Miracle-dz/UniFAR-FTUs huggingface dataset:
A Syntenic Cross Species Aneuploidy Genetic Screen Links RCAN1 Expression to β-Cell Mitochondrial Dysfunction in Type 2 Diabetes

Type 2 diabetes (T2D) is a complex metabolic disease associated with obesity, insulin resistance and hypoinsulinemia due to pancreatic β-cell dysfunction. Reduced mitochondrial function is thought to be central to β-cell dysfunction. Mitochondrial dysfunction and reduced insulin secretion are also observed in β-cells of humans with the most common human genetic disorder, Down syndrome (DS, Trisomy 21). To identify regions of chromosome 21 that may be associated with perturbed glucose homeostasis we profiled the glycaemic status of different DS mouse models. The Ts65Dn and Dp16 DS mouse lines were hyperglycemic, while Tc1 and Ts1Rhr mice were not, providing us with a region of chromosome 21 containing genes that cause hyperglycemia. We then examined whether any of these genes were upregulated in a set of ~5,000 gene expression changes we had identified in a large gene expression analysis of human T2D β-cells. This approach produced a single gene, RCAN1, as a candidate gene linking hyperglycemia and functional changes in T2D β-cells. Further investigations demonstrated that RCAN1 methylation is reduced in human T2D islets at multiple sites, correlating with increased expression. RCAN1 protein expression was also increased in db/db mouse islets and in human and mouse islets exposed to high glucose. Mice overexpressing RCAN1 had reduced in vivo glucose-stimulated insulin secretion and their β-cells displayed mitochondrial dysfunction including hyperpolarised membrane potential, reduced oxidative phosphorylation and low ATP production. This lack of β-cell ATP had functional consequences by negatively affecting both glucose-stimulated membrane depolarisation and ATP-dependent insulin granule exocytosis. Thus, from amongst the myriad of gene expression changes occurring in T2D β-cells where we had little knowledge of which changes cause β-cell dysfunction, we applied a trisomy 21 screening approach which linked RCAN1 to β-cell mitochondrial dysfunction in T2D.
Expression of growth factors and remodelling of the airway wall in bronchial asthma.

BACKGROUND: Bronchial asthma is characterised by airway structural changes, including mucosal inflammatory infiltration and subepithelial collagen deposition, that may represent the morphological basis for the chronicity of the disease. The relationship between airway wall thickness and growth factors in asthma has not been elucidated. METHODS: Bronchial biopsy specimens were obtained from 21 asthmatic patients and eight healthy subjects and the basement membrane thickness was measured by light microscopy and electron microscopy. At the same time the numbers of eosinophils and fibroblasts were assessed and the expression of transforming growth factor beta 1 (TGF-beta 1), platelet derived growth factor (PDGF), and insulin like growth factor (IGF) I in the bronchial mucosa was examined by immunostaining. The relationship between the degree of thickening of the subepithelial layer and both the clinical data and pulmonary function were also investigated. RESULTS: The basement membrane of the asthmatic patients was thicker than that of the healthy controls (median 8.09 versus 4.02 microns). Electron microscopic examination of the basement membrane revealed thickening of the subepithelial lamina reticularis; this thickening significantly correlated with the number of fibroblasts in the submucosa in the asthmatic subjects (rs = 0.88) but not in the controls (rs = 0.70). There was a significantly higher number of eosinophils in the airways of the asthmatic subjects than in the healthy subjects (EG1 + cells: 52.0 versus 2.0/mm2, EG2 + cells: 56.0 versus 1.5/mm2). The expression of each growth factor in the bronchial mucosa was similar in asthmatic and healthy subjects (TGF-beta 1: 18.0% versus 16.0%, PDGF: 37.0% versus 32.5%, IGF-I: 15.0% versus 8.0%). A weak but statistically significant correlation was found between the number of fibroblasts and the expression of TGF-beta 1 in asthmatic subjects (rs = 0.50). There was a significant correlation between the thickness of the subepithelial layer in asthmatic subjects and the attack score (rs = 0.58) and a significant inverse correlation between the subepithelial collagen thickness in asthmatic subjects and airway hypersensitivity (rs = -0.65). CONCLUSIONS: These findings indicate that the thickening of the subepithelial layer in bronchial asthma is due to an increase in fibroblasts, and that the thickness of the subepithelial collagen appears to be linked to an increase in bronchial responsiveness and exacerbation of clinical manifestations.
Volumetric measurement of perfusion and arterial transit delay using hadamard encoded continuous arterial spin labeling

Creating images of the transit delay from the labeling location to image tissue can aid the optimization and quantification of arterial spin labeling perfusion measurements and may provide diagnostic information independent of perfusion. Unfortunately, measuring transit delay requires acquiring a series of images with different labeling timing that adds to the time cost and increases the noise of the arterial spin labeling study. Here, we implement and evaluate a proposed Hadamard encoding of labeling that speeds the imaging and improves the signal‐to‐noise ratio efficiency. Volumetric images in human volunteers confirmed the theoretical advantages of Hadamard encoding over sequential acquisition of images with multiple labeling timing. Perfusion images calculated from Hadamard encoded acquisition had reduced signal‐to‐noise ratio relative to a dedicated perfusion acquisition with either assumed or separately measured transit delays, however. Magn Reson Med 69:1014–1022, 2013. © 2012 Wiley Periodicals, Inc.
Modeling Collective Crowd Behaviors in Video

Crowd behavior analysis is an interdisciplinary topic. Understanding the collective crowd behaviors is one of the fundamental problems both in social science and natural science. Research of crowd behavior analysis can lead to a lot of critical applications, such as intelligent video surveillance, crowd abnormal detection, and public facility optimization. In this thesis, we study the crowd behaviors in the real scene videos, propose computational frameworks and techniques to analyze these dynamic patterns of the crowd, and apply them for a lot of visual surveillance applications. Firstly we proposed Random Field Topic model for learning semantic regions of crowded scenes from highly fragmented trajectories. This model uses the Markov Random Field prior to capture the spatial and temporal dependency between tracklets and uses the source-sink prior to guide the learning of semantic regions. The learned semantic regions well capture the global structures of the scenes in long range with clear semantic interpretation. They are also able to separate different paths at fine scales with good accuracy. This work has been published in IEEE Conference on Computer Vision and Pattern Recognition (CVPR) 2011 [70]. To further explore the behavioral origin of semantic regions in crowded scenes, we proposed Mixture model of Dynamic Pedestrian-Agents to learn the collective dynamics from video sequences in crowded scenes. The collective dynamics of pedestrians are modeled as linear dynamic systems to capture long range moving patterns. Through modeling the beliefs of pedestrians and
Proceedings of the 1 st Workshop on Planning in Continuous Domains PCD 2013

This paper gives an overview of a new risk-sensitive, continuous plan executive called p-Sulu, as well as its full-horizon variant, the p-Sulu Planner. p-Sulu and the p-Sulu Planner provide two capabilities: 1) goal-directed planning in a continuous domain and 2) risk-sensitive planning that respects a user-speciﬁed upper bound on the probability of constraint violations. They both take as an input a new plan representation called a chance-constrained qualitative state plan (CCQSP), through which users specify the desired evolution of the plant state as well as the acceptable level of risk. Given a CCQSP, p-Sulu performs a real-time plan execution over a relatively short, receding planning horizon, while the p-Sulu Planner generates a sequence of actions over the entire duration of the plan in one shot, with paying more attention to optimality. We also present a distributed extension of p-Sulu, called dp-Sulu. We have deployed p-Sulu, dp-Sulu, and the p-Sulu Planner on various systems, including aerial vehicles, space vehicles, as well as buildings, and demonstrated their capabilities by simulations and experiments.
Inverse probability weighted estimation in survival analysis

Modern epidemiologic and clinical studies aimed at analyzing a time to an event endpoint T routinely collect, in addition to (possibly censored) information on T, high dimensional data often in the form of baseline (i.e. timeindependent covariates V (0)) and time-varying covariates V (t) , t > 0, measured at frequent intervals. Scientific interest, however, often focuses on a low dimensional functional β = β (FX) of the distribution FX of the (intended) full data X = ¡ T, V (T ) ¢ where V (t) ≡ {V (u) : 0 ≤ u ≤ t} . Inverse probability weighted augmented (AIPW) estimators of β meet the analytic challenge posed by these high dimensional data because they are consistent and asymptotically normal (CAN) under models that do not make assumptions about the parts of FX that are of little scientific interest. As such, they are not subject to biases induced by misspecification of models for these secondary parts of FX .
Role of novelty and ethanol history in locomotor stimulation induced by binge-like ethanol intake.

BACKGROUND The acute locomotor effects of voluntary ethanol (EtOH) intake in mice (stimulation/sedation) might be important behavioral indicators of an animals' propensity to engage in EtOH consumption and/or EtOH seeking behaviors. Using a binge-like EtOH intake model dubbed "Drinking-in-the-Dark (DID)," we recently observed home cage locomotor stimulation in C57BL/6J mice during an acute EtOH intake session, but acute home cage locomotor sedation following repeated EtOH exposures. To determine the role of novelty and/or EtOH history on these previously described locomotor effects, and to determine the relationship between these variables on locomotor activity immediately following DID intake, we conducted 2 separate experiments. METHODS In experiment 1, mice were given access to either EtOH or water, and locomotor activity was monitored immediately afterwards. In experiment 2, mice were given 13 days access to EtOH or water solution while home cage locomotor activity was monitored. On the 14th day, half of the water consuming animals received EtOH access for the first time. On the 15th day, all animals received EtOH access, and locomotion was assessed afterwards in locomotor activity testing chambers. RESULTS In experiment 1, locomotor activity following DID was positively associated with EtOH intake and blood EtOH concentrations (BECs). In experiment 2, the group that received EtOH for the first time on the 14th day did not display locomotor stimulation. Locomotor activity following DID EtOH intake was positively associated with BECs in all groups regardless of EtOH history. CONCLUSIONS These results suggest that (i) DID-induced locomotor stimulation in the home cage may involve relative familiarity with the DID procedures, and (ii) locomotor stimulation immediately following DID is directly related to the relative concentration of EtOH in blood; an effect that is not altered by prior EtOH history. These data add new evidence of the pharmacological actions of binge-like EtOH intake, and provide a basis by which we may explore the motivation and consequences of such binge consumption.
A general biodiversity–function relationship is mediated by trophic level

M. I. O’Connor, Dept of Zoology and Biodiversity Research Centre, Univ. of British Columbia, Vancouver, BC, V6T 1Z4, Canada. – A. Gonzalez and P. L. Thompson (http://orcid.org/0000-0002-5278-9045), Dept of Biology, McGill Univ., Montreal, QC Canada. – J. E. K. Byrnes (http://orcid.org/0000-0002-9791-9472), Dept of Biology, Univ. of Massachusetts Boston, Boston, MA, USA. – B. J. Cardinale, School of Natural Resources and Environment, Univ. of Michigan, Ann Arbor, MI, USA. – J. E. Duffy, Tennenbaum Marine Observatories Network, Smithsonian Institution, Washington DC, USA. – L. Gamfeldt, Dept of Marine Sciences, Univ. of Gothenburg, Göteborg, Sweden. – J. N. Griffin, Dept of Biosciences, Swansea Univ., Singleton Park, Swansea, UK. – D. Hooper, Dept of Biology, Western Washington Univ., Bellingham, WA, USA. – B. A. Hungate, Center for Ecosystem Science and Society, Dept of Biological Sciences, Northern Arizona Univ., Flagstaff AZ, USA. – A. Paquette, Centre for Forest Research, Univ. du Québec à Montréal, Centre-ville Station, Montréal, QC, Canada. – L. E. Dee, Inst. on the Environment, Univ. of Minnesota, Twin Cities, Saint Paul, MN, USA. – K. L. Dolan, Research Development Office, Univ. of California at San Francisco, San Francisco, CA, USA.
The memory of Katrina and the stock market response to hurricane-related news and events

This paper examines the relationship between hurricane news coverage and U.S stock market returns focusing on the costliest hurricanes following Katrina (Ike, Irene and Sandy) and Patricia, which was one of the strongest hurricanes on record worldwide. In particular, we investigate the reaction of the market to hurricane news coverage and the way the memory of Katrina affected the investors’ decisions during hurricanes Ike, Irene, Sandy and Patricia. Using an event study methodology, we find that the event of a hurricane generates a significant positive reaction on the stock returns, in the short-term, that fades away over a 20 day period. The empirical evidence shown here suggests that hurricane related news coverage has a negative effect on stock returns for all events excluding hurricane Irene. Moreover, Katrina related news still have a significant effect during each event even 10 years after it took place. The memory of Katrina has a positive correction effect over the initial negative reaction of investors to the hurricane related news-coverage.
Collaboration with an autonomous humanoid robot: A little gesture goes a long way

We report on an experiment in which a human collaborates with a small, autonomous, humanoid robotic toy. The experiment demonstrates that the robot's use of two simple gestures, namely orienting its head toward the addressee when it speaks and raising its arm in the direction of objects it refers to, significantly improve the human's perception of the robot's interaction skills and quality as a collaborator.
Body Mass Index in Adolescence and Number of Children in Adulthood

Background: Body weight is associated with reproduction and related behaviors, but it is unknown whether it has significance for fertility differences in the general population. We examined whether adolescent body mass index (BMI; kg/m2) predicted the number of children in adulthood 21 years later. Methods: The participants were 1298 Finnish women and men (ages 12, 15, and 18 years at baseline) followed in a prospective population-based cohort study (the Cardiovascular Risk in Young Finns) from year 1980 to 2001. Results: There was an inverted J-shaped association between BMI and the number of children, such that underweight adolescents had 10–16% fewer children in adulthood, overweight adolescents 4–8% fewer, and obese adolescents 32–38% fewer than individuals with normal adolescent weight. This association was similar in women and men, and independent of age, education, urbanicity of residence, and timing of menarche (in women). Adolescents with low or high BMI were less likely to have lived with a partner in adulthood, which partly accounted for their decreased number of children. The influence of adolescent BMI was independent of adulthood BMI in women but not in men. Age at menarche also predicted the number of children, such that women with early or late menarche had more children than those with average age at menarche. Conclusion: Underweight and especially obesity may have a negative impact on fertility in the general population. The increasing prevalence of obesity in children and adolescents may represent a concern for future reproductive health.
Avalanche boron fusion by laser picosecond block ignition with magnetic trapping for clean and economic reactor

Measured highly elevated gains of proton–boron (HB11) fusion (Picciotto et al., Phys. Rev. X 4, 031030 (2014)) confirmed the exceptional avalanche reaction process (Lalousis et al., Laser Part. Beams 32, 409 (2014); Hora et al., Laser Part. Beams 33, 607 (2015)) for the combination of the non-thermal block ignition using ultrahigh intensity laser pulses of picoseconds duration. The ultrahigh acceleration above $10^{20}~\text{cm}~\text{s}^{-2}$ for plasma blocks was theoretically and numerically predicted since 1978 (Hora, Physics of Laser Driven Plasmas (Wiley, 1981), pp. 178 and 179) and measured (Sauerbrey, Phys. Plasmas 3, 4712 (1996)) in exact agreement (Hora et al., Phys. Plasmas 14, 072701 (2007)) when the dominating force was overcoming thermal processes. This is based on Maxwell’s stress tensor by the dielectric properties of plasma leading to the nonlinear (ponderomotive) force $f_{\text{NL}}$ resulting in ultra-fast expanding plasma blocks by a dielectric explosion. Combining this with measured ultrahigh magnetic fields and the avalanche process opens an option for an environmentally absolute clean and economic boron fusion power reactor. This is supported also by other experiments with very high HB11 reactions under different conditions (Labaune et al., Nature Commun. 4, 2506 (2013)).
Gradient Evolution of Body Colouration in Surface- and Cave-Dwelling Poecilia mexicana and the Role of Phenotype-Assortative Female Mate Choice

Ecological speciation assumes reproductive isolation to be the product of ecologically based divergent selection. Beside natural selection, sexual selection via phenotype-assortative mating is thought to promote reproductive isolation. Using the neotropical fish Poecilia mexicana from a system that has been described to undergo incipient ecological speciation in adjacent, but ecologically divergent habitats characterized by the presence or absence of toxic H2S and darkness in cave habitats, we demonstrate a gradual change in male body colouration along the gradient of light/darkness, including a reduction of ornaments that are under both inter- and intrasexual selection in surface populations. In dichotomous choice tests using video-animated stimuli, we found surface females to prefer males from their own population over the cave phenotype. However, female cave fish, observed on site via infrared techniques, preferred to associate with surface males rather than size-matched cave males, likely reflecting the female preference for better-nourished (in this case: surface) males. Hence, divergent selection on body colouration indeed translates into phenotype-assortative mating in the surface ecotype, by selecting against potential migrant males. Female cave fish, by contrast, do not have a preference for the resident male phenotype, identifying natural selection against migrants imposed by the cave environment as the major driver of the observed reproductive isolation.
Tyrosine 8 contributes to catalysis but is not required for activity of rat liver glutathione S‐transferase, 1–1

Reaction of rat liver glutathione S‐transferase, isozyme 1–1, with 4‐(fluorosulfonyl)benzoic acid (4‐FSB), a xenobiotic substrate analogue, results in a time‐dependent inactivation of the enzyme to a final value of 35% of its original activity when assayed at pH 6.5 with l‐chloro‐2,4‐dinitrobenzene (CDNB) as substrate. The rate of inactivation exhibits a nonlinear dependence on the concentration of 4‐FSB from 0.25 mM to 9 mM, characterized by a KI of 0.78 mM and kmax of 0.011 min−1. S‐Hexylglutathione or the xenobiotic substrate analogue, 2,4‐dinitrophenol, protects against inactivation of the enzyme by 4‐FSB, whereas S‐methylglutathione has little effect on the reaction. These experiments indicate that reaction occurs within the active site of the enzyme, probably in the binding site of the xenobiotic substrate, close to the glutathione binding site. Incorporation of [3,5‐3H]‐4‐FSB into the enzyme in the absence and presence of S‐hexylglutathione suggests that modification of one residue is responsible for the partial loss of enzyme activity. Tyr 8 and Cys 17 are shown to be the reaction targets of 4‐FSB, but only Tyr 8 is protected against 4‐FSB by S‐hexylglutathione. DTT regenerates cysteine from the reaction product of cysteine and 4‐FSB, but does not reactivate the enzyme. These results show that modification of Tyr 8 by 4‐FSB causes the partial inactivation of the enzyme. The Michaelis constants for various substrates are not changed by the modification of the enzyme. The pH dependence of the enzyme‐catalyzed reaction of glutathione with CDNB for the modified enzyme, as compared with the native enzyme, reveals an increase of about 0.9 in the apparent pKa, which has been interpreted as representing the ionization of enzyme‐bound glutathione; however, this pKa of about 7.4 for modified enzyme remains far below the pK of 9.1 for the ‐SH of free glutathione. Previously, it was considered that Tyr 8 was essential for GST catalysis. In contrast, we conclude that Tyr 8 facilitates the ionization of the thiol group of glutathione bound to glutathione S‐transferase, but is not required for enzyme activity.
Thermoregulatory responses and adaptability of Anglo-nubian goats maintained in thermoneutral temperature and under heat stress

This study aimed to evaluate the physiological responses and adaptability of Anglo-Nubian goat breeds by Iberia and Benezra tests, maintained in bioclimatic chamber under different temperatures: 20, 24, 28 and 32oC, where temperature and air relative humidity and black globe humidity index (BGHI) were measured. The design was completely randomized with four treatments and six replicates. With the increase of temperature and the BGHI, increased the surface temperature, the cardiac and respiratory frequency, and the thermal gradient, the rectal temperature remained within normal limits. The adaptability tests indicated that animals in the temperatures of 28 and 32°C had the physiological parameters altered to maintain the warm-blooded, which BGHI values corresponding were 78.21 and 82.55 respectively, characterizing a warning and danger situation.
Clustering using objective functions and stochastic search

Summary. A new approach to clustering multivariate data, based on a multilevel linear mixed model, is proposed. A key feature of the model is that observations from the same cluster are correlated, because they share cluster‐specific random effects. The inclusion of cluster‐specific random effects allows parsimonious departure from an assumed base model for cluster mean profiles. This departure is captured statistically via the posterior expectation, or best linear unbiased predictor. One of the parameters in the model is the true underlying partition of the data, and the posterior distribution of this parameter, which is known up to a normalizing constant, is used to cluster the data. The problem of finding partitions with high posterior probability is not amenable to deterministic methods such as the EM algorithm. Thus, we propose a stochastic search algorithm that is driven by a Markov chain that is a mixture of two Metropolis–Hastings algorithms—one that makes small scale changes to individual objects and another that performs large scale moves involving entire clusters. The methodology proposed is fundamentally different from the well‐known finite mixture model approach to clustering, which does not explicitly include the partition as a parameter, and involves an independent and identically distributed structure.