Miracle-dz/UniFAR-FTUs huggingface dataset:
Is vitamin D a determinant of muscle mass and strength?

There remains little consensus on the link between vitamin levels and muscle mass or strength. We therefore investigated the association of serum 25‐hydroxyvitamin D (25(OH)D), 1,25‐dihydroxyvitamin D (1,25(OH)2D), and parathyroid hormone (PTH) levels with skeletal muscle mass and strength. We studied 311 men (mean age, 56 years; range, 23–91 years) and 356 women (mean age, 57 years; range, 21–97 years) representing an age‐stratified, random sample of community adults. Multivariate linear regression models were used to examine the association of skeletal muscle mass (by total body dual‐energy X‐ray absorptiometry) and strength (handgrip force and isometric knee extension moment) with each of 25(OH)D, 1,25(OH)2D, and PTH quartiles, adjusted for age, physical activity, fat mass, and season. We found no consistent association between 25(OH)D or PTH and any of our measurements of muscle mass or strength, in either men or women. However, in subjects younger than 65 years, there was a statistically significant association between low 1,25(OH)2D levels and low skeletal mass in both men and women and low isometric knee extension moment in women, after adjustment for potential confounders. Modestly low 25(OH)D or high PTH levels may not contribute significantly to sarcopenia or muscle weakness in community adults. The link between low 25(OH)D and increased fall risk reported by others may be due to factors that affect neuromuscular function rather than muscle strength. The association between low 1,25(OH)2D and low skeletal mass and low knee extension moment, particularly in younger people, needs further exploration. © 2011 American Society for Bone and Mineral Research
Activated B Cells Participating in the Anti-Myelin Response Are Excluded from the Inflamed Central Nervous System in a Model of Autoimmunity that Allows for B Cell Recognition of Autoantigen

Once activated, T cells gain the ability to access both healthy and inflamed nonlymphoid tissues. They are then reactivated to remain in the tissue and exert their effector function only if they encounter their specific Ag. In this study, we set out to determine if the same is true for B cells using a mouse model of CNS autoimmunity that incorporates both T and B cell recognition of a myelin autoantigen. Both T and B cells were common infiltrates of spinal cords in diseased mice. However, unlike T cells, anti-myelin B cells were excluded from the inflamed tissue. Further, CNS B cells did not have a phenotype consistent with Ag-specific activation as it occurs in lymphatic tissue. Instead, they expressed elevated levels of CD80, indicating that B cells may contribute to local inflammation through nonantigen-specific mechanisms.
Influence of Bundle Diameter and Attachment Point on Kinematic Behavior in Double Bundle Anterior Cruciate Ligament Reconstruction Using Computational Model

A protocol to choose the graft diameter attachment point of each bundle has not yet been determined since they are usually dependent on a surgeon's preference. Therefore, the influence of bundle diameters and attachment points on the kinematics of the knee joint needs to be quantitatively analyzed. A three-dimensional knee model was reconstructed with computed tomography images of a 26-year-old man. Based on the model, models of double bundle anterior cruciate ligament (ACL) reconstruction were developed. The anterior tibial translations for the anterior drawer test and the internal tibial rotation for the pivot shift test were investigated according to variation of bundle diameters and attachment points. For the model in this study, the knee kinematics after the double bundle ACL reconstruction were dependent on the attachment point and not much influenced by the bundle diameter although larger sized anterior-medial bundles provided increased stability in the knee joint. Therefore, in the clinical setting, the bundle attachment point needs to be considered prior to the bundle diameter, and the current selection method of graft diameters for both bundles appears justified.
Phylogeographical disjunction in abundant high‐dispersal littoral gastropods

Phylogeographical disjunctions in high‐dispersal marine taxa are variously ascribed to palaeogeographical conditions or contemporary ecological factors. Associated biogeographical studies, however, seldom incorporate the sampling design required to confidently discriminate among such competing hypotheses. In the current study, over 7800 gastropod specimens were examined for operculum colour, and 129 specimens genetically, to test ecological and historical biogeographical hypotheses relating to biogeographical disjunction in the Southern Hemisphere, and to southern Australia in particular. Mitochondrial DNA sequence analysis of the high‐dispersal intertidal gastropod Nerita atramentosa in southern Australia (88 specimens; 18 localities) revealed an east–west phylogeographical split involving two highly divergent clades (26.0 ± 1.9%) exhibiting minimal geographical overlap in the southeast. The eastern clade of Nerita atramentosa is also widespread in northern New Zealand (43 specimens, 10 localities), but no significant genetic differentiation is explained by the Tasman Sea, a 2000‐km‐wide oceanic barrier. Spatial genetic structure was not detected within either clade, consistent with the species’ dispersive planktotrophic phase lasting for 5–6 months. Digital analysis of operculum colouration revealed substantial differences between eastern (tan) and western (black) specimens. Genetic analysis and visual inspection of 88 Australian specimens revealed a completely nonrandom association between mtDNA data and operculum colouration. Independent examination of a further 7822 specimens from 14 sites in southern Australia revealed both colour morphs at all localities, but reinforced the phylogeographical data by indicating a marked turnover in colour morph abundance associated with a palaeogeographical barrier: Wilsons Promontory. This sharp biogeographical disjunction is in marked contrast to the species’ high dispersal abilities. The genetic similarity of Nerita morio (Easter Island) and the eastern Australian + New Zealand lineage (1.1 ± 0.3%) provides further evidence of long‐distance dispersal in southern Nerita. Phylogenetic relationships of nine species (four genera) of Neritidae, an almost exclusively tropical gastropod family, are consistent with the hypothesis that southern temperate black nerites comprise a monophyletic radiation.
Cross-Channel Estimation Using Supervised Probing and Sensing in Cognitive Radio Networks

Prior work in implementing spectrum sharing scenarios for cognitive radio networks has relied on the unlikely assumption of full cross-channel knowledge made available to the cognitive transmitter (CT) and/or the target primary receiver (PR). However, estimation of this cross-channel knowledge is not only important from a practical stand-point, but also in limiting the real interference power felt at the PR due to concurrent CT transmissions. We propose a supervised probing and sensing model, which enables the CT to gain a decent estimate of the cross-channel, assess the spectrum opportunities in its region of interference, and according to its throughput needs safely share or access primary user spectrum. With the probing power increment playing an essential part in the probing model, its optimization with respect to cross-channel estimation success and its influence on mean square error of the cross-channel estimation are discussed.
Genistein suppresses the mitochondrial apoptotic pathway in hippocampal neurons in rats with Alzheimer's disease

Genistein is effective against amyloid-β toxicity, but the underlying mechanisms are unclear. We hypothesized that genistein may protect neurons by inhibiting the mitochondrial apoptotic pathway, and thereby play a role in the prevention of Alzheimer's disease. A rat model of Alzheimer's disease was established by intraperitoneal injection of D-galactose and intracerebral injection of amyloid-β peptide (25–35). In the genistein treatment groups, a 7-day pretreatment with genistein (10, 30, 90 mg/kg) was given prior to establishing Alzheimer's disease model, for 49 consecutive days. Terminal deoxyribonucleotidyl transferase-mediated dUTP nick end labeling assay demonstrated a reduction in apoptosis in the hippocampus of rats treated with genistein. Western blot analysis showed that expression levels of capase-3, Bax and cytochrome c were decreased compared with the model group. Furthermore, immunohistochemical staining revealed reductions in cytochrome c and Bax immunoreactivity in these rats. Morris water maze revealed a substantial shortening of escape latency by genist-ein in Alzheimer's disease rats. These findings suggest that genistein decreases neuronal loss in the hippocampus, and improves learning and memory ability. The neuroprotective effects of genistein are associated with the inhibition of the mitochondrial apoptotic pathway, as shown by its ability to reduce levels of caspase-3, Bax and cytochrome c.
An ontological analysis of the relationship construct in conceptual modeling

Conceptual models or semantic data models were developed to capture the meaning of an application domain as perceived by someone. Moreover, concepts employed in semantic data models have recently been adopted in object-oriented approaches to systems analysis and design. To employ conceptual modeling constructs effectively, their meanings have to be defined rigorously. Often, however, rigorous definitions of these constructs are missing. This situation occurs especially in the case of the relationship construct. Empirical evidence shows that use of relationships is often problematical as a way of communicating the meaning of an application domain. For example, users of conceptual modeling methodologies are frequently confused about whether to show an association between things via a relationship, an entity, or an attribute. Because conceptual models are intended to capture knowledge about a real-world domain, we take the view that the meaning of modeling constructs should be sought in models of reality. Accordingly, we use ontology, which is the branch of philosophy dealing with models of reality, to analyze the meaning of common conceptual modeling constructs.Our analysis provides a precise definition of several conceptual modeling constructs. Based on our analysis, we derive rules for the use of relationships in entity-relationship conceptual modeling. Moreover, we show how the rules resolve ambiguities that exist in current practice and how they can enrich the capacity of an entity-relationship conceptual model to capture knowledge about an application domain.
Characteristics of Elderly Patients with Diabetes and End‐Stage Renal Disease

Because of a combination of demographic and social factors, such as the aging of the population in general, increased incidence of diabetes, and more liberal criteria for renal replacement therapy initiation, the proportion of the end‐stage renal disease (ESRD) patients with diabetes who are considered elderly is currently the fastest growing segment of incident ESRD population. Despite the fast growth of this group, it is poorly characterized in current literature. In this review, we attempt to summarize the data available to date regarding demographic composition, outcomes, choice of renal replacement therapy, and other management issues including renal transplantation. There is significant evidence that the elderly diabetic patients might differ from the general dialysis population regarding renal replacement modality, vascular access for dialysis, and that guidelines addressing chronic kidney disease (CKD) issues such as nutrition and blood pressure may need modification in this ESRD subgroup. At the same time, other areas such as anemia and bone mineral metabolism have not been adequately studied. Lastly, despite lower rates of kidney transplantation in this population, it confers significant survival advantages, similar to that seen in younger populations. As the fastest growing group in the incident ESRD population, these patients have issues related to clinical management, which represent very important areas for future research.
Studying the effect of cell division on expression patterns of the segment polarity genes

The segment polarity gene family, and its gene regulatory network, is at the basis of Drosophila embryonic development. The network's capacity for generating and robustly maintaining a specific gene expression pattern has been investigated through mathematical modelling. The models have provided several useful insights by suggesting essential network links, or uncovering the importance of the relative time scales of different biological processes in the formation of the segment polarity genes' expression patterns. But the developmental pattern formation process raises many other questions. Two of these questions are analysed here: the dependence of the signalling protein sloppy paired on the segment polarity genes and the effect of cell division on the segment polarity genes' expression patterns. This study suggests that cell division increases the robustness of the segment polarity network with respect to perturbations in biological processes.
Ground State Robustness as an Evolutionary Design Principle in Signaling Networks

The ability of an organism to survive depends on its capability to adapt to external conditions. In addition to metabolic versatility and efficient replication, reliable signal transduction is essential. As signaling systems are under permanent evolutionary pressure one may assume that their structure reflects certain functional properties. However, despite promising theoretical studies in recent years, the selective forces which shape signaling network topologies in general remain unclear. Here, we propose prevention of autoactivation as one possible evolutionary design principle. A generic framework for continuous kinetic models is used to derive topological implications of demanding a dynamically stable ground state in signaling systems. To this end graph theoretical methods are applied. The index of the underlying digraph is shown to be a key topological property which determines the so-called kinetic ground state (or off-state) robustness. The kinetic robustness depends solely on the composition of the subdigraph with the strongly connected components, which comprise all positive feedbacks in the network. The component with the highest index in the feedback family is shown to dominate the kinetic robustness of the whole network, whereas relative size and girth of these motifs are emphasized as important determinants of the component index. Moreover, depending on topological features, the maintenance of robustness differs when networks are faced with structural perturbations. This structural off-state robustness, defined as the average kinetic robustness of a network's neighborhood, turns out to be useful since some structural features are neutral towards kinetic robustness, but show up to be supporting against structural perturbations. Among these are a low connectivity, a high divergence and a low path sum. All results are tested against real signaling networks obtained from databases. The analysis suggests that ground state robustness may serve as a rationale for some structural peculiarities found in intracellular signaling networks.
Poor description of non-pharmacological interventions: analysis of consecutive sample of randomised trials

Objectives To evaluate the completeness of descriptions of non-pharmacological interventions in randomised trials, identify which elements are most frequently missing, and assess whether authors can provide missing details. Design Analysis of consecutive sample of randomised trials of non-pharmacological interventions. Data sources and study selection All reports of randomised trials of non-pharmacological interventions published in 2009 in six leading general medical journals; 133 trial reports, with 137 interventions, met the inclusion criteria. Data collection Using an eight item checklist, two raters assessed the primary full trial report, plus any reference materials, appendices, or websites. Questions about missing details were emailed to corresponding authors, and relevant items were then reassessed. Results Of 137 interventions, only 53 (39%) were adequately described; this was increased to 81 (59%) by using 63 responses from 88 contacted authors. The most frequently missing item was the “intervention materials” (47% complete), but it also improved the most after author response (92% complete). Whereas some authors (27/70) provided materials or further information, other authors (21/70) could not; their reasons included copyright or intellectual property concerns, not having the materials or intervention details, or being unaware of their importance. Although 46 (34%) trial interventions had further information or materials readily available on a website, many were not mentioned in the report, were not freely accessible, or the URL was no longer functioning. Conclusions Missing essential information about interventions is a frequent, yet remediable, contributor to the worldwide waste in research funding. If trial reports do not have a sufficient description of interventions, other researchers cannot build on the findings, and clinicians and patients cannot reliably implement useful interventions. Improvement will require action by funders, researchers, and publishers, aided by long term repositories of materials linked to publications.
Increased expression of AML1‐a and acquired chromosomal abnormalities in childhood acute lymphoblastic leukemia

A semi‐quantitative expression analysis of both AML1‐a and AML1‐total was performed by RT‐PCR in 19 children with acute lymphoblastic leukemia (ALL) at diagnosis. AML1‐a expression was assessed in 16 bone marrow (BM) and 13 peripheral blood (PB) samples whereas AML1‐total was assessed in 17 BM and 16 PB samples. These analyses were also carried out in 15 PB samples of healthy controls. In addition, 18/19 patients were karyotyped: 11 had an unmodified constitutional karyotype (CK) and seven exhibited acquired chromosomal abnormalities (ACA). The expression of AML1‐a was significantly increased in BM and PB when compared with the controls (p < 0.013 and p < 0.035, respectively). A significant increase was found in the expression of AML1‐a in BM of the ACA group compared with the CK group (p < 0.0009). The expression of AML1‐a in BM and PB showed a significant increase in the ACA group compared with controls (p < 0.00001 and p < 0.012, respectively); in contrast, the CK group did not differ from the controls. These observations may mean that the increase of AML1‐a favours the progression of leukemia. Copyright © 2005 John Wiley & Sons, Ltd.
Fluticasone Inhalation in Moderate Cases of Bronchopulmonary Dysplasia

Objective.This randomized, controlled trial was designed to determine the efficacy of inhaled fluticasone propionate on oxygen therapy weaning in a population of preterm infants who were born at <32 weeks of gestation and experienced moderate bronchopulmonary dysplasia (BPD). Methods.Thirty-two infants who were ≤32 weeks of gestation, had moderate BPD that required supplemental oxygen (fraction of inspired oxygen ≥0.25), and were aged between 28 and 60 days were randomized. Fluticasone propionate 125 μg twice daily for 3 weeks and once daily for a fourth week was delivered to infants who weighed between 500 and 1200 g. The dosage was doubled for infants who weighed ≥1200 g. Results.Compared with placebo, treatment had no effect on either duration of supplemental O2 therapy or ventilatory support as assessed by survival analysis. At 28 days, a trend toward a lower cortisol/creatinine ratio in the treatment group was noted compared with placebo (25.1 ± 18.9 vs 43 ± 14.4). In the fluticasone group at 28 days, the systolic arterial pressure (78 ± 3 vs 68 ± 3 mm Hg) and diastolic arterial pressure (43 ± 3.4 mm Hg vs 38 ± 2.0 mm Hg) were higher compared with baseline fluticasone values. The chest radiograph score was lower than baseline (2.8 ± 1.4 vs 3.7 ± 2.2) in the fluticasone group at 28 days. This study has a statistical power of 1.0 to detect a significant difference in the duration of oxygen supplementation of >21 days between the study groups. Conclusion.We conclude that fluticasone propionate reduces neither supplemental O2 use nor the need for ventilatory support in this patient population. However, fluticasone does have a positive radiologic effect in lowering chest radiograph scores. In addition, our data point to a possible association among inhaled fluticasone treatment and higher arterial blood pressure. Thus, the results of this investigation do not support the use of inhaled corticosteroids in the treatment of oxygen-dependent infants who have established moderate BPD.
Major Histocompatibility Complex (MHC) Class II-Peptide Complexes Arrive at the Plasma Membrane in Cholesterol-rich Microclusters*

Background: Antigen-specific CD4 T cells are activated by small numbers of antigenic peptide-MHC class II (pMHC-II) complexes on dendritic cells (DCs). Results: Newly generated pMHC-II complexes are present in small clusters on the DC surface. Conclusion: pMHC-II clusters permit efficient T cell activation. Significance: The appearance of clustered pMHC-II reveals the organization of the T cell antigen receptor ligand on the DC surface. Dendritic cells (DCs) function by stimulating naive antigen-specific CD4 T cells to proliferate and secrete a variety of immunomodulatory factors. The ability to activate naive T cells comes from the capacity of DCs to internalize, degrade, and express peptide fragments of antigenic proteins on their surface bound to MHC class II molecules (MHC-II). Although DCs express tens of thousands of distinct MHC-II, very small amounts of specific peptide-MHC-II complexes are required to interact with and activate T cells. We now show that stimulatory MHC-II I-Ak-HEL(46–61) complexes that move from intracellular antigen-processing compartments to the plasma membrane are not randomly distributed on the DC surface. Confocal immunofluorescence microscopy and quantitative immunoelectron microscopy reveal that the majority of newly generated MHC-II I-Ak-HEL(46–61) complexes are expressed in sub-100-nm microclusters on the DC membrane. These microclusters are stabilized in cholesterol-containing microdomains, and cholesterol depletion inhibits the stability of these clusters as well as the ability of the DCs to function as antigen-presenting cells. These results demonstrate that specific cohorts of peptide-MHC-II complexes expressed on the DC surface are present in cholesterol-dependent microclusters and that cluster integrity is important for antigen-specific naive CD4 T cell activation by DCs.
Regular, shape-polymorphic, parallel arrays in Haskell

We present a novel approach to regular, multi-dimensional arrays in Haskell. The main highlights of our approach are that it (1) is purely functional, (2) supports reuse through shape polymorphism, (3) avoids unnecessary intermediate structures rather than relying on subsequent loop fusion, and (4) supports transparent parallelisation. We show how to embed two forms of shape polymorphism into Haskell's type system using type classes and type families. In particular, we discuss the generalisation of regular array transformations to arrays of higher rank, and introduce a type-safe specification of array slices. We discuss the runtime performance of our approach for three standard array algorithms. We achieve absolute performance comparable to handwritten C code. At the same time, our implementation scales well up to 8 processor cores.