Miracle-dz/UniFAR-FTUs huggingface dataset:
ARAP3 Functions in Hematopoietic Stem Cells

ARAP3 is a GTPase-activating protein (GAP) that inactivates Arf6 and RhoA small GTPases. ARAP3 deficiency in mice causes a sprouting angiogenic defect resulting in embryonic lethality by E11. Mice with an ARAP3 R302,303A mutation (Arap3KI/KI) that prevents activation by phosphoinositide-3-kinase (PI3K) have a similar angiogenic phenotype, although some animals survive to adulthood. Here, we report that hematopoietic stem cells (HSCs) from rare adult Arap3KI/KI bone marrow are compromised in their ability to reconstitute recipient mice and to self-renew. To elucidate the potential cell-autonomous and non-cell-autonomous roles of ARAP3 in hematopoiesis, we conditionally deleted Arap3 in hematopoietic cells and in several cell types within the HSC niche. Excision of Arap3 in hematopoietic cells using Vav1-Cre does not alter the ability of ARAP3-deficient progenitor cells to proliferate and differentiate in vitro or ARAP3-deficient HSCs to provide multi-lineage reconstitution and to undergo self-renewal in vivo. Thus, our data suggest that ARAP3 does not play a cell-autonomous role in HSPCs. Deletion of Arap3 in osteoblasts and mesenchymal stromal cells using Prx1-Cre resulted in no discernable phenotypes in hematopoietic development or HSC homeostasis in adult mice. In contrast, deletion of Arap3 using vascular endothelial cadherin (VEC or Cdh5)-driven Cre resulted in embryonic lethality, however HSCs from surviving adult mice were largely normal. Reverse transplantations into VEC-driven Arap3 conditional knockout mice revealed no discernable difference in HSC frequencies or function in comparison to control mice. Taken together, our investigation suggests that despite a critical role for ARAP3 in embryonic vascular development, its loss in endothelial cells minimally impacts HSCs in adult bone marrow.
Experimental Study of Thermal Performance of Coil in Shell Heat Exchanger

Background/Objectives: An experimental investigation and a numerical study of characteristics of heat transfer of coil in shell heat exchanger is performed. Methods/Statistical Analysis: The effects of the change in shape of tube on the heat transfer are studied here. For this, a helical coil was designed and manufactured. The difference of this study from previous ones is that the geometry of the coil is different. Existing studies used only single stretch of helical coil but in this case there are two sets of helical coil connected by a small straight tube. The heat exchanger designed is of counter follow configuration to maximize the amount of heat transferred. In the experiment, keeping constant the flow rate of shell side, the side flow rate was kept on changing and for each tube side flow rate readings were taken for different temperatures. Wilson plots were plotted for obtaining the values of convective coefficient of heat transfer. Findings: The experimental set up was validated; the values for friction factor and Nusselt number were within agreeable limits of theoretical values. A numerical study of the heat exchanger was carried out using FLUENT. Applications/Improvements: The results obtain from FLUENT supports the value obtained from the experiment.
Complete Remission with Reduction of High-Risk Clones following Haploidentical NK-Cell Therapy against MDS and AML

Purpose: To evaluate the safety, efficacy, and immunobiological correlates of allogeneic NK-cell–based therapy in primary chemotherapy-refractory or relapsed high-risk myelodysplastic syndrome (MDS), secondary AML (MDS/AML), and de novo AML patients. Experimental Design: Sixteen patients received fludarabine/cyclophosphamide conditioning combined with total lymphoid irradiation followed by adoptive immunotherapy with IL2–activated haploidentical NK cells. Results: NK-cell infusions were well-tolerated, with only transient adverse events observed in the 16 patients. Six patients achieved objective responses with complete remission (CR), marrow CR, or partial remission (PR). Five patients proceeded to allogeneic hematopoietic stem cell transplantation (HSCT). Three patients are still free from disease >3 years after treatment. All evaluable patients with objective responses (5/5 evaluable) had detectable donor NK cells at days 7/14 following infusion and displayed reduction of tumor cell clones, some of which carried poor prognosis mutations. Residual lin−CD34+CD123+CD45RA+ blast cells in responders had increased total HLA class I and HLA-E expression. Responding patients displayed less pronounced activation of CD8+ T cells and lower levels of inflammatory cytokines following NK-cell infusion. Intriguingly, despite omission of systemic IL2, all patients displayed increased frequencies of activated Ki-67+CD127−FoxP3+CD25hiCD4+ Treg cells of recipient origin following NK-cell therapy. Conclusions: Overall, this study suggests that high-risk MDS is responsive to NK-cell therapy and supports the use of haploidentical NK-cell infusions as a bridge to HSCT in refractory patients. Objective clinical responses and reduction of high-risk clones were associated with detectable donor-derived NK cells, immunoediting of residual blast cells, and less pronounced host immune activation. Clin Cancer Res; 24(8); 1834–44. ©2018 AACR.
A Framework for Video-Driven Crowd Synthesis

We present a framework for video-driven crowd synthesis. Motion vectors extracted from input crowd video are processed to compute global motion paths. These paths encode the dominant motions observed in the input video. These paths are then fed into a behavior-based crowd simulation framework, which is responsible for synthesizing crowd animations that respect the motion patterns observed in the video. Our system synthesizes 3D virtual crowds by animating virtual humans along the trajectories returned by the crowd simulation framework. We also propose a new metric for comparing the "visual similarity" between the synthesized crowd and exemplar crowd. We demonstrate the proposed approach on crowd videos collected under different settings.
Monitoring the changes to the nutrient composition of fast foods following the introduction of menu labelling in New South Wales, Australia: an observational study

Abstract Objective The present study examined the energy (kilojoule) content of Australian fast-food menu items over seven years, before and after introduction of menu board labelling, to determine the impact of the introduction of the legislation. Design Analysis of the median energy contents per serving and per 100g of fast-food menu items. Change in energy content of menu items across the years surveyed and differences in energy content of standard and limited-time only menu items were analysed. Setting Five of Australia’s largest fast food chains: Hungry Jack’s, KFC, McDonald’s, Oporto and Red Rooster. Subjects All standard and limited-time only menu items available at each fast-food chain, collected annually for seven years, 2009–2015. Results Although some fast-food chains/menu item categories had significant increases in the energy contents of their menus at some time points during the 7-year period, overall there were no significant or systematic decreases in energy following the introduction of menu labelling (P=0·19 by +17 kJ/100 g, P=0·83 by +8 kJ/serving). Limited-time only items were significantly higher in median energy content per 100 g than standard menu items (+74 kJ/100 g, P=0·002). Conclusions While reformulation across the entire Australian fast-food supply has the potential to positively influence population nutrient intake, the introduction of menu labelling legislation in New South Wales, Australia did not lead to reduced energy contents across the five fast-food chains. To encourage widespread reformulation by the fast-food industry and enhance the impact of labelling legislation, the government should work with industry to set targets for reformulation of nutrient content.
Plasma Amino-Terminal Propeptide of C-Type Natriuretic Peptide Concentration in Normal-Weight and Obese Children

Objective: In studies on the relationship between amino-terminal propeptide of C-type natriuretic peptide (NT-proCNP) concentration and height velocity in children, CNP has been implicated as an emerging new growth marker during childhood. It has been reported that besides its well-studied role in growth, plasma CNP levels are reduced in overweight and/or obese adolescents, suggesting CNP as a potential biomarker in childhood obesity. The primary goal of this study was to test this hypothesis in a Turkish population. Methods: Consent was taken from 317 children [ages 0-18 (158 girls, 159 boys)] and their parents. All subjects were physically examined; anthropometric measurements were obtained. Body mass index was calculated. During routine blood work, 1 mL extra blood was taken. Plasma NT-proCNP concentration was measured by enzyme-linked immunosorbent assay. Results: Results confirmed the previously described relationship between plasma NT-proCNP concentration and growth velocity. Plasma NT-proCNP concentration showed a negative correlation with age, weight, and height in children. Gender was not a factor that alters the age-dependent plasma NT-proCNP concentration until puberty. Conclusion: Unlike previous reports, plasma NT-proCNP concentration of overweight/obese children was not significantly lower than that of children with normal weight in age groups analyzed in a Turkish population. Thus, it is too early to conclude that CNP is a potential biomarker in childhood obesity. Further studies are necessary to address this question.
Functional Traits, Flocking Propensity, and Perceived Predation Risk in an Amazonian Understory Bird Community

Within a community, different species might share similar predation risks, and, thus, the ability of species to signal and interpret heterospecific threat information may determine species’ associations. We combined observational, experimental, and phylogenetic approaches to determine the extent to which evolutionary history and functional traits determined flocking propensity and perceived predation risk (response to heterospecific alarm calls) in a lowland Amazonian bird community. We predicted that small birds that feed myopically and out in the open would have higher flocking propensities and account for a higher proportion of positive responses to alarms. Using generalized linear models and the incorporation of phylogeny on data from 56 species, our results suggest that phylogenetic relationships alongside body size, foraging height, vegetation density, and response to alarm calls influence flocking propensity. Conversely, phylogenetic relationships did not influence response to heterospecific alarm calls. Among functional traits, however, foraging strategy, foraging density, and flocking propensity partially explained responses to alarm calls. Our results suggest that flocking propensity and perceived predation risk are positively related and that functional ecological traits and evolutionary history may explain certain species’ associations.
Opioid Use Disorders Attributed to Tramadol Among Egyptian University Students

Background: Tramadol use is an overwhelming problem in Egypt with tremendous medical and social consequences especially among youth. Use liability among Egyptian university students is underevaluated. This study aimed to estimate the prevalence and associated correlates of tramadol use among students from Zagazig University, Egypt. Methods: A cross-sectional study included a total of 1135 undergraduate students, from 10 colleges in Zagazig University. Participants were randomly selected and assessed for tramadol use using The Drug Use Disorders Identification Test (DUDIT) and The Drug Use Disorders Identification Test—Extended (DUDIT-E). Results: The prevalence of tramadol use was 12.3% among university students, with higher prevalence in male (20.2%) than female students (2.4%). The average age at onset of tramadol use was 17.6 ± 2.1. Only 15% of the students with substance use were using tramadol alone whereas the rest (85%) were using at least 1 drug plus tramadol. One-fifth of these students started with tramadol as their first drug. Smoking, cannabis, and alcohol use predict tramadol use. About 60% of students who use tramadol had drug-related problems and 30% had dependence. Treatment readiness for tramadol use is negatively correlated with smoking and its duration. Conclusions: Tramadol use was common among university students, with higher prevalence among males. There is a considerable relationship between tramadol use, smoking, and use of other substances. Further population-based longitudinal studies need to investigate the causal relationship between tramadol use, smoking, and use of other substances.
Successful and Unsuccessful Response Inhibitions Differentially Affect the Effective Connectivity Between Insular, Presupplementary-Motor, and Striatal Areas

Successful response inhibition depends upon the delay between the cues that signal a response and its subsequent inhibition. Previous studies report activity in the right presupplementary motor area (rPreSMA), right anterior insula (rAI), and the right striatum (rSTR) when subjects attempt to inhibit responses. Although these regions are anatomically connected, how they interact during successful and unsuccessful inhibitions has not been studied. In this work, we used a temporal prediction task, functional MRI, and dynamic causal modeling to solve this question. We found selective direct activation of both the rPreSMA and the rAI during successful and unsuccessful inhibitions which also were associated with opposite modulatory effects on insular-striatal and presupplementary-motor striatal descending connections. Moreover, inputs to the rPreSMA during successful inhibitions were propagated to the rAI whereas inputs to the rAI during unsuccessful inhibitions were propagated to the rPreSMA. We interpret that the direct perturbation in the rPreSMA and the modulation of the rPreSMA → rSTR connections would facilitate response inhibition whereas weak insular activity would cause response inhibition to fail despite the existence of strong rAI → rSTR modulations. We discuss that descending connections could be nonlinearly modulated via activity of either the right inferior frontal gyrus or the left anterior cingulate cortex. From a predictive coding perspective, rAI activity during successful and unsuccessful inhibition would signal interoceptive information when subjects unexpectedly need to change behaviors.
Evaluation of Jackknife and Bootstrap for Defining Confidence Intervals for Pairwise Agreement Measures

Several research fields frequently deal with the analysis of diverse classification results of the same entities. This should imply an objective detection of overlaps and divergences between the formed clusters. The congruence between classifications can be quantified by clustering agreement measures, including pairwise agreement measures. Several measures have been proposed and the importance of obtaining confidence intervals for the point estimate in the comparison of these measures has been highlighted. A broad range of methods can be used for the estimation of confidence intervals. However, evidence is lacking about what are the appropriate methods for the calculation of confidence intervals for most clustering agreement measures. Here we evaluate the resampling techniques of bootstrap and jackknife for the calculation of the confidence intervals for clustering agreement measures. Contrary to what has been shown for some statistics, simulations showed that the jackknife performs better than the bootstrap at accurately estimating confidence intervals for pairwise agreement measures, especially when the agreement between partitions is low. The coverage of the jackknife confidence interval is robust to changes in cluster number and cluster size distribution.
Multiple Processes Regulate Long-Term Population Dynamics of Sea Urchins on Mediterranean Rocky Reefs

We annually monitored the abundance and size structure of herbivorous sea urchin populations (Paracentrotus lividus and Arbacia lixula) inside and outside a marine reserve in the Northwestern Mediterranean on two distinct habitats (boulders and vertical walls) over a period of 20 years, with the aim of analyzing changes at different temporal scales in relation to biotic and abiotic drivers. P. lividus exhibited significant variability in density over time on boulder bottoms but not on vertical walls, and temporal trends were not significantly different between the protection levels. Differences in densities were caused primarily by variance in recruitment, which was less pronounced inside the MPA and was correlated with adult density, indicating density-dependent recruitment under high predation pressure, as well as some positive feedback mechanisms that may facilitate higher urchin abundances despite higher predator abundance. Populations within the reserve were less variable in abundance and did not exhibit the hyper-abundances observed outside the reserve, suggesting that predation effects maybe more subtle than simply lowering the numbers of urchins in reserves. A. lixula densities were an order of magnitude lower than P. lividus densities and varied within sites and over time on boulder bottoms but did not differ between protection levels. In December 2008, an exceptionally violent storm reduced sea urchin densities drastically (by 50% to 80%) on boulder substrates, resulting in the lowest values observed over the entire study period, which remained at that level for at least two years (up to the present). Our results also showed great variability in the biological and physical processes acting at different temporal scales. This study highlights the need for appropriate temporal scales for studies to fully understand ecosystem functioning, the concepts of which are fundamental to successful conservation and management.
Clinical Characteristics of the Responders to Dipeptidyl Peptidase-4 Inhibitors in Korean Subjects with Type 2 Diabetes

We investigated characteristics associated with the efficacy of dipeptidyl peptidase-4 inhibitors (DPP4i) in Korean patients with type 2 diabetes. We reviewed medical records of 477 patients who had taken sitagliptin or vildagliptin longer than 40 weeks. Response to DPP4i was evaluated with HbA1c change after therapy (ΔHbA1c). The Student's t-test between good responders (GR: ΔHbA1c > 1.0%) and poor responders (PR: ΔHbA1c < 0.5%), a correlation analysis among clinical parameters, and a linear multivariate regression analysis were performed. The mean age was 60 yr, duration of diabetes 11 yr and HbA1c was 8.1%. Baseline fasting plasma glucose (FPG), HbA1c, C-peptide, and creatinine were significantly higher in the GR compared to the PR. Duration of diabetes, FPG, HbA1c, C-peptide and creatinine were significantly correlated with ΔHbA1c. In the multivariate analysis, age (r2 = 0.006), duration of diabetes (r2 = 0.019), HbA1c (r2 = 0.296), and creatinine levels (r2 = 0.024) were independent predictors for the response to DPP4i. Body mass index and insulin resistance were not associated with the response to DPP4i. In conclusion, better response to DPP4i would be expected in Korean patients with type 2 diabetes who have higher baseline HbA1c and creatinine levels with shorter duration of diabetes.
High-Throughput Identification of Potential Minor Histocompatibility Antigens by MHC Tetramer-Based Screening: Feasibility and Limitations

T-cell recognition of minor histocompatibility antigens (MiHA) plays an important role in the graft-versus-tumor (GVT) effect of allogeneic stem cell transplantation (allo-SCT). However, the number of MiHA identified to date remains limited, making clinical application of MiHA reactive T-cell infusion difficult. This study represents the first attempt of genome-wide prediction of MiHA, coupled to the isolation of T-cell populations that react with these antigens. In this unbiased high-throughput MiHA screen, both the possibilities and pitfalls of this approach were investigated. First, 973 polymorphic peptides expressed by hematopoietic stem cells were predicted and screened for HLA-A2 binding. Subsequently a set of 333 high affinity HLA-A2 ligands was identified and post transplantation samples from allo-SCT patients were screened for T-cell reactivity by a combination of pMHC-tetramer-based enrichment and multi-color flow cytometry. Using this approach, 71 peptide-reactive T-cell populations were generated. The isolation of a T-cell line specifically recognizing target cells expressing the MAP4K1IMA antigen demonstrates that identification of MiHA through this approach is in principle feasible. However, with the exception of the known MiHA HMHA1, none of the other T-cell populations that were generated demonstrated recognition of endogenously MiHA expressing target cells, even though recognition of peptide-loaded targets was often apparent. Collectively these results demonstrate the technical feasibility of high-throughput analysis of antigen-specific T-cell responses in small patient samples. However, the high-sensitivity of this approach requires the use of potential epitope sets that are not solely based on MHC binding, to prevent the frequent detection of T-cell responses that lack biological relevance.
Nickel exposure induces persistent mesenchymal phenotype in human lung epithelial cells through epigenetic activation of ZEB1

Nickel (Ni) is an environmental and occupational carcinogen, and exposure to Ni is associated with lung and nasal cancers in humans. Furthermore, Ni exposure is implicated in several lung diseases including chronic inflammatory airway diseases, asthma, and fibrosis. However, the mutagenic potential of Ni is low and does not correlate with its potent toxicity and carcinogenicity. Therefore, mechanisms underlying Ni exposure‐associated diseases remain poorly understood. Since the health risks of environmental exposures often continue post exposure, understanding the exposure effects that persist after the termination of exposure could provide mechanistic insights into diseases. By examining the persistent effects of Ni exposure, we report that Ni induces epithelial‐mesenchymal transition (EMT) and that the mesenchymal phenotype remains irreversible even after the termination of exposure. Ni‐induced EMT was dependent on the irreversible upregulation of ZEB1, an EMT master regulator, via resolution of its promoter bivalency. ZEB1, upon activation, downregulated its repressors as well as the cell‐cell adhesion molecule, E‐cadherin, resulting in the cells undergoing EMT and switching to persistent mesenchymal status. ZEB1 depletion in cells exposed to Ni attenuated Ni‐induced EMT. Moreover, Ni exposure did not induce EMT in ZEB1‐depleted cells. Activation of EMT, during which the epithelial cells lose cell‐cell adhesion and become migratory and invasive, plays a major role in asthma, fibrosis, and cancer and metastasis, lung diseases associated with Ni exposure. Therefore, our finding of irreversible epigenetic activation of ZEB1 by Ni exposure and the acquisition of persistent mesenchymal phenotype would have important implications in understanding Ni‐induced diseases.