Miracle-dz/UniFAR-FTUs huggingface dataset:
The N-Terminal Propeptide of Type III Procollagen in Patients with Acute Coronary Syndrome: A Link between Left Ventricular End-Diastolic Pressure and Cardiovascular Events

Background Despite the usefulness of N-terminal propeptide of type III procollagen (PIIINP) in detecting enhanced collagen turnover in patients with congestive heart failure, the value added by PIIINP to the use of clinical variables and echocardiography in relation to directly measured left ventricular (LV) end-diastolic pressure (EDP) and the outcome of acute coronary syndrome (ACS) has not been clearly defined. Methods and Results This study involved 168 adult patients with ACS, who underwent echocardiography, measurement of serum PIIINP levels, and cardiac catheterization. Pulsed wave tissue Doppler imaging (PWTDI), which revealed mean peak systolic (s′), early (e′), and late diastolic (a′) velocities, was carried out and the eas index of LV function was evaluated: e′/(a′×s′). The patients were divided into three study groups based on the degree of LVEDP – normal (<16 mmHg), intermediate (16–30 mmHg), and high (>30 mmHg) LVEDP. All patients were followed-up to determine cardiac-related death and revascularization. Patients with high LVEDP had significantly more PIIINP than those with intermediate or normal LVEDP (all post hoc p<0.05). The presence of coronary artery disease, the left atrial volume index (LAVI), the ratio of transmitral early and late diastolic flow velocities, a′, and the eas index were significantly correlated with LVEDP. According to multiple stepwise analysis, PIIINP, LAVI and the eas index were the three independent predictors of the level of LVEDP (PIIINP, p <0.001; LAVI, p = 0.007; eas index, p = 0.021). During follow-up (median, 24 months), 32 participants suffered from cardiac events, PIIINP and LAVI were significant predictors of cardiac mortality and hospitalization (PIIINP, hazard ratio (HR) 2.589, p = 0.002; LAVI, HR 1.040, p = 0.027). Conclusions PIIINP is a highly effective means to evaluate LVEDP in patients with ACS. The PIIINP is also correlated with cardiac mortality and revascularization, providing an additional means of evaluating and managing patients with ACS.
Climate change in the oceans: evolutionary versus phenotypically plastic responses of marine animals and plants

I summarize marine studies on plastic versus adaptive responses to global change. Due to the lack of time series, this review focuses largely on the potential for adaptive evolution in marine animals and plants. The approaches were mainly synchronic comparisons of phenotypically divergent populations, substituting spatial contrasts in temperature or CO2 environments for temporal changes, or in assessments of adaptive genetic diversity within populations for traits important under global change. The available literature is biased towards gastropods, crustaceans, cnidarians and macroalgae. Focal traits were mostly environmental tolerances, which correspond to phenotypic buffering, a plasticity type that maintains a functional phenotype despite external disturbance. Almost all studies address coastal species that are already today exposed to fluctuations in temperature, pH and oxygen levels. Recommendations for future research include (i) initiation and analyses of observational and experimental temporal studies encompassing diverse phenotypic traits (including diapausing cues, dispersal traits, reproductive timing, morphology) (ii) quantification of nongenetic trans‐generational effects along with components of additive genetic variance (iii) adaptive changes in microbe–host associations under the holobiont model in response to global change (iv) evolution of plasticity patterns under increasingly fluctuating environments and extreme conditions and (v) joint consideration of demography and evolutionary adaptation in evolutionary rescue approaches.
Induction of interferon gamma production by natural killer cell stimulatory factor: characterization of the responder cells and synergy with other inducers

We previously reported that natural killer cell stimulatory factor (NKSF), a heterodimeric lymphokine purified from the conditioned medium of human B lymphoblastoid cell lines, induces interferon gamma (IFN- gamma) production from resting peripheral blood lymphocytes (PBL) and synergizes with interleukin 2 in this activity. In this study, we show that human NKSF induces IFN-gamma production from both resting and activated human PBL and from freshly isolated murine splenocytes. Human T and NK cells produce IFN-gamma in response to NKSF, but resting PBL require the presence of nonadherent human histocompatibility leukocyte antigens DR+ (HLA-DR+) accessory cells to respond to NKSF. The mechanism(s) by which NKSF induces IFN-gamma production results in accumulation of IFN-gamma mRNA, is insensitive to cyclosporin A, and synergizes with those mediated by phytohemagglutinin, phorbol diesters, anti-CD3 antibodies, and allogeneic antigens, but not by Ca2+ ionophores. The ability of NKSF to directly induce IFN-gamma production and to synergize with other physiological IFN-gamma inducers, joined with the previously described ability to enhance lymphocyte cytotoxicity and proliferation, indicates that this lymphokine is a powerful immunopotentiating agent.
RAPID WATER FLOW AND TRANSPORT OF INORGANIC AND ORGANIC NITROGEN IN A HIGHLY AGGREGATED TROPICAL SOIL

Microaggregated tropical soils have shown high water conductivity even under unsaturated conditions in laboratory experiments. It is not clear, however, what depth the infiltrating soil water reaches during storm events under humid tropical conditions and how this relates to losses of N by leaching. Dynamics and fluxes of water and applied 15N were determined with high temporal resolution to a depth of 5 m in a Xanthic Hapludox of central Amazonia, Brazil. The soil water percolated to a depth of 0.9 m within 2 h of a rainfall event of 48 mm. Water fluxes were significantly slower below 0.9 m (17% of infiltration at 0–0.9 m) due to higher bulk densities. Percolation not only started rapidly after a rainfall event when soil water suction reached a certain threshold (ca. 20–30 hPa) but was also reduced to background levels less than 1 h after the rain had ended. Traces of labeled N reached 5 m within a few days, and 15N maintained high levels to a depth of 1.2 m throughout the rainy season. Organic N was a large proportion (36–44%) of the total N leaching and the proportion increased with depth. However, organic N percolated more slowly than nitrate. The demonstrated extreme short-term dynamics of water fluxes have implications for measurement design of water availability and solute leaching in microaggregated tropical soil that require correct time integrals of solution concentrations and soil water dynamics. Measurement intervals of 30 min or less were necessary in our study. Rapid water flows explain the observed high N losses from the topsoil of microaggregated tropical soil and the large nitrate accumulation in the deep soil to a depth of at least 5 m.
1000 Genomes Selection Browser 1.0: a genome browser dedicated to signatures of natural selection in modern humans

Searching for Darwinian selection in natural populations has been the focus of a multitude of studies over the last decades. Here we present the 1000 Genomes Selection Browser 1.0 (http://hsb.upf.edu) as a resource for signatures of recent natural selection in modern humans. We have implemented and applied a large number of neutrality tests as well as summary statistics informative for the action of selection such as Tajima’s D, CLR, Fay and Wu’s H, Fu and Li’s F* and D*, XPEHH, ΔiHH, iHS, FST, ΔDAF and XPCLR among others to low coverage sequencing data from the 1000 genomes project (Phase 1; release April 2012). We have implemented a publicly available genome-wide browser to communicate the results from three different populations of West African, Northern European and East Asian ancestry (YRI, CEU, CHB). Information is provided in UCSC-style format to facilitate the integration with the rich UCSC browser tracks and an access page is provided with instructions and for convenient visualization. We believe that this expandable resource will facilitate the interpretation of signals of selection on different temporal, geographical and genomic scales.
Face processing in humans is compatible with a simple shape–based model of vision

Understanding how the human visual system recognizes objects is one of the key challenges in neuroscience. Inspired by a large body of physiological evidence, a general class of recognition models has emerged, which is based on a hierarchical organization of visual processing, with succeeding stages being sensitive to image features of increasing complexity. However, these models appear to be incompatible with some well–known psychophysical results. Prominent among these are experiments investigating recognition impairments caused by vertical inversion of images, especially those of faces. It has been reported that faces that differ ‘featurally’ are much easier to distinguish when inverted than those that differ ‘configurally’; a finding that is difficult to reconcile with the physiological models. Here, we show that after controlling for subjects' expectations, there is no difference between ‘featurally’ and ‘configurally’ transformed faces in terms of inversion effect. This result reinforces the plausibility of simple hierarchical models of object representation and recognition in the cortex.
HER-2/neu status of primary breast cancer and corresponding metastatic sites in patients with advanced breast cancer treated with trastuzumab-based therapy.

BACKGROUND The aim of this prospective study was to investigate whether there were changes in HER-2/neu status in newly-developed metastatic lesions following treatment with trastuzumab in advanced breast cancer patients overexpressing HER-2/neu. The utility of serological assays for HER-2/neu in such patients was also studied. PATIENTS AND METHODS Sixteen patients with HER-2/neu-overexpressing tumors (15 were 3+ by immunohistochemistry (IHC) and one 2+ by IHC and positive by the chromogenic in situ hybridization (CISH) test) were included in the study. Fourteen patients underwent biopsy and 2 patients fine-needle aspiration (FNA) of newly-developed metastatic lesions following trastuzumab treatment. All samples were assayed for HER-2 by IHC and by the CISH test. Serial serum HER-2/neu (S-HER-2) levels were measured prior to (baseline values) and during trastuzumab-based treatment by enzyme-linked immunosorbent assay (ELISA) (cut-off point: 10 ng/ml) in all patients. The patients were divided into 2 groups: those with "altered HER-2/neu status" and those with "conserved HER-2/neu status" in the metastatic region. RESULTS Six out of the 16 (37%) ("altered HER-2/neu status") newly-developed metastatic lesions lost their HER-2/neu overexpression and scored 0 or +1 by IHC or negative on the CISH test, while in the remaining cases (10/16, 62.5%) ("conserved HER-2/neu status"), the HER-2/neu status was unchanged (+3 by IHC or a positive CISH test). Baseline S-HER-2 levels were elevated in 5 out of 16 patients (3 of "altered HER-2/neu status", 2 of "conserved HER-2/neu status"). The serum HER-2 (S-HER-2) levels declined and returned within the normal ranges in all these 5 patients as a response to trastuzumab treatment. Following the disease progression, the S-HER-2 levels of the 3 patients with "altered HER-2/neu status" remained normal, while those of 2 with "conserved HER-2/neu status" increased. There was no statistically significant difference in the number of chemotherapeutic treatments or the median time of treatment with trastuzumab or chemotherapy between the 2 groups. Time to tumor progression (TTP) was significantly shorter in the "altered HER-2/neu status" patients (median TTP for "altered HER-2/neu status": 9.5 months, and for "conserved HER-2/neu status": 12 months; p <0.001). CONCLUSION These data suggest that, for most patients with metastatic breast cancer treated with trastuzumab, the HER-2/neu expression as measured by IHC and/or CISH in newly-developed metastatic lesions was unchanged. However, a remarkable percentage of cases lost HER-2/neu overexpression. It is not clear whether this finding implies resistance or sensitivity to trastuzumab.
Analytical and experimental investigation of cracking in two-way reinforced concrete panels

In this study, the cracking behaviour of RC panels under a two-way loading condition is investigated analytically and experimentally. A modified FE bond layer model is introduced and shown to be much simpler to define, and yet, more accurate than perfect bond or link element bond models. FE analysis suggests a bi-linear curve for approximating the distribution of bond stresses at stabilized cracking. Several FE parametric studies are performed on a one-way tension member to obtain peak shear bond stresses, concrete tensile stresses due to internal restrained shrinkage, splitting tensile stresses caused by radial bond stresses, and the reduction in bond strength caused by longitudinal splitting cracks. The FE analysis of flexural beams suggests a new factor for estimation of the depth of effective tension area, which is defined through FE parametric study. In the experimental phase, three medium-scale RC panels are subjected to direct tension in one direction and bending in the perpendicular direction. The collected data consist of applied loads, steel and concrete stresses, crack propagation sequence, crack pattern, crack width, total elongation, and leakage observations. The crack pattern is mainly influenced by the shape of reinforcement mesh due to the presence of splitting tensile stresses. The formation of diagonal cracks depends on principal stresses that can be influenced by reinforcement ratio, ratio of loads in two directions, and clear concrete cover to bar diameter ratio. The bond strength is significantly weakened by the formation of orthogonal cracks along reinforcing bars. The crack width is increased under repeated loading especially at the first cycle. Residual crack widths remain in place even after complete unloading. Observations indicate that the water leakage is influenced by the crack width gradient. Finally, it is shown that one-way crack prediction models underestimate the crack width of two-way panels. A new set of analytical equations is developed for the prediction of cracking load, minimum and maximum spacing of cracks, and maximum crack width in a two-way panel. These equations are shown to predict the cracking behaviour of the tested panels more accurately than any other previously proposed model.
Paracrine Regulation of Angiogenesis and Adipocyte Differentiation During In Vivo Adipogenesis

Abstract— With an increasing incidence of obesity worldwide, rational strategies are needed to control adipogenesis. Growth of any tissue requires the formation of a functional and mature vasculature. To gain mechanistic insight into the link between active adipogenesis and angiogenesis, we developed a model to visualize noninvasively and in real time both angiogenesis and adipogenesis using intravital microscopy. Implanted murine preadipocytes induced vigorous angiogenesis and formed fat pads in a mouse dorsal skin-fold chamber. The newly formed vessels subsequently remodeled into a mature network consisting of arterioles, capillaries, and venules, whereas the preadipocytes differentiated into adipocytes as confirmed by increased aP2 expression. Inhibition of adipocyte differentiation by transfection of preadipocytes with a peroxisome proliferator-activated receptor &ggr; dominant-negative construct not only abrogated fat tissue formation but also reduced angiogenesis. Surprisingly, inhibition of angiogenesis by vascular endothelial growth factor receptor-2 (VEGFR2) blocking antibody not only reduced angiogenesis and tissue growth but also inhibited preadipocyte differentiation. We found that part of this inhibition stems from the paracrine interaction between endothelial cells and preadipocytes and that VEGF–VEGFR2 signaling in endothelial cells, but not preadipocytes, mediates this process. These findings reveal a reciprocal regulation of adipogenesis and angiogenesis, and suggest that blockade of VEGF signaling can inhibit in vivo adipose tissue formation. The full text of this article is available online at http://www.circresaha. org.
An Introduction to Collective Intelligence

This paper surveys the emerging science of how to design a “COllective INtelligence” (COIN). A COIN is a large multi-agent system where: i) There is little to no centralized communication or control. ii) There is a provided world utility function that rates the possible histories of the full system. In particular, we are interested in COINs in which each agent runs a reinforcement learning (RL) algorithm. The conventional approach to designing large distributed systems to optimize a world utility does not use agents running RL algorithms. Rather, that approach begins with explicit modeling of the dynamics of the overall system, followed by detailed hand-tuning of the interactions between the components to ensure that they “cooperate” as far as the world utility is concerned. This approach is labor-intensive, often results in highly nonrobust systems, and usually results in design techniques that have limited applicability. In contrast, we wish to solve the COIN design problem implicitly, via the “adaptive” character of the RL algorithms of each of the agents. This approach introduces an entirely new, profound design problem: Assuming the RL algorithms are able to achieve high rewards, what reward functions for the individual agents will, when pursued by those agents, result in high world utility? In other words, what reward functions will best ensure that we do not have phenomena like the tragedy of the commons, Braess’s paradox, or the liquidity trap? Although still very young, research specifically concentrating on the COIN design problem has already resulted in successes in artificial domains, in particular in packet-routing, the leader-follower problem, and in variants of Arthur’s El Farol bar problem. It is expected that as it matures and draws upon other disciplines related to COINs, this research will greatly expand the range of tasks addressable by human engineers. Moreover, in addition to drawing on them, such a fully developed science of COIN design may provide much insight into other already established scientific fields, such as economics, game theory, and population biology.
Cytosolic Phospholipase A2 Regulates TNF-Induced Production of Joint Destructive Effectors in Synoviocytes

Introduction Rheumatoid arthritis (RA) is an inflammatory disease of the joint characterized by chronic synovitis causing pain, swelling and loss of function due to destruction of cartilage and bone. The complex series of pathological events occurring in RA is largely regulated via excessive production of pro-inflammatory cytokines, the most prominent being tumor necrosis factor (TNF). The objective of this work was to elucidate possible involvement of group IVA cytosolic phospholipase A2 (cPLA2α) in TNF-induced regulation of synovitis and joint destructive effectors in RA, to evaluate the potential of cPLA2α as a future therapeutic target. Methods The involvement of cPLA2α in tumor necrosis factor (TNF)-induced intracellular signaling cascades in synoviocytes (synovial fibroblast-like cells) was analyzed by arachidonic acid (AA) release assay, synoviocyte enzyme activity assay, gene expression analysis by real-time PCR and ELISA immunoassay for the detection of prostaglandin E2 (PGE2), interleukin 8 (IL8) and stromelysin-1 (MMP3), respectively. Results Inhibitors of cPLA2α enzyme activity (AVX002, ATK) significantly reduced TNF-induced cellular release of AA, PGE2, IL8 and MMP3. This reduction was evident both at transcriptional, protein or metabolite levels. Interestingly, cPLA2α inhibition affected several key points of the arachidonyl cascade; AA-release, cyclooxygenase-2 (COX2) expression and PGE2 production. Furthermore, the results suggest that cPLA2α is subject to transcriptional auto-regulation as inhibition of cPLA2α resulted in reduced PLA2G4A gene expression in TNF-stimulated synoviocytes. Conclusions cPLA2α appears to be an important regulator of central effectors of inflammation and joint destruction, namely MMP3, IL8, COX2, and PGE2. Decreased transcription of the PLA2G4A and COX2 genes in response to cPLA2α enzyme inhibition further suggest a self-reinforcing effect of cPLA2α inhibition in response to TNF. Collectively, these results support that cPLA2α is an attractive therapeutic target candidate as its inhibition reduces the production of multiple key pro-inflammatory factors involved in RA pathogenesis.
α‐Synuclein modulation of Ca2+ signaling in human neuroblastoma (SH‐SY5Y) cells

Parkinson’s disease (PD) is characterized in part by the presence of α‐synuclein (α‐syn) rich intracellular inclusions (Lewy bodies). Mutations and multiplication of the α‐synuclein gene (SNCA) are associated with familial PD. Since Ca2+ dyshomeostasis may play an important role in the pathogenesis of PD, we used fluorimetry in fura‐2 loaded SH‐SY5Y cells to monitor Ca2+ homeostasis in cells stably transfected with either wild‐type α‐syn, the A53T mutant form, the S129D phosphomimetic mutant or with empty vector (which served as control). Voltage‐gated Ca2+ influx evoked by exposure of cells to 50 mM K+ was enhanced in cells expressing all three forms of α‐syn, an effect which was due specifically to increased Ca2+ entry via L‐type Ca2+ channels. Mobilization of Ca2+ by muscarine was not strikingly modified by any of the α‐syn forms, but they all reduced capacitative Ca2+ entry following store depletion caused either by muscarine or thapsigargin. Emptying of stores with cyclopiazonic acid caused similar rises of [Ca2+]i in all cells tested (with the exception of the S129D mutant), and mitochondrial Ca2+ content was unaffected by any form of α‐synuclein. However, only WT α‐syn transfected cells displayed significantly impaired viability. Our findings suggest that α‐syn regulates Ca2+ entry pathways and, consequently, that abnormal α‐syn levels may promote neuronal damage through dysregulation of Ca2+ homeostasis.
Translation, Validation and Reliability of the Kidney Diseases Quality of Life-Short Form (KDQOL-SF Form) Tool in Urdu.

OBJECTIVE To translate, validate and assess the reliability of kidney disease quality of life - short form (KDQOL-SF-36) in Urdu, national language of Pakistan. STUDY DESIGN Amulticentric descriptive cross-sectional study. PLACE AND DURATION OF STUDY Department of Nephrology, Mayo Hospital, Lahore, from February to July 2015. METHODOLOGY Patients of end-stage renal disease (ESRD) on maintenance hemodialysis (MHD) for more than three months, were included in the study. Patients of ESRD not on dialysis, and those with acute renal failure were excluded. The English version of KDQOL-SF-36 was translated in Urdu and then translated back in English; further validation was done by a senior professor of Punjab University, Lahore. RESULTS One hundred and thirty patients were included in the study. Fifty patients were from Mayo Hospital, 35 from Shalamar Hospital and 50 from Shaikh Zayed Hospital, Lahore. The internal consistency reliability coefficient for overall scale was 0.84. Twelve sub-scales (symptoms, effect of kidney disease, burden of kidney disease, cognitive function, quality of social interaction, sexual function, social support, physical functioning, role physical, pain, emotional well-being and role emotional) had more than 0.70 internal consistency reliability coefficient. Overall mean score of the domains i.e kidney disease component score (KDCS), physical component score (PCS), and mental component score (MCS) was 60.62 ±17.61, 43.12 ±19.54, and 49.27 ±14.52, respectively. Asignificant positive relationship was observed between KDCS and MCS domains, KDCS and PCS domains, PCS, and MCS domains. CONCLUSION The Urdu version of KDQOL-SF-36 is a reliable and valid version to measure QOLin kidney disease patients on dialysis in Pakistan.