2,985 research outputs found
Distributed Change Detection via Average Consensus over Networks
Distributed change-point detection has been a fundamental problem when
performing real-time monitoring using sensor-networks. We propose a distributed
detection algorithm, where each sensor only exchanges CUSUM statistic with
their neighbors based on the average consensus scheme, and an alarm is raised
when local consensus statistic exceeds a pre-specified global threshold. We
provide theoretical performance bounds showing that the performance of the
fully distributed scheme can match the centralized algorithms under some mild
conditions. Numerical experiments demonstrate the good performance of the
algorithm especially in detecting asynchronous changes.Comment: 15 pages, 8 figure
Ultrahard carbon film from epitaxial two-layer graphene
Atomically thin graphene exhibits fascinating mechanical properties, although
its hardness and transverse stiffness are inferior to those of diamond. To
date, there hasn't been any practical demonstration of the transformation of
multi-layer graphene into diamond-like ultra-hard structures. Here we show that
at room temperature and after nano-indentation, two-layer graphene on SiC(0001)
exhibits a transverse stiffness and hardness comparable to diamond, resisting
to perforation with a diamond indenter, and showing a reversible drop in
electrical conductivity upon indentation. Density functional theory
calculations suggest that upon compression, the two-layer graphene film
transforms into a diamond-like film, producing both elastic deformations and
sp2-to-sp3 chemical changes. Experiments and calculations show that this
reversible phase change is not observed for a single buffer layer on SiC or
graphene films thicker than 3 to 5 layers. Indeed, calculations show that
whereas in two-layer graphene layer-stacking configuration controls the
conformation of the diamond-like film, in a multilayer film it hinders the
phase transformation.Comment: Published online on Nature Nanotechnology on December 18, 201
Hitchin Equation, Singularity, and N=2 Superconformal Field Theories
We argue that Hitchin's equation determines not only the low energy effective
theory but also describes the UV theory of four dimensional N=2 superconformal
field theories when we compactify six dimensional theory on a
punctured Riemann surface. We study the singular solution to Hitchin's equation
and the Higgs field of solutions has a simple pole at the punctures; We show
that the massless theory is associated with Higgs field whose residual is a
nilpotent element; We identify the flavor symmetry associated with the puncture
by studying the singularity of closure of the moduli space of solutions with
the appropriate boundary conditions. For the mass-deformed theory the residual
of the Higgs field is a semi-simple element, we identify the semi-simple
element by arguing that the moduli space of solutions of mass-deformed theory
must be a deformation of the closure of the moduli space of the massless
theory. We also study the Seiberg-Witten curve by identifying it as the
spectral curve of the Hitchin's system. The results are all in agreement with
Gaiotto's results derived from studying the Seiberg-Witten curve of four
dimensional quiver gauge theory.Comment: 42 pages, 20 figures, Hitchin's equation for N=2 theory is derived by
comparing different order of compactification of six dimensional theory on
T^2\times \Sigma. More discussion about flavor symmetries. Typos are
correcte
FLORA: a novel method to predict protein function from structure in diverse superfamilies
Predicting protein function from structure remains an active area of interest, particularly for the structural genomics initiatives where a substantial number of structures are initially solved with little or no functional characterisation. Although global structure comparison methods can be used to transfer functional annotations, the relationship between fold and function is complex, particularly in functionally diverse superfamilies that have evolved through different secondary structure embellishments to a common structural core. The majority of prediction algorithms employ local templates built on known or predicted functional residues. Here, we present a novel method (FLORA) that automatically generates structural motifs associated with different functional sub-families (FSGs) within functionally diverse domain superfamilies. Templates are created purely on the basis of their specificity for a given FSG, and the method makes no prior prediction of functional sites, nor assumes specific physico-chemical properties of residues. FLORA is able to accurately discriminate between homologous domains with different functions and substantially outperforms (a 2–3 fold increase in coverage at low error rates) popular structure comparison methods and a leading function prediction method. We benchmark FLORA on a large data set of enzyme superfamilies from all three major protein classes (α, β, αβ) and demonstrate the functional relevance of the motifs it identifies. We also provide novel predictions of enzymatic activity for a large number of structures solved by the Protein Structure Initiative. Overall, we show that FLORA is able to effectively detect functionally similar protein domain structures by purely using patterns of structural conservation of all residues
Preferential Paths of Air-water Two-phase Flow in Porous Structures with Special Consideration of Channel Thickness Effects.
Accurate understanding and predicting the flow paths of immiscible two-phase flow in rocky porous structures are of critical importance for the evaluation of oil or gas recovery and prediction of rock slides caused by gas-liquid flow. A 2D phase field model was established for compressible air-water two-phase flow in heterogenous porous structures. The dynamic characteristics of air-water two-phase interface and preferential paths in porous structures were simulated. The factors affecting the path selection of two-phase flow in porous structures were analyzed. Transparent physical models of complex porous structures were prepared using 3D printing technology. Tracer dye was used to visually observe the flow characteristics and path selection in air-water two-phase displacement experiments. The experimental observations agree with the numerical results used to validate the accuracy of phase field model. The effects of channel thickness on the air-water two-phase flow behavior and paths in porous structures were also analyzed. The results indicate that thick channels can induce secondary air flow paths due to the increase in flow resistance; consequently, the flow distribution is different from that in narrow channels. This study provides a new reference for quantitatively analyzing multi-phase flow and predicting the preferential paths of immiscible fluids in porous structures
Histological Evaluation of Corneal Scar Formation in Pseudophakic Bullous Keratopathy
PURPOSE: To evaluate histological changes in the corneal stroma in pseudophakic bullous keratopathy. METHODS: Twenty-eight patients (28 eyes) with pseudophakic bullous keratopathy underwent therapeutic penetrating keratoplasty at Shandong Eye Institute between January 2006 and November 2011. The patients were divided into two groups according to the duration of bullous keratopathy (<1.0 year group or >1.0 year group), and three buttons from enucleated eyes with choroidal melanoma served as a control. In vivo confocal microscopy examination, hematoxylin-eosin, Masson's trichrome stain and Van Gieson staining were used for microscopic examination. The histological evaluation and scoring of the buttons for morphological changes, including the degree of stromal scars, neovascularization and inflammatory cells within the corneal buttons, were compared. To study the underlying mechanism, connective tissue growth factor (CTGF) and TGF-β immunohistochemistry were performed. RESULTS: Confocal microscopy examination and histological evaluation and scoring of the buttons showed that compared with the <1.0 year group, stromal scars, neovascularization and inflammatory cells were more severe in the >1.0 year group (P<0.05). There was an increase in CTGF- and TGF-β1-positive stromal cells in the >1.0 year group. CONCLUSIONS: During the progression of pseudophakic bullous keratopathy, stromal scars occurred more often in the patients that had a longer duration of disease. Cytokines such as CTGF and TGF-β1 may play a role in this pathological process and deserve further investigation
Wide-Scale Analysis of Human Functional Transcription Factor Binding Reveals a Strong Bias towards the Transcription Start Site
We introduce a novel method to screen the promoters of a set of genes with
shared biological function, against a precompiled library of motifs, and find
those motifs which are statistically over-represented in the gene set. The gene
sets were obtained from the functional Gene Ontology (GO) classification; for
each set and motif we optimized the sequence similarity score threshold,
independently for every location window (measured with respect to the TSS),
taking into account the location dependent nucleotide heterogeneity along the
promoters of the target genes. We performed a high throughput analysis,
searching the promoters (from 200bp downstream to 1000bp upstream the TSS), of
more than 8000 human and 23,000 mouse genes, for 134 functional Gene Ontology
classes and for 412 known DNA motifs. When combined with binding site and
location conservation between human and mouse, the method identifies with high
probability functional binding sites that regulate groups of biologically
related genes. We found many location-sensitive functional binding events and
showed that they clustered close to the TSS. Our method and findings were put
to several experimental tests. By allowing a "flexible" threshold and combining
our functional class and location specific search method with conservation
between human and mouse, we are able to identify reliably functional TF binding
sites. This is an essential step towards constructing regulatory networks and
elucidating the design principles that govern transcriptional regulation of
expression. The promoter region proximal to the TSS appears to be of central
importance for regulation of transcription in human and mouse, just as it is in
bacteria and yeast.Comment: 31 pages, including Supplementary Information and figure
Composite structural motifs of binding sites for delineating biological functions of proteins
Most biological processes are described as a series of interactions between
proteins and other molecules, and interactions are in turn described in terms
of atomic structures. To annotate protein functions as sets of interaction
states at atomic resolution, and thereby to better understand the relation
between protein interactions and biological functions, we conducted exhaustive
all-against-all atomic structure comparisons of all known binding sites for
ligands including small molecules, proteins and nucleic acids, and identified
recurring elementary motifs. By integrating the elementary motifs associated
with each subunit, we defined composite motifs which represent
context-dependent combinations of elementary motifs. It is demonstrated that
function similarity can be better inferred from composite motif similarity
compared to the similarity of protein sequences or of individual binding sites.
By integrating the composite motifs associated with each protein function, we
define meta-composite motifs each of which is regarded as a time-independent
diagrammatic representation of a biological process. It is shown that
meta-composite motifs provide richer annotations of biological processes than
sequence clusters. The present results serve as a basis for bridging atomic
structures to higher-order biological phenomena by classification and
integration of binding site structures.Comment: 34 pages, 7 figure
Exposure to general anesthesia and risk of alzheimer's disease: a systematic review and meta-analysis
<p>Abstract</p> <p>Background</p> <p>Alzheimer's disease (AD) is common among older adults and leads to significant disability. Volatile anesthetic gases administered during general anesthesia (GA) have been hypothesized to be a risk factor for the development of AD. The objective of this study is to systematically review the association between exposure to GA and risk of AD.</p> <p>Methods</p> <p>We searched electronic databases including MEDLINE, Embase, and Google scholar for observational studies examining the association between exposure to GA and risk of AD. We examined study quality using a modified version of the Newcastle-Ottawa risk of bias assessment for observational studies. We used standard meta-analytic techniques to estimate pooled odds ratios (OR) and 95% confidence intervals (CI). Subgroup and sensitivity analyses were undertaken to evaluate the robustness of the findings.</p> <p>Results</p> <p>A total of 15 case-control studies were included in the review. No cohort studies were identified that met inclusion criteria. There was variation in the methodological quality of included studies. There was no significant association between any exposure to GA and risk of AD (pooled OR: 1.05; 95% CI: 0.93 - 1.19, Z = 0.80, <it>p </it>= 0.43). There was also no significant association between GA and risk of AD in several subgroup and sensitivity analyses.</p> <p>Conclusions</p> <p>A history of exposure to GA is not associated with an increased risk of AD although there are few high-quality studies in this area. Prospective cohort studies with long-term follow-up or randomized controlled trials are required to further understand the association between GA and AD.</p
Novel prokaryotic expression of thioredoxin-fused insulinoma associated protein tyrosine phosphatase 2 (IA-2), its characterization and immunodiagnostic application
Background
The insulinoma associated protein tyrosine phosphatase 2 (IA-2) is one of the immunodominant autoantigens involved in the autoimmune attack to the beta-cell in Type 1 Diabetes Mellitus. In this work we have developed a complete and original process for the production and recovery of the properly folded intracellular domain of IA-2 fused to thioredoxin (TrxIA-2ic) in Escherichia coli GI698 and GI724 strains. We have also carried out the biochemical and immunochemical characterization of TrxIA-2icand design variants of non-radiometric immunoassays for the efficient detection of IA-2 autoantibodies (IA-2A).
Results
The main findings can be summarized in the following statements: i) TrxIA-2ic expression after 3 h of induction on GI724 strain yielded ≈ 10 mg of highly pure TrxIA-2ic/L of culture medium by a single step purification by affinity chromatography, ii) the molecular weight of TrxIA-2ic (55,358 Da) could be estimated by SDS-PAGE, size exclusion chromatography and mass spectrometry, iii) TrxIA-2ic was properly identified by western blot and mass spectrometric analysis of proteolytic digestions (63.25 % total coverage), iv) excellent immunochemical behavior of properly folded full TrxIA-2ic was legitimized by inhibition or displacement of [35S]IA-2 binding from IA-2A present in Argentinian Type 1 Diabetic patients, v) great stability over time was found under proper storage conditions and vi) low cost and environmentally harmless ELISA methods for IA-2A assessment were developed, with colorimetric or chemiluminescent detection.
Conclusions
E. coli GI724 strain emerged as a handy source of recombinant IA-2ic, achieving high levels of expression as a thioredoxin fusion protein, adequately validated and applicable to the development of innovative and cost-effective immunoassays for IA-2A detection in most laboratories.Fil: Guerra, Luciano Lucas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Faccinetti, Natalia Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Trabucchi, Aldana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Rovitto, Bruno David. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Sabljic, Adriana Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Poskus, Edgardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Iacono, Ruben Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Valdez, Silvina Noemi. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentin
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