Miracle-dz/UniFAR-FTUs huggingface dataset:
Involvement of Matrix Metalloproteinase in Thrombolysis-Associated Hemorrhagic Transformation After Embolic Focal Ischemia in Rats

Background and Purpose— Thrombolytic therapy with tissue plasminogen activator (tPA) for acute ischemic stroke remains complicated by risks of hemorrhagic transformation. In this study we used a previously established quantitative rat model of tPA-associated hemorrhage to test the hypothesis that matrix metalloproteinases (MMPs) are involved. Methods— Spontaneously hypertensive rats were subjected to embolic focal ischemia by placing homologous blood clots into the middle cerebral artery. Three groups of rats were studied: (1) untreated controls that received saline at 6 hours after ischemia; (2) rats that received tPA alone (10 mg/kg at 6 hours after ischemia); and (3) rats that received tPA plus the broad-spectrum MMP inhibitor BB-94 (50 mg/kg of BB-94 before ischemia and at 3 and 6 hours after ischemia plus tPA at 6 hours). Gelatin zymography was used to quantify MMP levels. A hemoglobin spectrophotometry method was used to quantify cerebral hemorrhage. Ischemic lesions were measured at 24 hours with tetrazolium staining. Results— At 6, 12, and 24 hours, pro-MMP-9 and cleaved MMP-9 were upregulated in ischemic brain. At 12 hours, tPA-treated rats showed significantly higher levels of pro-MMP-9 and cleaved MMP-9 than untreated controls. By 24 hours, all rats showed evidence of hemorrhagic transformation in the ischemic territory. Rats treated with BB-94 and tPA showed significantly reduced hemorrhage volumes compared with those that received tPA alone. There was no effect on infarct size. Conclusions— These results indicate that (1) tPA treatment increases levels of MMP-9 after embolic focal cerebral ischemia, (2) MMPs are involved in the mechanism of tPA-associated hemorrhage, and (3) combination therapies with MMP inhibitors may be useful for decreasing the risk and severity of this dreaded complication of thrombolytic therapy.
Speaker similarity evaluation of foreign-accented speech synthesis using HMM-based speaker adaptation

This paper describes a speaker discrimination experiment in which native English listeners were presented with natural and synthetic speech stimuli in English and were asked to judge whether they thought the sentences were spoken by the same person or not. The natural speech consisted of recordings of Finnish speakers speaking English. The synthetic stimuli were created using adaptation data from the same Finnish speakers. Two average voice models were compared: one trained on Finnish-accented English and the other on American-accented English. The experiments illustrate that listeners perform well at speaker discrimination when the stimuli are both natural or both synthetic, but when the speech types are crossed performance drops significantly. We also found that the type of accent in the average voice model had no effect on the listeners' speaker discrimination performance.
Simulations of inspiraling and merging double neutron stars using the Spectral Einstein Code

We present results on the inspiral, merger, and postmerger evolution of a neutron star-neutron star (NSNS) system. Our results are obtained using the hybrid pseudospectral-finite volume Spectral Einstein Code (SpEC). To test our numerical methods, we evolve an equal-mass system for ≈22 orbits before merger. This waveform is the longest waveform obtained from fully general-relativistic simulations for NSNSs to date. Such long (and accurate) numerical waveforms are required to further improve semianalytical models used in gravitational wave data analysis, for example, the effective one body models. We discuss in detail the improvements to SpEC’s ability to simulate NSNS mergers, in particular mesh refined grids to better resolve the merger and postmerger phases. We provide a set of consistency checks and compare our results to NSNS merger simulations with the independent bam code. We find agreement between them, which increases confidence in results obtained with either code. This work paves the way for future studies using long waveforms and more complex microphysical descriptions of neutron star matter in SpEC.
Behavioral / Systems / Cognitive Functional Magnetic Resonance Imaging Reveals the Neural Substrates of Arm Transport and Grip Formation in Reach-to-Grasp Actions in Humans

Cristiana Cavina-Pratesi,1 Simona Monaco,2,3 Patrizia Fattori,3 Claudio Galletti,3 Teresa D. McAdam,2,4 Derek J. Quinlan,2 Melvyn A. Goodale,2,4 and Jody C. Culham2,4 1Department of Psychology, Durham University, Durham DH1 3LE, United Kingdom, 2Department of Psychology, University of Western Ontario, London, Ontario, Canada N6A 5C2, 3Department of Human and General Physiology, University of Bologna, 40127 Bologna, Italy, and 4Neuroscience Program, University of Western Ontario, London, Ontario, Canada N6A 5K8
Serum Therapy for Tuberculosis Revisited: Reappraisal of the Role of Antibody-Mediated Immunity againstMycobacterium tuberculosis

SUMMARY Fifty years after the introduction of the first effective antimicrobial agents against Mycobacterium tuberculosis, this pathogen continues to be a tremendous public health problem. The rise in the number of resistant strains and the difficulties involved in the therapy of tuberculosis in immunocompromised AIDS patients have renewed the interest in the development of effective vaccines. To evaluate whether a potential vaccine against tuberculosis could prevent infection by eliciting a protective antibody response, we reviewed the history of antibody-mediated immunity against tuberculosis. Review of the literature of the past 100 years demonstrates that there is sufficient evidence to conclude that antibody-mediated immunity can modify the course of infection in certain situations. Based on our findings and on what is known in other systems, we propose that the role of antibody-mediated immunity to M. tuberculosis be reexamined, using advanced technology.
Explorer Treatment of periodontal disease for glycaemic control in people with diabetes

Transmissible spongiform encephalopathies (TSEs) are progressive neurodegenerative diseases and include bovine spongiform encephalopathy of cattle, chronic wasting disease (CWD) of deer and elk, scrapie in sheep and goats, and Creutzfeldt-Jakob disease in humans. An abnormally folded form of the prion protein (designated PrP TSE ) is typically associated with TSE infectivity and may constitute the major, if not sole, component of the infectious agent. Transmission of CWD and scrapie is mediated in part by an environmental reservoir of infectivity. Soil appears to be a plausible candidate for this reservoir. TSE agent transport through soil is expected to influence the accessibility of the pathogen to animals after deposition and must be understood to assess the risks associated with burial of infected carcasses. We report results of saturated column experiments designed to evaluate PrP TSE transport through five soils with relatively high sand or silt contents. Protease-treated TSE-infected brain homogenate was used as a model for PrP TSE present in decomposing infected tissue. Synthetic rainwater was used as the eluent
Predators select against high growth rates and risk–taking behaviour in domestic trout populations

Domesticated (farm) salmonid fishes display an increased willingness to accept risk while foraging, and achieve high growth rates not observed in nature. Theory predicts that elevated growth rates in domestic salmonids will result in greater risk–taking to access abundant food, but low survival in the presence of predators. In replicated whole–lake experiments, we observed that domestic trout (selected for high growth rates) took greater risks while foraging and grew faster than a wild strain. However, survival consequences for greater growth rates depended upon the predation environment. Domestic trout experienced greater survival when risk was low, but lower survival when risk was high. This suggests that animals with high intrinsic growth rates are selected against in populations with abundant predators, explaining the absence of such phenotypes in nature. This is, to our knowledge, the first large–scale field experiment to directly test this theory and simultaneously quantify the initial invasibility of domestic salmonid strains that escape into the wild from aquaculture operations, and the ecological conditions affecting their survival.
1 SYNOPTIC ENVIRONMENTS AND CONVECTIVE MODES ASSOCIATED WITH SIGNIFICANT TORNADOES IN THE CONTIGUOUS UNITED STATES

Tornado forecasting has evolved considerably since the formation of the Severe Local Storms (SELS) Center of the United States Weather Bureau in the early 1950s (Winston 1956), to the current variation of SELS known as the Storm Prediction Center (SPC). Forecasting in the early days of SELS was limited largely to pattern recognition, sounding analysis, and subjectively predicting changes in the convective environment (Schaefer 1986; Galway 1992). More recent advances in numerical modeling and detailed field observations have resulted in greater physical understanding of the processes supportive of severe thunderstorms and tornadoes (see the reviews by Bluestein 1999, Davies-Jones et al. 2001, and Wilhelmson and Wicker 2001). This increasing knowledge base has manifested itself in a more “ingredients-based” approach (Doswell et al. 1996) to severe storm forecasting focusing on parameters representing relevant physical processes (Johns and Doswell 1992; Moller 2001), and led to numerous observational studies aimed at identifying environmental characteristics associated with various types of severe thunderstorms and tornadoes (e.g., Johns et al. 1993, Rasmussen and Blanchard 1998, and Thompson et al. 2003 among others).
Thermal Ablation and Laser Shielding Characteristics of Ionic liquid-microseeded Functionalized Nanoclay/Resorcinol Formaldehyde Nanocomposites for Armor Protection

ABSTRACT Thermal ablation performance, thermal stability, and laser shielding characteristics of tailored nanoclay-resorcinol formaldehyde nanocomposites have been investigated. RF resin was modified with ionic liquid and a range of weight loadings of functionalized nanoclay through a facile in situ polymerization technique. Thermal ablation testing of the modified resin shows lower back-face temperature profiles and distinct reduction in linear and mass ablation rates, while thermogravimetric analysis results show enhanced thermal stability. Significant increase in the laser ablation energy and increased d-spacing of the surface modified nanoclay in resorcinol formaldehyde nanocomposite connote favorable polymer intercalation/exfoliation within the silicate layers. GRAPHICAL ABSTRACT
Factors influencing inpatient duration among insanity acquittees in a Malaysian mental institution

Objective: According to Malaysian law, defendants found not guilty by reason of insanity may be admitted to a psychiatric hospital and discharge is subject to the state ruler’s assent. The objective of this study is to examine the clinical, socio-demographic and forensic factors that influence inpatient duration of insanity acquittees in a Malaysian mental institution. Methods: This is a cross-sectional study of one hundred and twelve insanity acquittee inpatients in Hospital Bahagia Ulu Kinta from January 2007 to February 2007. Patients with a clinical diagnosis of schizophrenia, major depressive disorder and bipolar disorder were assessed using the Positive and Negative Syndrome Scale (PANSS), Hamilton Depression Rating Scale (HAMD) and Young Mania Rating Scale (YMRS) respectively. Other relevant socio- demographic, clinical and forensic factors were also assessed. Results: The inpatient duration varied widely from three months to forty-seven years with a median of seven years. Seventy five percent of patients were in remission. According to the multiple linear regression model, the strongest predictor of a longer duration of hospital stay for insanity acquittees was older age (p<0.001) followed by murder as the index offence (p=0.005). Good family support predicted a shorter inpatient duration. This model explains 56% of the variance in the inpatient duration. Conclusion: Social factors such as family support may be increasingly important in determining the discharge process of insanity acquittees besides clinical rehabilitation. Issues such as stigma of violent forensic patients and the role of community forensic rehabilitation services need to be further explored.
Targeted genomic detection of biosynthetic pathways: anaerobic production of hopanoid biomarkers by a common sedimentary microbe

The lipid biomarker principle requires that preservable molecules (molecular fossils) carry specific taxonomic, metabolic, or environmental information. Historically, an empirical approach was used to link specific taxa with the compounds they produce. The lipids extracted from numerous, but randomly cultured species provided the basis for the interpretation of biomarkers in both modern environments and in the geological record. Now, with the rapid sequencing of hundreds of microbial genomes, a more focused genomic approach can be taken to test phylogenetic patterns and hypotheses about the origins of biomarkers. Candidate organisms can be selected for study on the basis of genes that encode proteins fundamental to the synthesis of biomarker compounds. Hopanoids, a class of pentacyclic triterpenoid lipid biomarkers, provide an illustrative example. For many years, interpretations of biomarker data were made with the assumption that hopanoids are produced only by aerobic organisms. However, the recent discovery of 13C‐depleted hopanoids in environments undergoing anaerobic methane oxidation and in enrichment cultures of anammox planctomycetes indicates that some hopanoids are produced anaerobically. To further examine the potential distribution of hopanoid biosynthesis by anaerobes, we searched publicly available genomic databases for the presence of squalene‐hopene cyclase genes in known obligate or facultative anaerobes. Here we present evidence that Geobacter sulfurreducens, Geobacter metallireducens, and Magnetospirillum magnetotacticum, all bacteria common in anoxic environments, have the appropriate genes for hopanoid biosynthesis. We further show that these data accurately predict that G. sulfurreducens does produce a variety of complex hopanoids under strictly anaerobic conditions in pure culture.
Differential T cell receptor‐mediated signaling in naive and memory CD4 T cells

Naive and memory CD4 T cells differ in cell surface phenotype, function, activation requirements, and modes of regulation. To investigate the molecular bases for the dichotomies between naive and memory CD4 T cells and to understand how the T cell receptor (TCR) directs diverse functional outcomes, we investigated proximal signaling events triggered through the TCR/CD3 complex in naive and memory CD4 T cell subsets isolated on the basis of CD45 isoform expression. Naive CD4 T cells signal through TCR/CD3 similar to unseparated CD4 T cells, producing multiple tyrosine‐phosphorylated protein species overall and phosphorylating the T cell‐specific ZAP‐70 tyrosine kinase which is recruited to the CD3ζ subunit of the TCR. Memory CD4 T cells, however, exhibit a unique pattern of signaling through TCR/CD3. Following stimulation through TCR/CD3, memory CD4 T cells produce fewer species of tyrosine‐phosphorylated substrates and fail to phosphorylate ZAP‐70, yet unphosphorylated ZAP‐70 can associate with the TCR/CD3 complex. Moreover, a 26/28‐kDa phosphorylated doublet is associated with CD3ζ in resting and activated memory but not in naive CD4 T cells. Despite these differences in the phosphorylation of ZAP‐70 and CD3‐associated proteins, the ZAP‐70‐related kinase, p72syk, exhibits similar phosphorylation in naive and memory T cell subsets, suggesting that this kinase could function in place of ZAP‐70 in memory CD4T cells. These results indicate that proximal signals are differentially coupled to the TCR in naive versus memory CD4 T cells, potentially leading to distinct downstream signaling events and ultimately to the diverse functions elicited by these two CD4 T cell subsets.
Functional Characterization of a Novel Frameshift Mutation in the C-terminus of the Nav1.5 Channel Underlying a Brugada Syndrome with Variable Expression in a Spanish Family

Introduction We functionally analyzed a frameshift mutation in the SCN5A gene encoding cardiac Na+ channels (Nav1.5) found in a proband with repeated episodes of ventricular fibrillation who presented bradycardia and paroxysmal atrial fibrillation. Seven relatives also carry the mutation and showed a Brugada syndrome with an incomplete and variable expression. The mutation (p.D1816VfsX7) resulted in a severe truncation (201 residues) of the Nav1.5 C-terminus. Methods and Results Wild-type (WT) and mutated Nav1.5 channels together with hNavβ1 were expressed in CHO cells and currents were recorded at room temperature using the whole-cell patch-clamp. Expression of p.D1816VfsX7 alone resulted in a marked reduction (≈90%) in peak Na+ current density compared with WT channels. Peak current density generated by p.D1816VfsX7+WT was ≈50% of that generated by WT channels. p.D1816VfsX7 positively shifted activation and inactivation curves, leading to a significant reduction of the window current. The mutation accelerated current activation and reactivation kinetics and increased the fraction of channels developing slow inactivation with prolonged depolarizations. However, late INa was not modified by the mutation. p.D1816VfsX7 produced a marked reduction of channel trafficking toward the membrane that was not restored by decreasing incubation temperature during cell culture or by incubation with 300 μM mexiletine and 5 mM 4-phenylbutirate. Conclusion Despite a severe truncation of the C-terminus, the resulting mutated channels generate currents, albeit with reduced amplitude and altered biophysical properties, confirming the key role of the C-terminal domain in the expression and function of the cardiac Na+ channel.
Implication of caspases during maedi-visna virus-induced apoptosis.

Maedi-visna virus (MVV) causes encephalitis, pneumonia and arthritis in sheep. In vitro, MVV infection and replication lead to strong cytopathic effects characterized by syncytia formation and subsequent cellular lysis. It was demonstrated previously that MVV infection in vitro induces cell death of sheep choroid plexus cells (SCPC) by a mechanism that can be associated with apoptotic cell death. Here, the relative implication of several caspases during acute infection with MVV is investigated by employing diverse in vitro and in situ strategies. It was demonstrated using specific pairs of caspase substrates and inhibitors that, during in vitro infection of SCPC by MVV, the two major pathways of caspase activation (i.e. intrinsic and extrinsic pathways) were stimulated: significant caspase-9 and -8 activities, as well as caspase-3 activity, were detected. To study the role of caspases during MVV infection in vitro, specific, cell-permeable, caspase inhibitors were used. First, these results showed that both z-DEVD-FMK (a potent inhibitor of caspase-3-like activities) and z-VAD-FMK (a broad spectrum caspase inhibitor) inhibit caspase-9, -8 and -3 activities. Second, both irreversible caspase inhibitors, z-DEVD-FMK and z-VAD-FMK, delayed MVV-induced cellular lysis as well as virus growth. Third, during SCPC in vitro infection by MVV, cells were positively stained with FITC-VAD-FMK, a probe that specifically stains cells containing active caspases. In conclusion, these data suggest that MVV infection in vitro induces SCPC cell death by a mechanism that is strongly dependent on active caspases.
Journal of Software Maintenance and Evolution: Research and Practice a Decision Framework for Enterprise Resource Planning Maintenance and Upgrade: a Client Perspective

SUMMARY Over the last decade, many large organizations have been shifting from developing their own information system (IS) to licensing and installing large software packages known as enterprise resource planning (ERP) systems. These organizations now face the challenge of maintaining these costly systems and many are about to make their first upgrade decisions. The study reported herein aims to address the following research questions from the ERP-client perspective: (1) What are the fundamental factors driving ERP maintenance and upgrade decisions? (2) How do these factors differ from those for traditional custom, in-house software? and (3) Do existing software and hardware replacement models suffice for ERP maintenance and upgrade decision modeling? A single case study method and empirical data analysis were conducted and are presented here. We observe that ERP maintenance and upgrade characteristics are indeed unique in three ways: (1) most organizations maintain and upgrade their ERP systems in order to realize increased business benefits from the systems; (2) a new version upgrade reduces the number of ERP-client-done enhancement modifications; and (3) a new version upgrade potentially reduces future legal change patch (LCP) maintenance distributed by the ERP vendor. It was also found that on average LCP maintenance is almost as costly as user enhancements. Based on these findings, we conclude that the existing in-house software and hardware replacement models are insufficient for ERP situations. We propose a preliminary ERP decision model that overcomes the observed insufficiencies.
Growth factors in breast cancer.

I. Regulation of Mammary Cell Growth and Apoptosis A. Hormonal control of mammary development, proliferation, and lactational defferentation DEVELOPMENT of the normal breast, carcinogenesis of its epithelium breast, and progression of breast cancer are regulated by hormonal factors. The best defined of these factors are the endocrine steroids, peptides, and other molecules produced by the secretory cells of the ovaries, pituitary, endocrine pancreas, thyroid, and adrenal cortex. After their initial interaction with either nuclear or cell surface receptors, these hormones regulate cellular function. In addition, normal and malignant mammary tissues are able to synthesize locally acting hormone-like substances. One class of these factors is known as the paracrine hormones, factors released by one cell type which then modulate the function of neighboring cells of the same or different mammary cell type. A recently described variation on this theme is the class of juxtacrine factors. These factors are growth-.
The Role of Gender, Values, and Culture in Adolescent Bystanders’ Strategies

We examined the relationship between adolescent bystanders’ strategies for intervening in the bullying-like situation and their gender, values, and cultural origin. The sample consisted of 682 Estonian and Russian-Estonian adolescents (Mage = 13.02 years). They were shown a video of a bullying-like situation with a non-intervening adult bystander and asked to describe what they would do if they, instead of the adult, witnessed that situation. Only 10% said that they would not intervene. Girls were more likely than boys to suggest multiple actions. Adolescents who valued conformity were less likely to propose using physical aggression. Doing nothing was less likely suggested by those who placed more importance on conformity and less on power. Estonian adolescents were more likely than their Russian-Estonian peers to suggest finding out what is going on, and less likely to say that they would do nothing. The findings suggest that although most adolescents express willingness to help the victim, they might not actually know how to intervene.