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Agency: GTR | Branch: EPSRC | Program: | Phase: Training Grant | Award Amount: 3.94M | Year: 2014

The achievements of modern research and their rapid progress from theory to application are increasingly underpinned by computation. Computational approaches are often hailed as a new third pillar of science - in addition to empirical and theoretical work. While its breadth makes computation almost as ubiquitous as mathematics as a key tool in science and engineering, it is a much younger discipline and stands to benefit enormously from building increased capacity and increased efforts towards integration, standardization, and professionalism. The development of new ideas and techniques in computing is extremely rapid, the progress enabled by these breakthroughs is enormous, and their impact on society is substantial: modern technologies ranging from the Airbus 380, MRI scans and smartphone CPUs could not have been developed without computer simulation; progress on major scientific questions from climate change to astronomy are driven by the results from computational models; major investment decisions are underwritten by computational modelling. Furthermore, simulation modelling is emerging as a key tool within domains experiencing a data revolution such as biomedicine and finance. This progress has been enabled through the rapid increase of computational power, and was based in the past on an increased rate at which computing instructions in the processor can be carried out. However, this clock rate cannot be increased much further and in recent computational architectures (such as GPU, Intel Phi) additional computational power is now provided through having (of the order of) hundreds of computational cores in the same unit. This opens up potential for new order of magnitude performance improvements but requires additional specialist training in parallel programming and computational methods to be able to tap into and exploit this opportunity. Computational advances are enabled by new hardware, and innovations in algorithms, numerical methods and simulation techniques, and application of best practice in scientific computational modelling. The most effective progress and highest impact can be obtained by combining, linking and simultaneously exploiting step changes in hardware, software, methods and skills. However, good computational science training is scarce, especially at post-graduate level. The Centre for Doctoral Training in Next Generation Computational Modelling will develop 55+ graduate students to address this skills gap. Trained as future leaders in Computational Modelling, they will form the core of a community of computational modellers crossing disciplinary boundaries, constantly working to transfer the latest computational advances to related fields. By tackling cutting-edge research from fields such as Computational Engineering, Advanced Materials, Autonomous Systems and Health, whilst communicating their advances and working together with a world-leading group of academic and industrial computational modellers, the students will be perfectly equipped to drive advanced computing over the coming decades.

News Article | December 20, 2016
Site: www.eurekalert.org

When you're suddenly able to understand someone despite their thick accent, or finally make out the lyrics of a song, your brain appears to be re-tuning to recognize speech that was previously incomprehensible. University of California, Berkeley, neuroscientists have now observed this re-tuning in action by recording directly from the surface of a person's brain as the words of a previously unintelligible sentence suddenly pop out after the subject is told the meaning of the garbled speech. The re-tuning takes place within a second or less, they found. The observations confirm speculation that neurons in the auditory cortex that pick out aspects of sound associated with language - the components of pitch, amplitude and timing that distinguish words or smaller sound bits called phonemes - continually tune themselves to pull meaning out of a noisy environment. "The tuning that we measured when we replayed the garbled speech emphasizes features that are present in speech," said first author and UC Berkeley graduate student Chris Holdgraf. "We believe that this tuning shift is what helps you 'hear' the speech in that noisy signal. The speech sounds actually pop out from the signal." Such pop-outs happen all the time: when you learn to hear the words of a foreign language, for example, or latch onto a friend's conversation in a noisy bar. Or visually, when someone points out a number in what seems like a jumbled mass of colored dots, and somehow you cannot un-see that number. "Something is changing in the auditory cortex to emphasize anything that might be speech-like, and increasing the gain for those features, so that I actually hear that sound in the noise," said co-author Frédéric Theunissen, a UC Berkeley professor of psychology and a member of the Helen Wills Neuroscience Institute. "It's not like I am generating those words in my head. I really have the feeling of hearing the words in the noise with this pop-out phenomenon. It is such a mystery." "It is unbelievable how fast and plastic the brain is," added co-author Robert Knight, a UC Berkeley professor of psychology and Helen Wills Institute researcher. "In seconds or less, the electrical activity in the brain changes its response properties to pull out linguistic information. Behaviorally, this is a classic phenomenon, but this is the first time we have any evidence on how it actually works in humans." The findings will aid Knight and his colleagues in their quest to develop a speech decoder: a device implanted in the brain that would interpret people's imagined speech and help speechless patients, such as those paralyzed by Lou Gehrig's disease, communicate. Holdgraf, Knight, Theunissen and their colleagues will report their findings Dec. 20 in the journal Nature Communications. Working with epilepsy patients who had pieces of their skull removed and electrodes placed on the brain surface to track seizures - what is known as electrocorticography - Holdgraf presented seven subjects with a simple auditory test. He first played a highly garbled sentence, which almost no one initially understood. He then played a normal, easy to understand version of the sentence, and then immediately repeated the garbled version. Almost everyone understood the sentence the second time around, even though they initially found it unintelligible. The electrodes on the brain surface recorded major changes in neuronal activity before and after. When the garbled sentence was first played, activity in the auditory cortex as measured by the 468 electrodes was small. The brain could hear the sound, but couldn't do much with it, Knight said. When the clear sentence was played, the electrodes, as expected, recorded a pattern of neural activity consistent with the brain tuning into language. When the garbled sentence was played a second time, the electrodes recorded nearly the same language-appropriate neural activity, as if the underlying neurons had re-tuned to pick out words or parts of words. "They respond as if they were hearing unfiltered normal speech," Holdgraf said. "It changes the pattern of activity in the brain such that there is information there that wasn't there before. That information is this unfiltered speech." "Normal language activates tuning properties that are related to extraction of meaning and phonemes in the language," Knight said. "Here, after you primed the brain with the unscrambled sentence, the tuning to the scrambled speech looked like the tuning to language, which allows the brain to extract meaning out of noise." This trick is a testament to the brain's ability to automatically pick and choose information from a noisy and overwhelming environment, focusing only on what's relevant to a situation and discarding the rest. "Your brain tries to get around the problem of too much information by making assumptions about the world," Holdgraf said. "It says, 'I am going to restrict the many possible things I could pull out from an auditory stimulus so that I don't have to do a lot of processing.' By doing that, it is faster and expends less energy." That means, though, that noisy or garbled sound can be hard to interpret. Holdgraf and his colleagues showed how quickly the brain can be primed to tune in language. The neurons from which they recorded activity were not tuned to a single frequency, like a radio, Theunissen said. Rather, neurons in the upper levels of the auditory cortex respond to more complex aspects of sound, such as changes in frequency and amplitude - spectro-temporal modulation that we perceive as pitch, timbre and rhythm. While similar studies in animals, such as ferrets, have shown that neurons change how they filter or tune into a specific type of spectro-temporal modulation, the new results are the first in humans, and show a more rapid shift to process human language than has been seen in animals, he said. The researchers used an analysis technique first used by Theunissen to determine which complex characteristics of natural sound, like speech, neurons in the higher levels of the auditory cortex respond to, with a particular focus on songbird language. This is the first time the technique has been applied to humans to study how receptive fields change in neurons in the auditory cortex. Co-authors of the paper are Wendy de Heer of UC Berkeley's psychology department, postdoctoral fellows Brian Pasley and Jochem Rieger of the Helen Wills Neuroscience Institute, and neurologists Nathan Crone of Johns Hopkins School of Medicine in Baltimore, and Jack Lin of the UC Irvine Comprehensive Epilepsy Program. The work was supported by a graduate fellowship from the National Institute of Neurological Diseases and Stroke (NINDS 2R37NS021135, NIDCD R01 007293) and the Nielsen Corporation.

Vlasits A.L.,University of Washington | Vlasits A.L.,Helen Wills Neuroscience Institute | Simon J.A.,Fred Hutchinson Cancer Research Center | Raible D.W.,University of Washington | And 2 more authors.
Hearing Research | Year: 2012

Loss of mechanosensory hair cells in the inner ear accounts for many hearing loss and balance disorders. Several beneficial pharmaceutical drugs cause hair cell death as a side effect. These include aminoglycoside antibiotics, such as neomycin, kanamycin and gentamicin, and several cancer chemotherapy drugs, such as cisplatin. Discovering new compounds that protect mammalian hair cells from toxic insults is experimentally difficult because of the inaccessibility of the inner ear. We used the zebrafish lateral line sensory system as an in vivo screening platform to survey a library of FDA-approved pharmaceuticals for compounds that protect hair cells from neomycin, gentamicin, kanamycin and cisplatin. Ten compounds were identified that provide protection from at least two of the four toxins. The resulting compounds fall into several drug classes, including serotonin and dopamine-modulating drugs, adrenergic receptor ligands, and estrogen receptor modulators. The protective compounds show different effects against the different toxins, supporting the idea that each toxin causes hair cell death by distinct, but partially overlapping, mechanisms. Furthermore, some compounds from the same drug classes had different protective properties, suggesting that they might not prevent hair cell death by their known target mechanisms. Some protective compounds blocked gentamicin uptake into hair cells, suggesting that they may block mechanotransduction or other routes of entry. The protective compounds identified in our screen will provide a starting point for studies in mammals as well as further research discovering the cellular signaling pathways that trigger hair cell death. © 2012 Elsevier B.V.

Lara A.H.,Helen Wills Neuroscience Institute | Wallis J.D.,Helen Wills Neuroscience Institute | Wallis J.D.,University of California at Berkeley
Journal of Vision | Year: 2012

Temporary storage of information in visual short-term memory (VSTM) is a key component of many complex cognitive abilities. However, it is highly limited in capacity. Understanding the neurophysiological nature of this capacity limit will require a valid animal model of VSTM. We used a multiple-item color change detection task to measure macaque monkeys' VSTM capacity. Subjects' performance deteriorated and reaction times increased as a function of the number of items in memory. Additionally, we measured the precision of the memory representations by varying the distance between sample and test colors. In trials with similar sample and test colors, subjects made more errors compared to trials with highly discriminable colors. We modeled the error distribution as a Gaussian function and used this to estimate the precision of VSTM representations. We found that as the number of items in memory increases the precision of the representations decreases dramatically. Additionally, we found that focusing attention on one of the objects increases the precision with which that object is stored and degrades the precision of the remaining. These results are in line with recent findings in human psychophysics and provide a solid foundation for understanding the neurophysiological nature of the capacity limit of VSTM. © ARVO.

Sheridan M.A.,Boston University | Sheridan M.A.,Childrens Hospital Boston | Sarsour K.,Eli Lilly and Company | Jutte D.,University of California at Berkeley | And 3 more authors.
PLoS ONE | Year: 2012

The prefrontal cortex (PFC) develops from birth through late adolescence. This extended developmental trajectory provides many opportunities for experience to shape the structure and function of the PFC. To date, a few studies have reported links between parental socioeconomic status (SES) and prefrontal function in childhood, raising the possibility that aspects of environment associated with SES impact prefrontal function. Considering that behavioral measures of prefrontal function are associated with learning across multiple domains, this is an important area of investigation. In this study, we used fMRI to replicate previous findings, demonstrating an association between parental SES and PFC function during childhood. In addition, we present two hypothetical mechanisms by which SES could come to affect PFC function of this association: language environment and stress reactivity. We measured language use in the home environment and change in salivary cortisol before and after fMRI scanning. Complexity of family language, but not the child's own language use, was associated with both parental SES and PFC activation. Change in salivary cortisol was also associated with both SES and PFC activation. These observed associations emphasize the importance of both enrichment and adversity-reduction interventions in creating good developmental environments for all children. © 2012 Sheridan et al.

Sohl-Dickstein J.,Biophysics Graduate Group | Sohl-Dickstein J.,University of California at Berkeley | Battaglino P.B.,Stanford University | Battaglino P.B.,University of California at Berkeley | And 3 more authors.
Physical Review Letters | Year: 2011

Fitting probabilistic models to data is often difficult, due to the general intractability of the partition function. We propose a new parameter fitting method, minimum probability flow (MPF), which is applicable to any parametric model. We demonstrate parameter estimation using MPF in two cases: a continuous state space model, and an Ising spin glass. In the latter case, MPF outperforms current techniques by at least an order of magnitude in convergence time with lower error in the recovered coupling parameters. © 2011 American Physical Society.

Schaffer D.,Helen Wills Neuroscience Institute | Schaffer D.,California Stem Cell
4th International Conference on Biomolecular Engineering, ICBE 2013 | Year: 2013

Must better understand and engineer microenvironmental signaling mechanisms, both biochemical and biophysical to control stem cell function. Ephrins regulate neuronal differentiation of adult neyral stem cells and human pluripotent stem cells. Biomematic materials to spatially organize Eph receptors can potently activate signalling and regulate cell fate in vitro and in vivo. Engineered biomaterials offer the potential to create synthetic niches that recruit and regulate stem cells in vivo.

Cameron P.,Helen Wills Neuroscience Institute | Hiroi M.,Helen Wills Neuroscience Institute | Ngai J.,Helen Wills Neuroscience Institute | Scott K.,Helen Wills Neuroscience Institute | Scott K.,Howard Hughes Medical Institute
Nature | Year: 2010

The detection of water and the regulation of water intake are essential for animals to maintain proper osmotic homeostasis. Drosophila and other insects have gustatory sensory neurons that mediate the recognition of external water sources, but little is known about the underlying molecular mechanism for water taste detection. Here we identify a member of the degenerin/epithelial sodium channel family, PPK28, as an osmosensitive ion channel that mediates the cellular and behavioural response to water. We use molecular, cellular, calcium imaging and electrophysiological approaches to show that ppk28 is expressed in water-sensing neurons, and that loss of ppk28 abolishes water sensitivity. Moreover, ectopic expression of ppk28 confers water sensitivity to bitter-sensing gustatory neurons in the fly and sensitivity to hypo-osmotic solutions when expressed in heterologous cells. These studies link an osmosensitive ion channel to water taste detection and drinking behaviour, providing the framework for examining the molecular basis for water detection in other animals. © 2010 Macmillan Publishers Limited. All rights reserved.

Agarwal G.,Helen Wills Neuroscience Institute | Isacoff E.,Helen Wills Neuroscience Institute | Isacoff E.,University of California at Berkeley | Isacoff E.,Lawrence Berkeley National Laboratory
Journal of Neurophysiology | Year: 2011

Insect pheromonal glomeruli are thought to track the fine spatiotemporal features of one or a few odorants to aid conspecific localization. However, it is not clear whether they function differently from generalist glomeruli, which respond to many odorants. In this study, we test how DA1, a model pheromonal glomerulus in the fruit fly, represents the spatial and temporal properties of its input, compared with other glomeruli. We combine calcium imaging and electrical stimulation in an isolated brain preparation for a simultaneous, unbiased comparison of the functional organization of many glomeruli. In contrast to what is found in other glomeruli, we find that ipsilateral and contralateral stimuli elicit distinct spatial patterns of activity within DA1. DA1's output shows a greater preference for ipsilateral stimuli in males than in females. DA1 experiences greater and more rapid inhibition than other glomeruli, allowing it to report slight interantennal delays in stimulus onset in a "winner-take-all" manner. DA1's ability to encode spatiotemporal input features distinguishes it from other glomeruli in the fruit fly antennal lobe but relates it to pheromonal glomeruli in other insect species. We propose that DA1 is specialized to help the fly localize and orient with respect to pheromone sources. © 2011 the American Physiological Society.

Miller E.W.,Helen Wills Neuroscience Institute
Current Opinion in Chemical Biology | Year: 2016

Voltage imaging has the potential to unravel the contributions that rapid changes in membrane voltage make to cellular physiology, especially in the context of neuroscience. In particular, small molecule fluorophores are especially attractive because they can, in theory, provide fast and sensitive measurements of membrane potential dynamics. A number of classes of small molecule voltage indicators will be discussed, including dyes with improved two-photon voltage sensing, near infrared optical profiles for use in in vivo applications, and newly developed electron-transfer based indicators, or VoltageFluors, that can be tuned across a range of wavelengths to enable all-optical voltage manipulation and measurement. Limitations and a 'wish-list' for voltage indicators will also be discussed. © 2016 Elsevier Ltd.

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