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Search Results: 1 - 10 of 25159 matches for " Paul Dean "
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Cerebellar Motor Learning: When Is Cortical Plasticity Not Enough?
John Porrill,Paul Dean
PLOS Computational Biology , 2007, DOI: 10.1371/journal.pcbi.0030197
Abstract: Classical Marr-Albus theories of cerebellar learning employ only cortical sites of plasticity. However, tests of these theories using adaptive calibration of the vestibulo–ocular reflex (VOR) have indicated plasticity in both cerebellar cortex and the brainstem. To resolve this long-standing conflict, we attempted to identify the computational role of the brainstem site, by using an adaptive filter version of the cerebellar microcircuit to model VOR calibration for changes in the oculomotor plant. With only cortical plasticity, introducing a realistic delay in the retinal-slip error signal of 100 ms prevented learning at frequencies higher than 2.5 Hz, although the VOR itself is accurate up to at least 25 Hz. However, the introduction of an additional brainstem site of plasticity, driven by the correlation between cerebellar and vestibular inputs, overcame the 2.5 Hz limitation and allowed learning of accurate high-frequency gains. This “cortex-first” learning mechanism is consistent with a wide variety of evidence concerning the role of the flocculus in VOR calibration, and complements rather than replaces the previously proposed “brainstem-first” mechanism that operates when ocular tracking mechanisms are effective. These results (i) describe a process whereby information originally learnt in one area of the brain (cerebellar cortex) can be transferred and expressed in another (brainstem), and (ii) indicate for the first time why a brainstem site of plasticity is actually required by Marr-Albus type models when high-frequency gains must be learned in the presence of error delay.
Silent Synapses, LTP, and the Indirect Parallel-Fibre Pathway: Computational Consequences of Optimal Cerebellar Noise-Processing
John Porrill ,Paul Dean
PLOS Computational Biology , 2008, DOI: 10.1371/journal.pcbi.1000085
Abstract: Computational analysis of neural systems is at its most useful when it uncovers principles that provide a unified account of phenomena across multiple scales and levels of description. Here we analyse a widely used model of the cerebellar contribution to sensori-motor learning to demonstrate both that its response to intrinsic and sensor noise is optimal, and that the unexpected synaptic and behavioural consequences of this optimality can explain a wide range of experimental data. The response of the Marr-Albus adaptive-filter model of the cerebellar microcircuit to noise was examined in the context of vestibulo-ocular reflex calibration. We found that, when appropriately connected, an adaptive-filter model using the covariance learning rule to adjust the weights of synapses between parallel fibres and Purkinje cells learns weight values that are optimal given the relative amount of signal and noise carried by each parallel fibre. This optimality principle is consistent with data on the cerebellar role in smooth pursuit eye movements, and predicts that many synaptic weights must be very small, providing an explanation for the experimentally observed preponderance of silent synapses. Such a preponderance has in its turn two further consequences. First, an additional inhibitory pathway from parallel fibre to Purkinje cell is required if Purkinje cell activity is to be altered in either direction from a starting point of silent synapses. Second, cerebellar learning tasks must often proceed via LTP, rather than LTD as is widely assumed. Taken together, these considerations have profound behavioural consequences, including the optimal combination of sensori-motor information, and asymmetry and hysteresis of sensori-motor learning rates.
Splitting for Rare Event Simulation: A Large Deviation Approach to Design and Analysis
Thomas Dean,Paul Dupuis
Mathematics , 2007,
Abstract: Particle splitting methods are considered for the estimation of rare events. The probability of interest is that a Markov process first enters a set $B$ before another set $A$, and it is assumed that this probability satisfies a large deviation scaling. A notion of subsolution is defined for the related calculus of variations problem, and two main results are proved under mild conditions. The first is that the number of particles generated by the algorithm grows subexponentially if and only if a certain scalar multiple of the importance function is a subsolution. The second is that, under the same condition, the variance of the algorithm is characterized (asymptotically) in terms of the subsolution. The design of asymptotically optimal schemes is discussed, and numerical examples are presented.
The EUV emission from sun-grazing comets
Paul Bryans,W Dean Pesnell
Physics , 2012, DOI: 10.1088/0004-637X/760/1/18
Abstract: The Atmospheric Imaging Assembly (AIA) on the Solar Dynamics Observatory (SDO) has observed two sun-grazing comets as they passed through the solar atmosphere. Both passages resulted in a measurable enhancement of Extreme Ultraviolet (EUV) radiance in several of the AIA bandpasses. We explain this EUV emission by considering the evolution of the cometary atmosphere as it interacts with the ambient solar atmosphere. Molecules in the comet rapidly sublimate as it approaches the Sun. They are then photodissociated by the solar radiation field to create atomic species. Subsequent ionization of these atoms produces a higher abundance of ions than normally present in the corona and results in EUV emission in the wavelength ranges of the AIA telescope passbands.
Bench-to-bedside review: The promise of rapid infection diagnosis during sepsis using polymerase chain reaction-based pathogen detection
Paul M Dark, Paul Dean, Geoffrey Warhurst
Critical Care , 2009, DOI: 10.1186/cc7886
Abstract: Sepsis is the clinical syndrome resulting from a host's systemic inflammatory response to infection and is a major international health care problem. The Surviving Sepsis Campaign promotes an important concept of early, goal-directed management of sepsis as part of the evidence-based guidelines aimed at saving lives [1]. At the core of these guidelines are the early diagnosis of infection as a cause for the patient's systemic inflammatory response and the timely administration of appropriate antimicrobial chemotherapy.The consensus definitions of infection in critical care require microbiological evidence of pathogens to make a probable diagnosis (for example, Gram stain) or culture to confirm the diagnosis [2]. The Surviving Sepsis Campaign guidelines advocate obtaining at least whole blood and, where possible, other supporting clinical samples for culture prior to the administration of antibiotics, all achieved within 1 hour in a patient with presumed severe sepsis [1]. Current opinion in critical care favours the early use of antibiotics, guided by local pathogen surveillance, usually of a broad spectrum and high potency, that is equally applicable to all clinical settings in patients with suspected severe sepsis [1]. There is evidence showing that the correct initial choice of antibiotic saves more lives than virtually any other intensive care unit intervention [1,3-5]. This may require broad-spectrum cover in the face of as-yet-unidentified infection because delaying antibiotic therapy in sepsis has been shown to increase mortality and morbidity [6,7]. Unfortunately, the widespread use of broad-spectrum antibiotics is implicated in the emergence of drug-resistant organisms and rising rates of infection with Clostridium difficile and fungi. Therefore, early de-escalation of antimicrobial agents is a key aim of Surviving Sepsis Campaign guidelines in order to reduce this problem [1].Blood cultures have a central role in the detection of pathogenaemia in patients
Goodman’s New Riddle of Induction  [PDF]
Dean Lubin
Open Journal of Philosophy (OJPP) , 2012, DOI: 10.4236/ojpp.2012.21009
Abstract: In this paper, I consider Goodman’s new riddle of induction and how we should best respond to it. Noticing that all the emeralds so far observed are green, we infer (project) that all emeralds are green. However, all emeralds so far observed are also grue, so we could also infer that they are grue. Only one of these inductive inferences or projections could, however, be valid. For the hypothesis that all emeralds are green predicts that the next observed emerald will be green; whereas the hypothesis that they are grue predicts that it will blue. Goodman’s new riddle is the problem of saying why the inductive inference involving “green” is the valid one. Goodman’s own solution appeals to the idea of entrenchment. His idea is that “green” is a more entrenched predicate than “grue” in the sense that it has figured many more times in our past projections than has “grue”. In his view, this explains why “green” is projectible (can be used in valid inductive inferences) whereas “grue” isn’t. I argue that this response doesn’t go far enough and that we additionally need an explanation of why “green” is more entrenched than “grue”—that we are otherwise left with the unsatisfactory view that its superior entrenchment is a mere linguistic accident. I try to supplement Goodman’s solution with an explanation of this kind. I argue that “grue” is not entrenched be- cause past successful inductions involving “green” show that past projections that could have been made using what I call “grue-like” predicates—predicates which are like “grue” except that the times featuring in their definitions are past—would have been unsuccessful.
Modeling Population Growth: Exponential and Hyperbolic Modeling  [PDF]
Dean Hathout
Applied Mathematics (AM) , 2013, DOI: 10.4236/am.2013.42045

A standard part of the calculus curriculum is learning exponential growth models. This paper, designed to serve as a teaching aid, extends the standard modeling by showing that simple exponential models, relying on two points to fit parameters do not do a good job in modeling population data of the distant past. Moreover, they provide a constant doubling time. Therefore, the student is introduced to hyperbolic modeling, and it is demonstrated that with only two population data points, an amazing amount of information can be obtained, such as reasonably accurate doubling times that are a function of t, as well as accurate estimates of such entertaining topics as the total number of people that have ever lived on earth.

Synaptic Plasticity in Medial Vestibular Nucleus Neurons: Comparison with Computational Requirements of VOR Adaptation
John R. W. Menzies,John Porrill,Mayank Dutia,Paul Dean
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0013182
Abstract: Vestibulo-ocular reflex (VOR) gain adaptation, a longstanding experimental model of cerebellar learning, utilizes sites of plasticity in both cerebellar cortex and brainstem. However, the mechanisms by which the activity of cortical Purkinje cells may guide synaptic plasticity in brainstem vestibular neurons are unclear. Theoretical analyses indicate that vestibular plasticity should depend upon the correlation between Purkinje cell and vestibular afferent inputs, so that, in gain-down learning for example, increased cortical activity should induce long-term depression (LTD) at vestibular synapses.
Interaction between clopidogrel and proton-pump inhibitors and management strategies in patients with cardiovascular diseases
Paul A Gurbel, Udaya S Tantry, Dean J Kereiakes
Drug, Healthcare and Patient Safety , 2010, DOI: http://dx.doi.org/10.2147/DHPS.S7297
Abstract: teraction between clopidogrel and proton-pump inhibitors and management strategies in patients with cardiovascular diseases Review (3676) Total Article Views Authors: Paul A Gurbel, Udaya S Tantry, Dean J Kereiakes Published Date November 2010 Volume 2010:2 Pages 233 - 240 DOI: http://dx.doi.org/10.2147/DHPS.S7297 Paul A Gurbel1, Udaya S Tantry1, Dean J Kereiakes2 1Sinai Center for Thrombosis Research, Sinai Hospital of Baltimore, Baltimore, MD, USA; 2The Christ Hospital Heart and Vascular Center/The Lindner Research Center at The Christ Hospital, Cincinnati, OH, USA Abstract: Dual antiplatelet therapy (DAPT) with clopidogrel and aspirin has been successful in reducing ischemic events in a wide range of patients with cardiovascular diseases. However, the anti-ischemic effects of DAPT may also be associated with gastrointestinal (GI) complications including ulceration and bleeding particularly in ‘high risk’ and elderly patients. Current guidelines recommend the use of proton-pump inhibitors (PPIs) to reduce the risk of GI bleeding in patients treated with DAPT. However, pharmacodynamic studies suggest an effect of PPIs on clopidogrel metabolism with a resultant reduction in platelet inhibitory effects. Similarly, several observational studies have demonstrated reduced clopidogrel benefit in patients who coadministered PPIs. Although recent US Food and Drug Administration and European Medicines Agency statements discourage PPI (particularly omeprazole) and clopidogrel coadministration, the 2009 AHA/ACC/SCAI PCI guidelines do not support a change in current practice in the absence of adequately powered prospective randomized clinical trial data. The data regarding pharmacologic and clinical interactions between PPI and clopidogrel therapies are herein examined and treatment strategies are provided.
Faculty and Administrative Partnerships: Disciplinary Differences in Perceptions of Civic Engagement and Service-Learning at a Large, Research-Extensive University
Steven G. Buzinski,Paul Dean,Theresa A. Donofrio,Abram Fox
Partnerships : A Journal of Service-Learning and Civic Engagement , 2013, DOI: 10.7253/partj.v4i1.483
Abstract: In recent years, considerable energy has been expended attempting to define, evaluate and promote active learning pedagogies such as civic engagement and service-learning. Yet much of this scholarship treats civic engagement and service-learning at either a macroscopic level (studying an entire university system) or microscopic level (studying a particular course or project). There has been comparably less research examining how different disciplinary cultures influence the conceptualization and implementation of active learning pedagogies within individual institutions. This study draws on quantitative survey methodologies to examine faculty perceptions of civic engagement and service-learning at a major public research university within and across four disciplines: the Humanities, Behavioral and Social Sciences, Science, Technology, Engineering, and Mathematics (STEM), and the Applied Professions. Quantitative results reveal significant variance in disciplinary approaches to civic engagement and service-learning across a variety of measures including advocacy, concerns, and goals for active learning pedagogies. The findings suggest several strategies for recognizing disciplinary differences and encouraging collaboration among faculty and between disciplines on civic engagement and service-learning approaches in higher education.
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