Miracle-dz/UniFAR-FTUs huggingface dataset:
No primary association of MICA polymorphism with systemic lupus erythematosus.

OBJECTIVE To replicate the described association between MHC class I chain-related A (MICA) gene polymorphism and susceptibility to systemic lupus erythematosus (SLE). METHODS MICA transmembrane microsatellite polymorphism was genotyped using a polymerase chain reaction (PCR)-based method. Genotyping of HLA-B* and DRB1* was performed using PCR and detection with a reverse sequence-specific oligonucleotide (SSO) probe system. Combined data for these three loci (HLA-B*, DRB1* and MICA) were obtained from a total of 333 patients and 361 healthy controls. RESULTS Significant association with B*08 [P < 10(-7), odds ratio (OR) 3.17, 95% confidence interval (CI) 2.02-5.00], DRB1*0301 (P < 10(-7), OR 2.07, 95% CI 1.59-2.68) and MICA5.1 (P = 0.01, OR 1.23, 95% CI 1.04-1.46) was observed. The combinations DRB1*0301-MICA5.1-B8 and HLA-DRB1*0301-B*08-positive and MICA5-1-negative were more frequent among SLE patients (11.4 vs 3.3% in healthy controls, P = 3.9 x 10(-5), OR 3.76, 95% CI 1.85-7.73, and 6.9 vs 1.7%, P = 0.0007, OR 4.32, 95% CI 1.68-13.10, respectively). Additionally, individuals who were HLA-DRB1*0301-B*08-negative and MICA5-1-positive were less frequent among patients (22.2 vs 31.3% in healthy controls, P = 0.007, OR 0.63, 95% CI 0.44-0.89) and the magnitude of the OR was similar to that obtained in individuals negative for all the three factors (OR 0.69, 95% CI 050-0.94). Further analysis performed to detect independent association strongly suggested that the association between MICA5.1 and SLE is secondary to the linkage disequilibrium of this allele with B*08. CONCLUSIONS Our results do not support an independent association of MICA gene polymorphism with susceptibility to SLE.
Efficient Robbins-Monro procedure for binary data

The Robbins--Monro procedure does not perform well in the estimation of extreme quantiles, because the procedure is implemented using asymptotic results, which are not suitable for binary data. Here we propose a modification of the Robbins--Monro procedure and derive the optimal procedure for binary data under some reasonable approximations. The improvement obtained by using the optimal procedure for the estimation of extreme quantiles is substantial. Copyright Biometrika Trust 2004, Oxford University Press.
Assembly and Channel Opening of Outer Membrane Protein in Tripartite Drug Efflux Pumps of Gram-negative Bacteria*

Background: Pseudomonas aeruginosa mainly achieves multidrug resistance by use of the MexAB-OprM pump. Results: We determined the crystal structure of MexA. Electron microscopy work using MexA and OprM reveals that MexA makes a tip-to-tip interaction with OprM. Conclusion: We suggest an assembly and channel opening model for the pump. Significance: This study provides a better understanding of multidrug resistance in Gram-negative bacteria. Gram-negative bacteria are capable of expelling diverse xenobiotic substances from within the cell by use of three-component efflux pumps in which the energy-activated inner membrane transporter is connected to the outer membrane channel protein via the membrane fusion protein. In this work, we describe the crystal structure of the membrane fusion protein MexA from the Pseudomonas aeruginosa MexAB-OprM pump in the hexameric ring arrangement. Electron microscopy study on the chimeric complex of MexA and the outer membrane protein OprM reveals that MexA makes a tip-to-tip interaction with OprM, which suggests a docking model for MexA and OprM. This docking model agrees well with genetic results and depicts detailed interactions. Opening of the OprM channel is accompanied by the simultaneous exposure of a protein structure resembling a six-bladed cogwheel, which intermeshes with the complementary cogwheel structure in the MexA hexamer. Taken together, we suggest an assembly and channel opening model for the MexAB-OprM pump. This study provides a better understanding of multidrug resistance in Gram-negative bacteria.
Genetic Influences on the End-Stage Effector Phase of Arthritis

K/B×N T cell receptor transgenic mice are a model of inflammatory arthritis, most similar to rheumatoid arthritis, that is critically dependent on both T and B lymphocytes. Transfer of serum, or just immunoglobulins, from arthritic K/B×N animals into healthy recipients provokes arthritis efficiently, rapidly, and with high penetrance. We have explored the genetic heterogeneity in the response to serum transfer, thereby focussing on the end-stage effector phase of arthritis, leap-frogging the initiating events. Inbred mouse strains showed clear variability in their responses. A few were entirely refractory to disease induction, and those which did develop disease exhibited a range of severities. F1 analyses suggested that in most cases susceptibility was controlled in a polygenic additive fashion. One responder/nonresponder pair (C57Bl/6 × NOD) was studied in detail via a genome scan of F2 mice; supplementary information was provided by the examination of knock-out and congenic strains. Two genomic regions that are major, additive determinants of the rapidity and severity of K/B×N serum-transferred arthritis were highlighted. Concerning the first region, on proximal chromosome (chr)2, candidate assignment to the complement gene C5 was confirmed by both strain segregation analysis and functional data. Concerning the second, on distal chr1, coinciding with the Sle1 locus implicated in susceptibility to lupus-like autoimmune disease, a contribution by the fcgr2 candidate gene was excluded. Two other regions, on chr12 and chr18 may also contribute to susceptibility to serum-transferred arthritis, albeit to a more limited degree. The contributions of these loci are additive, but gene dosage effects at the C5 locus are such that it largely dominates. The clarity of these results argues that our focus on the terminal effector phase of arthritis in the K/B×N model will bear fruit.
Age of diagnosis among Medicaid-enrolled children with autism, 2001-2004.

OBJECTIVE This study examined child- and county-level factors associated with age of diagnosis of autism among Medicaid-enrolled children and the change in age of diagnosis over time. METHODS National Medicaid claims from 2002 to 2004 were used to identify age of diagnosis and characteristics of children younger than ten years old with a diagnosis of autism (ICD-9 codes 299, 299.0x, or 299.8x). These data were linked to county-level education and health care variables. Linear regression with random effects for state and county was used to examine associations between these variables and age of diagnosis. RESULTS A total of 28,722 Medicaid-enrolled children newly diagnosed with an autism spectrum disorder were identified. Their average age of diagnosis was 64.9 months. Adjusted average age of diagnosis dropped 5.0 months for autistic disorder and 1.8 months for other spectrum disorders during the study period. Asian children were diagnosed earlier than children in other racial or ethnic groups, although these differences were much more pronounced for other spectrum disorders than for autistic disorder. Children eligible for Medicaid through the poverty category were diagnosed earlier, on average, than children who were eligible through disability, foster care, or other reasons, although this difference decreased over time. Children in large urban or rural counties were diagnosed later than children in small urban or suburban counties. CONCLUSIONS Findings showed that diagnosis of autism occurs much later than it should among Medicaid-enrolled children, although timeliness is improving over time. Analyses suggest that most of the observed variation is accounted for by child-level variables, rather than county-level resources or state policies.
Transmitted Virus Fitness and Host T Cell Responses Collectively Define Divergent Infection Outcomes in Two HIV-1 Recipients

Control of virus replication in HIV-1 infection is critical to delaying disease progression. While cellular immune responses are a key determinant of control, relatively little is known about the contribution of the infecting virus to this process. To gain insight into this interplay between virus and host in viral control, we conducted a detailed analysis of two heterosexual HIV-1 subtype A transmission pairs in which female recipients sharing three HLA class I alleles exhibited contrasting clinical outcomes: R880F controlled virus replication while R463F experienced high viral loads and rapid disease progression. Near full-length single genome amplification defined the infecting transmitted/founder (T/F) virus proteome and subsequent sequence evolution over the first year of infection for both acutely infected recipients. T/F virus replicative capacities were compared in vitro, while the development of the earliest cellular immune response was defined using autologous virus sequence-based peptides. The R880F T/F virus replicated significantly slower in vitro than that transmitted to R463F. While neutralizing antibody responses were similar in both subjects, during acute infection R880F mounted a broad T cell response, the most dominant components of which targeted epitopes from which escape was limited. In contrast, the primary HIV-specific T cell response in R463F was focused on just two epitopes, one of which rapidly escaped. This comprehensive study highlights both the importance of the contribution of the lower replication capacity of the transmitted/founder virus and an associated induction of a broad primary HIV-specific T cell response, which was not undermined by rapid epitope escape, to long-term viral control in HIV-1 infection. It underscores the importance of the earliest CD8 T cell response targeting regions of the virus proteome that cannot mutate without a high fitness cost, further emphasizing the need for vaccines that elicit a breadth of T cell responses to conserved viral epitopes.
Self-rescue of an EXTENSIN mutant reveals alternative gene expression programs and candidate proteins for new cell wall assembly in Arabidopsis.

Plants encode a poorly understood superfamily of developmentally expressed cell wall hydroxyproline-rich glycoproteins (HRGPs). One, EXTENSIN3 (EXT3) of the 168 putative HRGPs, is critical in the first steps of new wall assembly, demonstrated by broken and misplaced walls in its lethal homozygous mutant. Here we report the findings of phenotypic (not genotypic) revertants of the ext3 mutant and in-depth analysis including microarray and qRT-PCR (polymerase chain reaction). The aim was to identify EXT3 substitute(s), thus gaining a deeper understanding of new wall assembly. The data show differential expression in the ext3 mutant that included 61% (P ≤ 0.05) of the HRGP genes, and ability to self-rescue by reprogramming expression. Independent revertants had reproducible expression networks, largely heritable over the four generations tested, with some genes displaying transgenerational drift towards wild-type expression levels. Genes for nine candidate regulatory proteins as well as eight candidate HRGP building materials and/or facilitators of new wall assembly or maintenance, in the (near) absence of EXT3 expression, were identified. Seven of the HRGP fit the current model of EXT function. In conclusion, the data on phenotype comparisons and on differential expression of the genes-of-focus provide strong evidence that different combinations of HRGPs regulated by alternative gene expression networks, can make functioning cell walls, resulting in (apparently) normal plant growth and development. More broadly, this has implications for interpreting the cause of any mutant phenotype, assigning gene function, and genetically modifying plants for utilitarian purposes.
Equivalence of Some Common Linear Feature Extraction Techniques for Appearance-Based Object Recognition Tasks

Recently, a number of empirical studies have compared the performance of PCA and ICA as feature extraction methods in appearance-based object recognition systems, with mixed and seemingly contradictory results. In this paper, we briefly describe the connection between the two methods and argue that whitened PCA may yield identical results to ICA in some cases. Furthermore, we describe the specific situations in which ICA might significantly improve on PCA
Argumentation Mechanism Design for Preferred Semantics

Recently Argumentation Mechanism Design (ArgMD) was introduced as a paradigm for studying argumentation using game-theoretic techniques. To date, this framework has been used to study under what conditions a direct mechanism based on Dung's grounded semantics is strategy-proof (i.e. truth-enforcing) when knowledge of arguments is private to self-interested agents. In this paper, we study Dung's preferred semantics in order to understand under what conditions it is possible to design strategy-proof mechanisms. This is challenging since, unlike with the grounded semantics, there may be multiple preferred extensions, forcing a mechanism to select one. We show that this gives rise to interesting strategic behaviour, and we show that in general it is not possible to have a strategy-proof mechanism that selects amongst the preferred extensions in a non-biased manner. We also investigaet refinements of preferred semantics which induce unique outcomes, namely the skeptical-preferred and ideal semantics.
Impact of communication skills training on parents perceptions of care: intervention study.

AIM This paper is a report of a study of the effects of communication-skills training for healthcare professionals on parents' perceptions of information, care and continuity. BACKGROUND As training in communication skills has been more and more integrated into clinical practice it has been subject to an increasing number of studies. However, the majority of studies have been conducted in outpatient clinics, have only targeted physicians, and have not been evaluated from the perspective of patients. METHOD This intervention study, conducted from 2005 to 2007, was performed to investigate the effect of a 3-day communication course offered to all healthcare professionals in a department of paediatrics. In a pre-/post-test design, the effect of the intervention was evaluated by the parents using electronic questionnaires filled in on touch-screen computers located centrally in the wards. RESULTS A total of 895 parents answered the questionnaires before the course (80%) and 1937 answered after the course (72%). For the questions on care and continuity, the proportion of satisfied parents increased statistically significantly for 4 out of 13 questions, e.g. Did you feel that the staff understood you situation? and Did you find that the information given by the different nurses was consistent? For the information questions, no statistically significant differences were found. CONCLUSION It is possible to incorporate key communication skills into clinical practice by targeting all healthcare professionals. Communication skills training using interactive methods such as role-play and feedback on video recordings is recommended.
A State-Dependent Model for Inflation Forecasting

We develop a parsimonious bivariate model of inflation and unemployment that allows for persistent variation in trend inflation and the NAIRU. The model, which consists of five unobserved components (including the trends) with stochastic volatility, implies a time-varying VAR for changes in the rates of inflation and unemployment. The implied backwards-looking Phillips curve has a time-varying slope that is steeper in the 1970s than in the 1990s. Pseudo out-of-sample forecasting experiments indicate improvements upon univariate benchmarks. Since 2008, the implied Phillips curve has become steeper and the NAIRU has increased.
Physicochemical Characteristics and Immunomodulatory Activities of Three Polysaccharide-Protein Complexes of Longan Pulp

Three polysaccharide-protein complexes of longan pulp (LP1-3) were isolated in this work. Their physicochemical characteristics and immunomodulatory effects on splenocytes, natural killer (NK) cells and macrophages in vitro were investigated. The carbohydrate portions of LP1-3 were principally composed of glucose, arabinose and mannose. LP3 displayed the maximal moisture absorption, and the thermal stability of LP2 was obviously higher than that of LP1 and LP3. All of them showed the characteristic polysaccharide and protein bands in the Fourier Transform Infrared (FTIR) spectrum. For a certain dose, all the fractions could significantly stimulate splenocyte proliferation, macrophage phagocytosis against neutral red, and NK cell cytotoxicity against YAC-1 lymphoma cell (P < 0.05). The results demonstrated that the polysaccharide-protein complexes of longan pulp have medical potential as immunotherapeutic adjuvants due to their immunomodulatory activities.
An open framework for foundational proof-carrying code

Today's software systems often use many different computation features and span different abstraction levels (e.g., user code and runtime-system code). To build foundational certified systems, it is hard to have a single verification system supporting all computation features. In this paper we present an open framework for foundational proof-carrying code (FPCC). It allows program modules to be specified and certified separately using different type systems or program logics. Certified modules (i.e., code and proof) can be linked together to build fully certified systems. The framework supports modular verification and proof reuse. It is also expressive enough so that invariants established in specific verification systems are preserved even when they are embedded into our framework. Our work presents the first FPCC framework that systematically supports interoperation between different verification systems. It is fully mechanized in the Coq proof assistant with machine-checkable soundness proof.
Affinity-driven system design exploration for heterogeneous multiprocessor SoC

Continuous advances in silicon technology enable the development of complex system-on-chip as cooperation among digital signal processors (DPSs), general purpose processors (GPPs), and specific hardware components. The impact of this choice is not only limited to the target architecture, but also encompasses the overall system specification. It is thus crucial to manage such a complexity using high-level specification languages and a tool chain supporting the designer throughout a set of strategic decisions, such as the identification of a set of possible target architectures, the verification of the correctness of the specification, and the partitioning of the specification onto a set of computational resources. This paper addresses this type of problem by proposing a design flow supporting the system-level design of heterogeneous multiprocessor system-on-chip (MP-SoC), by extracting information from the system description (e.g., SystemC) - statically and in a fast manner - and by providing a set of quantitative measures correlating the type of executor, the functionality, and a timing estimation. Partitioning and architecture selection are built on top of this data and the final analysis of the selected hardware-software solution over the identified candidates is finally submitted to a timing verification via simulation. Note that the possibility of actually performing a comprehensive design space exploration, in general, is tightly influenced by the interaction between partitioning/architecture-selection and timing simulation in the design flow; for this reason, the description of this aspect is particularly emphasized in the presentation of the methodology. To show the applicability of the proposed methodology, two relevant case studies are described in the paper.
Text-Free User Interfaces for Illiterate and Semi-Literate Users

We describe work toward the goal of a user interface designed such that even novice, illiterate users require absolutely no intervention from anyone at all to use. Our text-free user interface is based on many hours of ethnographic design conducted in collaboration with a community of illiterate domestic labourers in three Bangalore slums. An ethnographic design process was used to understand what kind of application subjects would be interested in, how they respond to computing technology, and how they react to specific UI elements. We built two applications using these principles, one for job search for domestic labourers, and another for a generic map that could be used for navigating a city. The resulting designs are based on key lessons that we gained through the design process. The paper describes the design process, the design principles which evolved out of the process, the final application design, and results from initial user testing. Our results confirm previous work that emphasizes the need for semi-abstracted graphics and voice feedback, but we additionally find that some aspects of design for illiterate users that have been previously overlooked (such as a consistent help feature). Results also show that the text-free designs are strongly preferred over standard text-based interfaces by the communities which we address, and that they are potentially able to bring even complex computer functions within the reach of users who are unable to read
Cytochrome P450 pharmacogenetics in African populations

Abstract The Cytochrome P450 (CYP450) family of enzymes is involved in the oxidative metabolism of many therapeutic drugs, carcinogens and various endogenous substrates. These enzymes are highly polymorphic at an inter-individual and inter-ethnic level. Polymorphisms or genetic variations account for up to 30% of inter-individual differences seen in a variety of drug responses. The frequencies of the different metabolizer categories (slow, intermediate, extensive and ultra-rapid), the distribution of genetic variants, genotype–phenotype correlations and the clinical importance of the CYP450 enzymes have been extensively documented in Caucasian and Oriental populations. Limited data exists for African populations, despite the fact that this knowledge is critically important for these populations who experience a heavy burden of communicable and non-communicable diseases. In addition, the costs incurred through adverse drug reactions and non-responsiveness to therapy could be reduced through the wide-scale application of pharmacogenetics. This review provides an overview and investigation of CYP450 genotypic and phenotypic reports published from 1980 to present in African populations. Our findings confirm the high degree of variability that is expected when comparing individuals of African origin to other ethnic groups and also highlight the distribution of clinically relevant CYP450 alleles amongst the various African populations. The notable discordance in genotypic and phenotypic data amongst African populations exemplifies the need for in-depth and well-orchestrated molecular and pharmacological investigations of these populations in the future, for which whole genome sequencing and association studies will be critical.
Task scheduling strategies for workflow-based applications in grids

Grid applications require allocating a large number of heterogeneous tasks to distributed resources. A good allocation is critical for efficient execution. However, many existing grid toolkits use matchmaking strategies that do not consider overall efficiency for the set of tasks to be run. We identify two families of resource allocation algorithms: task-based algorithms, that greedily allocate tasks to resources, and workflow-based algorithms, that search for an efficient allocation for the entire workflow. We compare the behavior of workflow-based algorithms and task-based algorithms, using simulations of workflows drawn from a real application and with varying ratios of computation cost to data transfer cost. We observe that workflow-based approaches have a potential to work better for data-intensive applications even when estimates about future tasks are inaccurate.