Miracle-dz/UniFAR-FTUs huggingface dataset:
Complex-type N-glycan recognition by potent broadly neutralizing HIV antibodies

Broadly neutralizing HIV antibodies (bNAbs) can recognize carbohydrate-dependent epitopes on gp120. In contrast to previously characterized glycan-dependent bNAbs that recognize high-mannose N-glycans, PGT121 binds complex-type N-glycans in glycan microarrays. We isolated the B-cell clone encoding PGT121, which segregates into PGT121-like and 10-1074–like groups distinguished by sequence, binding affinity, carbohydrate recognition, and neutralizing activity. Group 10-1074 exhibits remarkable potency and breadth but no detectable binding to protein-free glycans. Crystal structures of unliganded PGT121, 10-1074, and their likely germ-line precursor reveal that differential carbohydrate recognition maps to a cleft between complementarity determining region (CDR)H2 and CDRH3. This cleft was occupied by a complex-type N-glycan in a “liganded” PGT121 structure. Swapping glycan contact residues between PGT121 and 10-1074 confirmed their importance for neutralization. Although PGT121 binds complex-type N-glycans, PGT121 recognized high-mannose-only HIV envelopes in isolation and on virions. As HIV envelopes exhibit varying proportions of high-mannose- and complex-type N-glycans, these results suggest promiscuous carbohydrate interactions, an advantageous adaptation ensuring neutralization of all viruses within a given strain.
The Cys allele of the DRD2 Ser311Cys polymorphism has a dominant effect on risk for schizophrenia: Evidence from fixed‐ and random‐effects meta‐analyses

Previously we derived independent estimates of the effect of the dopamine D2 receptor (DRD2) Ser311Cys polymorphism on risk for schizophrenia using fixed‐ and random‐effects meta‐analyses. Both analyses identified a significant association between the Cys allele and schizophrenia, but neither included all available data. Furthermore, genotype data were not evaluated in either analysis, thus precluding any determination of the mode of inheritance. The present study was conducted to resolve discrepancies between the existing meta‐analyses, and provide more comprehensive and accurate estimates of the nature and magnitude of the influence of the Ser311Cys polymorphism on risk for schizophrenia. All discrepancies between the two sets of previously meta‐analyzed studies were identified and resolved to the mutual satisfaction of the authors, and the final dataset was analyzed independently by fixed‐ and random‐effects meta‐analyses. A total of 27 samples, comprising 3,707 schizophrenia patients and 5,363 control subjects, were included in the analyses of allelic association, while smaller numbers of studies and subjects were included in each of the genotypic association analyses. A significant effect of the Cys allele was observed under both fixed‐effects (odds ratio [OR] = 1.4; P = 0.002) and random‐effects (OR = 1.4; P = 0.007) models. Cys/Ser heterozygotes were at elevated risk for schizophrenia when compared to Ser/Ser homozygotes (fixed‐ and random‐effects OR = 1.4, ps ≤ 0.005), but Cys/Cys homozygotes were at no elevated risk relative to heterozygotes (OR = 1.0, ps ≥ 0.948). There was no evidence of heterogeneity, excessive influence of any single study, or publication bias in any of the analyses, suggesting that the effect of this DRD2 polymorphism on schizophrenia risk is reliable and uniform across populations, and our estimates of its magnitude are robust and accurate. © 2006 Wiley‐Liss, Inc.
Effects of an educational intervention based on the protection motivation theory and implementation intentions on first and second pap test practice in Iran.

BACKGROUND Few Iranian women take the Papanicolaou test despite its important role in preventing cervical cancer. This study aimed to determine the effectiveness of an educational intervention based on the protection motivation theory (PMT) variables and implementation intentions in the first and second Pap test practice among Iranian women. MATERIALS AND METHODS In this quasi-randomized controlled trial, 200 women who were referred to 30 primary health care clinics in Tehran were randomly selected. PMT variables and Pap test practice were measured at baseline and again after 3 and 15 months. The 4-week educational intervention program was conducted for the intervention group. RESULTS Following the intervention, the mean scores of self-efficacy, perceived vulnerability, and behavior intention variables were significantly higher in the intervention group when compared to the control group (p<0.05). No significant differences were found in the perceived severity, response efficacy, response cost, and fear between the two groups following the intervention. Higher percent of women in the intervention group had obtained first and second Pap test compared to the controls. CONCLUSIONS The PMT and implementation intentions provide a suitable theory-based framework for developing educational interventions regarding Pap test practice in Iran.
Chelator-Buffered Nutrient Solution is Ineffective in Extracting NI From Seeds of Alyssum

Hyperaccumulator species of the genera Alyssum can accumulate 100 times more Ni than normal crops and are therefore used for phytomining and phytoextraction of nickel contaminated soils. Basic studies on the physiology and metal uptake mechanisms of these plants are needed to increase efficiency and uptake capacity of Nickel (Ni) by hyperaccumulators. Recent attempts to disclose if those hyperaccumulator species require higher Ni level than normal plants failed because of the high Ni content in the seeds (7000–9000 μg g−1). In this study, we attempted to use chelator buffered nutrient solution to deplete Ni from the seed/seed coat and to obtain low Ni seedlings of Alyssum cultivars to be used in physiology studies. HEDTA-buffered nutrient solution did not deplete Ni from the seeds, perhaps because Ni was mainly localized within the seedling embryonic tissues with greatest Ni enrichment in the cotyledons and hypocotyls. We could not observe any positive correlation between seed fitness and germination capacity with seed Ni content. Investigation of nickel localization in Alyssum seeds using synchrotron X-ray microfluorescence (μ-SXRF) showed that nickel is localized in the embryonic tissues with greatest Ni enrichment observed in the cotyledons and hypocotyl.
Staying responsive to the world: Modality‐specific and ‐nonspecific contributions to speeded auditory, tactile, and visual stimulus detection

Sustained responsiveness to external stimulation is fundamental to many time‐critical interactions with the outside world. We used functional magnetic resonance imaging during speeded stimulus detection to identify convergent and divergent neural correlates of maintaining the readiness to respond to auditory, tactile, and visual stimuli. In addition, using a multimodal condition, we investigated the effect of making stimulus modality unpredictable. Relative to sensorimotor control tasks, all three unimodal detection tasks elicited stronger activity in the right temporo‐parietal junction, inferior frontal cortex, anterior insula, dorsal premotor cortex, and anterior cingulate cortex as well as bilateral mid‐cingulum, midbrain, brainstem, and medial cerebellum. The multimodal detection condition additionally activated left dorsal premotor cortex and bilateral precuneus. Modality‐specific modulations were confined to respective sensory areas: we found activity increases in relevant, and decreases in irrelevant sensory cortices. Our findings corroborate the modality independence of a predominantly right‐lateralized core network for maintaining an alert (i.e., highly responsive) state and extend previous results to the somatosensory modality. Monitoring multiple sensory channels appears to induce additional processing, possibly related to stimulus‐driven shifts of intermodal attention. The results further suggest that directing attention to a given sensory modality selectively enhances and suppresses sensory processing—even in simple detection tasks, which do not require inter‐ or intra‐modal selection. Hum Brain Mapp, 2012. © 2011 Wiley Periodicals, Inc.
Iterative resolvent methods for general mixed variational inequalities

In this paper, we use the technique of updating the solution to suggest and analyze a class of new self-adaptive splitting methods for solving general mixed variational inequalities. It is shown that these modified methods converge for pseudomonotone operators, which is a weaker condition than monotonicity. Proof of convergence is very simple. Since general mixed variational include variational inequalities and complementarity problems as special cases, our results continue to hold for these problems.
An investigation into the effects of code coupling on team dynamics and productivity

During the past three decades a number of theories have been proposed to explain the idiosyncrasies of software development as a team activity. The paper compares and combines these theories into a coherent model of software development that links software coupling and dependency management with team productivity. As a practical test of this model, the paper then investigates, the effects of coupling in two large commercial systems. It achieves this by using the VCML Views visualisation technique, developed by the authors, to expose the system wide coupling found in the code and how this coupling develops during the lifetime of a project. It then compares the resultant VCML views with simple attributes of the two projects to derive a set of important conclusions. In particular, it finds that unmanaged coupling within the code is a good indicator of potential productivity bottlenecks; that the number of programmers on a project is not necessarily a good indicator of programmer productivity; and that the architecture of a software system can radically alter the number of programmers that can effectively work together on a system.
Practical Bayesian Optimization of Machine Learning Algorithms

The use of machine learning algorithms frequently involves careful tuning of learning parameters and model hyperparameters. Unfortunately, this tuning is often a "black art" requiring expert experience, rules of thumb, or sometimes brute-force search. There is therefore great appeal for automatic approaches that can optimize the performance of any given learning algorithm to the problem at hand. In this work, we consider this problem through the framework of Bayesian optimization, in which a learning algorithm's generalization performance is modeled as a sample from a Gaussian process (GP). We show that certain choices for the nature of the GP, such as the type of kernel and the treatment of its hyperparameters, can play a crucial role in obtaining a good optimizer that can achieve expertlevel performance. We describe new algorithms that take into account the variable cost (duration) of learning algorithm experiments and that can leverage the presence of multiple cores for parallel experimentation. We show that these proposed algorithms improve on previous automatic procedures and can reach or surpass human expert-level optimization for many algorithms including latent Dirichlet allocation, structured SVMs and convolutional neural networks.
Multiplex RT-PCR Amplification of HIV Genes to Create a Completely Autologous DC-Based Immunotherapy for the Treatment of HIV Infection

Background Effective therapy for HIV-infected individuals remains an unmet medical need. Promising clinical trials with dendritic cell (DC)-based immunotherapy consisting of autologous DC loaded with autologous virus have been reported, however, these approaches depend on large numbers of HIV virions to generate sufficient doses for even limited treatment regimens. Methodology/Principal Findings The present study describes a novel approach for RT-PCR amplification of HIV antigens. Previously, RT-PCR amplification of autologous viral sequences has been confounded by the high mutation rate of the virus which results in unreliable primer-template binding. To resolve this problem we developed a multiplex RT-PCR strategy that allows reliable strain-independent amplification of highly polymorphic target antigens from any patient and requires neither viral sequence data nor custom-designed PCR primers for each individual. We demonstrate the application of our RT-PCR process to amplify translationally-competent RNA encoding regions of Gag, Vpr, Rev and Nef. The products amplified using this method represent a complex mixture of autologous antigens encoded by viral quasispecies. We further demonstrate that DCs electroporated with in vitro-transcribed HIV RNAs are capable of stimulating poly-antigen-specific CD8+ T cell responses in vitro. Conclusion/Significance This study describes a strategy to overcome patient to patient viral diversity enabling strain-independent RT-PCR amplification of RNAs encoding sequence divergent quasispecies of Gag, Vpr, Rev and Nef from small volumes of infectious plasma. The approach allows creation of a completely autologous therapy that does not require advance knowledge of the HIV genomic sequences, does not have yield limitations and has no intact virus in the final product. The simultaneous use of autologous viral antigens and DCs may provoke broad patient-specific immune responses that could potentially induce effective control of viral loads in the absence of conventional antiretroviral drug therapy.
Intercellular adhesion molecule-4 and CD36 are implicated in the abnormal adhesiveness of sickle cell SAD mouse erythrocytes to endothelium

Background Abnormal adhesiveness of red blood cells to endothelium has been implicated in vaso-occlusive crisis of sickle cell disease. The present study examined whether the SAD mouse model exhibits the same abnormalities of red blood cell adhesion as those found in human sickle cell disease. Design and Methods The repertoire of adhesive molecules on murine erythrocytes and bEnd.3 microvascular endothelial cells was determined by flow cytometry using monoclonal antibodies or by western blotting. Adhesion was investigated in dynamic conditions and measured at different shear stresses. Results CD36, CD47 and intercellular adhesion molecular-4, but not Lutheran blood group antigen/basal cell adhesion molecule, are present on mouse mature erythrocytes. α4β1 are not expressed on SAD and wild type reticulocytes. Endothelial bEnd.3 cells express αVβ3, α4β1, CD47, vascular cell adhesion molecule-1, and Lutheran blood group antigen/basal cell adhesion molecule, but not CD36. Adhesion of SAD red cells is: (i) 2- to 3-fold higher than that of wild type red cells; (ii) further increased on platelet activating factor-activated endothelium; (iii) not stimulated by epinephrine; (iv) inhibited after treating the endothelium with a peptide reproducing one of the binding sequences of mouse intercellular adhesion molecular-4, or with mon-oclonal antibody against murine αv integrin; and (v) inhibited after pretreatment of red blood cells with anti-mouse CD36 monoclonal antibodies. The combination of treatments with intercellular adhesion molecular-4 peptide and anti-CD36 monoclonal antibodies eliminates excess adhesion of SAD red cells. The phosphorylation state of intercellular adhesion molecular-4 and CD36 is probably not involved in the over-adhesiveness of SAD erythrocytes. Conclusions Intercellular adhesion molecular-4/αvβ3 and CD36/thrombospondin interactions might contribute to the abnormally high adhesiveness of SAD red cells. The SAD mouse is a valuable animal model for investigating adhesion processes of sickle cell disease.
Genetic Constraints and the Evolution of Display Trait Sexual Dimorphism by Natural and Sexual Selection

The evolution of sexual dimorphism involves an interaction between sex‐specific selection and a breakdown of genetic constraints that arise because the two sexes share a genome. We examined genetic constraints and the effect of sex‐specific selection on a suite of sexually dimorphic display traits in Drosophila serrata. Sexual dimorphism varied among nine natural populations covering a substantial portion of the species range. Quantitative genetic analyses showed that intersexual genetic correlations were high because of autosomal genetic variance but that the inclusion of X‐linked effects reduced genetic correlations substantially, indicating that sex linkage may be an important mechanism by which intersexual genetic constraints are reduced in this species. We then explored the potential for both natural and sexual selection to influence these traits, using a 12‐generation laboratory experiment in which we altered the opportunities for each process as flies adapted to a novel environment. Sexual dimorphism evolved, with natural selection reducing sexual dimorphism, whereas sexual selection tended to increase it overall. To this extent, our results are consistent with the hypothesis that sexual selection favors evolutionary divergence of the sexes. However, sex‐specific responses to natural and sexual selection contrasted with the classic model because sexual selection affected females rather than males.
A novel clustering algorithm based on quantum games

Enormous successes have been made by quantum algorithms during the last decade. In this paper, we combine the quantum game with the problem of data clustering, and then develop a quantum-game-based clustering algorithm, in which data points in a dataset are considered as players who can make decisions and implement quantum strategies in quantum games. After each round of a quantum game, each player's expected payoff is calculated. Later, he uses a link-removing-and-rewiring (LRR) function to change his neighbors and adjust the strength of links connecting to them in order to maximize his payoff. Further, algorithms are discussed and analyzed in two cases of strategies, two payoff matrixes and two LRR functions. Consequently, the simulation results have demonstrated that data points in datasets are clustered reasonably and efficiently, and the clustering algorithms have fast rates of convergence. Moreover, the comparison with other algorithms also provides an indication of the effectiveness of the proposed approach.
Secretion of TcpF by the Vibrio cholerae Toxin-Coregulated Pilus Biogenesis Apparatus Requires an N-Terminal Determinant

ABSTRACT Type IV pili are important for microcolony formation, biofilm formation, twitching motility, and attachment. We and others have shown that type IV pili are important for protein secretion across the outer membrane, similar to type II secretion systems. This study explored the relationship between protein secretion and pilus formation in Vibrio cholerae. The toxin-coregulated pilus (TCP), a type IV pilus required for V. cholerae pathogenesis, is necessary for the secretion of the colonization factor TcpF (T. J. Kirn, N. Bose, and R. K. Taylor, Mol. Microbiol. 49:81–92, 2003). This phenomenon is not unique to V. cholerae; secreted virulence factors that are dependent on the presence of components of the type IV pilus biogenesis apparatus for secretion have been reported with Dichelobacter nodosus (R. M. Kennan, O. P. Dhungyel, R. J. Whittington, J. R. Egerton, and J. I. Rood, J. Bacteriol. 183:4451–4458, 2001) and Francisella tularensis (A. J. Hager et al., Mol. Microbiol. 62:227–237, 2006). Using site-directed mutagenesis, we demonstrated that the secretion of TcpF is dependent on the presence of selected amino acid R groups at position five. We were unable to find other secretion determinants, suggesting that Y5 is the major secretion determinant within TcpF. We also report that proteins secreted in a type IV pilus biogenesis apparatus-dependent manner have a YXS motif within the first 15 amino acids following the Sec cleavage site. The YXS motif is not present in proteins secreted by type II secretion systems, indicating that this is unique to type IV pilus-mediated secretion. Moreover, we show that TcpF interacts with the pilin TcpA, suggesting that these proteins are secreted by the type IV pilus biogenesis system. These data provide a starting point for understanding how type IV pili can mediate secretion of virulence factors important for bacterial pathogenesis.
Multifactor analysis and simulation of the surface runoff and soil infiltration at different slope gradients

The surface runoff and soil infiltration exert significant influence on soil erosion. The effects of slope gradient/length (SG/SL), individual rainfall amount/intensity (IRA/IRI), vegetation cover (VC) and antecedent soil moisture (ASM) on the runoff depth (RD) and soil infiltration (INF) were evaluated in a series of natural rainfall experiments in the South of China. RD is found to correlate positively with IRA, IRI, and ASM factors and negatively with SG and VC. RD decreased followed by its increase with SG and ASM, it increased with a further decrease with SL, exhibited a linear growth with IRA and IRI, and exponential drop with VC. Meanwhile, INF exhibits a positive correlation with SL, IRA and IRI and VC, and a negative one with SG and ASM. INF was going up and then down with SG, linearly rising with SL, IRA and IRI, increasing by a logit function with VC, and linearly falling with ASM. The VC level above 60% can effectively lower the surface runoff and significantly enhance soil infiltration. Two RD and INF prediction models, accounting for the above six factors, were constructed using the multiple nonlinear regression method. The verification of those models disclosed a high Nash-Sutcliffe coefficient and low root-mean-square error, demonstrating good predictability of both models.
Domination Problems in Nowhere-Dense Classes of Graphs

We investigate the parameterized complexity of generalisations and variations of the dominating set problem on classes of graphs that are nowhere dense. In particular, we show that the distance-d dominating-set problem, also known as the (k,d)-centres problem, is fixed-parameter tractable on any class that is nowhere dense and closed under induced subgraphs. This generalises known results about the dominating set problem on H-minor free classes, classes with locally ex- cluded minors and classes of graphs of bounded expansion. A key feature of our proof is that it is based simply on the fact that these graph classes are uniformly quasi-wide, and does not rely on a structural decomposition. Our result also establishes that the distance-d dominating-set problem is FPT on classes of bounded expansion, answering a question of Neˇˇ ril and Ossona de Mendez.