Miracle-dz/UniFAR-FTUs huggingface dataset:
Tissue‐Level Mechanisms Responsible for the Increase in Bone Formation and Bone Volume by Sclerostin Antibody

Bone formation can be remodeling‐based (RBF) or modeling‐based (MBF), the former coupled to bone resorption and the latter occurring directly on quiescent surfaces. Unlike osteoanabolic therapies such as parathyroid hormone (PTH) 1‐34 that increase bone remodeling and thus both formation and resorption, sclerostin antibody (Scl‐Ab) increases bone formation while decreasing bone resorption. With this unique profile, we tested our hypothesis that Scl‐Ab primarily elicited MBF by examining bones from Scl‐Ab–treated ovariectomized (OVX) rats and male cynomolgus monkeys (cynos). Histomorphometry was performed to quantify and characterize bone surfaces in OVX rats administered vehicle or Scl‐Ab (25 mg/kg) subcutaneously (sc) twice/week for 5 weeks and in adolescent cynos administered vehicle or Scl‐Ab (30 mg/kg) sc every 2 weeks for 10 weeks. Fluorochrome‐labeled surfaces in L2 vertebra and femur endocortex (cynos only) were considered to be MBF or RBF based on characteristics of their associated cement lines. In OVX rats, Scl‐Ab increased MBF by eightfold (from 7% to 63% of bone surface, compared to vehicle). In cynos, Scl‐Ab markedly increased MBF on trabecular (from 0.6% to 34%) and endocortical surfaces (from 7% to 77%) relative to vehicle. Scl‐Ab did not significantly affect RBF in rats or cynos despite decreased resorption surface in both species. In cynos, Scl‐Ab resulted in a greater proportion of RBF and MBF containing sequential labels from week 2, indicating an increase in the lifespan of the formative site. This extended formation period was associated with robust increases in the percent of new bone volume formed. These results demonstrate that Scl‐Ab increased bone volume by increasing MBF and prolonged the formation period at both modeling and remodeling sites while reducing bone resorption. Through these unique effects on bone formation and resorption, Scl‐Ab may prove to be an effective therapeutic to rapidly increase bone mass in diseases such as osteoporosis. © 2014 American Society for Bone and Mineral Research.
Serum and dietary magnesium and the risk for type 2 diabetes mellitus: the Atherosclerosis Risk in Communities Study.

BACKGROUND Experimental studies in animals and cross-sectional studies in humans have suggested that low serum magnesium levels might lead to type 2 diabetes; however, this association has not been examined prospectively. METHODS We assessed the risk for type 2 diabetes associated with low serum magnesium level and low dietary magnesium intake in a cohort of nondiabetic middle-aged adults (N = 12,128) from the Atherosclerosis Risk in Communities Study during 6 years of follow-up. Fasting serum magnesium level, categorized into 6 levels, and dietary magnesium intake, categorized into quartiles, were measured at the baseline examination. Incident type 2 diabetes was defined by self-report of physician diagnosis, use of diabetic medication, fasting glucose level of at least 7.0 mmol/L (126 mg/dL), or nonfasting glucose level of at least 11.1 mmol/L (200 mg/dL). RESULTS Among white participants, a graded inverse relationship between serum magnesium levels and incident type 2 diabetes was observed. From the highest to the lowest serum magnesium levels, there was an approximate 2-fold increase in incidence rate (11.1, 12.2, 13.6, 12.8, 15.8, and 22.8 per 1000 person-years; P = .001). This graded association remained significant after simultaneous adjustment for potential confounders, including diuretic use. Compared with individuals with serum magnesium levels of 0.95 mmol/L (1.90 mEq/L) or greater, the adjusted relative odds of incident type 2 diabetes rose progressively across the following lower magnesium categories: 1.13 (95% CI, 0.79-1.61), 1.20 (95% CI, 0.86-1.68), 1.11 (95% CI, 0.80-1.56), 1.24 (95% CI, 0.86-1.78), and 1.76 (95% CI, 1.18-2.61) (for trend, P = .01). In contrast, little or no association was observed in black participants. No association was detected between dietary magnesium intake and the risk for incident type 2 diabetes in black or white participants. CONCLUSIONS Among white participants, low serum magnesium level is a strong, independent predictor of incident type 2 diabetes. That low dietary magnesium intake does not confer risk for type 2 diabetes implies that compartmentalization and renal handling of magnesium may be important in the relationship between low serum magnesium levels and the risk for type 2 diabetes.
In-Order Transition-based Constituent Parsing

Both bottom-up and top-down strategies have been used for neural transition-based constituent parsing. The parsing strategies differ in terms of the order in which they recognize productions in the derivation tree, where bottom-up strategies and top-down strategies take post-order and pre-order traversal over trees, respectively. Bottom-up parsers benefit from rich features from readily built partial parses, but lack lookahead guidance in the parsing process; top-down parsers benefit from non-local guidance for local decisions, but rely on a strong encoder over the input to predict a constituent hierarchy before its construction. To mitigate both issues, we propose a novel parsing system based on in-order traversal over syntactic trees, designing a set of transition actions to find a compromise between bottom-up constituent information and top-down lookahead information. Based on stack-LSTM, our psycholinguistically motivated constituent parsing system achieves 91.8 F1 on the WSJ benchmark. Furthermore, the system achieves 93.6 F1 with supervised reranking and 94.2 F1 with semi-supervised reranking, which are the best results on the WSJ benchmark.
Uganda: lessons for aids control in Africa

Uganda has the one of the oldest recognised AIDS epidemics. The first people found to be sick with AIDS in 1982 in southwestern Uganda became infected in the mid-1970s. For several years, Uganda has been widely recognised as the first and most dramatic African success story, with estimated national HIV prevalence falling from about 15 per cent in 1992 to 5 per cent in 2001. This is truly good news! As the epidemic proceeds through its third decade, many observers suggest that Uganda's prevention efforts are a model to follow. What is the situation there, and what can we learn from Uganda?
Identification and in silico analyses of novel TGFBR1 and TGFBR2 mutations in Marfan syndrome‐related disorders

Very recently, heterozygous mutations in the genes encoding transforming growth factor beta receptors I (TGFBR1) and II (TGFBR2) have been reported in Loeys‐Dietz aortic aneurysm syndrome (LDS). In addition, dominant TGFBR2 mutations have been identified in Marfan syndrome type 2 (MFS2) and familial thoracic aortic aneurysms and dissections (TAAD). In the past, mutations of these genes were associated with atherosclerosis and several human cancers. Here, we report a total of nine novel and one known heterozygous sequence variants in the TGFBR1 and TGFBR2 genes in nine of 70 unrelated individuals with MFS‐like phenotypes who previously tested negative for mutations in the gene encoding the extracellular matrix protein fibrillin‐1 (FBN1). To assess the pathogenic impact of these sequence variants, in silico analyses were performed by the PolyPhen, SIFT, and Fold‐X algorithms and by means of a 3D homology model of the TGFBR2 kinase domain. Our results showed that in all but one of the patients the pathogenic effect of at least one sequence variant is highly probable (c.722C>T, c.799A>C, and c.1460G>A in TGFBR1 and c.773T>G, c.1106G>T, c.1159G>A, c.1181G>A, and c.1561T>C in TGFBR2). These deleterious alleles occurred de novo or segregated with the disease in the families, indicating a causative association between the sequence variants and clinical phenotypes. Since TGFBR2 mutations found in patients with MFS‐related disorders cannot be distinguished from heterozygous TGFBR2 mutations reported in tumor samples, we emphasize the importance of segregation analysis in affected families. In order to be able to find the mutation that is indeed responsible for a MFS‐related phenotype, we also propose that genetic testing for sequence alterations in TGFBR1 and TGFBR2 should be complemented by mutation screening of the FBN1 gene. Hum Mutat 27(8), 760–769, 2006. © 2006 Wiley‐Liss, Inc.
Walking for Well-Being: Are Group Walks in Certain Types of Natural Environments Better for Well-Being than Group Walks in Urban Environments?

The benefits of walking in natural environments for well-being are increasingly understood. However, less well known are the impacts different types of natural environments have on psychological and emotional well-being. This cross-sectional study investigated whether group walks in specific types of natural environments were associated with greater psychological and emotional well-being compared to group walks in urban environments. Individuals who frequently attended a walking group once a week or more (n = 708) were surveyed on mental well-being (Warwick Edinburgh Mental Well-being Scale), depression (Major Depressive Inventory), perceived stress (Perceived Stress Scale) and emotional well-being (Positive and Negative Affect Schedule). Compared to group walks in urban environments, group walks in farmland were significantly associated with less perceived stress and negative affect, and greater mental well-being. Group walks in green corridors were significantly associated with less perceived stress and negative affect. There were no significant differences between the effect of any environment types on depression or positive affect. Outdoor walking group programs could be endorsed through “green prescriptions” to improve psychological and emotional well-being, as well as physical activity.
Comparison of Continuous Drip of Midazolam or Lidocaine in the Treatment of Intractable Neonatal Seizures

Seizures constitute the most common neurological symptom in the neonatal period. Treatment usually involves the administration of intravenous benzodiazepines followed by either phenobarbital or phenytoin. For nonresponsive cases, continuous intravenous drip of either midazolam or lidocaine has been suggested for seizure control. Some reports suggest that seizures themselves may have a deleterious effect on long-term neurological outcome. Therefore, there is a need to find treatment regimens with better efficacy to provide maximum seizure control. The authors compared the effectiveness of lidocaine and midazolam in the treatment of intractable seizures in newborn infants born at or after 36 weeks of gestation who suffered from hypoxic-ischemic encephalopathy and who had their cerebral activity monitored. Thirty infants were included in the study: 22 received lidocaine, and 8 received midazolam. Seventeen (77%) infants had a good or partial response to lidocaine, and 4 (50%) had a partial response to midazolam. Of 20 infants diagnosed with hypoxic-ischemic encephalopathy grade 2, 18 (90%) responded to second-line treatment (14 [93%] of 15 to lidocaine and 4 [80%] of 5 to midazolam). Among 10 infants with hypoxic-ischemic encephalopathy grade 3, only 3 (30%) responded to second-line treatment (all 3 to lidocaine, none to midazolam). The findings suggest that lidocaine may be more effective than midazolam in reducing or controlling refractory neonatal seizures. The lower response rate to midazolam was more evident in infants with severe hypoxic-ischemic encephalopathy (grade 3).
On stability of the resolved acceleration control

Resolved acceleration control is a method for motion control of robot manipulators in task space where a desired end-effector pose trajectory is specified. We consider the orientation part of the pose given by the Euler parameters or unit quaternion. The main contribution is a novel proof of asymptotic stability based in the use of a strict Lyapunov function. This is a one stage procedure which improves previously reported analysis where two-stage mechanisms are in general invoked: first demonstrating stability and then convergence.
The role of Ang (1-7) in mediating the chronic hypotensive effects of losartan in normal rats

Hypothesis The following studies were designed to test the hypothesis that Ang (1-7) contributes to the chronic hypotensive effects of the angiotensin II AT1-receptor antagonist, losartan, in normal rats. Introduction We have previously shown a chronic, hypotensive response to the AT1-receptor antagonist, losartan, in normotensive rats. The mechanism of this response is not completely understood. Previous studies by others have demonstrated a role for Ang (1-7) in the beneficial antihypertensive effects of angiotensin-converting enzyme (ACE) inhibition. This is thought to be due to vasodilatory effects of increased levels of Ang (1-7) during ACE inhibition. Since it has now been shown that Ang (1-7) levels are also increased during AT1 antagonism, we designed experiments to test the hypothesis above. Materials and methods Sprague-Dawley rats were instrumented with venous catheters and radiotelemetric pressure transducers and commenced on a normal (0.4%) NaCl diet. Arterial pressure responses were measured in rats treated with losartan (10 mg/kg/day) (LOS rats, n=8) and compared with those treated with losartan and the Ang (1-7) antagonist, A779 (24 µg/kg/hour) (A779/LOS rats, n=11) for 10 days. Results By day 7 of treatment, mean arterial pressure had dropped by 27±1 mmHg in LOS rats, in contrast with a decrease of only 21±2 mmHg in A779/LOS rats. This attenuated response in rats treated with A779 became more prominent and continued through day 10 of losartan treatment. Conclusion These results support the hypothesis that the chronic hypotensive effects of losartan in normal rats are mediated in part through the actions of Ang (1-7).
Inefficient proteasomal‐degradation pathway stabilizes AP‐2α and activates HER‐2/neu gene in breast cancer

HER‐2/neu proto‐oncogene is overexpressed in about one fourth of human breast cancers. AP‐2 transcription factors bind to the HER‐2/neu gene promoter and activate its expression. In a striking concurrence, anomalous abundance of AP‐2α protein or its homolog AP‐2γ is also detected with HER‐2/neu protein in mammary tumor‐derived cell lines. This suggests that the deregulation of AP‐2 is the preceding pathogenic event and probably the pivotal one in this type of mammary carcinogenesis. We examined the process of AP‐2α gene expression in mammary carcinoma cell lines to identify where the aberration had occurred. We found no amplification of the AP‐2α gene. Its promoter was marginally upregulated; however, it did not significantly increase the mRNA levels. When the AP‐2α protein was examined, a remarkable stability was seen in breast cancer cell lines MDA‐MB‐453 and SK‐BR‐3, with a half‐life of over 30 hr. This is sharply higher than the approximate 1 hr observed in mammary epithelial cell line MCF‐10A and murine cell line NIH 3T3. Treatment of MCF‐10A and NIH 3T3 cells with the proteasome inhibitor MG‐132 showed that AP‐2α was ubiquitinated and its level significantly increased. Moreover, this increase was accompanied by elevated levels HER‐2/neu protein. In contrast, weaker ubiquitination of AP‐2α was seen in MDA‐MB‐453 and SK‐BR‐3 cancer cells, and MG‐132 treatment did not raise the AP‐2α level any further. These results uncover that unusual stability is the main mechanism that raises the levels of AP‐2 proteins, and in addition, provide the first clue that defective ubiquitin‐dependent proteasomal‐degradation pathway is possibly the prime cause that affects the HER‐2/neu gene and culminates in breast cancer. © 2005 Wiley‐Liss, Inc.
Bartonella vinsonii subsp.berkhoffii as an Agent of Afebrile Blood Culture-Negative Endocarditis in a Human

ABSTRACT We report a case of endocarditis in a human infected withBartonella vinsonii subsp. berkhoffii, which causes bacteremia and endocarditis in dogs. Bacterial identification was established by PCR amplification and sequencing of an intergenic spacer region (ITS1), 16S ribosomal DNA, and a gene encoding citrate synthase (gltA). Bartonella antibodies were detected by immunofluorescence.
Antagonism by Nalmefene of Systemic and Intrathecal Morphine-Induced Analgesia in Mice 1

Abstract Nalmefene is an orally active opiate antagonist structurally related to naloxone and naltrexone. In this study using two different strains of mice (Swiss Cox and ICR), the antagonist activity of nalmefene given subcutaneously (sc) was quantified by determination of the apparent pA 2 values against the antinociceptive activity (tail flick and hot plate tests) of morphine given sc or intrathecally (lumbar spinal cord). The apparent pA 2 values (constrained to a slope of —1) were 8.06 (7.79-8.33) in Swiss Cox mice and 7.81 (7.62-8.00) in ICR mice in the tail flick test with sc morphine. These values were larger than the corresponding value for naloxone in ICR mice, 7.35 (7.10-7.60). The hot plate test provided similar results: the apparent pA 2 values for nalmefene with sc morphine were 8.14 (7.89-8.39) in Swiss Cox mice and 7.81 (7.65-7.97) in ICR mice, values which were different from naloxone 7.33 (7.23-7.42) in ICR mice. Apparent pA 2 values for nalmefene with intrathecal morphine were not different from those for naloxone in the tail flick test. Thus, these sets of results suggest that it may be worthwhile to further determine whether systemic nalmefene might possibly possess an advantage over naloxone in antagonizing systemic side effects of morphine arising from local spinal morphine administration.
The impact of transformational and transactional leadership styles on knowledge creation in Sri Lankan software industry

This study examines leadership factors that affect knowledge creation in Sri Lankan software industry. For this study, transformational and transactional leadership styles are considered and their effect on knowledge creation is assessed. Organizational culture is considered to have a moderating effect on the relationship between leadership behaviors and knowledge creation. The study is based on four variables; two independent variables, transformational leadership and transactional leadership, one moderating variable, organizational culture and one dependent variable, knowledge creation. According to the findings of the research with participant (n=152) feedback, both transformational leadership and transactional leadership have strong positive correlations with knowledge creation. Organizational culture moderates the correlation between transactional leadership and knowledge creation. Among the individual factors of transformational and transactional leadership, Individualized consideration has the highest positive correlation with knowledge creation. Organizational culture found to be moderating the knowledge creation through transactional leadership while culture has no moderating effect on knowledge creation through transformational leadership. The research suggests that affective leadership practices can positively contribute to the knowledge creation in software development organizations.
Precision determination of the density of a single crystal silicon sphere and evaluation of the Avogadro constant

Density measurements with relative uncertainty of 1/spl times/10/sup -7/ have been made on a highly polished 1-kg single crystal silicon sphere with out-of-roundness <40 nm. Roundness was profiled using a 2-D Talyrond machine and 3-D profiles were produced. The diameter was obtained using optical interferometry for a series of breadth measurements at carefully selected points and by combining them with roundness data. The mass was obtained relative to a 1-kg stainless steel reference with appropriate corrections for air buoyancy and for convection currents due to small temperature differentials. Surface oxide thickness was measured using optical ellipsometry and the data were corrected for this oxide thickness. The molar mass, crystal quality and lattice parameter have been measured elsewhere, enabling a determination of the Avogadro constant to be made. The purpose is to obtain a definition of the kilogram in terms of a specific number of /sup 12/C atoms.
The Class I HLA Repertoire of Pancreatic Islets Comprises the Nonclassical Class Ib Antigen HLA-G

Selective expression of the human class Ib HLA molecule HLA-G in immunologically protected sites and its function in the inhibition of NK and T-cell effector functions support an important role of this molecule in immunoregulation. Here, we demonstrate that HLA-G is constitutively expressed in the endocrine compartment of the human pancreas. Surface expression of this HLA determinant in endocrine cells is regulated in response to growth and inflammatory stimuli. Furthermore, we provide evidence that HLA-G expressed in this tissue may associate with a subset of insulin-containing granules and may be shuttled to the cell surface in response to secretory stimuli. Thus, HLA-G presentation by endocrine cells may be regulated in concert with their secretory activity. These results identify the expression of a major histocompatibility complex locus with putative regulatory functions in human pancreatic islets, a finding with potentially important implications for the progression of autoimmunity as well as for the establishment of transplant tolerance to this tissue.
Dissociation of Frontal and Cerebellar Activity in a Cognitive Task: Evidence for a Distinction between Selection and Search

Human brain imaging studies have found that increases in functional activation in left-frontal cortex during cognitive tasks are often accompanied by similar increases in right-cerebellar regions. The present study used functional magnetic resonance imaging (fMRI) to investigate the distinctive contributions of these regions using a word stem completion task. Stems with many possible completions (MANY condition) were alternately presented with stems that had few possible completions (FEW condition), and subjects were asked to covertly complete each stem with a word and press a response switch for each successful completion. Prominent increases in activation in the MANY, relative to the FEW, condition were observed in the left middle frontal gyrus (Brodmann areas 9/10) and left caudate nucleus. In contrast, portions of the right-cerebellar hemisphere (posterior quadrangular lobule and superior semilunar lobule) and cerebellar vermis exhibited increases in the FEW, relative to the MANY, condition. This double dissociation suggests that the frontal and cerebellar regions make distinctive contributions to cognitive performance, with left-frontal (and striatal) activations reflecting response selection, which increases in difficulty when there are many appropriate responses, and right-cerebellar activation reflecting the search for responses, which increases in difficulty when even a single appropriate response is hard to retrieve.
Binding Characteristics of SLE Anti‐DNA Autoantibodies to Catecholestrogen‐modified DNA

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease in which anti‐double‐stranded DNA antibody is a classic autoantibody that characterizes SLE. A role for oestrogens in the pathogenesis of SLE has been suspected for many years but the exact patho‐aetiology remains elusive. In this study, the binding of SLE autoantibodies with native and 4‐OHE2‐NO‐modified plasmid DNA were assessed. Binding specificity of antibodies was analysed by direct binding and inhibition enzyme‐linked immunosorbent assay, quantitative precipitin titration and gel retardation assay. Anti‐DNA IgG from SLE sera, purified on Protein A‐Agarose matrix, exhibited increased recognition of 4‐OHE2‐NO‐DNA than native DNA (P < 0.001). Gel retardation assay further substantiated the enhanced recognition of modified DNA by anti‐DNA autoantibodies. The affinity of anti‐DNA antibodies for modified polymer was found to be high as calculated by using Langmuir plot. DNA modified by 4‐OHE2‐NO presents unique neo‐epitopes that might be one of the factor in antigen‐driven induction of SLE autoantibodies.