25 resultados para playing
Resumo:
A molecular dynamics simulation study of aqueous solution of LiCl is reported as a function of pressure. Experimental measurements of conductivity of Li+ ion as a function of pressure shows an increase in conductivity with pressure. Our simulations are able to reproduce the observed trend in conductivity. A number of relevant properties have been computed in order to understand the reasons for the increase in conductivity with pressure. These include radial distribution function, void and neck distributions, hydration or coordination numbers, diffusivity, velocity autocorrelation functions, angles between ion-oxygen and dipole of water as well as OH vector, mean residence time for water in the hydration shell, etc. These show that the increase in pressure acts as a structure breaker. The decay of the self part of the intermediate scattering function at small wave number k shows a bi-exponential decay at 1 bar which changes to single exponential decay at higher pressures. The k dependence of the ratio of the self part of the full width at half maximum of the dynamic structure factor to 2Dk(2) exhibits trends which suggest that the void structure of water is playing a role. These support the view that the changes in void and neck distributions in water can account for changes in conductivity or diffusivity of Li+ with pressure. These results can be understood in terms of the levitation effect. (C) 2012 American Institute of Physics. http://dx.doi.org/10.1063/1.4756909]
Resumo:
Neuronal assemblies often exhibit stimulus-induced rhythmic activity in the gamma range (30-80 Hz), whose magnitude depends on the attentional load. This has led to the suggestion that gamma rhythms form dynamic communication channels across cortical areas processing the features of behaviorally relevant stimuli. Recently, attention has been linked to a normalization mechanism, in which the response of a neuron is suppressed (normalized) by the overall activity of a large pool of neighboring neurons. In this model, attention increases the excitatory drive received by the neuron, which in turn also increases the strength of normalization, thereby changing the balance of excitation and inhibition. Recent studies have shown that gamma power also depends on such excitatory-inhibitory interactions. Could modulation in gamma power during an attention task be a reflection of the changes in the underlying excitation-inhibition interactions? By manipulating the normalization strength independent of attentional load in macaque monkeys, we show that gamma power increases with increasing normalization, even when the attentional load is fixed. Further, manipulations of attention that increase normalization increase gamma power, even when they decrease the firing rate. Thus, gamma rhythms could be a reflection of changes in the relative strengths of excitation and normalization rather than playing a functional role in communication or control.
Resumo:
Host cell remodelling is a hallmark of malaria pathogenesis. It involves protein folding, unfolding and trafficking events and thus participation of chaperones such as Hsp70s and Hsp40s is well speculated. Until recently, only Hsp40s were thought to be the sole representative of the parasite chaperones in the exportome. However, based on the re-annotated Plasmodium falciparum genome sequence, a putative candidate for exported Hsp70 has been reported, which otherwise was known to be a pseudogene. We raised a specific antiserum against a C-terminal peptide uniquely present in PfHsp70-x. Immunoblotting and immunofluorescence-based approaches in combination with sub-cellular fractionation by saponin and streptolysin-O have been taken to determine the expression and localization of PfHsp70-x in infected erythrocyte. The re-annotated sequence of PfHsp70-x reveals it to be a functional protein with an endoplasmic reticulum signal peptide. It gets maximally expressed at the schizont stage of intra-erythrocytic life cycle. Majority of the protein localizes to the parasitophorous vacuole and some of it gets exported to the erythrocyte compartment where it associates with Maurer's clefts. The identification of an exported parasite Hsp70 chaperone presents us with the fact that the parasite has evolved customized chaperones which might be playing crucial roles in aspects of trafficking and host cell remodelling.
Resumo:
The forces that cause deformation of western North America have been debated for decades. Recent studies, primarily based on analysis of crustal stresses in the western United States, have suggested that the deformation of the region is mainly controlled by gravitational potential energy (GPE) variations and boundary loads, with basal tractions due to mantle flow playing a relatively minor role. We address these issues by modelling the deviatoric stress field over western North America from a 3-D finite element mantle circulation model with lateral viscosity variations. Our approach takes into account the contribution from both topography and shallow lithosphere structure (GPE) as well as that from deeper mantle flow in one single model, as opposed to separate lithosphere and circulation models, as has been done so far. In addition to predicting the deviatoric stresses we also jointly fit the constraints of geoid, dynamic topography and plate motion both globally and over North America, in order to ensure that the forces that arise in our models are dynamically consistent. We examine the sensitivity of the dynamic models to different lateral viscosity variations. We find that circulation models that include upper mantle slabs yield a better fit to observed plate velocities. Our results indicate that a model of GPE variations coupled with mantle convection gives the best fit to the observational constraints. We argue that although GPE variations control a large part of the deformation of the western United States, deeper mantle tractions also play a significant role. The average deviatoric stress magnitudes in the western United States range 30-40 MPa. The cratonic region exhibits higher coupling to mantle flow than the rest of the continent. We find that a relatively strong San Andreas fault gives a better fit to the observational constraints, especially that of plate velocity in western North America.
Resumo:
Moore's Law has driven the semiconductor revolution enabling over four decades of scaling in frequency, size, complexity, and power. However, the limits of physics are preventing further scaling of speed, forcing a paradigm shift towards multicore computing and parallelization. In effect, the system is taking over the role that the single CPU was playing: high-speed signals running through chips but also packages and boards connect ever more complex systems. High-speed signals making their way through the entire system cause new challenges in the design of computing hardware. Inductance, phase shifts and velocity of light effects, material resonances, and wave behavior become not only prevalent but need to be calculated accurately and rapidly to enable short design cycle times. In essence, to continue scaling with Moore's Law requires the incorporation of Maxwell's equations in the design process. Incorporating Maxwell's equations into the design flow is only possible through the combined power that new algorithms, parallelization and high-speed computing provide. At the same time, incorporation of Maxwell-based models into circuit and system-level simulation presents a massive accuracy, passivity, and scalability challenge. In this tutorial, we navigate through the often confusing terminology and concepts behind field solvers, show how advances in field solvers enable integration into EDA flows, present novel methods for model generation and passivity assurance in large systems, and demonstrate the power of cloud computing in enabling the next generation of scalable Maxwell solvers and the next generation of Moore's Law scaling of systems. We intend to show the truly symbiotic growing relationship between Maxwell and Moore!
Resumo:
An increase in the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel conductance reduces input resistance, whereas the consequent increase in the inward h current depolarizes the membrane. This results in a delicate and unique conductance-current balance triggered by the expression of HCN channels. In this study, we employ experimentally constrained, morphologically realistic, conductance-based models of hippocampal neurons to explore certain aspects of this conductance-current balance. First, we found that the inclusion of an experimentally determined gradient in A-type K+ conductance, but not in M-type K+ conductance, tilts the HCN conductance-current balance heavily in favor of conductance, thereby exerting an overall restorative influence on neural excitability. Next, motivated by the well-established modulation of neuronal excitability by synaptically driven high-conductance states observed under in vivo conditions, we inserted thousands of excitatory and inhibitory synapses with different somatodendritic distributions. We measured the efficacy of HCN channels, independently and in conjunction with other channels, in altering resting membrane potential (RMP) and input resistance (R-in) when the neuron received randomized or rhythmic synaptic bombardments through variable numbers of synaptic inputs. We found that the impact of HCN channels on average RMP, R in, firing frequency, and peak-to-peak voltage response was severely weakened under high-conductance states, with the impinging synaptic drive playing a dominant role in regulating these measurements. Our results suggest that the debate on the role of HCN channels in altering excitability should encompass physiological and pathophysiological neuronal states under in vivo conditions and the spatiotemporal interactions of HCN channels with other channels.
Resumo:
The classical Erdos-Szekeres theorem states that a convex k-gon exists in every sufficiently large point set. This problem has been well studied and finding tight asymptotic bounds is considered a challenging open problem. Several variants of the Erdos-Szekeres problem have been posed and studied in the last two decades. The well studied variants include the empty convex k-gon problem, convex k-gon with specified number of interior points and the chromatic variant. In this paper, we introduce the following two player game variant of the Erdos-Szekeres problem: Consider a two player game where each player playing in alternate turns, place points in the plane. The objective of the game is to avoid the formation of the convex k-gon among the placed points. The game ends when a convex k-gon is formed and the player who placed the last point loses the game. In our paper we show a winning strategy for the player who plays second in the convex 5-gon game and the empty convex 5-gon game by considering convex layer configurations at each step. We prove that the game always ends in the 9th step by showing that the game reaches a specific set of configurations.
Resumo:
Uracil DNA glycosylases (UDGs) are an important group of DNA repair enzymes, which pioneer the base excision repair pathway by recognizing and excising uracil from DNA. Based on two short conserved sequences (motifs A and B), UDGs have been classified into six families. Here we report a novel UDG, UdgX, from Mycobacterium smegmatis and other organisms. UdgX specifically recognizes uracil in DNA, forms a tight complex stable to sodium dodecyl sulphate, 2-mercaptoethanol, urea and heat treatment, and shows no detectable uracil excision. UdgX shares highest homology to family 4 UDGs possessing Fe-S cluster. UdgX possesses a conserved sequence, KRRIH, which forms a flexible loop playing an important role in its activity. Mutations of H in the KRRIH sequence to S, G, A or Q lead to gain of uracil excision activity in MsmUdgX, establishing it as a novel member of the UDG superfamily. Our observations suggest that UdgX marks the uracil-DNA for its repair by a RecA dependent process. Finally, we observed that the tight binding activity of UdgX is useful in detecting uracils in the genomes.
Resumo:
Einstein established the theory of general relativity and the corresponding field equation in 1915 and its vacuum solutions were obtained by Schwarzschild and Kerr for, respectively, static and rotating black holes, in 1916 and 1963, respectively. They are, however, still playing an indispensable role, even after 100 years of their original discovery, to explain high energy astrophysical phenomena. Application of the solutions of Einstein's equation to resolve astrophysical phenomena has formed an important branch, namely relativistic astrophysics. I devote this article to enlightening some of the current astrophysical problems based on general relativity. However, there seem to be some issues with regard to explaining certain astrophysical phenomena based on Einstein's theory alone. I show that Einstein's theory and its modified form, both are necessary to explain modern astrophysical processes, in particular, those related to compact objects.
Resumo:
Hydrogen peroxide (H2O2) is a key reactive oxygen species and a messenger in cellular signal transduction apart from playing a vital role in many biological processes in living organisms. In this article, we present phenyl boronic acid-functionalized quinone-cyanine (QCy-BA) in combination with AT-rich DNA (exogenous or endogenous cellular DNA), i.e., QCy-BA subset of DNA as a stimuli-responsive NIR fluorescence probe for measuring in vitro levels of H2O2. In response to cellular H2O2 stimulus, QCy-BA converts into QCy-DT, a one-donor-two-acceptor (D2A) system that exhibits switch-on NIR fluorescence upon binding to the DNA minor groove. Fluorescence studies on the combination probe QCy-BA subset of DNA showed strong NIR fluorescence selectively in the presence of H2O2. Furthermore, glucose oxidase (GOx) assay confirmed the high efficiency of the combination probe QCy-BA subset of DNA for probing H2O2 generated in situ through GOx-mediated glucose oxidation. Quantitative analysis through fluorescence plate reader, flow cytometry and live imaging approaches showed that QCy-BA is a promising probe to detect the normal as well as elevated levels of H2O2 produced by EGF/Nox pathways and post-genotoxic stress in both primary and senescent cells. Overall, QCy-BA, in combination with exogenous or cellular DNA, is a versatile probe to quantify and image H2O2 in normal and disease-associated cells.