gov & 221AD301 Phase 3 Study of Aducanumab (BIIB037) in Early Alzheimer's Disease - Full Text View - ClinicalTrials.gov ) that should have initial results in 2020 and final results in 2022. Crenezumab (see #1) is also being tested in an FDA phase 3 registration trial in AD patients, that will finish in 2023 (A Study of Crenezumab Versus Placebo to Evaluate the Efficacy and Safety in Participants With Prodromal to Mild Alzheimer's Disease (AD) - Full Text View - ClinicalTrials.gov). Another anti-β-amyloid MAb, BAN2401 (Eisai & Biogen), had disappointing initial results (A Study to Evaluate Safety, Tolerability, and Efficacy of BAN2401 in Subjects With Early Alzheimer's Disease - Full Text View - ClinicalTrials.gov), but an extension suggested there might be benefit, and the companies are considering starting a Phase 3 registration trial.Other, Phase 1 & Phase 2 efforts to develop and test anti-β-amyloid treatments continue to be sponsored by industry or academiaMeanwhile, there’s plenty of other research on AD, particularly the tau protein (that normally stabilizes microtubules), that becomes hyperphosphorylated, misfolded, and stacked into paired helical filaments (PHF), which aggregate and form the other neuropathological hallmark of AD: tangle like amyloid deposits of PHF-Tau. The appearance of Tau tangles seems much more closely linked to onset of cognitive impairment than β-amyloid plaques. Various anti-Tau MAbs are starting to be looked at in AD (as well as progressive supranuclear palsy, PSP, a frontotemporal dementia, caused by a different isoform of Tau).Negative treatment trials with anti-β-amyloid therapies have called the ‘amyloid cascade hypothesis’ into question. However, it’s important to point out that, regardless of whether anti-β-amyloid therapies are beneficial, the importance of β-amyloid and APP in the pathogenesis of AD is a settled question.Nevertheless, it’s also quite obvious that β-amyloid alone does not cause AD. In fact, the only dementia associated with β-amyloid alone is a vascular dementia, caused by β-amyloid deposits in brain blood vessels - congophilic amyloid angiopathy, CAA. AD requires both β-amyloid plaques and Tau tangles. AD is, by far, the most common cause of dementia, and for many people, Alzheimer’s is synonymous with dementia. However, there are a number of other causes of dementia.AD characteristically begins with problems in short term memory (ie, you forget that someone just told you it’s 12 o’clock, & you ask again, “what time is it?”). The other dementias typically start with different symptoms: frontotemporal dementia (FTD) begins with changes in behavior, personality, or in language (primary progressive aphasia) or movement (PSP, corticobasal syndrome, & ALS: interesting & important, little known fact - FTD and amyotrophic lateral sclerosis, ALS, Lou Gehrig’s disease, overlap genetically). Lewy body dementia (LBD) starts with waxing and waning level of consciousness, visual hallucinations or Parkinson’s disease, along with problems in judgment & planning. Vascular dementia (VD) is associated with subcortical strokes or vascular damage that can present with myriad different deficits (depending on the location of vascular damage). VD progresses in ‘stairstep’ fashion (sudden loss of function rather than gradual changes), but usually does not have the characteristic lateralized loss of function (e.g, hemiparalysis) of a large cortical stroke.AD, FTD, LBD, and VD are all associated with aging (although FTD often begins before age 65). Along with their characteristic clinical presentations, they also have unique neuropathologic features: FTD is associated with deposits of misfolded Tau or TDP43. LBD Lewy bodies are made up of misfolded alpha-synuclein (also found in Parkinsons’s disease). VD has characteristic microvascular changes. For more details, see John K Hsiao's answer to By the time the first symptoms of Alzheimer's disease show up, how much damage has the brain sustained?The incidence of dementia seems to be decreasing in recent decades (at least in 1st world nations). This is probably due to improvements in vascular health and fewer strokes, secondary to better control of blood pressure and hyperlipidemia. The SPRINT-MIND study recently demonstrated that tighter blood pressure control reduces incidence of mild cognitive impairment and dementia (AAIC 2018 | Alzheimer's Association) There’s some controversy surrounding the study (tighter blood pressure control also increases incidence of other side effects like falls), but the finding itself is encouraging for prevention of VD.I’m actually optimistic about NIA’s prevention trials in FAD and ApoE4 (see 1–4, above). We won’t know the results until the early 2020’s, but an anti-β-amyloid treatment should have a good chance of preventing dementia in people at high risk due to excessive β-amyloid. The proof of the pudding is in the eating, of course, and we’re not going to be getting a taste until 2022.I’m not so optimistic that aducanumab, crenezumab, or BAN2401 (see 5, above), or other anti-β-amyloid interventions will work in symptomatic AD patients, or work much better than AChE-I’s and memantine. The research focus in recent years has been on the earliest stages of AD and prevention of onset. However, we must not ignore people with mild or moderate illness, particularly the 5% or so with early onset, presenile AD (FAD is actually a tiny fraction of presenile AD), who are young enough that they often have family responsibilities when they fall ill.The problem is that we don’t actually understand what drives neurodegeneration, or why neurons die & cognitive abilities are lost in people with dementia. This isn’t due to a lack of research. There are a lot of different molecules or strategies in the developmental pipeline that might lead to a breakthrough, but nothing - except perhaps anti-Tau MAb’s - that give immediate cause for excitement.There is one, very hopeful development that hasn’t gotten a lot of attention from the lay press: we can now diagnose AD in living individuals. That may not sound all that important. After all, we’ve been diagnosing patients with AD since Alzheimer wrote his paper. However, in the past, a definitive, neuropathological diagnosis could only be made postmortem, when a demented person’s brain was sliced up and examined. Alzheimer’s disease requires 3 things: dementia, β-amyloid plaques, and Tau tangles. Dementia can only be diagnosed in the living, while, in the past, plaques and tangles could only be seen in brains of the dead.In the late 2000’s, positron emission tomography (PET) radiotracers were developed that bound specifically to β-amyloid plaques and could be visualized using PET neuroimaging. Then, in 2014, PET radiotracers for Tau tangles were developed, allowing us to visualize Tau tangles in the living human brain. We can now document the presence or absence of AD specific neuropathology when dementia is first diagnosed - years, if not decades before the person dies. Brain magnetic resonance imaging (MRI) has also advanced greatly, allowing us to measure subtle changes in neuroanatomical structure (e.g., hippocampal shape and volume), as well as microvascular changes associated with VD. There’s still lots of neuropathology (alpha-synuclein, TDP43, FTD 4RTau) we can’t see, yet; but we can now trace the development of AD plaques and tangles as well as changes in brain gray and white matter as someone transitions from normal to mild cognitive impairment to actual dementia. 2014 was only 4 years ago, & the picture so far of how the brain changes during the course of dementia is still very fuzzy: incomplete, certainly, & at times, surprising.The human brain is incredibly complicated, and as impressive as modern neuroimaging methods have become, we don’t have a cure for AD in hand. Technology will continue to advance, of course, so it’s hard not to feel hope. At the same time, we were confident, back when the amyloid cascade hypothesis was first put forward, that a cure was just around the corner. There have been more than a few twists and turns since that early optimism.We already have some idea about how to prevent vascular dementia. Use of anti-β-amyloid treatments have a good chance of preventing AD in people with FAD or carriers of the ApoE4 allele. It will take time, but I am confident that we will find a cure for plaque & tangle AD dementia, as well as for the proteinopathies associated with FTD and LBD. Managing specific neuropathological diseases should be feasible, once we understand the pathophysiological processes driving them.The problem comes with aging, itself. The major risk factor for all of the dementias is age. Eventually, we all lose the vigor and acuity of youth. A centenarian isn’t going to compete with a 40 year old physically, let alone an athlete in their 20’s. Cognitive abilities fade & the brain exhibits, so called “normal” atrophy as we age. Alzheimer’s disease is a disease in peoples’ 50′s, 60’s, 70’s, 80’s, even 90’s; but by age 90, at least half of people will be diagnosed as demented. Moreover, in the oldest old, it is rare to see plaques and tangles alone: multiple neuropathologies accumulate as we age.At what point does prevention or treatment of dementia become prevention or treatment of aging? Researchers are trying to understand how time itself ravages the body and the mind. The good news is that we are learning that aging’s effects are malleable, to a degree. AD, FTD, and LBD all involve normal proteins misfolding and aggregating to form amyloid deposits. Impaired proteostasis is a hallmark of aging tissue: aging cells aren’t good at clearing out their garbage. Finding a way to reverse deficits in proteostasis related to aging might benefit all dementias. We should spend more time & effort on understanding the brain’s aging process.So that’s about where things stand with respect to a cure for Alzheimer’s, at the beginning of 2019. We understand less than we think and less than we need to know. Progress is slow but real. We will learn more this next year, & it’s possible that my answer to this question will change considerably by the end of 2019. Then again, it might not.

Neuroscience, a subdivision of Biology/ Life Sciences, deals with the structure and function of the nervous system and brain. It is the study of how the nervous system develops, its structure, and what it does. Neuroscientists focus on the brain and its impact on behavior and cognitive functions. Not only is neuroscience concerned with the normal functioning of the nervous system, but also what happens to the nervous system when people have neurological, psychiatric and neurodevelopmental disorders.It is an interdisciplinary science which liaises closely with other disciplines, such as mathematics, linguistics, engineering, computer science, chemistry, philosophy, psychology, and medicine.A 100 Year Journey Through the Mind:1) Beginning of Modern Neuroscience:The Neuron Doctrine of Santiago Ramon Y Cajal (1899-1911)Neurons are the functional signaling units of the nervous system - Principle of dynamic polarization2) Synaptic Transmission:Charles S. Sherrington (1906): Understood the reflex synapses: excitatory/inhibitoryJohn C. Eccles: Discovered the ionic mechanism through which neurons generate excitation and inhibition3) Hans Berger publishes his findings about the first human electroencephalogram -19294) B. F. Skinner: publishes The Behavior of Organisms that describes operant conditioning (1938)5) Kenneth Cole: develops the voltage clamp- 1949National Institute of Mental Health, USA was establishedDonald Olding Hebb publishes The Organization of Behavior: A Neuropsychological Theory - 19496) Brenda Milner discusses patient HM who suffers from memory loss of hippocampal surgery- 19537) Development of the Nervous System: (1956)Organizers (fibroblast growth factor)Genes involved in neural circuitsControl of neural survivalNerve Growth Factor – Rita Levi MontalciniApoptosis - Robert HorvitzMolecular factors in axons guidanceRita Levi Montalcini Robert Horvitz8) W. Penfield devised motor and sensory homunculus- 19579) Alan Lloyd Hodgkin, Andrew Fielding Huxley and John Carew Eccles, shared Nobel Prize for work on the mechanisms of the giant squid neuron cell membrane -196310) Julius Axelrod, Bernard Katz and Ulf Svante von Euler share Nobel Prize for work on neurotransmitters- 1970*Also not to forget the contribution of Otto Loewi for the discovery of Acetylcholine as neurotransmitter in 1920-21.11) Timothy Bliss and Terje Lomo describe long-term potentiation- 1973:12) First Positron Emission Tomography (PET) Scanner developed - 1974The first functional brain imaging technology, PET could effectively be used to evaluate what areas of the brain were active during various mental processes versus looking at the structure of the brain through conventional CT.13) Patch Clamp Technique- 1976:This discovery made it possible to record the currents of single ion channel molecules for the first time, which improved understanding of the involvement of channels in fundamental cell processes such as Action Potentials and nerve activity.14) Roger Wolcott Sperry awarded Nobel Prize-functions brain hemispheres- 198115) Giacomo Rizzolatti describes mirror neurons in area F5 of the monkey premotor cortex-1992fMRI Technique- 1992:Three studies in 1992 were the first to explore using the Blood Oxygen Level Dependent (BOLD) contrast in humans. Kenneth Kwong and colleagues, used a gradient-echo Echo Planar Imaging (EPI) sequence at a magnetic field strength of 1.5 T to study activation in the visual cortex. Ogawa and others conducted the study using a higher field (4.0 T) and showed that the BOLD signal depended on T2* loss of magnetization.16) Arvid Carlsson, Paul Greengard and Eric Kandel share the Nobel Prize for their discoveries concerning signal transduction in the nervous system-2000:Arvid Carlsson: Dopamine, an important neurotransmitter in Parkinson's pathophysiology.Paul Greengard has shown how dopamine and several other chemical transmitters exert their effects in the nerve cell.Eric Kandel: A schematic description of how molecular changes in a synapse may produce "short term memory" and "long term memory" in the sea slug, Aplysia.17) The Blue Brain Project - 2005:This project is an attempt to create a synthetic brain by reverse engineering mammalian brain circuitry. The aim of the project, founded by the Brain and Mind Institute of the Ecole Polytechnique Federale de Lausanne (EPFL) in Switzerland, is to study the brain's architectural and functional principles.18) Optogenetics- Controlling the brain with light:It is a biological technique which involves the use of light to control neurons in living tissue, that have been genetically modified to express light-sensitive ion channels. It is a neuromodulation method employed in neuroscience that uses a combination of techniques from optics and genetics to control and monitor the activities of individual neurons in living tissue—even within freely-moving animals—and to precisely measure the effects of those manipulations in real-time.19) "Flip the switch on, and the rats remember. Flip it off, and the rats forget -- A cortical neural prosthesis for restoring and enhancing memory- 2011:Biomedical engineers from Wake Forest University and University of Southern Califonia, analyze and duplicate the neural mechanism of learning in rats. Using an electronic system that duplicates the neural signals associated with memory, they managed to replicate the brain function in rats associated with long-term learned behavior, even when the rats had been drugged to forget.20) US President Barack Obama announces the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative- 201321) John O'Keefe, Edvard Moser, and May-Britt Moser share the Nobel Prize for their discoveries about cells that constitute a positioning system in the brain-2014:22) Sonogenetics - 2015:Team of scientists led by Prof. Sreekanth Chalasani from Salk Institute have bred worms with genetically modified nervous systems that can be controlled by bursts of sound waves.Edit 1:23) Monkeys 'driving' wheelchairs using just their THOUGHTS: Primates are filmed controlling chairs using brain electrodes- 2016:Neuroscientists at Duke University have developed a 'wireless brain-machine interface' or BMI, that allows a monkey to control a robotic wheelchair (illustrated above). This allowed experts to record the activity of their premotor and sensorimotor cortical neurons - two brain regions involved in movement and sensation. Dr. Miguel Nicholelis believes that the experiment will give hope to people with disabilities who have lost most muscle control and mobility due to quadriplegia or ALS.Developments in imaging technology, genetics, brain chemistry and computing are promising fresh insights into the workings of the mind and mental illness. In the next 100 years, we can anticipate a future where we have cures for most brain diseases like Alzheimer’s, Parkinson’s and schizophrenia. We can foresee the future of neuroscience being focused largely on personalized medicine. The research will be focused on improving treatments so that we can stop disease before it starts. We can imagine a future where we will be researching and teaching inoculations against brain disease that will be tailored to our individual genes and environment.Unlike putting a man on the moon, where we knew exactly where the goal was and the problem was largely an engineering problem, understanding the brain is a series of engineering problems and a series of intellectually creative, imaginative understandings, and it’s going to require the coordination of creativity across every scientific discipline that we know.

Daily life of an IAS officerCandidates who successfully clear the UPSC Civil Services Exam get the first taste of life as an IAS officer as soon as they join the Lal Bahadur Shastri National Academy of Administration (LBSNAA). The day to day life of an IAS officer during training is very disciplined and starts at 6 am sharp. The following is the schedule usually followed at LBSNAA:6 am: Morning exercise/horse riding training for 60 minutes7 am to 9 am: Free time for morning activities9:30 am onwards: 8-10 hours of academic activity including lectures, sports and extracurricular activities.Officer trainees are left free before and after dinner to socialise and prepare for the next day. Outdoor activities such as treks to nearby rural areas to learn to cope with adversity and understand the lifestyle of rural India are an integral part of training. The training of IAS officers also includes Bharat Darshan (a study tour of India).Once a trainee graduates as an IAS officer, their schedule changes according to their allotted post. A typical day for an officer posted in the field would begin at 9 am and would involve going through various daily reports, supervising various daily tasks of the department or district, visiting different areas to review the implementation of developmental activities and meetings.These activities can stretch into the late evening and usually end by about 9 pm.During emergencies such as natural disasters, riots etc. an IAS officer might put in continuous work coordinating response and relief teams well beyond normal duty hours.IAS Officer Life – RolesIAS officers’ functional roles depend on the type of assignment they get. There are three types of assignments given to them:FieldState Secretariat/Public Sector UndertakingsCentral SecretariatThe field assignments are considered the toughest roles that an IAS officer may be called upon to fulfil. The following are the basic functions of the Civil Services:Handling affairs of the government, including framing, implementing and reviewing policies.Consulting with various departments and elected representatives for the above functions.Management and disbursement of various public funds allocated for different schemes.Supervising implementation of various schemes and policies of the government.Responding to emergencies such as natural disasters, major accidents and riots in their jurisdiction and coordinating relief activities.The assignment specific roles that civil servants perform are discussed below:Field Assignments: An IAS officers’ first posting after training is usually a field assignment. The various levels where they work have their own complexities.Sub Divisional Functions: As a Sub Divisional Magistrate, maintenance of law and order, overseeing developmental and administrative activities within the Sub -Division.District Level Functions: As a District Magistrate, Collector or Deputy Commissioner, perform the same functions as an SDM at the district level and also supervise SDMs in their role.Field assignments usually end at the district level for most IAS officers. Many of them move to positions within the state government and work in the State Secretariat.State Secretariat Assignments: State Secretariat postings involve using the experience and expertise gained in the field to advise elected representatives formulate policies and make decisions regarding government processes.Public Sector Undertakings: Many officers get posted to PSU cadres on deputation and become part of the higher management of various Public Sector Undertakings such as power discoms, industrial units etc.Central Secretariat Assignments: Secretarial level postings at the level of the Central government deal with policy review, formulation and implementation for different ministries.Many IAS officers are also deputed to international bodies such as the United Nations. There are provisions to depute IAS officers to private organizations for short tenures as well.IAS officer powerCode of Criminal Procedure (1973): Sections 107,108,109,110,133,144 and 176 list out powers for maintaining law and order given to MagistratesTenancy Laws define the powers of a collector regarding revenueNational Disaster Management Act list out powers of Chief Secretaries and Magistrates while directing disaster relief operations.Arms Act, Drug Licenses Act, Essential Commodities Act etc. list out IAS officers’ power to enforce regulations in different situations.These are the main laws that deal with powers of IAS, though there are close to 300 laws that define them on a case to case basis. These rules are also provided in an abridged form in the All India Service Manuals which are updated from time to time by the Department of Personnel and Training. The service manuals also list out the IAS conduct rules. All civil servants are answerable to state and central legislatures.IAS officer careerThe following is the career path that most IAS officers take. The career paths diverge after probation depending on the allotted cadre.Phase I Training at LBSNAATraining at the district level in the allotted cadrePhase II Training at LBSNAA which includes a week-long foreign attachment with one of India’s diplomatic missions abroadCentral Government attachment at the nominal position of an Assistant Secretary for three monthsPosting as SDM/Joint Magistrate/Sub CollectorPosting as Municipal Commissioner, DDO/CDOPosting as DM/CollectorPosting at State Secretariats at Director/Joint Secretary level.Deputation to the Central Government can be opted for during any stage of service after serving for a few years.Principal/Additional Secretary in the State Secretariat/Central SecretariatChief Secretary of a stateCabinet SecretaryThe highest position an IAS officer can aspire to is the position of the Cabinet Secretary of India. In state bureaucracy, Chief Secretary of states is the highest one can go.IAS officer salaryThe 7th Central Pay Commission has stipulated a basic pay of Rs 56100 for newly inducted IAS officers. There are a total of 18 pay levels for IAS with the Cabinet Secretary of the Union getting the highest pay at Rs. 250000. In addition to this, IAS officers usually get the following perks while in service:Subsidised government accommodation. District level postings get the best houses among any government service in India.Household help such as cooks, gardeners etc. depending on requirement.Security cover depending on requirement.Government transportation is provided in most district and state level postings. Central deputations have less vehicular facilities extended to IAS and only officers above a certain rank get government vehicles.Mobile, internet and telephone charges are reimbursed.Free stay in government rest houses and bungalows during the course of duty.IAS officers are also entitled to a monthly pension after retirement based on their rank and length of service.You can read about the detailed IAS officers salary per month here.The Indian Administrative Service (IAS) also allows officers to proceed on paid study leave for up to two years to study at any reputed university in India and abroad.The life of an IAS officer is both challenging and satisfying for a driven individual. It is the perfect opportunity for youngsters to directly participate in the administration and development of their country.TN Seshan, the man who cleaned up India’s elections, was one of the IAS toppers in 1955. As the Chief Election Commissioner, he implemented a variety of reforms in the electoral process in India that earned him the ire of many politicians but also endeared him to the people of this country. Another civil servant who brought about a major transformation in the country is E Sreedharan, India’s ‘Metro Man’. Sreedharan, a Padma Vibhushan awardee, was responsible for the timely execution of the Delhi Metro project. He was known for boldly side-lining political pressure and circumventing political interventions for speedy execution of projects.There are remote hamlets in our country even today where the most basic needs are lacking and people’s lives are miserable. Imagine being responsible for bringing drinking water, transportation facilities, health facilities, educational institutions, sanitation, nutrition and dignity into the lives of people in such places.* source BYJU”S websitePlease go through website for further information.Thanks.