Miracle-dz/UniFAR-FTUs huggingface dataset:
Genome‐Wide Survey of Runs of Homozygosity Identifies Recessive Loci for Bone Mineral Density in Caucasian and Chinese Populations

Runs of homozygosity (ROHs), in which both parental alleles are identical, have been proposed to have recessive effects on multiple human complex diseases. Osteoporosis is a common complex disease characterized by low bone mineral density (BMD), which is highly heritable. And recessive loci that contribute to BMD variations have been identified. In this study, we performed a genome‐wide ROHs association study using our SNP array data from three GWAS samples including 4,900 subjects from Caucasian and Chinese populations. Significant results were further subjected to replication in 3,747 additional subjects. ROHs associated with BMD were also tested for associations with osteoporotic fractures in a GWAS fracture sample. Combining results from all the samples, we identified 697 autosomal regions with ROHs. Among these, we detected genome‐wide significant associations between BMD and 6 ROHs, including ROH1q31.3, 1p31.1, 3q26.1, 11q12.1, 21q22.1 and 15q22.3 (combined P = 6.29 × 10‐5 ‐ 3.17 × 10‐8). Especially, ROH1p31.1 was found to be associated with increased risk of osteoporotic hip fractures (odds ratio [OR] = 3.71, P = 0.032). To investigate the functional relevance of the identified ROHs, we performed cis‐expression quantitative trait locus (eQTL) analysis in lymphoblast cell lines. Three ROHs, including ROH1p31.1, 11q12.1, and 15q22.3, were found to be significantly associated with mRNA expression levels of their nearby genes (PeQTL < 0.05). In summary, our findings reveal that ROHs could play as recessive‐acting determinants contributing to the pathogenesis of osteoporosis. Further molecular and functional studies are needed to explore and clarify the potential mechanism. © 2015 American Society for Bone and Mineral Research.
Awareness of SEC Enforcement and Auditor Reporting Decisions

We find that non-Big 4 audit offices with greater awareness of SEC enforcement are more likely to issue first-time going concern reports to distressed clients; where SEC “awareness” is measured using (1) audit office proximity to SEC regional offices, and (2) proximity to specific SEC enforcement actions against auditors. We also show that these non-Big 4 audit offices issue more going concern opinions to clients who do not subsequently fail, indicating a conservative bias that reduces the informativeness of audit reports. This conservative reporting bias is also associated with higher audit fees and higher auditor switching rates. These findings are important because non-Big 4 firms now audit 39 percent of SEC registrants and issue 88 percent of going concern audit reports. For Big 4 offices, we find some evidence that awareness of SEC enforcement may improve reporting accuracy by reducing Type II errors (failing to issue a going concern report to a company that fails), although the number of cases is small.
Preparation and characterization of titanium—segmented polyurethane composites for bone tissue engineering

Segmented polyurethanes were prepared with polycaprolactone diol as soft segment and 4,4-methylene-bis cyclohexyl diisocyanate and l-glutamine as the rigid segment. These polyurethanes were filled with 1 wt. % to 5 wt. % titanium particles (Ti), physicochemically characterized and their biocompatibility assessed using human dental pulp stem cells and mice osteoblasts. Physicochemical characterization showed that composites retained the properties of the semicrystalline polyurethane as they exhibited a glass transition temperature (Tg) between −35°C and −45°C, melting temperature (Tm) at 52°C and crystallinity close to 40% as determined by differential scanning calorimetry. In agreement with this, X-ray diffraction showed reflections at 21.3° and 23.6° for polycaprolactone diol and reflections at 35.1°, 38.4°, and 40.2° for Ti particles suggesting that these particles are not acting as nucleating sites. The addition of up to 5 wt. % of Ti reduced both, tensile strength and maximum strain from 1.9 MPa to 1.2 MPa, and from 670% to 172% for pristine and filled polyurethane, respectively. Although there were differences between composites at low strain rates, no significant differences in mechanical behavior were observed at higher strain rate where a tensile stress of 8.5 MPa and strain of 223% were observed for 5 wt. % composites. The addition to titanium particles had a beneficial effect on both human dental pulp stem cells and osteoblasts viability, as it increased with the amount of titanium in composites up to 10 days of incubation.
A new diarrhoeic syndrome with ataxia in young Charolais calves: clinical and microbiological studies

A new diarrhoeic syndrome was examined clinically in 19 one to two-week old Charolais calves. It differs from other digestive disorders in calves of this age in the discrete diarrhoeic signs, the absence of dehydration and the presence of signs of ataxia. The microbiological study carried out for three consecutive years in 58 sick calves and nine healthy control calves demonstrated the special role of E coli possessing virulence markers from septicaemic strains (CS31A, Col V). The clinical signs could be the result of bacteraemia with subacute E coli endotoxaemia.
Human Interaction Recognition Using Independent Subspace Analysis Algorithm

Human interaction recognition has been widely studied because it has great scientific importance and many practical applications. Most existing methods rely on spatio-temporal local features (i.e. SIFT), human poses, and human joints to model human interactions. Motivated by the success of deep learning networks, we introduce a three-layer convolutional network which uses the Independent Subspace Analysis (ISA) algorithm to learn hierarchical invariant features from videos. The obtained invariant features are used as the inputs to a standard bag-of-features (BOF) model to recognize human interactions. We investigate the performance of our approach and the effectiveness of hierarchical invariant features on video sequences of the UT-Interaction dataset which contain both interacting persons and irrelevant pedestrians in the scenes. Experimental results show that our three-layer convolutional ISA network is able to learn features which are effective to represent complex activities such as human interactions in realistic environments.
Autologous bone marrow grafting combined with demineralized bone matrix improves consolidation of docking site after distraction osteogenesis.

BACKGROUND Distraction osteogenesis is used for the reconstruction of extensive osseous defects. Delay in docking site consolidation results in significant prolongation of this surgical procedure. The primary aim of the present study was to retrospectively compare three different treatment options, all aimed at improving and accelerating docking site consolidation. We further sought to clarify whether the application of autologous bone marrow cells combined with demineralized bone matrix would substantially improve docking site consolidation. METHODS Between 1995 and 2008, forty-three patients (mean age, 38.28 years) were managed with bone transport for the treatment of a tibial bone defect (mean length, 9.49 cm). The patients were divided into three groups according to the "docking site procedure" used: closed compression (Group A), surgical debridement of the docking site and application of autologous iliac bone graft (Group B), or surgical debridement and local application of bone marrow concentrate and demineralized bone matrix (Group C). Docking site consolidation was assessed both radiographically and clinically, and the results were statistically analyzed. RESULTS The median "healing time" required for docking site consolidation was significantly longer in the compression group as compared with the demineralized bone matrix plus bone marrow group (p = 0.021), whereas there was no difference between the other groups. There was no significant difference among the groups in terms of complication rates (p = 0.702). Docking site consolidation was completed prior to regenerate consolidation in nine of the ten patients in Group C and in 13.6% of the patients in Group B, whereas in all of the remaining patients, completion of regenerate healing always preceded docking site consolidation. CONCLUSIONS The application of demineralized bone matrix and autologous bone marrow is at least equivalent to autologous cancellous bone graft in terms of substantially reducing docking site healing time compared with closed compression alone. The application of demineralized bone matrix and autologous bone marrow is an effective treatment option, with minimal donor site morbidity, for reducing consolidation time of the docking site in tibial defects treated with distraction osteogenesis.
Control of latent Mycobacterium tuberculosis infection is dependent on CD8 T cells

It is estimated that one‐third of the world's population is infected with Mycobacterium tuberculosis, but that only 10% of infected people break down with the disease. In the remaining 90% the infection remains clinically latent. In the present study, the immune mechanisms controlling the latent phase of tuberculosis infection were evaluated in a mouse model of latency and reactivation. Mice aerosol‐infected with M. tuberculosis were treated with anti‐mycobacterial drugs resulting in very low, stable bacterial numbers (<500 CFU in the spleen and lung) for 10–12 weeks followed by reactivation of the disease with increasing bacterial numbers. During latency, pathological changes in the lung had almost completely resolved and lymphocyte number and turnover were at the pre‐infection level. The CD4 subset was highly active during the acute phase of infection and could be detected by intracellular staining for IFN‐γ as well as after antigen‐specific stimulation with mycobacterial antigens. The CD8 subset was not involved in the acute stage of infection, but this subset was active and produced IFN‐γ during the latent phase of infection. In vivo depletion of T cell subsets supported these findings with a 6–7‐fold increase in bacterial numbers in the lung following anti‐CD4 treatment during the acute phase, while anti‐CD8 treatment did not have an effect. The opposite was found during the latent phase where anti‐CD8 treatment as well as anti‐IFN‐γ treatment both resulted in a 10‐fold increase in bacterial numbers in the lung, while anti‐CD4 treatment induced only a modest change.
Hippocampal long‐term depression is enhanced, depotentiation is inhibited and long‐term potentiation is unaffected by the application of a selective c‐Jun N‐terminal kinase inhibitor to freely behaving rats

Synaptic plasticity is regarded as the major candidate mechanism for synaptic information storage and memory formation in the hippocampus. Mitogen‐activated protein kinases have recently emerged as an important regulatory factor in many forms of synaptic plasticity and memory. As one of the subfamilies of mitogen‐activated protein kinases, extracellular‐regulated kinase is involved in the in vitro induction of long‐term potentiation (LTP), whereas p38 mediates metabotropic glutamate receptor‐dependent long‐term depression (LTD) in vitro. Although c‐Jun N‐terminal kinase (JNK) has also been implicated in synaptic plasticity, the in vivo relevance of JNK activity to different forms of synaptic plasticity remains to be further explored. We investigated the effect of inhibition of JNK on different forms of synaptic plasticity in the dentate gyrus of freely behaving adult rats. Intracereboventricular application of c‐Jun N‐terminal protein kinase‐inhibiting peptide (D‐JNKI) (96 ng), a highly selective JNK inhibitor peptide, did not affect basal synaptic transmission but reduced neuronal excitability with a higher dose (192 ng). Application of D‐JNKI, at a concentration that did not affect basal synaptic transmission, resulted in reduced specific phosphorylation of the JNK substrates postsynaptic density 95kD protein (PSD 95) and c‐Jun, a significant enhancement of LTD and a facilitation of short‐term depression into LTD. Both LTP and short‐term potentiation were unaffected. An inhibition of depotentiation (recovery of LTP) occurred. These data suggest that suppression of JNK‐dependent signalling may serve to enhance synaptic depression, and indirectly promote LTP through impairment of depotentiation.
Recent Advances in Soil Quality Assessment in the United States

Soil quality is a concept that is useful as an educational and assessment tool. A number of assessment tools have been developed including: the Soil Conditioning Index (SCI), the Soil Management Assessment Framework (SMAF), the AgroEcosystem Performance Assessment Tool (AEPAT), and the new Cornell "Soil Health Assessment". The SMAF and AEPAT were developed as malleable tools for assessing soil response to management. The Cornell Assessment builds on the SMAF approach to score laboratory tests in terms of soil function. This paper updates efforts to improve availability and utility, implementation, and future research goals associated with the SMAF. Additional scoring curves have been developed for percentage water-filled pore space (%WFPS), soil test potassium (K), and β-glucosidase activity. A web- based version of the SMAF is available. The SMAF has been implemented as part of the Conservation Effects Assessment Project (CEAP). Combining the SMAF and a CEAP survey approach appears to be a successful method for identifying soil quality risks at the watershed scale. Future plans include developing approaches for using the SMAF for model output and in spatially variable fields as well as adapting the SMAF for wide use by soil testing laboratories.
FIBER TYPES AND METABOLIC POTENTIALS OF SKELETAL MUSCLES IN SEDENTARY MAN AND ENDURANCE RUNNERS *

This description of some of the present knowledge on skeletal muscle fibers, their metabolic potentials, and their interplay with the degree of physical activity has revealed that skeletal muscle of man has a very large capacity for adaptation. Moreover, this adaptability appears to be of utmost importance for the metabolic response as well as for performance. Although all this is true, it should not distract us from the fact that we are lacking the most important information. The questions that need to be answered are: What triggers the changes to take place? Which are the regulatory mechanisms?
Outcome expectations for exercise scale: utility and psychometrics.

OBJECTIVES The purpose of this study was to develop a measure of outcome expectations for exercise specifically for the older adult (The Outcome Expectations for Exercise [OEE] Scale), and to test the reliability and validity of this measure in a sample of older individuals. This scale was developed based on Bandura's theory of self-efficacy and the work of prior researchers in the development of measures of outcome expectations. METHODS The OEE scale, which was completed during a face-to-face interview, was tested in a sample of 175 residents in a continuing care retirement community. RESULTS There was support for the internal consistency of the OEE scale (alpha coefficient of .89), and some support for reliability based on a structural equation modeling approach that used R2 estimates, although less than half of these were greater than 0.5. There was evidence of validity of the measure based on: (a) a confirmatory factor analysis in which the model fit the data (normed fit index [NFI] = .99, root mean square error of approximation [RMSEA] - .07, chi2/df = 2.8); (b) support for the hypothesis that those who exercised regularly had higher OEE scores than those who did not (F = 31.3, p < .05, eta squared = .15); and (c) a statistically significant relationship between outcome expectations and self-efficacy expectations (r = .66). DISCUSSION This study provides some initial support for the reliability and validity of the OEE scale. Outcome expectations for exercise were related to exercise behavior in the older adult, and the OEE scale can help identify older adults with low outcome expectations for exercise. Interventions can then be implemented to help these individuals strengthen their outcome expectations, which may subsequently improve exercise behavior.
Expression of Helicobacter pylori Virulence Factors and Associated Expression Profiles of Inflammatory Genes in the Human Gastric Mucosa

ABSTRACT Helicobacter pylori virulence factors have been suggested to be important in determining the outcome of infection. The H. pylori adhesion protein BabA2 is thought to play a crucial role in bacterial colonization and in induction of severe gastric inflammation, particularly in combination with expression of CagA and VacA. However, the influence of these virulence factors on the pathogenesis of H. pylori infection is still poorly understood. To address this question, the inflammatory gene expression profiles for two groups of patients infected with triple-negative strains (lacking expression of cagA, babA2, and vacAs1 but expressing vacAs2) and triple-positive strains (expressing cagA, vacAs1, and babA2 but lacking expression of vacAs2) were investigated. The gene expression patterns in the antrum gastric mucosa from patients infected with different H. pylori strains were very similar, and no differentially expressed genes could be identified by pairwise comparisons. Our data thus suggest that there is a lack of correlation between the host inflammatory responses in the gastric mucosa and expression of the babA2, cagA, and vacAs1 genes.
Soluble c-Met receptors inhibit phosphorylation of c-Met and growth of hepatocyte growth factor: c-Met–dependent tumors in animal models

c-Met is a receptor tyrosine kinase frequently overexpressed or amplified in many types of human cancers. Hepatocyte growth factor (HGF, also known as scatter factor) is the only known ligand for c-Met. In this study, soluble human and murine c-Met receptor-Fc fusion proteins were generated and were shown to bind to human and murine HGF as measured by fluorescence-activated cell sorting and surface plasmon resonance (Biacore) assays. Also, both human and murine c-Met-Fc showed activity in functional cell assays, inhibiting HGF-induced c-Met phosphorylation in PC3 and 4T1 cells, respectively, and inhibiting HGF-driven cellular invasion in a dose-dependent manner. Pharmacokinetic analysis showed that both reagents were suitable for in vivo testing. Systemic administration of human c-Met-Fc significantly inhibited tumor growth in the human HGF-dependent U-87 MG xenograft model at daily doses of 30 or 100 μg (P < 0.0001). Similarly, murine c-Met-Fc, at 100 μg daily, significantly inhibited tumor growth in the murine HGF–dependent CT-26 syngeneic tumor model (P < 0.002). Human and murine c-Met-Fc seemed to be well-tolerated in animals. In conclusion, both mouse and human versions of c-Met-Fc effectively block HGF-induced activation of c-Met and inhibit growth of tumor xenografts, providing further evidence that c-Met is an important target for oncology therapeutics. [Mol Cancer Ther 2009;8(5):1119–25]
Long-term Outcome of 104 Patients after Lumbar Sequestrectomy According to Williams

OBJECTIVEThe authors report the late outcome of 104 consecutive patients after Williams’ sequestrectomy for virgin lumbar disc herniation. METHODSThe clinical records and the mailed questionnaires of 38 women and 66 men operated consecutively between March 1991 and November 1993 were analyzed retrospectively. In these 104 patients, 105 Williams’ sequestrectomies were performed. RESULTSThe mean age at operation was 50.5 years (range, 23.2–86.7 yr), and follow-up ranged from 4.1 to 6.9 years (mean, 5.3 yr). Success rates, including excellent, good, and fair results, were 92.5%, 94.7%, and 93.3% for lumbalgia, radicular pain, and neurological dysfunction, respectively. Only a few patients did not improve or presented with worsened symptoms. Three of four patients with cauda equina syndrome recovered immediately after the intervention. There were eight (7.7%) minor postoperative complications, which were treated conservatively. Three women and three men (5.8%) underwent a revision procedure for a recurrent lumbar disc herniation at the same level after 0.4 to 3.1 years (mean, 1.8 yr). Two (1.9%) of these patients underwent further operations because of reherniation, and they required internal instrumentation eventually because of failed back surgery syndrome. CONCLUSIONWilliams’ conservative approach with sequestrectomy alone is a safe operative modality. It should be used whenever possible. As demonstrated in our series with a long follow-up time, the results are as favorable as or better than results after standard microsurgical lumbar discectomy with curettement of the interspace. Whether the incidence of failed back surgery syndrome can be reduced by this approach remains to be proved.
Enhanced fluorescence cell imaging with metal-coated slides

The last decade has witnessed momentous advances in fluorescence microscopy. The introduction of novel fluorescent markers, together with the development of original microscopy techniques, made it possible to study biomolecular interactions in living cells and to examine the structure and function of living tissues. The emergence of these innovative techniques had a remarkable impact on all the life sciences. However, many biological and medical applications involve the detection of minute quantities of biomolecules, and are limited by the signal weakness in common observation conditions. Here, we show that silver and gold-coated microscope slides can be used as mirror substrates to efficiently improve detection sensitivity when fluorescence microscopy is applied to micrometer-thick biological samples. We report a fourfold enhancement of the fluorescence signal and a noticeable strengthening of the image contrast, when mirror substrates are used with standard air microscope objectives. We demonstrate that metal-coated substrates provide the means to get sensitivity-enhanced fluorescence detection with dry optics, while keeping a wide field observation and a large depth of field. This is a crucial advantage for automated and high-throughput applications to cell and tissue diagnostic analysis.
A Poxvirus Protein That Binds to and Inactivates IL-18, and Inhibits NK Cell Response1

IL-18 induces IFN-γ and NK cell cytotoxicity, making it a logical target for viral antagonism of host defense. We demonstrate that the ectromelia poxvirus p13 protein, bearing homology to the mammalian IL-18 binding protein, binds IL-18, and inhibits its activity in vitro. Binding of IL-18 to the viral p13 protein was compared with binding to the cellular IL-18R. The dissociation constant of p13 for murine IL-18 is 5 nM, compared with 0.2 nM for the cellular receptor heterodimer. Mice infected with a p13 deletion mutant of ectromelia virus had elevated cytotoxicity for YAC-1 tumor cell targets compared with control animals. Additionally, the p13 deletion mutant virus exhibited decreased levels of infectivity. Our data suggest that inactivation of IL-18, and subsequent impairment of NK cell cytotoxicity, may be one mechanism by which ectromelia evades the host immune response.