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MIT Open Access Articles
Mostrando recursos 41 - 60 de 16,101
Distributional sensitivity analysis - Allaire, Douglas L.; Willcox, Karen E.
Among the uses for global sensitivity analysis is factor prioritization. A key assumption for this is that a given factor can, through further research, be fixed to some point on its domain. For factors containing epistemic uncertainty, this is an optimistic assumption, which can lead to inappropriate resource allocation. Thus, this research develops an original method, referred to as distributional sensitivity analysis, that considers which factors would on average cause the greatest reduction in output variance, given that the portion of a particular factor's variance that can be reduced is a random variable. A key aspect of the method is...
Coherent Theta Oscillations and Reorganization of Spike Timing in the Hippocampal- Prefrontal Network upon Learning - Benchenane, Karim; Peyrache, Adrien; Khamassi, Mehdi; Gioanni, Yves; Battaglia, Francesco P.; Wiener, Sidney I.; Tierney, Patrick
To study the interplay between hippocampus and medial prefrontal cortex (Pfc) and its importance for learning and memory consolidation, we measured the coherence in theta oscillations between these two structures in rats learning new rules on a Y maze. Coherence peaked at the choice point, most strongly after task rule acquisition. Simultaneously, Pfc pyramidal neurons reorganized their phase, concentrating at hippocampal theta trough, and synchronous cell assemblies emerged. This synchronous state may result from increased inhibition exerted by interneurons on pyramidal cells, as measured by cross-correlation, and could be modulated by dopamine: we found similar hippocampal-Pfc theta coherence increases and...
Wind tunnel testing of a novel wingsuit design - Blair, Kim B.; Berry, Michael S.; Las Fargeas, Jonathan
A wingsuit is a special suit that is worn to allow the user to fly after jumping off of a high cliff. The wingsuit creates an airfoil shape by adding wings of material between the arms and the sides as well as a tail consisting of material between the legs. The wingsuit allows for the creation of lift and thus human flying. A new and novel wingsuit design is proposed based on the design of a delta wing aircraft. This new wingsuit has material leading from the side of the head and connecting to the top of the arms, extending...
Multimodality Imaging Atlas of Coronary Atherosclerosis - Donnelly, Patrick; Maurovich-Horvat, Pál; Vorpahl, Marc; Nakano, Masataka; Kaple, Ryan K.; Warger, William; Tanaka, Atsushi; Tearney, Guillermo; Virmani, Renu; Hoffmann, Udo
NEW HIGH-RESOLUTION IMAGING TECHNOLOGIES HAVE ENHANCED OUR UNDERSTANDING OF THE CORONARY atherosclerotic disease process, and this atlas provides a multimodality pictorial review of the development of histologically verified coronary atherosclerosis. A modified American Heart Association classification scheme system based on morphological plaque features and the propensity of plaque for thrombosis or cause of sudden cardiac death has recently been proposed. This classification scheme incorporates 5 categories of coronary atherosclerotic lesions (Table 1) (1 and 2). These categories include nonatherosclerotic lesions (intimal thickening and intimal xanthoma) and progressive atherosclerotic lesions (pathological intimal thickening, fibroatheroma, thin fibrous cap atheroma, rupture, erosion, calcified...
Pricing in the Market for Anticancer Drugs - Howard, David H.; Bach, Peter B.; Berndt, Ernst R.; Conti, Rena M.
In 2011, Bristol-Myers Squibb set the price of its newly approved melanoma drug ipilimumab— brand name Yervoy—at $120,000 for a course of therapy. The drug was associated with an incremental increase in life expectancy of four months. Drugs like ipilimumab have fueled the perception that the launch prices of new anticancer drugs and other drugs in the so-called "specialty" pharmaceutical market have been increasing over time and that increases are unrelated to the magnitude of the expected health benefits. In this paper, we discuss the unique features of the market for anticancer drugs and assess trends in the launch prices...
A Feud that Wasn't: Acetylcholine Evokes Dopamine Release in the Striatum - Surmeier, D. James; Graybiel, Ann M.; Graybiel, Ann M.
In this issue of Neuron, Threlfell et al. (2012) report that synchronous activation of cholinergic interneurons evokes striatal dopamine release by activating presynaptic nicotinic acetylcholine receptors. These findings call for a fundamental reevaluation of the long-standing view that dopamine and acetylcholine “feud” over control of striatal circuitry.
Dynamic ham-sandwich cuts in the plane - Abbott, Timothy G.; Burr, Michael A.; Chan, Timothy M.; Demaine, Erik D.; Demaine, Martin L.; Hugg, John; Kane, Daniel; Langerman, Stefan; Nelson, Jelani; Rafalin, Eynat; Seyboth, Kathryn; Yeung, Vincent
We design efficient data structures for dynamically maintaining a ham-sandwich cut of two point sets in the plane subject to insertions and deletions of points in either set. A ham-sandwich cut is a line that simultaneously bisects the cardinality of both point sets. For general point sets, our first data structure supports each operation in O(n[1 over 3]+ε) amortized time and O(n[4 over 3]+ε) space. Our second data structure performs faster when each point set decomposes into a small number k of subsets in convex position: it supports insertions and deletions in O(logn) time and ham-sandwich queries in O(klog4n)O(klog4n) time....
Digital Signaling and Hysteresis Characterize Ras Activation in Lymphoid Cells - Das, Jayajit; Ho, Mary; Zikherman, Julie; Govern, Christopher; Yang, Ming; Weiss, Arthur; Chakraborty, Arup K.; Roose, Jeroen P.
Activation of Ras proteins underlies functional decisions in diverse cell types. Two molecules, RasGRP and SOS, catalyze Ras activation in lymphocytes. Binding of active Ras to SOS' allosteric pocket markedly increases SOS' activity establishing a positive feedback loop for SOS-mediated Ras activation. Integrating in silico and in vitro studies, we demonstrate that digital signaling in lymphocytes (cells are “on” or “off”) is predicated upon feedback regulation of SOS. SOS' feedback loop leads to hysteresis in the dose-response curve, which can enable a capacity to sustain Ras activation as stimuli are withdrawn and exhibit “memory” of past encounters with antigen. Ras...
Minimum product set sizes in nonabelian groups of order pq - Deckelbaum, Alan
Let G be a nonabelian group of order pq, where p and q are distinct odd primes. We analyze the minimum product set cardinality μG(r,s)=min|AB|μG(r,s)=min|AB|, where A and B range over all subsets of G of cardinalities r and s , respectively. In this paper, we completely determine μG(r,s)μG(r,s) in the case where G has order 3p and conjecture that this result can be extended to all nonabelian groups of order pq. We also prove that for every nonabelian group of order pq there exist 1⩽r,s⩽pq1⩽r,s⩽pq such that μG(r,s)>μZ/pqZ(r,s)μG(r,s)>μ[subscript Z over pqZ(r,s)].
The distance geometry of music - Demaine, Erik D.; Gomez-Martin, Francisco; Meijer, Henk; Rappaport, David; Taslakian, Perouz; Winograd, Terry; Wood, David R.; Toussaint, Godfried
We demonstrate relationships between the classic Euclidean algorithm and many other fields of study, particularly in the context of music and distance geometry. Specifically, we show how the structure of the Euclidean algorithm defines a family of rhythms which encompass over forty timelines (ostinatos) from traditional world music. We prove that these Euclidean rhythms have the mathematical property that their onset patterns are distributed as evenly as possible: they maximize the sum of the Euclidean distances between all pairs of onsets, viewing onsets as points on a circle. Indeed, Euclidean rhythms are the unique rhythms that maximize this notion of...
Accurate Sound Localization in Reverberant Environments Is Mediated by Robust Encoding of Spatial Cues in the Auditory Midbrain - Devore, Sasha; Ihlefeld, Antje; Hancock, Kenneth; Shinn-Cunningham, Barbara; Delgutte, Bertrand
In reverberant environments, acoustic reflections interfere with the direct sound arriving at a listener's ears, distorting the spatial cues for sound localization. Yet, human listeners have little difficulty localizing sounds in most settings. Because reverberant energy builds up over time, the source location is represented relatively faithfully during the early portion of a sound, but this representation becomes increasingly degraded later in the stimulus. We show that the directional sensitivity of single neurons in the auditory midbrain of anesthetized cats follows a similar time course, although onset dominance in temporal response patterns results in more robust directional sensitivity than expected,...
A Proposal for Integrated Efficacy-to-Effectiveness (E2E) Clinical Trials - Selker, H P; Eichler, H-G; Stockbridge, N L; Mehta, C R; Kaitin, K I; McElwee, N E; Honig, P K; Erban, J K; D’Agostino, R B; Oye, Kenneth A.
We propose an “efficacy-to-effectiveness” (E2E) clinical trial design, in which an effectiveness trial would commence seamlessly upon completion of the efficacy trial. Efficacy trials use inclusion/exclusion criteria to produce relatively homogeneous samples of participants with the target condition, conducted in settings that foster adherence to rigorous clinical protocols. Effectiveness trials use inclusion/exclusion criteria that generate heterogeneous samples that are more similar to the general patient spectrum, conducted in more varied settings, with protocols that approximate typical clinical care. In E2E trials, results from the efficacy trial component would be used to design the effectiveness trial component, to confirm and/or discern...
A mathematical model of the footprint of the CO[subscript 2] plume during and after injection in deep saline aquifer systems - MacMinn, Christopher W.; Juanes, Ruben
We present a sharp-interface mathematical model of CO[subscript 2] migration in saline aquifers, which accounts for gravity override, capillary trapping, natural groundwater flow, and the shape of the plume during the injection period. The model leads to a nonlinear advection–diffusion equation, where the diffusive term is due to buoyancy forces, not physical diffusion. For the case of interest in geological CO[subscript 2] storage, in which the mobility ratio is very unfavorable, the mathematical model can be simplified to a hyperbolic equation. We present a complete analytical solution to the hyperbolic model. The main outcome is a closed-form expression that predicts...
Disrupted in Schizophrenia 1 Regulates Neuronal Progenitor Proliferation via Modulation of GSK3β/β-Catenin Signaling - Mao, Yingwei; Ge, Xuecai; Frank, Christopher L.; Madison, Jon M.; Koehler, Angela N.; Doud, Mary Kathryn; Tassa, Carlos; Berry, Erin M.; Soda, Takahiro; Singh, Karun K.; Biechele, Travis; Petryshen, Tracey L.; Moon, Randall T.; Haggarty, Stephen J.; Tsai, Li-Huei
The Disrupted in Schizophrenia 1 (DISC1) gene is disrupted by a balanced chromosomal translocation (1; 11) (q42; q14.3) in a Scottish family with a high incidence of major depression, schizophrenia, and bipolar disorder. Subsequent studies provided indications that DISC1 plays a role in brain development. Here, we demonstrate that suppression of DISC1 expression reduces neural progenitor proliferation, leading to premature cell cycle exit and differentiation. Several lines of evidence suggest that DISC1 mediates this function by regulating GSK3β. First, DISC1 inhibits GSK3β activity through direct physical interaction, which reduces β-catenin phosphorylation and stabilizes β-catenin. Importantly, expression of stabilized β-catenin overrides...
Superinduction for pattern groups - Marberg, Eric; Thiem, Nathaniel
It is well known that the representation theory of the finite group of unipotent upper-triangular matrices U[subscript n] over a finite field is a wild problem. By instead considering approximately irreducible representations (supercharacters), one obtains a rich combinatorial theory analogous to that of the symmetric group, where we replace partition combinatorics with set-partitions. This paper studies Diaconis–Isaacs' concept of superinduction in pattern groups. While superinduction shares many desirable properties with usual induction, it no longer takes characters to characters. We begin by finding sufficient conditions guaranteeing that superinduction is in fact induction. It turns out for two natural embeddings of...
Elastic-net regularization in learning theory - De Mol, Christine; De Vito, Ernesto; Rosasco, Lorenzo Andrea
Within the framework of statistical learning theory we analyze in detail the so-called elastic-net regularization scheme proposed by Zou and Hastie [H. Zou, T. Hastie, Regularization and variable selection via the elastic net, J. R. Stat. Soc. Ser. B, 67(2) (2005) 301–320] for the selection of groups of correlated variables. To investigate the statistical properties of this scheme and in particular its consistency properties, we set up a suitable mathematical framework. Our setting is random-design regression where we allow the response variable to be vector-valued and we consider prediction functions which are linear combinations of elements (features) in an infinite-dimensional...
Wnt Signaling and the Polarity of the Primary Body Axis - Petersen, Christian P.; Reddien, Peter
How animals establish and pattern the primary body axis is one of the most fundamental problems in biology. Data from diverse deuterostomes (frog, fish, mouse, and amphioxus) and from planarians (protostomes) suggest that Wnt signaling through β-catenin controls posterior identity during body plan formation in most bilaterally symmetric animals. Wnt signaling also influences primary axis polarity of pre-bilaterian animals, indicating that an axial patterning role for Wnt signaling predates the evolution of bilaterally symmetric animals. The use of posterior Wnt signaling and anterior Wnt inhibition might be a unifying principle of body plan development in most animals.
Technical Challenges in Using Human Induced Pluripotent Stem Cells to Model Disease - Saha, Krishanu; Jaenisch, Rudolf
Reprogramming of human somatic cells uses readily accessible tissue, such as skin or blood, to generate embryonic-like induced pluripotent stem cells (iPSCs). This procedure has been applied to somatic cells from patients who are classified into a disease group, thus creating “disease-specific” iPSCs. Here, we examine the challenges and assumptions in creating a disease model from a single cell of the patient. Both the kinetics of disease onset and progression as well as the spatial localization of disease in the patient's body are challenges to disease modeling. New tools in genetic modification, reprogramming, biomaterials, and animal models can be used...
The Continuing Puzzle of the Great Oxidation Event - Sessions, Alex L.; Doughty, David M.; Welander, Paula V.; Summons, Roger E.; Newman, Dianne K.
The rise of atmospheric O[subscript 2] was a milestone in the history of life. Although O[subscript 2] itself is not a climate-active gas, its appearance would have removed a methane greenhouse present on the early Earth and potentially led to dramatic cooling. Moreover, by fundamentally altering the biogeochemical cycles of C, N, S and Fe, its rise first in the atmosphere and later in the oceans would also have had important indirect effects on Earth's climate. Here, we summarize major lines of evidence from the geological literature that pertain to when and how O[subscript 2] first appeared in significant amounts...
Reading the Book of Memory: Sparse Sampling versus Dense Mapping of Connectomes - Seung, H. Sebastian
Many theories of neural networks assume rules of connection between pairs of neurons that are based on their cell types or functional properties. It is finally becoming feasible to test such pairwise models of connectivity, due to emerging advances in neuroanatomical techniques. One method will be to measure the functional properties of connected pairs of neurons, sparsely sampling pairs from many specimens. Another method will be to find a “connectome,” a dense map of all connections in a single specimen, and infer functional properties of neurons through computational analysis. For the latter method, the most exciting prospect would be to...