Miracle-dz/UniFAR-FTUs huggingface dataset:
Activation of Protein Kinase Cζ Is Essential for Cytokine-induced Metalloproteinase-1, -3, and -9 Secretion from Rabbit Smooth Muscle Cells and Inhibits Proliferation*

Several matrix metalloproteinases (MMPs), including MMP-1, -3, and -9, mediate matrix destruction during chronic inflammatory diseases such as arthritis and atherosclerosis. MMP up-regulation by inflammatory cytokines involves interactions between several transcription factors, including activator protein-1 and nuclear factor κB (NF-κB). The upstream regulatory pathways are less well understood. We investigated the role of isoforms of protein kinase C (PKC) in basic fibroblast growth factor- and interleukin-1α-mediated MMP production from cultured rabbit aortic smooth muscle cells. A synthetic PKC inhibitor, RO318220, inhibited MMP-1, -3, and -9 production by 89 ± 3, 75 ± 18, and 89 ± 9%, respectively. However, down-regulation of conventional and novel isoforms did not inhibit but rather increased MMP-9 production by 48 ± 16%, implicating an atypical PKC isoform. Consistent with this, PKCζ protein levels and activity were stimulated 3.3- and 13-fold, respectively, by basic fibroblast growth factor plus interleukin-1α and antisense oligonucleotides to PKCζ significantly decreased MMP-9 formation by 62 ± 18% compared with scrambled sequences. Moreover, adenovirus-mediated overexpression of a dominant-negative (DN) PKCζ reduced MMP-1, -3, and -9 production by 78 ± 9, 76 ± 8, and 76 ± 5%, respectively. DN-PKCζ inhibited NF-κB DNA binding but did not affect ERK1/2 activation or AP-1 binding. Antisense PKCζ oligonucleotides and DN-PKCζ stimulated cell proliferation by 89 ± 14% (n = 4) and 305 ± 74% (n = 3), respectively (both p < 0.05). Our results show that PKCζ is essential for cytokine-induced up-regulation of MMP-1, -3, and -9, most likely by activating NF-κB. Selective inhibition of PKCζ is therefore a possible strategy to inhibit MMP production in inflammatory diseases such as atherosclerosis.
The Sandia GeoModel : theory and user's guide.

The mathematical and physical foundations and domain of applicability of Sandia's GeoModel are presented along with descriptions of the source code and user instructions. The model is designed to be used in conventional finite element architectures, and (to date) it has been installed in five host codes without requiring customizing the model subroutines for any of these different installations. Although developed for application to geological materials, the GeoModel actually applies to a much broader class of materials, including rock-like engineered materials (such as concretes and ceramics) and even to metals when simplified parameters are used. Nonlinear elasticity is supported through an empirically fitted function that has been found to be well-suited to a wide variety of materials. Fundamentally, the GeoModel is a generalized plasticity model. As such, it includes a yield surface, but the term 'yield' is generalized to include any form of inelastic material response including microcrack growth and pore collapse. The geomodel supports deformation-induced anisotropy in a limited capacity through kinematic hardening (in which the initially isotropic yield surface is permitted to translate in deviatoric stress space to model Bauschinger effects). Aside from kinematic hardening, however, the governing equations are otherwise isotropic. The GeoModel is a genuine unificationmore » and generalization of simpler models. The GeoModel can employ up to 40 material input and control parameters in the rare case when all features are used. Simpler idealizations (such as linear elasticity, or Von Mises yield, or Mohr-Coulomb failure) can be replicated by simply using fewer parameters. For high-strain-rate applications, the GeoModel supports rate dependence through an overstress model. « less
A joint genomewide linkage analysis of symptoms of alcohol dependence and conduct disorder.

BACKGROUND A large linkage peak for alcohol dependence (AD) was detected on chromosome 4q in the Irish Affected Sib Pair Study of Alcohol Dependence (IASPSAD). Are the susceptibility genes underlying this peak specific for AD or do they increase risk for externalizing disorders more generally? Can we, in the IASPSAD, replicate prior evidence for linkage to conduct disorder (CD)? METHODS The 733 all possible sibling pairs in IASPSAD were typed for 1,020 short-tandem-repeat genetic markers. Univariate and bivariate linkage analyses were conducted by the program sequential oligogenic linkage analysis routines (SOLAR), for both the raw and the transformed number of symptoms of AD (ADsx) and number of symptoms of CD (CDsx). In the bivariate analyses, specificity was assessed by the ratio of the variance accounted for in ADsx and CDsx by the quantitative trait locus. RESULTS In the univariate linkage analyses, no evidence for linkage to CDsx was found under the 4q peak for ADsx and the largest peaks for CDsx were seen on chromosomes 1q (LOD=3.16) and 14p (LOD=2.36). In the bivariate linkage analysis, the 4q peak had high specificity for AD (AD/CD ratio of 39.9). Several smaller peaks, on chromosomes 1, 7, and 10, had moderate specificity for CD but also impacted on risk for AD, with AD/CD ratios of 0.18 to 0.32. CONCLUSIONS Genes under the 4q linkage peak for AD in the IASPSAD impact specifically on risk for AD rather than more broadly on risk for externalizing syndromes. Suggestive linkages were found in several locations for CD, 2 of which broadly replicate prior findings. The bivariate analyses identified genomic locations containing susceptibility loci that impacted on risk for both CDsx and ADsx.
Characterization Of Nickel Oxide Electrochromic Films

NicNickel oxide (Ni0) thin films deposited by electron-beam evaporation were studied using Fourier Transform Infrared Spectroscopy(FTIR), Rutherford Backscattering Spectroscopy (RBS), and spectrophotometry. Evaporated nickel oxide films ehibited good electrochromic behavior and a coloring efficiency of 30.1 cm2/C coating was 4.41 g/cc and stoichiometry was Nio1.4; both established by RBS. The infrared spectral properties of the as-deposited film was consistent with the structure being Ni0x. After repetitive electrochromic cycling in 1N KOH, the film changed to a structure more similiar to the hydrated nickel hydoxide films previously reported in the literature.
Detection of galactomannan in bronchoalveolar lavage of the intensive care unit patients at risk for invasive aspergillosis

Background and Purpose: Invasive aspergillosis (IA) is one of the most common life-threatening fungal infections among the critically ill patients including intensive care unit (ICU) patients. Delayed diagnosis and therapy may lead to poor outcomes. Diagnosis may be facilitated by a test for molecular biomarkers, i.e. detection of galactomannan (GM) antigen based on enzyme immunoassay, which is of increasing interest in the clinical settings for the diagnosis of IA. In the present study, we assessed GM testing of bronchoalveolar lavage (BAL) ﬂuid as a tool for early diagnosis of IA among ICU patients who were at risk for developing IA. Material and Methods: A prospective study was performed in ICU patients with underlying predisposing conditions for IA between August 2010 and September 2011. BAL samples for direct microscopic examination, culture, and GM detection were obtained once or twice weekly. GM in BAL levels was measured using the Platellia Aspergillus EIA test kit. According to modified European Organization for the Research and Treatment of Cancer/ Mycoses Study Group (EORTC/MSG) criteria, patients were classified as having probable or possible IA. Results: Out of 43 suspected patients to IA, 13 (30.2%) cases showed IA. According to the criteria presented by EORTC/MSG, they were categorized as: 4 cases (30.8%) of possible IA and 9 (69.2%) of probable IA. Out of 21 BAL samples from patients with IA, 11 (52.4%) had at least one positive BAL GM index. Using a cutoff index of 0.5, the sensitivity and specificity, positive and negative predictive values of GM detection in BAL fluid were 100%, 85.7%, 65.7% and 96%, respectively. The sensitivity and specificity was 73% and 92.7% at cutoff ≥1.0, respectively. In 6 of 13 IA cases, BAL culture or direct microscopic examination remained negative, whereas GM in BAL was positive. Conclusion: Our data have revealed that the sensitivity of GM detection in BAL was better than that of conventional tests. It seems that GM detection in BAL is beneficial to establish or exclude the early diagnosis of IA in ICU patients.
Posterior Medial Frontal Cortex Activity Predicts Post-Error Adaptations in Task-Related Visual and Motor Areas

As Seneca the Younger put it, “To err is human, but to persist is diabolical. ” To prevent repetition of errors, human performance monitoring often triggers adaptations such as general slowing and/or attentional focusing. The posterior medial frontal cortex (pMFC) is assumed to monitor performance problems and to interact with other brain areas that implement the necessary adaptations. Whereas previous research showed interactions between pMFC and lateral-prefrontal regions, here we demonstrate that upon the occurrence of errors the pMFC selectively interacts with perceptual and motor regions and thereby drives attentional focusing toward task-relevant information and induces motor adaptation observed as post-error slowing. Functional magnetic resonance imaging data from an interference task reveal that error-related pMFC activity predicts the following: (1) subsequent activity enhancement in perceptual areas encoding task-relevant stimulus features; (2) activity suppression in perceptual areas encoding distracting stimulus features; and (3) post-error slowing-related activity decrease in the motor system. Additionally, diffusion-weighted imaging revealed a correlation of individual post-error slowing and white matter integrity beneath pMFC regions that are connected to the motor inhibition system, encompassing right inferior frontal gyrus and subthalamic nucleus. Thus, disturbances in task performance are remedied by functional interactions of the pMFC with multiple task-related brain regions beyond prefrontal cortex that result in a broad repertoire of adaptive processes at perceptual as well as motor levels.
Hemodynamic Effects of Sodium-Glucose Cotransporter 2 Inhibitors

It is widely accepted that obesity and type 2 diabetes mellitus (T2DM) increase the risk of heart failure (HF) independently of underlying coronary artery disease. The changes in myocardial structure or function associated with diabetes have been termed diabetic cardiomyopathy. Corresponding to changes in the risk factors for HF, an epidemiologic transition is underway from HF with a reduced ejection fraction to HF with a preserved ejection fraction. Hyperglycemia can damage the myocardium, even before diagnosis of diabetes, but intensive glycemic control has no impact on the risk of HF in patients with T2DM. Recent clinical studies have demonstrated that sodium-glucose cotransporter 2 (SGLT2) inhibitors, which inhibit renal reabsorption of glucose, decrease the risk of HF in T2DM patients. The cardioprotective mechanisms involved appear to be multifactorial and have been the subject of considerable debate. This review focuses on the hemodynamic effects of SGLT2 inhibitors in T2DM patients and the mechanisms by which these drugs decrease the risk of HF.
Interaction of cells with immune complexes: adherence, release of constituents, and tissue injury.

Neutrophils are essential mediators of tissue damage in many forms of immune complex-induced injury. In vitro, they have been shown to release some of their content of injurious constituents upon reaction with immune complexes (Fig. 10). If the complexes are distributed along a nonphagocytosable surface, degranulation to the exterior of the cell is observed. When the complexes were phagocytized, however, degranulation into the phagocytic vacuole, and some loss of enzymes into the surrounding medium, occurred. This may have resulted from a momentary opening of the vacuole to allow ingestion of additional particles, as was demonstrated with the electron microscope. This phenomenon was particularly noticeable when the particles were relatively large. Far more immune complex is required to induce release when in a phagocytosable form than when on a nonphagocytosable membrane. Neutrophils may be attracted to sites of immune complex deposition in many parts of the body (arteries, heart, skin, brain, kidney, joints) by complement-mediated processes. In some situations, e.g. in the joint fluid, they would encounter free immune complexes, phagocytose them, and release enzymes. In many others, in which immune complexes may be distributed along surfaces, such as in the glomerulus, adherence of neutrophils may also lead to release of injurious constituents (proteases, collagenase, elastase, permeability factors) capable of digesting and injuring the tissues.
An Energy-Aware Routing Algorithm for Quality-Oriented Wireless Video Delivery

Energy consumption has been a critical factor for video services on mobile devices. Existing energy-aware video delivery solutions focus on reducing the energy consumption at either networks or mobile devices, at the expense of decreasing video quality. This paper proposes E-Mesh, an energy-aware wireless routing algorithm which balances the need for energy saving with that of maintaining good quality of video content. E-Mesh is deployed at the network layer and works in conjunction with an innovative energy-aware MAC-layer duty cycle management scheme. Both simulation and perceptual testing were performed investigating the performance of E-Mesh. In particular, the impact of E-Mesh on content delivery data rate, network topology scale, and device mobility were studied. Results demonstrate that E-Mesh obtains up to 23% energy savings at roughly the same content delivery quality level, in comparison with the state-of-the-art IEEE 802.11s routing protocol.
Expert and crowdsourced annotation of pronunciation errors for automatic scoring systems

This paper evaluates and compares different approaches to collecting judgments about pronunciation accuracy of nonnative speech. We compare the common approach, which requires expert linguists to provide a detailed phonetic transcription of non-native English speech, with word-level judgments collected from multiple naive listeners using a crowdsourcing platform. In both cases we found low agreement between annotators on what words should be marked as errors. We compare the error detection task to a simple transcription task in which the annotators were asked to transcribe the same fragments using standard English spelling. We argue that the transcription task is a simpler and more practical way of collecting annotations which also leads to more valid data for training an automatic scoring system.
Middle-distance running acutely influences the concentration and composition of serum bile acids: Potential implications for cancer risk?

Background This study was aimed to investigate the acute effect of medium-distance running on bile acids concentration and composition, in order to verify whether the positive impact of physical exercise on cancer risk may also be mediated by variation of bile acids concentration and composition in serum. Methods The concentration and composition of serum bile acids was analyzed in 30 middle-aged and healthy recreational athletes with a reference liquid chromatography-mass spectrometry technique, immediately before and shortly after the end of the running trial. The concentration of bile acids after the run was adjusted for plasma volume change. Results All athletes successfully completed the trial. After correction of values for the individual plasma volume change calculated after the run, the serum concentration of total bile acids was found to be significantly reduced by approximately 46%. A statistically significant decrease was observed for cholic, deoxycholic, chenodeoxycholic, ursodeoxycholic, glycoursodeoxycholic and hyodeoxycholic acids, whereas the concentration of the remaining compounds remained unvaried after the run. A considerable variation of bile acids profile was also observed. No significant association was found between running performance and variation of bile acids concentrations. Conclusion These results show that middle distance running acutely decreases the concentration of total bile acids in serum, especially that of the more mutagenic and carcinogenic compounds, so providing an intriguing support to the favorable effects of physical exercise for lowering the risk of many gastrointestinal cancers.
Spatiotemporally consistent genomic signatures of reproductive isolation in a moving hybrid zone

Studies of hybrid zone dynamics often investigate a single sampling period and draw conclusions from that temporal snapshot. Stochasticity can, however, result in loci with spurious outlier patterns, which is exacerbated by limited temporal or geographic sampling. Comparing admixed populations from different geographic regions is one way to detect repeatedly divergent genomic regions potentially involved in reproductive isolation. Temporal comparisons also allow us to control partially for the role of stochasticity, but the power of temporal sampling has not yet been adequately explored. In North America, black‐capped (Poecile atricapillus) and Carolina (P. carolinensis) chickadees hybridize in a contact zone extending from New Jersey to Kansas. The hybrid zone is likely maintained by strong intrinsic selection against hybrids, and it is moving north. We used a reduced representation genomic approach and temporally spaced sampling—two samples of ∼80 individuals separated by a decade—to determine the pattern and consistency of selection and genomic introgression in the chickadee hybrid zone. We report consistently low introgression for highly divergent loci between P. atricapillus and P. carolinensis in this moving hybrid zone. This is strong evidence that these loci may be linked to genomic regions involved in reproductive isolation between chickadees.
Physiological and genetic analysis of the carbon regulation of the NAD-dependent glutamate dehydrogenase of Saccharomyces cerevisiae

We found that cells of Saccharomyces cerevisiae have an elevated level of the NAD-dependent glutamate dehydrogenase (NAD-GDH; encoded by the GDH2 gene) when grown with a nonfermentable carbon source or with limiting amounts of glucose, even in the presence of the repressing nitrogen source glutamine. This regulation was found to be transcriptional, and an upstream activation site (GDH2 UASc) sufficient for activation of transcription during respiratory growth conditions was identified. This UAS was found to be separable from a neighboring element which is necessary for the nitrogen source regulation of the gene, and strains deficient for the GLN3 gene product, required for expression of NAD-GDH during growth with the activating nitrogen source glutamate, were unaffected for the expression of NAD-GDH during growth with activating carbon sources. Two classes of mutations which prevented the normal activation of NAD-GDH in response to growth with nonfermentable carbon sources, but which did not affect the nitrogen-regulated expression of NAD-GDH, were found and characterized. Carbon regulation of GDH2 was found to be normal in hxk2, hap3, and hap4 strains and to be only slightly altered in a ssn6 strain; thus, in comparison with the regulation of previously identified glucose-repressed genes, a new pathway appears to be involved in the regulation of GDH2.
Ambient Temperature Influences Australian Native Stingless Bee (Trigona carbonaria) Preference for Warm Nectar

The interaction between flowers and insect pollinators is an important aspect of the reproductive mechanisms of many plant species. Several laboratory and field studies indicate that raising flower temperature above ambient can be an advantage in attracting pollinators. Here we demonstrate that this preference for warmer flowers is, in fact, context-dependent. Using an Australian native bee as a model, we demonstrate for the first time a significant shift in behaviour when the ambient temperature reaches 34°C, at which point bees prefer ambient temperature nectar over warmer nectar. We then use thermal imaging techniques to show warmer nectar maintains the flight temperature of bees during the period of rest on flowers at lower ambient temperatures but the behavioural switch is associated with the body temperature rising above that maintained during flight. These findings suggest that flower-pollinator interactions are dependent upon ambient temperature and may therefore alter in different thermal environments.
The familial aggregation of common psychiatric and substance use disorders in the National Comorbidity Survey: A family history study

Background Most family studies of psychiatric disorders examine one syndrome at a time, and identify probands in clinical rather than epidemiological settings. Method In the National Comorbidity Survey, 5877 respondents were asked about the history of five psychiatric disorders in their parents: major depression (MD), generalised anxiety disorder (GAD), antisocial personality disorder (ASP), alcohol abuse/dependence (AAD) and drug abuse/dependence (DAD). Results Significant familial aggregation was seen for all disorders. Controlling for other disorders produced only modest reductions in the odds ratios for MD. GAD and AAD and larger reductions for ASP and DAD. The familial transmission of these disorders can be explained by underlying vulnerabilities to internalising and to externalising disorders transmitted across generations with moderate fidelity. Conclusions Familial aggregation of common psychiatric and substance use disorders is substantial in epidemiologic samples. The examined environmental adversities account for little of the observed parent-offspring transmission of these conditions.
Physicochemical Characteristics of Gelatin from Abdominal Skin of Yellowfin Tuna (Thunnus albacares)

Physicochemical characteristics of gelatin extracted from abdominal skin of yellowfin tuna (Thunnus albacares), were investigated by comparing its proximate composition, pH, amino acid composition, viscoelastic properties, gel strength and SDS-PAGE patterns, with those of bovine and porcine gelatins. The effects of gelatin concentration, maturation time, heat and freeze treatments on the gel strength of yellowfin tuna abdominal skin gelatin were studied. Amounts of $\alpha$-chains, $\beta$- and $\gamma$-components of yellowfin tuna abdominal skin gelatin were higher than those of the two mammailan gelatins. Yellowfin tuna abdominal skin gelatin had the lowest imino acids (proline and hydroxyproline) content, which was consistent with that of other fishes. However, yellowfin tuna abdominal skin gelatin was highest in glycine, alanine, and lysine. The gel strengths of all gelatins were proportional to the concentration of gelatin, but yellowfin tuna abdominal skin gelatin exhibited the greatest gel strength at each concentration. Yellowfin tuna abdominal skin gelatin required a longer maturation time than the two mammalian gelatins to form a firm gel. Higher heating temperature decreased the gel strength of yellow fin tuna abdominal skin gelatin more than in the two mammalian gelatins. Freezing decreased the gel strength of bovine gelatin only slightly, but longer freezing times resulted in greater reductions in gel strength in the yellowfin tuna abdominal skin and porcine gelatins.