Miracle-dz/UniFAR-FTUs huggingface dataset:
Bayesian model selection using test statistics

Summary. Existing Bayesian model selection procedures require the specification of prior distributions on the parameters appearing in every model in the selection set. In practice, this requirement limits the application of Bayesian model selection methodology. To overcome this limitation, we propose a new approach towards Bayesian model selection that uses classical test statistics to compute Bayes factors between possible models. In several test cases, our approach produces results that are similar to previously proposed Bayesian model selection and model averaging techniques in which prior distributions were carefully chosen. In addition to eliminating the requirement to specify complicated prior distributions, this method offers important computational and algorithmic advantages over existing simulation‐based methods. Because it is easy to evaluate the operating characteristics of this procedure for a given sample size and specified number of covariates, our method facilitates the selection of hyperparameter values through prior‐predictive simulation.
Multimodal Human-Human-Robot Interactions (MHHRI) Dataset for Studying Personality and Engagement

In this paper we introduce a novel dataset, the Multimodal Human-Human-Robot-Interactions (MHHRI) dataset, with the aim of studying personality simultaneously in human-human interactions (HHI) and human-robot interactions (HRI) and its relationship with engagement. Multimodal data was collected during a controlled interaction study where dyadic interactions between two human participants and triadic interactions between two human participants and a robot took place with interactants asking a set of personal questions to each other. Interactions were recorded using two static and two dynamic cameras as well as two biosensors, and meta-data was collected by having participants fill in two types of questionnaires, for assessing their own personality traits and their perceived engagement with their partners (self labels) and for assessing personality traits of the other participants partaking in the study (acquaintance labels). As a proof of concept, we present baseline results for personality and engagement classification. Our results show that (i) trends in personality classification performance remain the same with respect to the self and the acquaintance labels across the HHI and HRI settings; (ii) for extroversion, the acquaintance labels yield better results as compared to the self labels; (iii) in general, multi-modality yields better performance for the classification of personality traits.
Role of the PXR gene locus in inflammatory bowel diseases

Background: The pregnane X receptor gene (PXR/NR1I2) has been recently associated with an increased risk for inflammatory bowel disease (IBD), although a subsequent case‐control study failed to replicate the original association in an independent population. This nuclear receptor regulates genes involved in the detoxification process in the liver and intestine, like ABCB1/MDR1. PXR expression was significantly reduced in the colon of patients with ulcerative colitis (UC), but remained unaffected in Crohn's disease (CD) patients. Considering previous results, we aimed at investigating the impact of this locus on IBD predisposition in the Spanish population. Methods: Three PXR polymorphisms, including the 1 more strongly correlated with IBD risk in the initial study at −25385C/T (rs3814055) and the 6 haplotypes conformed by them, were analyzed in 365 UC and 331 CD patients and compared with 550 ethnically matched controls. Results: The overall haplotypic distribution showed a significant difference between UC and CD patients (P = 0.05; χ2 = 10.84). Among UC patients a significant difference was seen between those with extensive colitis and controls (P = 0.004; χ2 = 17.04), mainly due to the presence of a risk haplotype (rs3814055*T//rs6784598*C//rs2276707*C: P = 0.001; odds ratio [OR] = 1.66, 95% confidence interval [CI] 1.20–2.30). Patients with extensive UC carrying the −25385T allele showed increased susceptibility compared with left‐sided colitis patients and with healthy subjects. In patients with extensive UC a significantly different distribution of genotypes of the MDR1 G/A change located in intron 3 (rs3789243) was observed between carriers/noncarriers of the −25385T risk allele (P = 0.005). Conclusions: Our data seem to support the association of the PXR locus with extensive UC and the interaction between PXR and MDR1 genes. (Inflamm Bowel Dis 2007)
Drosophila Lin-52 Acts in Opposition to Repressive Components of the Myb-MuvB/dREAM Complex

ABSTRACT The Drosophila melanogaster Myb-MuvB/dREAM complex (MMB/dREAM) participates in both the activation and repression of developmentally regulated genes and origins of DNA replication. Mutants in MMB subunits exhibit diverse phenotypes, including lethality, eye defects, reduced fecundity, and sterility. Here, we used P-element excision to generate mutations in lin-52, which encodes the smallest subunit of the MMB/dREAM complex. lin-52 is required for viability, as null mutants die prior to pupariation. The generation of somatic and germ line mutant clones indicates that lin-52 is required for adult eye development and for early embryogenesis via maternal effects. Interestingly, the maternal-effect embryonic lethality, larval lethality, and adult eye defects could be suppressed by mutations in other subunits of the MMB/dREAM complex. These results suggest that a partial MMB/dREAM complex is responsible for the lethality and eye defects of lin-52 mutants. Furthermore, these findings support a model in which the Lin-52 and Myb proteins counteract the repressive activities of the other members of the MMB/dREAM complex at specific genomic loci in a developmentally controlled manner.
Adaptation behavior of skilled infant bouncers to different spring frequencies

Infants explore their environments through repetitive movements that are constrained or facilitated by the environmental context. In this study, we evaluated how skilled bouncers adapted to bouncing in systems with four different spring conditions (natural frequencies of 0.9, 1.15, 1.27 and 1.56 Hz). Trunk kinematics and vertical ground reaction forces (VGRFs) were recorded from three pre-walking infants (mean age 10.6 ±0.9 months). Bounce frequency, trunk displacement, peak VGRF, percent of time on the ground and time to peak force as a function of time on the ground were analyzed. In addition, infant bounce frequencies were compared to measured oscillations of an inert mass equivalent to each infant’s mass. All infants bounced above the natural frequency of the spring system in all conditions suggesting that they did not behave solely like mass-spring systems. Infants produced asymmetrical VGRF loading patterns suggesting that a timing component, such as bounce frequency, was regulated. Skilled infants consistently increased their bounce frequency as their vertical trunk displacement decreased; however, the mode for regulating bounce frequency differed from infant to infant.
The TREAT‐NMD Duchenne Muscular Dystrophy Registries: Conception, Design, and Utilization by Industry and Academia

Duchenne muscular dystrophy (DMD) is an X‐linked genetic disease, caused by the absence of the dystrophin protein. Although many novel therapies are under development for DMD, there is currently no cure and affected individuals are often confined to a wheelchair by their teens and die in their twenties/thirties. DMD is a rare disease (prevalence <5/10,000). Even the largest countries do not have enough affected patients to rigorously assess novel therapies, unravel genetic complexities, and determine patient outcomes. TREAT‐NMD is a worldwide network for neuromuscular diseases that provides an infrastructure to support the delivery of promising new therapies for patients. The harmonized implementation of national and ultimately global patient registries has been central to the success of TREAT‐NMD. For the DMD registries within TREAT‐NMD, individual countries have chosen to collect patient information in the form of standardized patient registries to increase the overall patient population on which clinical outcomes and new technologies can be assessed. The registries comprise more than 13,500 patients from 31 different countries. Here, we describe how the TREAT‐NMD national patient registries for DMD were established. We look at their continued growth and assess how successful they have been at fostering collaboration between academia, patient organizations, and industry.
Promising candidates for the treatment of chronic hepatitis C

Chronic hepatitis C virus (HCV) infection is the cause of an emerging global pandemic of chronic liver disease. Current pegylated IFN-α/ribavirin combination therapies are merely 54 – 56% efficacious and are often poorly tolerated. Popular strategies to improve upon existing therapies include efforts to decrease the dosing regime, improve the safety profile and specifically target the liver, the site of HCV replication. A clear goal of novel therapies is to significantly improve the therapeutic response for HCV-infected patients. One popular scheme to accomplish this is to directly target the viral enzymes involved in HCV RNA replication. While peptidomimetics have been pursued as potent and specific inhibitors of the serine protease, nucleoside analogues and non-nucleoside small molecules have been explored as RNA-dependent RNA polymerase inhibitors with promising potential. Advances in the understanding of HCV replication at the molecular level that stem from the use of the subgenomic replicon system, in vitro enzyme assays and from co-crystallographic structure solutions of the replication enzymes with novel inhibitors have propelled these compounds into clinical development. As these candidates are developed further, there is great hope for a cure for all those chronically infected with HCV.
Atracurium: its speed of onset. A comparison with suxamethonium.

Forty healthy pauents were randomly selected to receive either atracurium 0 6 mg kg-1, or summethonium 1 mg kg-1. Onset of neuromuscular blockade and the time to full peripheral paralysis were measured using a train-of-four stimulus repeated once every 12 s. Atracurium appeared to be a potent non-depolanzmg muscle relaxant, with a rapid onset of action. However, full peripheral paralysis took longer to achieve than with suxamethonium. There were no significant problems with recovery.
Spontaneous pulsation of the retinal veins.

The classical theory of spontaneous pulsation of the retinal veins is that during systole intraocular pressure exceeds venous pressure, causing the veins to collapse. We show that this theory is internally inconsistent and not in accord with experimental data. It is inconsistent in assuming both (a) that oscillations of intraocular pressure (IOP) occur because the veins cannot immediately discharge the systolic arterial inflow and (b) that retinal venous pressure (RVP) can fluctuate independently of IOP during the cardiac cycle. It is not in accord with experimental data, which shows that RVP always exceeds IOP and that fluctuations in the latter are instantly transmitted to the former. We present an alternative theory that does not have these problems. We assume the following. (1) Inflow to the retinal venous tree from the capillaries is constant, the pulsatile arterial flow having been completely damped by the arterioles and capillaries. (2) Outflow from the central retinal vein (CRV) varies during the cardiac cycle because oscillations of IOP, transmitted to the intraocular CRV, are of greater amplitude than oscillations in cerebrospinal fluid pressure, transmitted to the extraocular CRV. By showing that the radial blood flow distending the veins obeys a diffusion equation and by employing an "equivalent cylinder" analysis of the branched venous tree to simplify the boundary conditions, we demonstrate that, with the above assumptions and the additional assumption of low amplitude of radial flow, the CRV will pulsate, and the pulsations will remain confined to a small segment near the exit point. The proposed theory can explain disappearance of pulsation with intracranial hypertension, intensification of pulsation in glaucoma, and variability in the linear extent and amplitude of pulsation among normal individuals. The theory may also be applied to other venous pulsations, such as the respiratory pulsation of the terminal portions of large veins entering the thorax or the cardiac cycle pulsation of the superior vena cava.
Marked differences in the frequency of microsatellite instability in gastric cancer from different countries

Objective:Previous studies have reported variable rates of microsatellite instability (MSI) in gastric cancer. We investigated the frequency of MSI in invasive gastric carcinoma of patients from three geographic regions.Methods:Genomic DNA from gastric cancer and nontumor tissue from 22 Korean, 20 Colombian, and 26 U.S. patients was amplified with five microsatellite markers.Results:MSI was more frequently seen in gastric cancer from Korea, affecting 50% of patients, in contrast with gastric cancers from the U.S. (7%) and Colombia (15%) (p= 0.003 and p= 0.03, respectively). MSI at one locus was significantly more frequent in gastric cancer from individuals >65 yr (p= 0.01). MSI was similarly associated with both diffuse and intestinal types of gastric cancer.Conclusion:MSI affects the two major histological types of gastric cancer, and was more frequent in gastric cancer from Korea than in the other countries, suggesting that the relative importance of different pathways of gastric carcinogenesis may vary in diverse regions of the world.
A modified Risser grading system predicts the curve acceleration phase of female adolescent idiopathic scoliosis.

BACKGROUND The Risser sign can be assessed with the United States method or the European method. The Tanner-Whitehouse method estimates skeletal age on the basis of hand radiography and digital skeletal age. Digital skeletal age scores between 400 and 425 are associated with the beginning of the curve acceleration phase or peak growth velocity in adolescent idiopathic scoliosis. The first objective of the present study was to evaluate the agreement between the two Risser grading systems. The second objective was to identify which grading system best predicts a digital skeletal age of between 400 and 425. The third objective was to explore a new system that could be used to replace the Risser method. METHODS One hundred female patients with adolescent idiopathic scoliosis were recruited in this cross-sectional descriptive study. Each patient was evaluated with posteroanterior spine and hand radiographs. The Risser sign was measured according to both the United States and European grading systems. Digital skeletal age was calculated, and triradiate cartilage ossification was assessed. RESULTS With use of kappa statistics, moderate agreement between the United States and European grading systems was seen. Risser stages alone were not good predictors of the curve acceleration phase. A new system with three groups was tested, and the second group (Risser 0 with closed triradiate cartilage and Risser 1) was the best predictor of a digital skeletal age score of between 400 and 425. CONCLUSIONS Two Risser grading systems coexist, and the agreement between them is moderate. No Risser stage was found to be a good clinical landmark for the beginning of the curve acceleration phase of adolescent idiopathic scoliosis. A new group, Risser 0 with closed triradiate cartilage and Risser 1, was the best predictor of the beginning of the curve acceleration phase. This new system is easy to implement and is based on findings that are available on spine radiographs. It should be used at the first visit and for scoliosis follow-up to assess skeletal maturity and correlation with the curve acceleration phase.
In‐vitro anti‐inflammatory activity of Pinus sylvestris and Plantago lanceolata extracts: effect on inducible NOS, COX‐1, COX‐2 and their products in J774A.1 murine macrophages

Extracts of the plant species Pinus sylvestris L. and Plantago lanceolata L. have been used in traditional medicine for the treatment of certain respiratory diseases, but little is known about their precise effects and mechanisms of action. In this study, we investigated the effect of these plant extracts on the production of nitric oxide (NO) and prostaglandin E2, NO synthase (NOS) type II, cyclooxygenase‐1 (COX‐1) and COX‐2 mRNA expression in the murine macrophage cell line J774A.1. We found that Pinus sylvestris and Plantago lanceolata extracts inhibited NO production in a concentration‐dependent manner in this cell line, without obvious cytotoxic effects as tested by MTT assay. The Plantago lanceolata extract at all doses used, and the Pinus sylvestris extract at high doses, showed significant scavenging of NO radicals released by the NO donor PAPA‐NONOate. Our data also show that pre‐treatment with these extracts significantly inhibits inducible NOS (iNOS) mRNA production in this cell line, without affecting COX‐1 mRNA expression. COX‐2 mRNA levels and PGE2 levels induced by lipopolysaccharide/interferon‐γ were not modified upon pre‐treatment with the extracts. Thus, our results suggest that the anti‐inflammatory properties of Pinus sylvestris and Plantago lanceolata extracts may reflect decreased NO production, possibly due to inhibitory effects on iNOS gene expression or to NO‐scavenging activity.
Synergistic regulation of endothelial tight junctions by antioxidant (Se) and polyunsaturated lipid (GLA) via Claudin‐5 modulation

Tight junctions (TJs) in endothelial cells act as cell–cell adhesion structures, governing paracellular permeability (PCP). Disruption can lead to leaky vascular bed and potentially to oedema and swelling of tissues, the aetiology of mastalgia. These changes may also cause vascular spread of cancer cells. This study aimed to determine whether the function of TJs in endothelial cells can be strengthened by gamma linolenic acid (GLA), selenium (Se) and iodine (I) in the presence of 17beta‐estradiol (17β‐estradiol), which causes leakage of endothelial cells by disruption of TJs in endothelium. GLA, I, and Se individually increased transendothelial resistance. The combination of all three agents also had a significant effect on TER. Addition of GLA/Se/I reduced PCP of the endothelial cells. Treatment with GLA/Se/I reversed the effect of 17β‐estradiol in reducing TER and increasing PCP. Immunofluorescence revealed that after treatment with Se/I/GLA over 24 h there was increasing relocation to endothelial cell–cell junctions of the TJ proteins Claudin‐5, Occludin, and ZO‐1. Interestingly, this relocation was particularly evident with treatments containing I when probing with Claudin‐5 and those containing Se for Occludin. There was a small increase in overall protein levels when examined by Western blotting after treatment with GLA/Se/I when probed with Claudin‐5 and Occludin. We report that GLA, I, and Se alone, or in combination are able to strengthen the function of TJs in human endothelial cells, by way of regulating the distribution of Claudin‐5, Occludin, and ZO‐1. Interestingly, this combination was also able to completely reverse the effect of 17β‐estradiol in these cells. J. Cell. Biochem. 98: 1308–1319, 2006. © 2006 Wiley‐Liss, Inc.
Pyruvate Dehydrogenase Kinase 1 Participates in Macrophage Polarization via Regulating Glucose Metabolism

The M1 and M2 polarized phenotypes dictate distinctive roles for macrophages as they participate in inflammatory disorders. There has been growing interest in the role of cellular metabolism in macrophage polarization. However, it is currently unclear whether different aspects of a specific metabolic program coordinately regulate this cellular process. In this study, we found that pyruvate dehydrogenase kinase 1 (PDK1), a key regulatory enzyme in glucose metabolism, plays an important role in the differential activation of macrophages. Knockdown of PDK1 diminished M1, whereas it enhanced M2 activation of macrophages. Mechanistically, PDK1 knockdown led to diminished aerobic glycolysis in M1 macrophages, which likely accounts for the attenuated inflammatory response in these cells. Furthermore, we found that mitochondrial respiration is enhanced during and required by the early activation of M2 macrophages. Suppression of glucose oxidation, but not that of fatty acids, inhibits this process. Consistent with its inhibitory role in early M2 activation, knockdown of PDK1 enhanced mitochondrial respiration in macrophages. Our data suggest that two arms of the glucose metabolism synergistically regulate the differential activation of macrophages. Our findings also highlight the central role of PDK1 in this event via controlling glycolysis and glucose oxidation.
Effects of metabolic perturbation on plasma homovanillic acid in schizophrenia. Relationship to prefrontal cortex volume.

OBJECTIVE Several recent hypotheses suggest that deficits in normal prefrontal cortical inhibition of subcortical dopamine activity result in dysregulated dopamine function and may contribute to the pathophysiology of schizophrenia. These effects seem to be more consistently demonstrable during stressful perturbation of the dopamine system, as opposed to during the resting state. We have developed a novel paradigm involving infusion of the glucose analog, 2-deoxyglucose (2DG), to examine the effects of perturbation on the dopamine metabolite, plasma homovanillic acid (HVA), in schizophrenics and healthy controls. DESIGN Pharmacologic doses of 2DG (50 mg/kg) and placebo were infused in a double-blind manner. 2-Deoxyglucose-induced effects on plasma HVA were related to magnetic resonance imaging-derived prefrontal cortex volumes. SUBJECTS Schizophrenic outpatients (N = 18) and healthy volunteers (N = 11) participated in the study. RESULTS Schizophrenic patients, as compared with controls, had significantly greater 2DG-induced plasma HVA elevations. These effects were observed in subgroups of neuroleptic-free and neuroleptic-treated patients. Other neuroendocrine (plasma cortisol), physiologic (heart rate, diastolic blood pressure, temperature) and behavioral (self-ratings of stress, fatigue) variables were significantly effected by 2DG but did not differeniate schizophrenics and controls suggesting that the effects on plasma HVA may be relatively specific. Magnetic resonance imaging-derived volumes of the prefrontal cortex were significantly and inversely correlated to 2DG-related peak changes in plasma HVA levels in the schizophrenics. CONCLUSION These data support the hypothesis that schizophrenia is associated with abnormal regulation of dopamine and that this deficit may be related to reduced frontal cortical inhibitory influences.