Miracle-dz/UniFAR-FTUs huggingface dataset:
CD25+ FoxP3+ Memory CD4 T Cells Are Frequent Targets of HIV Infection In Vivo

ABSTRACT Interleukin 2 (IL-2) signaling through the IL-2 receptor alpha chain (CD25) facilitates HIV replication in vitro and facilitates homeostatic proliferation of CD25+ FoxP3+ CD4+ T cells. CD25+ FoxP3+ CD4+ T cells may therefore constitute a suitable subset for HIV infection and plasma virion production. CD25+ FoxP3+ CD4+ T cell frequencies, absolute numbers, and the expression of CCR5 and cell cycle marker Ki67 were studied in peripheral blood from HIV+ and HIV− study volunteers. Different memory CD4+ T cell subsets were then sorted for quantification of cell-associated HIV DNA and phylogenetic analyses of the highly variable EnvV1V3 region in comparison to plasma-derived virus sequences. In HIV+ subjects, 51% (median) of CD25+ FoxP3+ CD4+ T cells expressed the HIV coreceptor CCR5. Very high frequencies of Ki67+ cells were detected in CD25+ FoxP3+ memory CD4+ T cells (median, 27.6%) in comparison to CD25− FoxP3− memory CD4+ T cells (median, 4.1%; P < 0.0001). HIV DNA content was 15-fold higher in CD25+ FoxP3+ memory CD4+ T cells than in CD25− FoxP3− T cells (P = 0.003). EnvV1V3 sequences derived from CD25+ FoxP3+ memory CD4+ T cells did not preferentially cluster with plasma-derived sequences. Quasi-identical cell-plasma sequence pairs were rare, and their proportion decreased with the estimated HIV infection duration. These data suggest that specific cellular characteristics of CD25+ FoxP3+ memory CD4+ T cells might facilitate efficient HIV infection in vivo and passage of HIV DNA to cell progeny in the absence of active viral replication. The contribution of this cell population to plasma virion production remains unclear. IMPORTANCE Despite recent advances in the understanding of AIDS virus pathogenesis, which cell subsets support HIV infection and replication in vivo is incompletely understood. In vitro, the IL-2 signaling pathway and IL-2-dependent cell cycle induction are essential for HIV infection of stimulated T cells. CD25+ FoxP3+ memory CD4 T cells, often referred to as regulatory CD4 T cells, depend on IL-2 signaling for homeostatic proliferation in vivo. Our results show that CD25+ FoxP3+ memory CD4+ T cells often express the HIV coreceptor CCR5, are significantly more proliferative, and contain more HIV DNA than CD25− FoxP3− memory CD4 T cell subsets. The specific cellular characteristics of CD25+ FoxP3+ memory CD4+ T cells probably facilitate efficient HIV infection in vivo and passage of HIV DNA to cell progeny in the absence of active viral replication. However, the contribution of this cell subset to plasma viremia remains unclear.
Mechanism of atrioventricular nodal facilitation in rabbit heart: role of proximal AV node.

The phenomenon of atrioventricular (AV) nodal "facilitation," described in traditional "black box"-functional studies, implies enhanced AV nodal dromotropic function. We investigated the role of atrial prematurities in the modulation of the nodal cellular responses in the mechanism of AV nodal facilitation. Atrial and His (H) bundle electrograms and microelectrode recordings from proximal AV nodal cells were analyzed in 15 superfused rabbit AV node preparations. The pacing protocol consisted of 30 basic beats (S1; coupling interval S1-S1= 300 ms) followed by a facilitating prematurity (S2; coupling intervals S1-S2of 300, 200, 150, and 130 ms) followed by the test beat (S3; coupling interval S2-S3scanned in 5-ms steps). Conduction curves (S2-H2vs. S1-S2, S3-H3vs. S2-S3, and S3-H3vs. H2-S3) were constructed. Facilitation (i.e., shortening of S3-H3when S1-S2was shortened) was demonstrated in all preparations using the H2-S3( P < 0.001) but not the S2-S3format. Microelectrode recordings revealed a causal relationship between the improved proximal AV nodal cellular responses in facilitation and the prolonged S2-S3interval. There was no evidence for enhanced nodal dromotropic function directly resulting from the introduction of the facilitating beats. Thus facilitation is based on inherent cycle-length-dependent properties of the AV node during application of a complex pacing protocol and primarily reflects the uncontrolled modulation of the proximal cellular response.
Cathepsin S Controls the Trafficking and Maturation of Mhc Class II Molecules in Dendritic Cells

Before a class II molecule can be loaded with antigenic material and reach the surface to engage CD4+ T cells, its chaperone, the class II-associated invariant chain (Ii), is degraded in a stepwise fashion by proteases in endocytic compartments. We have dissected the role of cathepsin S (CatS) in the trafficking and maturation of class II molecules by combining the use of dendritic cells (DC) from CatS−/− mice with a new active site–directed probe for direct visualization of active CatS. Our data demonstrate that CatS is active along the entire endocytic route, and that cleavage of the lysosomal sorting signal of Ii by CatS can occur there in mature DC. Genetic disruption of CatS dramatically reduces the flow of class II molecules to the cell surface. In CatS−/− DC, the bulk of major histocompatibility complex (MHC) class II molecules is retained in late endocytic compartments, although paradoxically, surface expression of class II is largely unaffected. The greatly diminished but continuous flow of class II molecules to the cell surface, in conjunction with their long half-life, can account for the latter observation. We conclude that in DC, CatS is a major determinant in the regulation of intracellular trafficking of MHC class II molecules.
My favourite things to do and my favourite people : Using draw-and-write to discover salient aspects of children’s self-concept

This study explores the potential of the ‘draw-and-write’ method for inviting children to communicate salient aspects of their self-concept. Irish primary school children aged 10-13 years drew and wrote about their favourite people and things to do (social and active self). Children drew and described many salient activities (39 in total) and people – including pets. Results suggest that widely-used, adult-constructed self-esteem scales for children, while multi-dimensional, are limited, and that ‘draw-and-write’ is an effective multimodal method with which children can express their social and active self-concepts.
UvA-DARE (

Generative ﬂows are attractive because they admit exact likelihood optimization and efﬁcient image synthesis. Recently, Kingma & Dhariwal (2018) demonstrated with Glow that generative ﬂows are capable of generating high quality images. We generalize the 1 × 1 convolutions proposed in Glow to invertible d × d convolutions, which are more ﬂexible since they operate on both channel and spatial axes. We propose two methods to produce invertible convolutions that have receptive ﬁelds identical to standard convolutions: Emerging convolutions are obtained by chaining speciﬁc autoregressive convolutions, and periodic convolutions are decoupled in the frequency domain. Our experiments show that the ﬂexibility of d × d convolutions signiﬁcantly improves the performance of generative ﬂow models on galaxy images, CIFAR10 and ImageNet.
Disentangling scatter in long-term concentration–discharge relationships: the role of event types

Abstract. Relationships between nitrate concentrations and discharge rates (C–Q) at the catchment outlet can provide insights into sources, mobilization and biogeochemical transformations of nitrate within the catchment. Nitrate C–Q relationships often exhibit considerable scatter that might be related to variable hydrologic conditions during runoff events at sampling time, corresponding to variable sources and flow paths despite similar discharge (Q) rates. Although previous studies investigated the origins of this scatter in individual or in a few catchments, the role of different runoff event types across a large set of catchments is not yet fully understood. This study combines a hydrological runoff event classification framework with low-frequency nitrate samples in 184 catchments to explore the role of different runoff events in shaping long-term C–Q relationships and their variability across contrasting catchments. In most of the catchments, snow-impacted events produce positive deviations of concentrations, indicating an increased nitrate mobilization compared to the long-term pattern. In contrast, negative deviations occur mostly for rainfall-induced events with dry antecedent conditions, indicating the occurrence of lower nitrate concentrations (C) in river flows than their long-term pattern values during this type of event. Pronounced differences in event runoff coefficients among different event types indicate their contrasting levels of hydrologic connectivity that in turn might play a key role in controlling nitrate transport due to the activation of faster flow paths between sources and streams. Using long-term, low-frequency nitrate data, we demonstrate that runoff event types shape observed scatter in long-term C–Q relationships according to their level of hydrologic connectivity. In addition, we hypothesize that the level of biogeochemical attenuation of catchments can partially explain the spatial variability of the scatter during different event types.
Disentangling Scatter in Long-Term Concentration-Discharge Relationships: the Role of Event Types

Low-frequency data combined with runoff event classification in a large number of contrasting catchments Abstract L17 revised manuscript: “This study combines a hydrological runoff event classification framework with low-frequency nitrate samples in 184 catchments to explore the role of different runoff events in shaping long-term C-Q relationships and their variability across contrasting catchments. “
Comparison of Methods for the Measurement of Piezoelectric Coefficients

The charge constant of piezoelectric material is one of the crucial constant values. At the present time, the measurement of this value is mostly realized by means of three techniques: the frequency method, the laser interferometer technique, and the quasi-static method. These techniques have been practically applied to piezoelectric ceramic samples. Our paper presents comparison of the individual methods with regard to their accuracy and the demands placed on the instrumentation and preparation of the piezoelectric material samples. A “soft” ceramic product marketed under the production code of NCE51 was used in the experiments. The methods are described in detail, including the process of sample preparation, description of the experiments, and procedure of calculating coefficients from the measured values.
The key role of crevasse splays in prograding river systems: Analysis of evolving floodplain accommodation and its implications for architecture and reservoir potential

A generic life cycle applies to crevasse splays in non-degradational fluvial systems, typically ending in healing and abandonment. Crevasse-splay channels adjust to a graded equilibrium profile through proximal erosion and distal deposition, with their distal termini acting as a (prograding) local base level. When proximal incision advances to below the maximum flooding level, a reflux of floodwater occurs during the waning stage of flooding. The resultant decrease in gradient ultimately leads to the backfilling and abandonment of a crevasse splay, provided that the elevation at its distal fringe remains higher than that of the trunk channel floor. Consecutive crevasse splays form an alluvial ridge through lateral amalgamation and subsequent vertical stacking, perching the active river above the surrounding floodplain. Superelevation of the channel thalweg above the distal termini of a prograding crevasse splay leads to avulsion. A high-resolution morphological reconstruction of both the active (and recently abandoned) river(s) and the surrounding floodplain has been established to test the proposed life cycle of crevasse splays and evaluate its role in autogenic avulsion and organisation of the fluvial system. An avulsion can only occur when an overbank path of steepest descent reaches the system base level in a shorter distance (which may partially reuse the existing channel or remnant channel depressions) than the along-channel distance to its terminus. Crevasse splays prograde along this overbank flow path and capture an increasing portion of the total discharge, accelerating their development. When the crevasse apex incises down to or below its trunk channel thalweg, the avulsion is complete. The overbank path of steepest descent (i.e., avulsion path) is governed by floodplain topography, which is largely formed of abandoned alluvial ridges. This leads to compensational stacking of successive prograding channel belts, resulting in fan of amalgamated ridges.
Preferential Elimination of Older Erythrocytes in Circulation and Depressed Bone Marrow Erythropoietic Activity Contribute to Cadmium Induced Anemia in Mice

Feeding cadmium chloride (50 or 1000 ppm CdCl2 in drinking water, ad libitum) to C57BL/6 mice resulted in a significant and sustained fall in blood erythrocyte count and hemoglobin levels that started 4 and 3 weeks after the start of 50 and 1000 ppm cadmium doses respectively. A transient yet significant reticulocytosis occurred during the first 4 weeks of cadmium treatment. Using the recently developed double in vivo biotinylation (DIB) technique, turnover of erythrocyte cohorts of different age groups was simultaneously monitored in control and cadmium treated mice. A significant accumulation of younger erythrocytes and a concomitant decline in the relative proportions of older erythrocytes in circulation was observed in both 50 and 1000 ppm cadmium groups indicating that older erythrocytes were preferentially eliminated in cadmium induced anemia. A significant increase in the erythropoietin levels in plasma was seen in mice exposed to 1000 ppm cadmium. Levels of inflammatory cytokines (IL1A, IL6, TNFα, IFNγ) were however not significantly altered in cadmium treated mice. A significant increase in cellular levels of reactive oxygen species (ROS) was observed in older erythrocytes in circulation but not in younger erythrocytes. Erythropoietic activity in the bone marrows and spleens of cadmium treated mice was examined by monitoring the relative proportion of cells belonging to the erythroid line of differentiation in these organs. Erythroid cells in bone marrow declined markedly (about 30%) in mice in the 1000 ppm cadmium group but the decline was not significant in the 50 ppm cadmium group. Cells representing various stages of erythroid differentiation in bone marrow and spleen were enumerated flow cytometrically by double staining with anti-Ter119 and anti-transferrin receptor (CD71) monoclonal antibodies. Decline of erythroid cells was essentially confined to pro-erythroblast and erythroblast-A, along with a concurrent increase in the splenic erythroid population indicating a stress response. In short cadmium exposure causes preferential clearance of older erythrocytes from circulation along with a depressed erythropoietic activity at higher doses.
Automatic Spike Sorting Using Tuning Information

Abstract Current spike sorting methods focus on clustering neurons' characteristic spike waveforms. The resulting spike-sorted data are typically used to estimate how covariates of interest modulate the firing rates of neurons. However, when these covariates do modulate the firing rates, they provide information about spikes' identities, which thus far have been ignored for the purpose of spike sorting. This letter describes a novel approach to spike sorting, which incorporates both waveform information and tuning information obtained from the modulation of firing rates. Because it efficiently uses all the available information, this spike sorter yields lower spike misclassification rates than traditional automatic spike sorters. This theoretical result is verified empirically on several examples. The proposed method does not require additional assumptions; only its implementation is different. It essentially consists of performing spike sorting and tuning estimation simultaneously rather than sequentially, as is currently done. We used an expectation-maximization maximum likelihood algorithm to implement the new spike sorter. We present the general form of this algorithm and provide a detailed implementable version under the assumptions that neurons are independent and spike according to Poisson processes. Finally, we uncover a systematic flaw of spike sorting based on waveform information only.
Initial Public Offerings: An Analysis of Theory and Practice

We survey 336 chief financial officers (CFOs) to compare practice to theory in the areas of initial public offering (IPO) motivation, timing, underwriter selection, underpricing, signaling, and the decision to remain private. We find the primary motivation for going public is to facilitate acquisitions. CFOs base IPO timing on overall market conditions, are well informed regarding expected underpricing, and feel underpricing compensates investors for taking risk. The most important positive signal is past historical earnings, followed by underwriter certification. CFOs have divergent opinions about the IPO process depending on firm-specific characteristics. Finally, we find the main reason for remaining private is to preserve decision-making control and ownership. GREAT EFFORT, THEORETICAL AND EMPIRICAL, has been made to understand managerial decision-making in the initial public offering (IPO) process. Most empirical IPO research relies on publicly available stock return data or data contained in Securities and Exchange Commission (SEC) filings. In this study we extend the IPO literature by analyzing unique data from surveys of chief financial officers (CFOs) to compare CFO perspectives to prevailing academic theory. Specifically, we examine the following seven issues: motivations for going public, timing of the IPO, underwriter selection, underpricing, signaling, IPO process issues, and the decision to stay private. We survey three subsamples of firms, namely, those that successfully completed an IPO, those that began the process but chose to withdraw the issue, and those that are large enough to go public, but have not attempted an IPO.
Effects of rosuvastatin and atorvastatin compared over 52 weeks of treatment in patients with hypercholesterolemia.

BACKGROUND Despite the demonstrated benefits of low-density lipoprotein cholesterol (LDL-C) reduction in reducing the risk of coronary heart disease, many patients receiving lipid-lowering therapy fail to achieve LDL-C goals. We compared the effects of rosuvastatin and atorvastatin in reducing LDL-C and achieving LDL-C goals in patients with primary hypercholesterolemia. METHODS AND RESULTS In this 52-week, randomized, double-blind, multicenter trial (4522IL/0026), 412 patients with LDL-C 160 to <250 mg/dL received a 5-mg dose of rosuvastatin (n = 138), a 10-mg dose of rosuvastatin (n = 134), or a 10-mg dose of atorvastatin (n = 140) for 12 weeks; during the following 40 weeks, dosages could be sequentially doubled up to 80 mg if National Cholesterol Education Program Adult Treatment Panel II (ATP-II) LDL-C goals were not achieved. At 12 weeks, 5- and 10-mg doses of rosuvastatin were associated with significantly greater LDL-C reductions than 10-mg doses of atorvastatin (46% and 50% vs 39%, both P <.001). At 12 weeks, both rosuvastatin dosages brought more patients to within ATP-II and European LDL-C goals than atorvastatin (86% and 89% vs 73% and 75%, and 86% vs 55%, respectively). At 52 weeks, compared with atorvastatin, both initial rosuvastatin treatment groups significantly reduced LDL-C (47% and 53% vs 44%, P <.05 and P <.001). Overall, more patients in the initial rosuvastatin 10-mg group achieved their ATP-II LDL-C goal than those in the initial atorvastatin 10-mg group (98% vs 87%), with 82% of patients treated with rosuvastatin achieving their goal at the 10-mg starting dosage without the need for titration, compared with 59% of patients treated with atorvastatin. Both treatments were well tolerated over 52 weeks. CONCLUSION Compared with atorvastatin, rosuvastatin produced greater reductions in LDL-C, which may offer advantages in LDL-C goal attainment over existing lipid-lowering therapies.
Proteomic profiling of oil bodies isolated from the unicellular green microalga Chlamydomonas reinhardtii: With focus on proteins involved in lipid metabolism

Oil bodies are sites of energy and carbon storage in many organisms including microalgae. As a step toward deciphering oil accumulation mechanisms in algae, we used proteomics to analyze purified oil bodies from the model microalga Chlamydomonas reinhardtii grown under nitrogen deprivation. Among the 248 proteins (≥2 peptides) identified by LC‐MS/MS, 33 were putatively involved in the metabolism of lipids (mostly acyl‐lipids and sterols). Compared with a recently reported Chlamydomonas oil body proteome, 19 new proteins of lipid metabolism were identified, spanning the key steps of the triacylglycerol synthesis pathway and including a glycerol‐3‐phosphate acyltransferase (GPAT), a lysophosphatidic acid acyltransferase (LPAT) and a putative phospholipid:diacylglycerol acyltransferase (PDAT). In addition, proteins putatively involved in deacylation/reacylation, sterol synthesis, lipid signaling and lipid trafficking were found to be associated with the oil body fraction. This data set thus provides evidence that Chlamydomonas oil bodies are not only storage compartments but also are dynamic structures likely to be involved in processes such as oil synthesis, degradation and lipid homeostasis. The proteins identified here should provide useful targets for genetic studies aiming at increasing our understanding of triacyglycerol synthesis and the role of oil bodies in microalgal cell functions.
Finger Length Ratio (2D:4D) and Dimensions of Sexual Orientation

Background: It has been suggested that both adult sexual orientation and the 2nd to 4th finger length ratio (2D:4D) are influenced by prenatal testosterone levels. Bearing this in mind, 2D:4D has been tested as a proxy measure of the putative prenatal testosterone impact on adult human homosexuality, but the results are inconsistent. To date, most studies in this field of research comprise categorical group comparison of heterosexuals and homosexuals with respect to their 2D:4D. Aims: The purpose of our study was to evaluate 2D:4D and the dimensional perspective of sexual orientation in addition to categorical results. Methods: We examined a community-based sample of 409 subjects and calculated correlations of 2D:4D and sexual orientation as a continuum ranging from homosexual to heterosexual. Results: We found a significant negative correlation of 2D:4D with homosexual orientation (fantasy, attraction, activity and general score) in women, but not in men. Conclusions: Our results indicate that with higher prenatal testosterone levels in women, the likelihood of homosexual orientation might increase. We hypothesize a continuous neurohormonal sexual differentiation of the brain, most notably for women, that overrides categories and results in varying dimensions of sexual orientation. This hypothesis contrasts with the predominant suggestion of fixed organizational effects of androgens in the brain and a categorical sexual orientation.