392 research outputs found
Single atom quantum walk with 1D optical superlattices
A proposal for the implementation of quantum walks using cold atom technology
is presented. It consists of one atom trapped in time varying optical
superlattices. The required elements are presented in detail including the
preparation procedure, the manipulation required for the quantum walk evolution
and the final measurement. These procedures can be, in principle, implemented
with present technology.Comment: 6 pages, 7 figure
Structural basis for hemoglobin capture by Staphylococcus aureus cell-surface protein, IsdH
Pathogens must steal iron from their hosts to establish infection. In mammals, hemoglobin (Hb) represents the largest reservoir of iron, and pathogens express Hb-binding proteins to access this source. Here, we show how one of the commonest and most significant human pathogens, Staphylococcus aureus, captures Hb as the first step of an iron-scavenging pathway. The x-ray crystal structure of Hb bound to a domain from the Isd (iron-regulated surface determinant) protein, IsdH, is the first structure of a Hb capture complex to be determined. Surface mutations in Hb that reduce binding to the Hb-receptor limit the capacity of S. aureus to utilize Hb as an iron source, suggesting that Hb sequence is a factor in host susceptibility to infection. The demonstration that pathogens make highly specific recognition complexes with Hb raises the possibility of developing inhibitors of Hb binding as antibacterial agents. © 2011 by The American Society for Biochemistry and Molecular Biology, Inc
Neural Network Parameterizations of Electromagnetic Nucleon Form Factors
The electromagnetic nucleon form-factors data are studied with artificial
feed forward neural networks. As a result the unbiased model-independent
form-factor parametrizations are evaluated together with uncertainties. The
Bayesian approach for the neural networks is adapted for chi2 error-like
function and applied to the data analysis. The sequence of the feed forward
neural networks with one hidden layer of units is considered. The given neural
network represents a particular form-factor parametrization. The so-called
evidence (the measure of how much the data favor given statistical model) is
computed with the Bayesian framework and it is used to determine the best form
factor parametrization.Comment: The revised version is divided into 4 sections. The discussion of the
prior assumptions is added. The manuscript contains 4 new figures and 2 new
tables (32 pages, 15 figures, 2 tables
Stimulation of MMP-11 (stromelysin-3) expression in mouse fibroblasts by cytokines, collagen and co-culture with human breast cancer cell lines
BACKGROUND: Matrix metalloproteinases (MMPs) are central to degradation of the extracellular matrix and basement membrane during both normal and carcinogenic tissue remodeling. MT1-MMP (MMP-14) and stromelysin-3 (MMP-11) are two members of the MMP family of proteolytic enzymes that have been specifically implicated in breast cancer progression. Expressed in stromal fibroblasts adjacent to epithelial tumour cells, the mechanism of MT1-MMP and MMP-11 induction remains unknown. METHODS: To investigate possible mechanisms of induction, we examined the effects of a number of plausible regulatory agents and treatments that may physiologically influence MMP expression during tumour progression. Thus NIH3T3 and primary mouse embryonic fibroblasts (MEFs) were: a) treated with the cytokines IL-1β, IL-2, IL-6, IL-8 and TGF-β for 3, 6, 12, 24, and 48 hours; b) grown on collagens I, IV and V; c) treated with fibronectin, con-A and matrigel; and d) co-cultured with a range of HBC (human breast cancer) cell lines of varied invasive and metastatic potential. RESULTS: Competitive quantitative RT-PCR indicated that MMP-11 expression was stimulated to a level greater than 100%, by 48 hour treatments of IL-1β, IL-2, TGF-β, fibronectin and collagen V. No other substantial changes in expression of MMP-11 or MT1-MMP in either tested fibroblast culture, under any treatment conditions, were observed. CONCLUSION: We have demonstrated significant MMP-11 stimulation in mouse fibroblasts using cytokines, matrix constituents and HBC cell lines, and also some inhibition of MT1-MMP. Our data suggest that the regulation of these genes in the complex stromal-epithelial interactions that occur in human breast carcinoma, is influenced by several mechanisms
Reinforcement learning or active inference?
This paper questions the need for reinforcement learning or control theory when optimising behaviour. We show that it is fairly simple to teach an agent complicated and adaptive behaviours using a free-energy formulation of perception. In this formulation, agents adjust their internal states and sampling of the environment to minimize their free-energy. Such agents learn causal structure in the environment and sample it in an adaptive and self-supervised fashion. This results in behavioural policies that reproduce those optimised by reinforcement learning and dynamic programming. Critically, we do not need to invoke the notion of reward, value or utility. We illustrate these points by solving a benchmark problem in dynamic programming; namely the mountain-car problem, using active perception or inference under the free-energy principle. The ensuing proof-of-concept may be important because the free-energy formulation furnishes a unified account of both action and perception and may speak to a reappraisal of the role of dopamine in the brain
HVEM Signalling Promotes Colitis
Background
Tumor necrosis factor super family (TNFSF) members regulate important processes involved in cell proliferation, survival and differentiation and are therefore crucial for the balance between homeostasis and inflammatory responses. Several members of the TNFSF are closely associated with inflammatory bowel disease (IBD). Thus, they represent interesting new targets for therapeutic treatment of IBD.
Methodology/Principal Findings
We have used mice deficient in TNFSF member HVEM in experimental models of IBD to investigate its role in the disease process. Two models of IBD were employed: i) chemical-induced colitis primarily mediated by innate immune cells; and ii) colitis initiated by CD4+CD45RBhigh T cells following their transfer into immuno-deficient RAG1-/- hosts. In both models of disease the absence of HVEM resulted in a significant reduction in colitis and inflammatory cytokine production.
Conclusions
These data show that HVEM stimulatory signals promote experimental colitis driven by innate or adaptive immune cells
Brief Report: Question-Asking and Collateral Language Acquisition in Children with Autism
The literature suggests children with autism use communication primarily for requests and protests, and almost never for information-seeking. This study investigated whether teaching “Where” questions using intrinsic reinforcement procedures would produce the generalized use of the question, and whether concomitant improvements in related language structures, provided as answers to the children’s questions, would occur. In the context of a multiple baseline across participants design, data showed that the children could rapidly acquire and generalize the query, and that there were collateral improvements in the children’s use of language structures corresponding to the answers to the questions the children asked. The results are discussed in the context of teaching child initiations to improve linguistic competence in children with autism
Performance of the CMS Cathode Strip Chambers with Cosmic Rays
The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device
in the CMS endcaps. Their performance has been evaluated using data taken
during a cosmic ray run in fall 2008. Measured noise levels are low, with the
number of noisy channels well below 1%. Coordinate resolution was measured for
all types of chambers, and fall in the range 47 microns to 243 microns. The
efficiencies for local charged track triggers, for hit and for segments
reconstruction were measured, and are above 99%. The timing resolution per
layer is approximately 5 ns
VCAM-1 and VLA-4 Modulate Dendritic Cell IL-12p40 Production in Experimental Visceral Leishmaniasis
Vascular cell adhesion molecule-1 (VCAM-1) interacts with its major ligand very late antigen-4 (VLA-4) to mediate cell adhesion and transendothelial migration of leukocytes. We report an important role for VCAM-1/VLA-4 interactions in the generation of immune responses during experimental visceral leishmaniasis caused by Leishmania donovani. Our studies demonstrate that these molecules play no direct role in the recruitment of leukocytes to the infected liver, but instead contribute to IL-12p40-production by splenic CD8+ dendritic cells (DC). Blockade of VCAM-1/VLA-4 interactions using whole antibody or anti-VCAM-1 Fab′ fragments reduced IL-12p40 mRNA accumulation by splenic DC 5 hours after L. donovani infection. This was associated with reduced anti-parasitic CD4+ T cell activation in the spleen and lowered hepatic IFNγ, TNF and nitric oxide production by 14 days post infection. Importantly, these effects were associated with enhanced parasite growth in the liver in studies with either anti-VCAM-1 or anti-VLA-4 antibodies. These data indicate a role for VCAM-1 and VLA-4 in DC activation during infectious disease
Identifying candidate genes affecting developmental time in Drosophila melanogaster: pervasive pleiotropy and gene-by-environment interaction
<p>Abstract</p> <p>Background</p> <p>Understanding the genetic architecture of ecologically relevant adaptive traits requires the contribution of developmental and evolutionary biology. The time to reach the age of reproduction is a complex life history trait commonly known as developmental time. In particular, in holometabolous insects that occupy ephemeral habitats, like fruit flies, the impact of developmental time on fitness is further exaggerated. The present work is one of the first systematic studies of the genetic basis of developmental time, in which we also evaluate the impact of environmental variation on the expression of the trait.</p> <p>Results</p> <p>We analyzed 179 co-isogenic single <it>P[GT1]-</it>element insertion lines of <it>Drosophila melanogaster </it>to identify novel genes affecting developmental time in flies reared at 25°C. Sixty percent of the lines showed a heterochronic phenotype, suggesting that a large number of genes affect this trait. Mutant lines for the genes <it>Merlin </it>and <it>Karl </it>showed the most extreme phenotypes exhibiting a developmental time reduction and increase, respectively, of over 2 days and 4 days relative to the control (a co-isogenic <it>P</it>-element insertion free line). In addition, a subset of 42 lines selected at random from the initial set of 179 lines was screened at 17°C. Interestingly, the gene-by-environment interaction accounted for 52% of total phenotypic variance. Plastic reaction norms were found for a large number of developmental time candidate genes.</p> <p>Conclusion</p> <p>We identified components of several integrated time-dependent pathways affecting egg-to-adult developmental time in <it>Drosophila</it>. At the same time, we also show that many heterochronic phenotypes may arise from changes in genes involved in several developmental mechanisms that do not explicitly control the timing of specific events. We also demonstrate that many developmental time genes have pleiotropic effects on several adult traits and that the action of most of them is sensitive to temperature during development. Taken together, our results stress the need to take into account the effect of environmental variation and the dynamics of gene interactions on the genetic architecture of this complex life-history trait.</p
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