Miracle-dz/UniFAR-FTUs huggingface dataset:
Transforming growth factor β is dispensable for the molecular orchestration of Th17 cell differentiation

Interleukin (IL)-17–producing T helper (Th17) cells play a critical role in the pathophysiology of several autoimmune disorders. The differentiation of Th17 cells requires the simultaneous presence of an unusual combination of cytokines: IL-6, a proinflammatory cytokine, and transforming growth factor (TGF) β, an antiinflammatory cytokine. However, the molecular mechanisms by which TGF-β exerts its effects on Th17 cell differentiation remain elusive. We report that TGF-β does not directly promote Th17 cell differentiation but instead acts indirectly by blocking expression of the transcription factors signal transducer and activator of transcription (STAT) 4 and GATA-3, thus preventing Th1 and Th2 cell differentiation. In contrast, TGF-β had no effect on the expression of retinoic acid receptor–related orphan nuclear receptor γt, a Th17-specific transcription factor. Interestingly, in Stat-6−/−T-bet−/− mice, which are unable to generate Th1 and Th2 cells, IL-6 alone was sufficient to induce robust differentiation of Th17 cells, whereas TGF-β had no effect, suggesting that TGF-β is dispensable for Th17 cell development. Consequently, BALB/c Stat-6−/−T-bet−/− mice, but not wild-type BALB/c mice, were highly susceptible to the development of experimental autoimmune encephalomyelitis, which could be blocked by anti–IL-17 antibodies but not by anti–TGF-β antibodies. Collectively, these data provide evidence that TGF-β is not directly required for the molecular orchestration of Th17 cell differentiation.
Analysis of apoptosis in peripheral blood and synovial tissue very early after initiation of infliximab treatment in rheumatoid arthritis patients.

OBJECTIVE Infliximab treatment results in a decrease in synovial cellularity as early as 48 hours after initiation of therapy in patients with rheumatoid arthritis (RA). This study was undertaken to investigate whether infliximab induces apoptosis within the first 24 hours after infusion. METHODS The percentage of apoptotic cells was determined by flow cytometry in blood drawn from 21 patients directly before, 1 hour after, and 24 hours after infliximab infusion. Synovial tissue samples obtained before, 1 hour after (n = 5), or 24 hours after (n = 5) initiation of therapy were subjected to immunohistochemistry to detect active caspase 3 and to TUNEL assay and electron microscopy to detect apoptosis. In addition, plasma levels of nucleosomes (generated during apoptosis) and C4b/c (an indicator of complement activation) were measured. RESULTS There were no signs of apoptosis induction in peripheral blood monocytes or lymphocytes after infliximab treatment. Circulating lymphocyte counts were increased within 1 hour after infusion (P < 0.05). There was no definite evidence of apoptosis induction in the synovium, except in 1 patient 24 hours after the infliximab infusion. Consistent with these results, there was no increase in nucleosome levels nor were there signs of complement activation. CONCLUSION Our findings indicate that the rapid decrease in synovial cellularity observed after initiation of anti-tumor necrosis factor antibody therapy cannot be explained by apoptosis induction at the site of inflammation. It is tempting to speculate that the striking effects on synovial inflammation may be explained by other mechanisms, such as decreased migration toward the synovial compartment and reduced retention in the inflamed synovium.
Competitive altruism: from reciprocity to the handicap principle

Current work on cooperation is focused on the theory of reciprocal altruism. However, reciprocity is just one way of getting a return on an investment in altruism and is difficult to apply to many examples. Reciprocity theory addresses how animals respond dynamically to others so as to cooperate without being exploited. I discuss how introducing differences in individual generosity together with partner choice into models of reciprocity can lead to an escalation in altruistic behaviour. Individuals may compete for the most altruistic partners and non–altruists may become ostracized. I refer to this phenomenon as competitive altruism and propose that it can represent a move away from the dynamic responsiveness of reciprocity. Altruism may be rewarded in kind, but rewards may be indirectly accrued or may not involve the return of altruism at all, for example if altruists tend to be chosen as mates. This variety makes the idea of competitive altruism relevant to behaviours which cannot be explained by reciprocity. I consider whether altruism might act as a signal of quality, as proposed by the handicap principle. I suggest that altruistic acts could make particularly effective signals because of the inherent benefits to receivers. I consider how reciprocity and competitive altruism are related and how they may be distinguished.
An Investigation of Diffuse Interstellar Gas toward a Large, Low-Extinction Window into the Inner Galaxy

Hα and Hβ spectroscopy with the Wisconsin Hα Mapper (WHAM) reveals a strong concentration of high-velocity emission in a ≈5° × 5° area centered near (l, b) = (27°, - 3°), known as the Scutum cloud. The high velocities imply that we are detecting optical emission from near the plane of the Galaxy out to the tangent point at heliocentric distances of D☉ ≳ 6 kpc, assuming that the gas participates in circular Galactic rotation. The ratio of the Hα to Hβ emission as a function of velocity suggests that dust along these lines of sight produces a total visual extinction of AV ≈ 3 at D☉ ~ 6 kpc. This makes it possible to use optical emission lines to explore the physical conditions of ionized gas in the inner Galaxy. At a Galactocentric distance RG ≈ 4 kpc, for example, we find that the H+ has an rms midplane density of ≈1 cm-3 with a vertical scale height of ≈300 pc. We also find evidence for an increase in the flux of Lyman continuum photons and an increase in the ratio of ionized to neutral hydrogen toward the inner Galaxy. We have extended the measurements of E(B - V) in this direction to distances far beyond what has been accessible through stellar photometry and find E(B - V)/NH to be near the local mean of 1.7 × 10-22 cm2 mag, with evidence for an increase in this ratio at RG ≈ 4 kpc. Finally, our observations of [N II] λ6583, [S II] λ6716, and [O III] λ5007 toward the window reveal that in the inner Galaxy the temperature of the gas and the ionization state of oxygen increase with increasing height from the midplane.
Evaluation of soil‐loss contribution areas on loess soils in SouthEast Poland

Results of soil‐loss assessments on loess‐derived silt soils are presented. The studies were conducted on plots of different length maintained in continuous bare fallow conditions. Analysing runoff events separately, soil losses per unit area varied with plot length. Description of the soil‐erosion process in terms of (1) maximum soil loss per unit area and (2) the effective distance of soil transport allows us to overcome problems with data interpretation. Smaller values of soil loss per unit area could then be connected with (1) impeded development of erosion process on plots of shorter length and (2) over‐estimation of soil loss contribution area on longer plots. The method of determination of soil‐loss contribution area was the main reason of the differences between soil losses, observed and predicted from the Universal Soil Loss Equation. Studies conducted showed that eroded soil material was transported short distances (from 2 to 13 m). The maximum soil loss per unit area was well correlated with rainfall amount, whilst the effective distance of soil transport was affected by many factors, including rainfall amount and initial state of soil roughness. Copyright © 2002 John Wiley & Sons, Ltd.
An Optimization Framework for Opportunistic Multipath Routing in Wireless Mesh Networks

We consider wireless mesh networks, and exploit the inherent broadcast nature of wireless by making use of multipath routing. We present an optimization framework that enables us to derive optimal flow control, routing, scheduling, and rate adaptation schemes, where we use network coding to ease the routing problem. We prove optimality and derive a primal-dual algorithm that lays the basis for a practical protocol. We use simulation to show on realistic topologies that we can achieve 20-200% throughput improvement compared to single path routing, and several times compared to a recent related opportunistic protocol (MORE).
On feedback stabilisation of switched discrete-time systems via Lie-algebraic techniques

This paper studies the stabilisation of switched discrete-time linear control systems under arbitrary switching. A sufficient condition for the uniform global exponential stability (UGES) of such systems is the existence of a common quadratic Lyapunov function (CQLF) for the component subsystems. The existence of such CQLF can be ensured using Lie-algebraic techniques by the existence of a nonsingular similarity transformation that simultaneously triangularises the closed-loop evolution maps of the component subsystems. The present work formulates a Lie-algebraic feedback design problem in terms of invariant subspaces and proposes an iterative algorithm that seeks a set of feedback maps that guarantee the existence of a CQLF, and thus UGES of the switched feedback system. The main contribution of the paper is to show that this algorithm will find the required feedback maps if and only if the Lie-algebraic problem has a solution.
Community incidence of pathogen-specific gastroenteritis: reconstructing the surveillance pyramid for seven pathogens in seven European Union member states

SUMMARY By building reconstruction models for a case of gastroenteritis in the general population moving through different steps of the surveillance pyramid we estimated that millions of illnesses occur annually in the European population, leading to thousands of hospitalizations. We used data on the healthcare system in seven European Union member states in relation to pathogen characteristics that influence healthcare seeking. Data on healthcare usage were obtained by harmonized cross-sectional surveys. The degree of under-diagnosis and underreporting varied by pathogen and country. Overall, underreporting and under-diagnosis were estimated to be lowest for Germany and Sweden, followed by Denmark, The Netherlands, UK, Italy and Poland. Across all countries, the incidence rate was highest for Campylobacter spp. and Salmonella spp. Incidence estimates resulting from the pyramid reconstruction approach are adjusted for biases due to different surveillance systems and are therefore a better basis for international comparisons than reported data.
Alpha helix shortening in 1522 MSP‐1 conserved peptide analogs is associated with immunogenicity and protection against P. falciparum malaria

1522 is a nonimmunogenic conserved high‐activity binding peptide (HABP) belonging to Plasmodium falciparum MSP‐1 protein N‐terminal fragment. The key amino acids in binding to red blood cells (RBC) were identified and replaced by others having similar mass but different charge. Because conserved HABPs are not antigenic nor immunogenic, immunogenicity and protectivity studies were then conducted on them in the Aotus monkey. 1H‐NMR studies included the lead peptide 1522 as well as the analogs 9782, 13446, 13448, and 13442 to relate their structure to biological function. All the peptides presented α‐helical structure, with differences observed in helix location and extension. The nonprotective 1522 peptide was totally helical from the N‐ to the C‐terminus, very similar to nonprotective 13442 and 13448 peptides whose extension was almost totally helical. The 9782 and 13446 protective peptides, however, possessed a shorter helical region where modified critical binding residues were not included. A more flexible region was generated at the C‐terminus in those peptides with a shorter helical region, leading to a greater number of conformers. These data suggest that peptide flexibility results in increased interaction with immune system molecules, generating protective immunity. Proteins 2003;50:400–409. © 2003 Wiley‐Liss, Inc.
Neural regulation of the circadian vasopressin rhythm in cerebrospinal fluid: a pre-eminent role for the suprachiasmatic nuclei

The neuroanatomical system responsible for the generation and expression of the circadian vasopressin rhythm in cerebrospinal fluid (CSF) is investigated. CSF was serially withdrawn in individual, unanesthetized, unrestrained rats after neuroendocrine extirpations or stereotaxic brain lesions were made; the peptide was assayed using a sensitive and specific radioimmunoassay. Hypophysectomy or pinealectomy did not eliminate vasopressin from CSF; both day and night-time peptide levels in hypophysectomized rats were elevated above control levels. Complete lesions of the suprachiasmatic nuclei (SCN) abolished both the rhythm and in most cases the measurable level of peptide in CSF. Neither lesions of the paraventricular nuclei nor hypothalamic knife cuts interrupting most neural efferents from the SCN had this effect; in these cases, vasopressin rhythms persisted with diminished amplitude. Our results suggest that the circadian CSF vasopressin rhythm is produced by a neural system topographically separate from the classical magnocellular hypothalamo-neurohypophyseal system for the secretion of peptide into blood. The SCN are an important component of this new system and are necessary for the generation of the CSF rhythm.
Weakly Supervised Learning of Deep Metrics for Stereo Reconstruction

Deep-learning metrics have recently demonstrated extremely good performance to match image patches for stereo reconstruction. However, training such metrics requires large amount of labeled stereo images, which can be difficult or costly to collect for certain applications (consider, for example, satellite stereo imaging). The main contribution of our work is a new weakly supervised method for learning deep metrics from unlabeled stereo images, given coarse information about the scenes and the optical system. Our method alternatively optimizes the metric with a standard stochastic gradient descent, and applies stereo constraints to regularize its prediction. Experiments on reference data-sets show that, for a given network architecture, training with this new method without ground-truth produces a metric with performance as good as state-of-the-art baselines trained with the said ground-truth. This work has three practical implications. Firstly, it helps to overcome limitations of training sets, in particular noisy ground truth. Secondly it allows to use much more training data during learning. Thirdly, it allows to tune deep metric for a particular stereo system, even if ground truth is not available.
Association of cholecystokinin-A receptor gene polymorphism with alcohol dependence in a Japanese population.

AIMS Cholecystokinin (CCK), one of the most abundant neurotransmitter peptides, interacts with dopamine. Dopaminergic neurotransmission between the ventral tegmental area and the limbic forebrain is a critical neurobiological component of alcohol and drug self-administration. CCK modulates dopamine release in the nucleus accumbens via the CCK-A receptor (R). We recently determined the transcriptional start site of the human CCK-AR gene, and detected two sequence changes (-81A/G and -128G/T) in the promoter region. The aims of the present study were to determine the prevalence of the -81A/G and -128G/T polymorphism of the CCK-AR gene between alcoholics and normal control subjects and the occurrences of the polymorphisms in subtypes of alcoholics. METHODS The above polymorphisms were examined in 435 alcoholics and 1490 control subjects. We excluded subjects with inactive ALDH2 and employed the subjects with ALDH2*1/2*1 (384 alcoholics and 792 controls). RESULTS The allelic frequency of -81G in the CCK-AR gene polymorphism (-81A/G) was significantly higher in alcoholics than in control subjects. However, there were no differences between the two groups with respect to the frequency of -128G/T. Alcoholic patients with antisocial personality disorder and with first-degree alcoholic relatives were significantly associated with a higher frequency of the -81G allele. In addition, the age of onset of alcohol dependence was significantly earlier in patients with this allele. CONCLUSIONS The CCK-AR gene -81A/G polymorphism, especially in the -81G allele, may be associated with intractable alcoholism.
PANTHER version 7: improved phylogenetic trees, orthologs and collaboration with the Gene Ontology Consortium

Protein Analysis THrough Evolutionary Relationships (PANTHER) is a comprehensive software system for inferring the functions of genes based on their evolutionary relationships. Phylogenetic trees of gene families form the basis for PANTHER and these trees are annotated with ontology terms describing the evolution of gene function from ancestral to modern day genes. One of the main applications of PANTHER is in accurate prediction of the functions of uncharacterized genes, based on their evolutionary relationships to genes with functions known from experiment. The PANTHER website, freely available at http://www.pantherdb. org, also includes software tools for analyzing genomic data relative to known and inferred gene functions. Since 2007, there have been several new developments to PANTHER: (i) improved phylogenetic trees, explicitly representing speciation and gene duplication events, (ii) identification of gene orthologs, including least diverged orthologs (best one-to-one pairs), (iii) coverage of more genomes (48 genomes, up to 87% of genes in each genome; see http://www.pantherdb.org/panther/summaryStats.jsp), (iv) improved support for alternative database identifiers for genes, proteins and microarray probes and (v) adoption of the SBGN standard for display of biological pathways. In addition, PANTHER trees are being annotated with gene function as part of the Gene Ontology Reference Genome project, resulting in an increasing number of curated functional annotations.
The lateral diffusion of lipid probes in the surface membrane of Schistosoma mansoni

The technique of fluorescence recovery after photobleaching was used to measure the lateral diffusion of fluorescent lipid analogues in the surface membrane of Schistosoma mansoni. Our data reveal that although some lipids could diffuse freely others exhibited restricted lateral diffusion. Quenching of lipid fluorescence by a non-permeant quencher, trypan blue, showed that there was an asymmetric distribution of lipids across the double bilayer of mature parasites. Those lipids that diffused freely were found to reside mainly in the external monolayer of the outer membrane whereas lipids with restricted lateral diffusion were located mainly in one or more of the monolayers beneath the external monolayer. Formation of surface membrane blebs allowed us to measure the lateral diffusion of lipids in the membrane without the influence of underlying cytoskeletal structures. The restricted diffusion found on the normal surface membrane of mature parasites was found to be released in membrane blebs. Quenching of fluorescent lipids on blebs indicated that all probes were present almost entirely in the external monolayer. Juvenile worms exhibited lower lateral diffusion coefficients than mature parasites: in addition, the lipids partitioned into the external monolayer. The results are discussed in terms of membrane organization, cytoskeletal contacts, and biological significance.
Difficulties in identifying antibodies in the Dombrock blood group system in multiply alloimmunized patients

BACKGROUND: Although red cell (RBC) antibodies of the Dombrock blood group system have been reported to cause acute and delayed hemolytic transfusion reactions, the difficulty in identifying these antibodies in patients with multiple RBC alloantibodies has not previously been discussed. The cases of four sickle cell disease patients who developed Dombrock system antibodies after transfusion, three of which were discovered in association with hemolytic transfusion reactions, are reported. CASE REPORTS: Patient 1 was a 36‐year‐old woman with multiple RBC alloantibodies. Because of the lack of an increment in hematocrit after transfusion, an investigation was performed; it revealed anti‐ Do(b) in the serum. Patient 2 was a 30‐year‐old woman with known anti‐ C, ‐E, ‐K, ‐S, ‐Fya, and ‐Bga. She had received a transfusion 10 days previously. Before further transfusion was begun, antibody identification revealed weak nonspecific reactions, which were thought to be HLA antibodies. She developed acute hemolysis during RBC exchange for acute chest syndrome; anti‐Doa was identified in both the serum and eluate. She received 2 units of Do(a‐) RBCs without complication. Patient 3 was a 35‐year‐old woman with known anti‐C, ‐E, ‐K, ‐Fya, and ‐ N and a warm autoantibody. Two weeks after transfusion, she had a delayed hemolytic transfusion reaction coincident with the identification of anti‐Doa. Patient 4 was a 33‐year‐old woman with known anti‐C, ‐V, ‐K, ‐Fya, ‐Fy3, Jkb, ‐S, ‐N, and ‐Ytb, who developed anti‐Doa 8 weeks after transfusion. CONCLUSION: An association of Dombrock blood group system antibodies with hemolytic reactions is demonstrated in alloimmunized sickle cell disease patients. In all four cases, identification of Dombrock system antibodies was delayed because high‐titer low‐avidity antibodies, HLA antibodies, or autoantibodies were thought to explain the serologic findings. The presence of Dombrock system antibodies should be considered when unexplained serologic reactivity occurs during antibody identification in this population.
Macro- and Microstructural Magnetic Resonance Imaging Indices Associated With Diabetes Among Community-Dwelling Older Adults

OBJECTIVE To better understand the association between diabetes and cognitive impairment, we evaluated macro- and microstructural brain MRI measures for the total brain and regions of interest (ROIs) in a group of community-dwelling elders with and without diabetes. RESEARCH DESIGN AND METHODS MRI measures were obtained on 308 elders (mean age 83.3 years; n = 85 with diabetes) from the Health ABC Healthy Brain Substudy. We performed a series of linear regressions and used standardized β values to estimate the cross-sectional association between diabetes and macrostructural (gray matter volume [GMV] and white matter hyperintensities [WMHs]) and microstructural (mean diffusivity [MD] and fractional anisotropy [FA]) measures for the total brain and ROIs. Models were adjusted for age, race, and sex; GMV values for ROIs were also adjusted for total brain volume (TBV). RESULTS In multivariate-adjusted models, diabetes was associated with lower total GMV (P = 0.0006), GMV in the putamen (P = 0.02 for left and right), and TBV (P = 0.04) and greater cerebral atrophy (P = 0.02). There was no association with WMHs. On microstructural measures, diabetes was associated with reduced FA for total white matter (P = 0.006) and greater MD for the hippocampus (P = 0.006 left; P = 0.01 right), dorsolateral prefrontal cortex (P = 0.0007, left; P = 0.002, right), left posterior cingulate (P = 0.02), and right putamen (P = 0.02). Further adjustment for stroke, hypertension, and myocardial infarction produced similar results. CONCLUSIONS In this cross-sectional study, elders with diabetes compared with those without had greater brain atrophy and early signs of neurodegeneration. Further studies are needed to determine whether these structural changes associated with diabetes predict risk of cognitive decline.