Miracle-dz/UniFAR-FTUs huggingface dataset:
Interactions between Zinc and Allosteric Modulators of the Glycine Receptor

The glycine receptor is a pentameric ligand-gated ion channel that is involved in fast inhibitory neurotransmission in the central nervous system. Zinc is an allosteric modulator of glycine receptor function, enhancing the effects of glycine at nanomolar to low-micromolar concentrations and inhibiting its effects at higher concentrations. Low-nanomolar concentrations of contaminating zinc in electrophysiological buffers are capable of synergistically enhancing receptor modulation by other compounds, such as ethanol. This suggests that, unless accounted for, previous studies of glycine receptor modulation were measuring the effects of modulator plus comodulation by zinc on receptor function. Since zinc is present in vivo at a variety of concentrations, it will influence glycine receptor modulation by other pharmacologic agents. We investigated the utility of previously described “zinc-enhancement–insensitive” α1 glycine receptor mutants D80A, D80G, and W170S to probe for interactions between zinc and other allosteric modulators at the glycine receptor. We found that only the W170S mutation conferred complete abolishment of zinc enhancement across a variety of agonist and zinc concentrations. Using α1 W170S receptors, we established that, in addition to ethanol, zinc interacts with inhalants, but not volatile anesthetics, to synergistically enhance channel function. Additionally, we determined that this interaction is abolished at higher zinc concentrations when receptor-enhancing binding sites are saturated, suggesting a mechanism by which modulators such as ethanol and inhalants are capable of increasing receptor affinity for zinc, in addition to enhancing channel function on their own.
An energy‐based conformer library for side chain optimization: Improved prediction and adjustable sampling

Side chain optimization is a fundamental component of protein modeling applications such as docking, structural prediction, and design. In these applications side chain flexibility is often provided by rotamer or conformer libraries, which are collections of representative side chain conformations. Here we demonstrate that the sampling provided by the library can be substantially improved by adding an energetic criterion to its creation. The result of the new procedure is the Energy‐Based library, a conformer library selected according to the propensity of its elements to fit energetically into natural protein environments. The new library performs outstandingly well in side chain optimization, producing structures with significantly lower energies and resulting in improved side chain conformation prediction. In addition, because the library was created as an ordered list, its size can be adjusted to any desired level. This feature provides unprecedented versatility in tuning sampling. It allows to precisely balance the number of conformers required by each amino acid type, equalizing their chances to fit into structural environments. It also allows to scale the amount of sampling to the specific requirement of any given side optimization problem. A rotameric version of the library was also produced with the same method to support applications that require a dihedral‐only description of side chain conformation. The libraries are available at http://seneslab.org/EBL. Proteins 2012; © 2012 Wiley Periodicals, Inc.
Finite Quotients of Symplectic Groups VS Mapping Class Groups

We show that the Schur multiplier of Sp(2g,Z/DZ) is Z/2Z, when D is divisible by 4. We give several proofs of this statement, a first one using Deligne’s non-residual finiteness theorem and recent results of Putman, a second one using K-theory arguments based on the work of Barge and Lannes and a third one based on the Weil representations of symplectic groups arising in abelian Chern-Simons theory. We can also retrieve this way Deligne’s non-residual finiteness of the universal central extension ^ Sp(2g,Z) and a sharp result since ^ Sp(2g,Z) surjects on the non-trivial central extension of Sp(2g,Z/DZ) by Z/2Z, when g � 3. We prove then that the essential second homology of finite quotients of symplectic groups over a Dedekind domain of arithmetic type are torsion groups of uniformly bounded size. In contrast, quantum representations produce for every prime p, finite quotients of the mapping class group of genus g � 3 whose essential second homology has p-torsion. We further derive that all central extensions of the mapping class group are residually finite and deduce that mapping class groups have Serre’s property A2 for trivial modules, contrary to symplectic groups. Eventually we compute the module of coinvariants H2(sp2g(2))Sp(2g,Z/2kZ) = Z/2Z.
Beyond the Commons: Investigating the Value of Personalizing Web Search

We investigate the diverse goals people have when they issue the same query to a Web search engine, and the ability of current search tools to address such diversity, in order to understand the potential value of personalizing search results. Great variance was found in the results different individuals rated as relevant for the same query—even when those users expressed their underlying informational goal in the same way. The analysis suggests that, while current Web search tools do a good job of retrieving results to satisfy the range of intentions people may associate with a query, they do not do a very good job of discerning an individual’s unique search goal. We discuss the implications of this study on the design of search systems and suggest areas for additional research.
Arabidopsis Formin3 Directs the Formation of Actin Cables and Polarized Growth in Pollen Tubes[W]

Cytoplasmic actin cables are the most prominent actin structures in plant cells, but the molecular mechanism underlying their formation is unknown. The function of these actin cables, which are proposed to modulate cytoplasmic streaming and intracellular movement of many organelles in plants, has not been studied by genetic means. Here, we show that Arabidopsis thaliana formin3 (AFH3) is an actin nucleation factor responsible for the formation of longitudinal actin cables in pollen tubes. The Arabidopsis AFH3 gene encodes a 785–amino acid polypeptide, which contains a formin homology 1 (FH1) and a FH2 domain. In vitro analysis revealed that the AFH3 FH1FH2 domains interact with the barbed end of actin filaments and have actin nucleation activity in the presence of G-actin or G actin-profilin. Overexpression of AFH3 in tobacco (Nicotiana tabacum) pollen tubes induced excessive actin cables, which extended into the tubes' apices. Specific downregulation of AFH3 eliminated actin cables in Arabidopsis pollen tubes and reduced the level of actin polymers in pollen grains. This led to the disruption of the reverse fountain streaming pattern in pollen tubes, confirming a role for actin cables in the regulation of cytoplasmic streaming. Furthermore, these tubes became wide and short and swelled at their tips, suggesting that actin cables may regulate growth polarity in pollen tubes. Thus, AFH3 regulates the formation of actin cables, which are important for cytoplasmic streaming and polarized growth in pollen tubes.
The Representation and Use of Focus in a System for Understanding Dialogs

As a dialog progresses the objects and actions that are most relevant to the conversation, and hence in the focus of attention of the dialog participants, change. This paper describes a representation of focus for language understanding systems, emphasizing its use in understanding task-oriented dialogs. The representation highlights that part of the knowledge base relevant at a given point in a dialog. A model of the task is used both to structure the focus representation and to provide an index into potentially relevant concepts in the knowledge base The use of the focus representation to make retrieval of items from the knowledge base more efficient is described.
Blocking of classical complement pathway inhibits endothelial adhesion molecule expression and preserves ischemic myocardium from reperfusion injury.

Myocardial injury after ischemia (I) and reperfusion (R) is related to leukocyte activation with subsequent release of cytokines and oxygen-derived free radicals as well as complement activation. In our study, the cardioprotective effects of exogenous C1 esterase inhibitor (C1 INH) were examined in a rat model of myocardial I + R (i.e., 20 min + 24 hr or 48 hr). The C1 INH (10, 50 and 100 U/kg) administered 2 min before reperfusion significantly attenuated myocardial injury after 24 hr of R compared to vehicle treated rats (P < .001). Further, cardiac myeloperoxidase activity (i.e., a marker of PMN [polymorphonuclear leukocyte] accumulation) in the ischemic area was significantly reduced after C1 INH treatment compared to vehicle treated animals (0.81 +/- 0.1, 0.34 +/- 0.13, 0.13 +/- 0.1 vs. 1.44 +/- 0.3 U/100 mg tissue, P < .001). In addition, C1 INH (100 U/kg) significantly attenuated myocardial injury and neutrophil infiltration even after 48 hr of reperfusion compared to vehicle treatment. Immunohistochemical analysis of ischemic-reperfused myocardial tissue demonstrated activation of classical complement pathway by deposition of C1q on cardiac myocytes and cardiac vessels. In addition, expression of the endothelial adhesion molecules P-selectin and intercellular adhesion molecule 1 (ICAM-1) was observed after reperfusion of the ischemic myocardium. In this regard, C1 INH administration abolished expression of P-selectin and ICAM-1 on the cardiac vasculature after myocardial ischemia and reperfusion. Blocking the classical complement pathway by exogenous C1 INH appears to be an effective means to preserve ischemic myocardium from injury after 24 and 48 hr of reperfusion. The mechanisms of this cardioprotective effect appears to be due to blocking of complement activation and reduced endothelial adhesion molecule expression with subsequent reduced PMN-endothelium interaction, resulting in diminished cardiac necrosis.
Resolution improvement in digital holography: comparison between synthetic aperture method and spatial averaging method

In the last two decades digital holography emerged as one of the most promising techniques for obtaining the complex object-wave (amplitude and phase). However, due to the coherent nature of the light source used in digital holography, the reconstructed hologram is subjected to speckle noise. Moreover, the resolution and size of the sensor employed in digital holography are smaller compared to the formerly used holographic plates in optical holography. This results in a reduced resolution for the reconstructed hologram. This paper discusses two resolution improvement methods, which are both based on the same recording process. However, the recorded data is processed differently to obtain a resolution improved reconstruction. The two methods are compared in terms of corresponding optical resolution, phase accuracy and processing time.
Survival of Medicare patients after enrollment in hospice programs.

BACKGROUND Each year more than 220,000 Medicare beneficiaries receive care from hospice programs designed to enhance the quality of the end of life. Enrollment requires certification by a physician that the patient has a life expectancy of less than six months. We examined how long before death patients enrolled in hospice programs. METHODS Using 1990 Medicare claim data, we analyzed the characteristics and survival of 6451 hospice patients followed for a minimum of 27 months with respect to mortality. RESULTS The patients' mean age was 76.4 years; 92.4 percent were white. Half the patients were women, and 80.2 percent had cancer of some type. The most common diagnoses were lung cancer (21.4 percent), colorectal cancer (10.5 percent), and prostate cancer (7.4 percent). The median survival after enrollment was only 36 days, and 15.6 percent of the patients died within 7 days. At the other extreme, 14.9 percent of the patients lived longer than six months. Survival varied substantially according to diagnosis, even after adjustment for age and co-existing conditions. The unadjusted survival after enrollment was shortest for those with renal failure, those with leukemia or lymphoma, and those with liver or biliary cancer; it was longest for those with chronic lung disease, those with dementia, and those with breast cancer. Patients at for-profit, larger, outpatient, or newer hospices lived longer after enrollment than those in other types of hospice programs. CONCLUSIONS Most patients who enter hospice care do so late in the course of their terminal illnesses. The timing of enrollment in hospice programs varies substantially with the characteristics of the patients and the hospices.
An Overview of Hybrid Water Supply Systems in the Context of Urban Water Management: Challenges and Opportunities

This paper presents a critical review of the physical impacts of decentralized water supply systems on existing centralized water infrastructures. This paper highlights the combination of centralized and decentralized systems, which is referred to as hybrid water supply systems. The system is hypothesized to generate more sustainable and resilient urban water systems. The basic concept is to use decentralized water supply options such as rainwater tanks, storm water harvesting and localized wastewater treatment and reuse in combination with centralized systems. Currently the impact of hybrid water supply technologies on the operational performance of the downstream infrastructure and existing treatment processes is yet to be known. The paper identifies a number of significant research gaps related to interactions between centralized and decentralized urban water services. It indicates that an improved understanding of the interaction between these systems is expected to provide a better integration of hybrid systems by improved sewerage and drainage design, as well as facilitate operation and maintenance planning. The paper also highlights the need for a framework to better understand the interaction between different components of hybrid water supply systems.
Bending and buckling analyses of functionally graded material (FGM) size-dependent nanoscale beams including the thickness stretching effect

This paper addresses theoretically the bending and buckling behaviors of size-dependent nanobeams made of functionally graded materials (FGMs) including the thickness stretching effect. The size-dependent FGM nanobeam is investigated on the basis of the nonlocal continuum model. The nonlocal elastic behavior is described by the differential constitutive model of Eringen, which enables the present model to become effective in the analysis and design of nanostructures. The present model incorporates the length scale parameter (nonlocal parameter) which can capture the small scale effect, and furthermore accounts for both shear deformation and thickness stretching effects by virtue of a sinusoidal variation of all displacements through the thickness without using shear correction factor. The material properties of FGM nanobeams are assumed to vary through the thickness according to a power law. The governing equations and the related boundary conditions are derived using the principal of minimum total potential energy. A Navier-type solution is developed for simply-supported boundary conditions, and exact expressions are proposed for the deflections and the buckling load. The effects of nonlocal parameter, aspect ratio and various material compositions on the static and stability responses of the FGM nanobeam are discussed in detail. The study is relevant to nanotechnology deployment in for example aircraft structures.
Toward Circumventing Collinearity Effect in Nonlinear Spectral Mixture Analysis by Using a Spectral Shape Measure

Nonlinear spectral mixture analysis (NSMA) is a widely used unmixing algorithm. It can fit the mixed spectra adequately, but collinearity effect among true and virtual endmembers will decrease the retrieval accuracies of endmember fractions. Use of linear spectral mixture analysis (LSMA) can effectively reduce the degree of collinearity in the NSMA. However, the inadequate modeling of mixed spectra in the LSMA will also yield retrieval errors, especially for the cases where the multiple scattering is not ignorable. In this study, a generalized spectral unmixing scheme based on a spectral shape measure, i.e. spectral information divergence (SID), was applied to overcome the limitations of the conventional NSMA and LSMA. Two simulation experiments were undertaken to test the performances of the SID, LSMA and NSMA in the mixture cases of treesoil, tree-concrete and tree-grass. Results demonstrated that the SID yielded higher accuracies than the LSMA for almost all the mixture cases in this study. On the other hand, performances of the SID method were comparable with the NSMA for the tree-soil and tree-grass mixture cases, but significantly better than the NSMA for the tree-concrete mixture case. All the results indicate that the SID method is fairly effective to circumvent collinearity effect within the NSMA, and compensate the inadequate modeling of mixed spectra within the LSMA.
A 3.3-Gbps bit-serial block-interlaced min-sum LDPC decoder in 0.13-μm CMOS

A bit-serial architecture for multi-Gbps LDPC decoding is demonstrated to alleviate the routing congestion which is the main limitation for LDPC decoders. We report on a 3.3-Gbps 0.13-μm CMOS prototype. It occupies 7.3-mm2 core area with 1416-mW maximum power consumption from a 1.2-V supply. We demonstrate how early termination and supply voltage scaling can improve the decoder energy efficiency. Finally, the same architecture is applied to a (2048, 1723) LDPC code compliant with the 10GBase-T standard.
Candidate Causal Regulatory Effects by Integration of Expression QTLs with Complex Trait Genetic Associations

The recent success of genome-wide association studies (GWAS) is now followed by the challenge to determine how the reported susceptibility variants mediate complex traits and diseases. Expression quantitative trait loci (eQTLs) have been implicated in disease associations through overlaps between eQTLs and GWAS signals. However, the abundance of eQTLs and the strong correlation structure (LD) in the genome make it likely that some of these overlaps are coincidental and not driven by the same functional variants. In the present study, we propose an empirical methodology, which we call Regulatory Trait Concordance (RTC) that accounts for local LD structure and integrates eQTLs and GWAS results in order to reveal the subset of association signals that are due to cis eQTLs. We simulate genomic regions of various LD patterns with both a single or two causal variants and show that our score outperforms SNP correlation metrics, be they statistical (r2) or historical (D'). Following the observation of a significant abundance of regulatory signals among currently published GWAS loci, we apply our method with the goal to prioritize relevant genes for each of the respective complex traits. We detect several potential disease-causing regulatory effects, with a strong enrichment for immunity-related conditions, consistent with the nature of the cell line tested (LCLs). Furthermore, we present an extension of the method in trans, where interrogating the whole genome for downstream effects of the disease variant can be informative regarding its unknown primary biological effect. We conclude that integrating cellular phenotype associations with organismal complex traits will facilitate the biological interpretation of the genetic effects on these traits.
Evaluation of Effect of Various Nanofillers on Technological Properties of NBR/NR Blend Vulcanized Using BIAT-CBS System

Owing to processing ease and resistance to oils and chemicals, NBR is widely used in many industries. But since neat NBR has only poor tensile properties, it is better to use suitable blends of NR and NBR after incorporating appropriate nanoingredients before vulcanization. It is well established that nanoparticles can be easily dispersed in a more uniform pattern in polymer matrix, thereby enhancing the technological properties of the elastomer vulcanizate. Since there are no systematic comparative studies on technological properties of NBR/NR blend containing different nanoingredients, efforts have been made in this study to investigate cure and technological properties like tensile properties, tear resistance, compression set, hardness, abrasion loss and swelling value of NBR/NR (80/20) blend vulcanizates containing stearic acid-coated nano-zinc oxide (ZOS), nano-BIAT, nano-silicate-coated CaCO3, PEO-coated calcium silicate, and surface-modified carbon nanotubes (CNT). XRD and electron microscopy have been used for morphological analysis. The nano ingredients were effective in enhancing the technological properties of the vulcanizates. Among the nanofillers, modified CNT was found to impart superior properties to NBR/NR blend due to more intercalation.
An Evolutionary Algorithm Approach for Feature Generation from Sequence Data and Its Application to DNA Splice Site Prediction

Associating functional information with biological sequences remains a challenge for machine learning methods. The performance of these methods often depends on deriving predictive features from the sequences sought to be classified. Feature generation is a difficult problem, as the connection between the sequence features and the sought property is not known a priori. It is often the task of domain experts or exhaustive feature enumeration techniques to generate a few features whose predictive power is then tested in the context of classification. This paper proposes an evolutionary algorithm to effectively explore a large feature space and generate predictive features from sequence data. The effectiveness of the algorithm is demonstrated on an important component of the gene-finding problem, DNA splice site prediction. This application is chosen due to the complexity of the features needed to obtain high classification accuracy and precision. Our results test the effectiveness of the obtained features in the context of classification by Support Vector Machines and show significant improvement in accuracy and precision over state-of-the-art approaches.
Safety of anti‐IgE treatment with omalizumab in children with seasonal allergic rhinitis undergoing specific immunotherapy simultaneously

Kamin W, Kopp MV, Erdnuess F, Schauer U, Zielen S, Wahn U. Safety of anti‐IgE treatment with omalizumab in children with seasonal allergic rhinitis undergoing specific immunotherapy simultaneously. Pediatr Allergy Immunol 2010: 21: e160–e165. © 2009 John Wiley & Sons A/S
Twelve tips for developing training programs for international medical graduates

Background: International Medical Graduates (IMGs) are a diverse group of doctors who provide essential health services in many western countries, and hospitals are increasingly relying upon IMGs to fill vacancies in all staff grades. Clinical skills and experience vary greatly between doctors, and orientation and clinical skills training is a way of addressing any identified deficiencies. Work done: This paper relates the experiences of establishing a training program and support services for IMGs working in the public hospital system in Tasmania, Australia, and offers advice for other agencies contemplating establishing similar programs. Conclusions: A ‘hub and spoke’ model is a useful model to adopt: a central coordinating office designs and implements programs informed by best available evidence, and clinical educators on site at healthcare facilities implement programs and provide direct assistance and orientation. Broad-based programs attending to orientation, doctor's families’ needs, communication skills and clinical skills training are required. Support from health administrators is essential. Practice points Understand the practices and certification requirements of your jurisdiction. Involve IMGs with the planning and implementation of programs. Consider the needs of spouses and families. Orientation to health systems is of paramount importance.