Miracle-dz/UniFAR-FTUs huggingface dataset:
Molecular and cellular bases for the protective effects of dopamine D1 receptor antagonist, SCH23390, against methamphetamine-induced neurotoxicity in the rat brain

Methamphetamine (METH) is a potent psychostimulant known to cause cognitive abnormalities and neurodegenerative changes in the brains of METH abusers. One approach for developing therapies for METH abuse is to understand the molecular mechanisms of toxicity of the drug. Investigations in our laboratory and elsewhere have shown that single intraperitoneal injections of METH (30-40 mg/kg of body weight) can cause damage to striatal and cortical monoaminergic systems and induce neuronal apoptosis in the striatum of rodents via activation of endoplasmic reticulum (ER) and mitochondrial death pathways. Hence, the purpose of this thesis was to investigate if toxic binge METH injections can cause ER- and mitochondria-induced stress in the rat striatum. Recent studies have suggested that dopamine (DA) D1 and D2 receptors might mediate neuronal apoptosis in the striatum after single toxic METH doses. We therefore hypothesized that signaling through these two types of DA receptors might activate toxic effects of the binge METH regimen. The role of DA D1 or D2 receptors in METH-induced cell death pathways was thus examined by using pharmacological inhibitors of these receptors. In this dissertation, I report that binge METH regimen caused differential changes in immediate early genes (IEGs) that are known to influence synaptic changes in the brain. METH-induced changed in the expression of the IEGs were dependent on DA D1 receptor stimulation. The second study examined the effects of binge METH on the expression of ER stress- and mitochondrial dysfunction-responsive genes. Pretreatment with the DA D1 receptor antagonist, SCH23390, caused complete inhibition of METH-induced ER and mitochondrial stresses whereas the DA D2 receptor antagonist, raclopride, provided only partial blockade. SCH23390 also blocked METH-induced hyperthermia whereas raclopride failed to do so. Interestingly, both antagonists attenuated METH-induced dopaminergic and serotonergic deficits in the striatum. Moreover, SCH23390 but not raclopride blocked METH-induced serotonergic deficits in cortical tissues. I also found that METH treatment induced upregulation of activin βA mRNA, increased TGF-β and phosphorylated Smad2 proteins in the rat striatum. SCH23390 pretreatment completely blocked all these effects whereas raclopride did not block METH-induced increases in TGF-β expression.
Titin is a major human disease gene.

Titin is a giant multi-functional sarcomeric filament that provides passive stiffness to cardiac myocytes. At its N terminus, titin is embedded in the Z-disk of the sarcomere. The rest of the molecule is divided between an elastic I-band region, a thick filament-binding A-band region, and the M-band region where the C terminus is embedded (Figure 1A, bottom). 1 The extensible I-band region of titin functions as a molecular spring that develops passive force during diastole when sarcomeres are stretched.2 This force is important for centering the A-band in the sarcomere3 and, together with the extracellular matrix, for defining diastolic stiffness.2 Other regions of titin (Z-disk, A-band, and M-band) are involved in numerous cellular processes including force-dependent signaling.4 Here we discuss recently discovered post-transcriptional and post-translational modifications of titin and address their roles in acquired cardiac disease, including dilated cardiomyopathy (DCM) and heart failure with preserved ejection fraction (HFpEF, often termed diastolic heart failure; for the purposes of this study we restrict the term HFpEF to HF patients with left ventricular EF > 0.50 in the absence of hypertrophic cardiomyopathy or valvular, infiltrative, or pericardial disease). The review also focuses on recent work that reveals mutations in the titin gene as a major source of familial cardiomyopathies, including mutations in the spring region of titin linked to arrhythmogenic right ventricular dysplasia5 and mutations in the A-band region of titin responsible for ≈30% of DCM cases.6 These findings have given rise to the emerging view that titin gene is a major disease gene. Figure 1. Schematic of titin in the sarcomere ( A ) and mechanisms for modifying titin-based passive tension ( B and C ). A , Bottom: Single titin molecules (shown in blue and yellow) span from Z-disk (N terminus) to M-band (C terminus). Middle: Composition of extensible I-band …
Species delimitation in Trametes: a comparison of ITS, RPB1, RPB2 and TEF1 gene phylogenies

Trametes is a cosmopolitan genus of white rot polypores, including the “turkey tail” fungus, T. versicolor. Although Trametes is one of the most familiar genera of polypores, its species-level taxonomy is unsettled. The ITS region is the most commonly used molecular marker for species delimitation in fungi, but it has been shown to have a low molecular variation in Trametes resulting in poorly resolved phylogenies and unclear species boundaries, especially in the T. versicolor species complex (T. versicolor sensu stricto, T. ochracea, T. pubescens, T. ectypa). Here we evaluate the performance of three protein-coding genes (TEF1, RPB1, RPB2) for species delimitation and phylogenetic reconstruction in Trametes. We obtained 59 TEF1, 34 RPB1 and 55 RPB2 sequences from 69 individuals, focusing on the T. versicolor complex and performed phylogenetic analyses with maximum likelihood and parsimony methods. All three protein-coding genes outperformed ITS for separating species in the T. versicolor complex. The multigene phylogenetic analysis shows the highest amount of resolution and supported nodes separating T. ectypa, T. ochracea, T. pubescens and T. versicolor with strong support. In addition three slineages are resolved in the species complex of T. elegans. The T. elegans complex includes three species: T. elegans (based on material from Puerto Rico, Belize, the Philippines), T. aesculi (from North America) and T. repanda (from Papua New Guinea, the Philippines, Venezuela). The utility of gene markers varies, with TEF1 having the highest PCR and sequencing success rate and RPB1 offering the best backbone resolution for the genus.
An empirical study on how expert knowledge affects bug reports

Bug reports are crucial software artifacts for both software maintenance researchers and practitioners. A typical use of bug reports by researchers is to evaluate automated software maintenance tools: a large repository of reports is used as input for a tool, and metrics are calculated from the tool's output. But this process is quite different from practitioners, who distinguish between reports written by experts, such as programmers, and reports written by non‐experts, such as users. Practitioners recognize that the content of a bug report depends on its author's expert knowledge. In this paper, we present an empirical study of the textual difference between bug reports written by experts and non‐experts. We find that a significant difference exists and that this difference has a significant impact on the results from a state‐of‐the‐art feature location tool. Through an additional study, we also found no evidence that these encountered differences were caused by the increased usage of terms from the source code in the expert bug reports. Our recommendation is that researchers evaluate maintenance tools using different sets of bug reports for experts and non‐experts. Copyright © 2016 John Wiley & Sons, Ltd.
Superconductivity across Lifshitz transition and anomalous insulating state in surface K–dosed (Li0.8Fe0.2OH)FeSe

Surface K–dosed (Li0.8Fe0.2OH)FeSe provides new clues to understand the mechanism of FeSe-based superconductors. In iron-based superconductors, understanding the relation between superconductivity and electronic structure upon doping is crucial for exploring the pairing mechanism. Recently, it was found that, in iron selenide (FeSe), enhanced superconductivity (Tc of more than 40 K) can be achieved via electron doping, with the Fermi surface only comprising M-centered electron pockets. By using surface K dosing, scanning tunneling microscopy/spectroscopy, and angle-resolved photoemission spectroscopy, we studied the electronic structure and superconductivity of (Li0.8Fe0.2OH)FeSe in the deep electron-doped regime. We find that a Γ-centered electron band, which originally lies above the Fermi level (EF), can be continuously tuned to cross EF and contribute a new electron pocket at Γ. When this Lifshitz transition occurs, the superconductivity in the M-centered electron pocket is slightly suppressed, and a possible superconducting gap with a small size (up to ~5 meV) and a dome-like doping dependence is observed on the new Γ electron pocket. Upon further K dosing, the system eventually evolves into an insulating state. Our findings provide new clues to understand superconductivity versus Fermi surface topology and the correlation effect in FeSe-based superconductors.
Adaptation of Mycobacterium to hospital disinfectants

The present work aimed to assess to morphological and phenotypical alterations, triggered by Mycobacterium vaccae, after exposure to hospital disinfectants; the activation of efflux pumps; and test the cross-resistance between hospital disinfectants and antibiotics. The minimal inhibitory concentrations of adapted and non-adapted M. vaccae cells to disinfectants were determined, and susceptibility assays were performed. The cells were exposed simultaneously to the disinfectant and to other compound. An antibiotic: levofloxacin or teicoplanin; or an efflux pumps inhibitor: thioridazine or omeprazole. Cellular aggregation and adjustment of the fatty acids composition were alterations observed during the experiments. Furthermore, the adapted cells showed to be more susceptible than non-adapted cells, since adapted cells were only able to grow in presence of omeprazole. Additionally, non-adapted cells exposed to levofloxacin showed a better growth than the control cells. These results suggest that non-adapted bacteria made use of efflux pumps, specifically in the case of levofloxacin, whereas with adapted bacteria possibly occurred cross-resistance between omeprazole and disinfectants. Nevertheless, cannot be excluded the occurrence of other adaptive mechanisms.
American-Indian diabetes mortality in the Great Plains Region 2002–2010

Objective To compare American-Indian and Caucasian mortality rates from diabetes among tribal Contract Health Service Delivery Areas (CHSDAs) in the Great Plains Region (GPR) and describe the disparities observed. Research design and methods Mortality data from the National Center for Vital Statistics and Seer*STAT were used to identify diabetes as the underlying cause of death for each decedent in the GPR from 2002 to 2010. Mortality data were abstracted and aggregated for American-Indians and Caucasians for 25 reservation CHSDAs in the GPR. Rate ratios (RR) with 95% CIs were used and SEER*Stat V.8. 0.4 software calculated age-adjusted diabetes mortality rates. Results Age-adjusted mortality rates for American-Indians were significantly higher than those for Caucasians during the 8-year period. In the GPR, American-Indians were 3.44 times more likely to die from diabetes than Caucasians. South Dakota had the highest RR (5.47 times that of Caucasians), and Iowa had the lowest RR, (1.1). Reservation CHSDA RR ranged from 1.78 to 10.25. Conclusions American-Indians in the GPR have higher diabetes mortality rates than Caucasians in the GPR. Mortality rates among American-Indians persist despite special programs and initiatives aimed at reducing diabetes in these populations. Effective and immediate efforts are needed to address premature diabetes mortality among American-Indians in the GPR.
Pulmonary embolism: one-year follow-up with echocardiography doppler and five-year survival analysis.

BACKGROUND The long-term prognosis for patients with pulmonary embolism (PE) is dependent on the underlying disease, degree of pulmonary hypertension (PH), and degree of right ventricular (RV) dysfunction. A precise description of the time course of pulmonary artery pressure (PAsP)/RV function is therefore of importance for the early identification of persistent PH/RV dysfunction in patients treated for acute PE. Other objectives were to identify variables associated with persistent PH/RV dysfunction and to analyze the 5-year survival rate for patients alive 1 month after inclusion. METHODS AND RESULTS Echocardiography Doppler was performed in 78 patients with acute PE at the time of diagnosis and repeatedly during the next year. A 5-year survival analysis was made. The PAsP decreased exponentially until the beginning of a stable phase, which was </=38 days. The recovery of RV function occurred during the same time period. Risk factors for persistent PH/RV dysfunction and the 5-year mortality rate were analyzed using multiple logistic regression models. A PAsP of >50 mm Hg at the time of diagnosis of acute PE was associated with persistent PH after 1 year. The 5-year mortality rate was associated with underlying disease. Only patients with persistent PH in the stable phase required pulmonary thromboendarterectomy within 5 years. CONCLUSIONS An echocardiography Doppler investigation performed 6 weeks after diagnosis of acute PE can identify patients with persistent PH/RV dysfunction and may be of value in planning the follow-up and care of these patients.
Enhancing Creativity of Strategic Decision Processes by Technological Roadmapping and Foresight

The quality of a company's strategic planning is a key factor influencing its competitiveness and development prospects. We will demonstrate how an appropriate choice of user inter¬faces, knowledge acquisition tools and analytic decision support methods can stimulate the creativity of the strategic planners taking part in technological road mapping. With strategic planning formalized as a multicriteria decision problem, the usual process of debating and brainstorming is better focused on reaching a consensus solution in an efficient way. An intelligent road mapping support tool and publicly available technological foresight results assure a high quality of data gathering and interaction of experts with stakeholders. Real options are used to evaluate the opportunities, threats, challenges, and flexibility during the planning period. The above approach has been implemented as an intranet application and used to apply information technology (IT) foresight outcomes to establish IT investment plans in innovative companies that develop new products and launch them on the market.
Drug-Eluting Stents for the Treatment of Vertebral Artery Origin Stenosis

Purpose: To present our experience with the use of drug-eluting stents (DES) in patients with symptomatic vertebral artery ostium stenosis (VAOS). Methods: Between 2003 and 2008, 28 consecutive patients (17 men; mean age 66 years) with symptomatic extracranial vertebral artery stenosis were treated with a paclitaxel-eluting stent. All patients were prospectively scheduled for serial clinical, duplex, and angiographic follow-up to identify restenosis. Results: After stent implantation, the mean stenosis was reduced from 68% to 9%. There were no periprocedural neurological complications. After a mean follow-up of 16 months (range 5–41), no strokes, worsening of symptoms, or deaths occurred. Angiographic restenosis >50% was seen in 6 (21.4%) patients. Restenosis occurred significantly more often in patients with an ipsilateral subclavian artery stenosis (p=0.01). Radiography during follow-up angiography revealed stent fracture in 1 patient and stent compression/kinking in 11 (39%) of the patients. Stent compression and recoil, not intimal hyperplasia, were the major contributing factors to restenosis. Conclusion: Compared to the restenosis rate of bare metal stents reported in the literature, DES seems to be superior for the treatment of VAOS. However, stent compression and recoil are relevant problems contributing to restenosis. Further improvement of the materials for the interventional treatment of VAOS seems necessary.
Empirical mode decomposition based weighted frequency feature for speech-based emotion classification

This paper focuses on speech based emotion classification utilizing acoustic data. The most commonly used acoustic features are pitch and energy, along with prosodic information like rate of speech. We propose the use of a novel feature based on instantaneous frequency obtained from the speech, in addition to the aforementioned features, in order to take into account the vocal tract parameters as well as vocal chord excitation. The proposed features employ the recently emerged empirical mode decomposition to decompose speech into AM-FM signals that are symmetric about zero and suitable for Hilbert transformation to extract the instantaneous frequency. The proposed features provide a relative increase in classification accuracy of approximately 9% when appended to established acoustic features.
Differential disinhibition of the neonatal hypothalamic– pituitary–adrenal axis in brain‐specific CRH receptor 1‐knockout mice

In the adult, corticotropin‐releasing hormone (CRH) is the key mediator for the behavioural and neuroendocrine response to stress. It has also been hypothesized that, during postnatal development of the stress system, CRH controls the activity of the HPA axis and mediates the effects of early disturbances, e.g. 24 h of maternal deprivation. In the current study we investigated the function of specific brain corticotropin‐releasing hormone receptor type 1 (CRHR1) subpopulations in the control of the HPA axis during postnatal development under basal conditions as well as after 24 h of maternal deprivation. We used two conditional CRHR1‐deficient mouse lines which lack this receptor, either specifically in forebrain and limbic structures (Cam‐CRHR1) or in all neurons (Nes‐CRHR1). Basal circulating corticosterone was increased in Nes‐CRHR1 mice compared to controls. Corticosterone response to maternal deprivation was significantly increased in both CRHR1‐deficient lines. In the paraventricular nucleus, Cam‐CRHR1 animals displayed enhanced CRH and decreased vasopressin expression levels. In contrast, gene expression in Nes‐CRHR1 pups was strikingly similar to that in maternally deprived control pups. Furthermore, maternal deprivation resulted in an enhanced response of Cam‐CRHR1 pups in the brain, while expression levels in Nes‐CRHR1 mouse pups were mostly unchanged. Our results demonstrate that brainstem and/or hypothalamic CRHR1 contribute to the suppression of basal corticosterone secretion in the neonate, while limbic and/or forebrain CRHR1 dampen the activation of the neonatal HPA axis induced by maternal deprivation.
Therapeutic potential of interleukin-17 in inflammation and autoimmune diseases

Introduction: Interleukin-17 (IL-17) is a proinflammatory cytokine that mainly produced by T helper 17 (Th17) cells. In this article, we discussed the role of IL-17 in inflammation and autoimmune diseases, and the therapeutic strategies targeting IL-17. Areas covered: In this article, we discussed the proinflammatory cytokine IL-17 and IL-17 receptors signals, and their regulation. IL-17 expression was abnormal in the bacterium, virus and fungus infection, and its higher level caused the tissue inflammation. IL-17 was involved in the pathological process of autoimmune diseases, such as systemic sclerosis, rheumatoid arthritis, ankylosing spondylitis and systemic lupus erythematosus, and IL-17 has been put as a therapeutic target in the clinic. Expert opinion: IL-17/IL-17R signals and their application in inflammation process still need to be explored. Therapeutic strategies targeting IL-17 in autoimmune diseases ameliorated the inadequate response to anti-TNF-α therapy.
Osteoarthritis of the hip: an occupational disease in farmers.

OBJECTIVE--To test the hypothesis that farmers are at high risk of hip osteoarthritis and to investigate possible causes for such a hazard. DESIGN--Cross sectional survey. SETTING--Five rural general practices. SUBJECTS--167 male farmers aged 60-76 and 83 controls from mainly sedentary jobs. All those without previous hip replacement underwent radiography of the hip. MAIN OUTCOME MEASURES--Hip replacement for osteoarthritis or radiological evidence of hip osteoarthritis. RESULTS--Prevalence of hip osteoarthritis was higher in farmers than controls and especially in those who had farmed for over 10 years (odds ratio 9.3, 95% confidence interval 1.9 to 44.5). The excess could not be attributed to any one type of farming, and heavy lifting seems the likely explanation. CONCLUSIONS--Manual handling in agriculture should be limited where possible. Consideration should be given to making hip osteoarthritis a prescribed industrial disease in farmers. There may be wider implications for the prevention of hip osteoarthritis in the general population.
Relationship Between Metabolism and the Lateral Transport of IAA in Corn Coleoptiles.

The lateral movement of IAA in coleoptiles of Zea mays has been investigated under aerobic and anaerobic conditions. The IAA-1-(14)C was supplied asymmetrically to the apical end of the segment. The results were as follows: A) In air more (14)C was found in the lower half of horizontal segments supplied with an upper donor than in the half opposite the donor in vertical segments. The enhanced lateral movement of (14)C in geotropically stimulated segments of corn coleoptiles under aerobic conditions has thus been confirmed. B) This increased lateral movement of (14)C in geotropically stimulated segments is greatly reduced, but is not completely abolished, under anaerobic conditions. C) The lateral movement of (14)C in vertical segments is significantly less under anaerobic conditions than in air. D) Under anaerobic conditions, the lateral movement of (14)C in horizontal segments can be reduced to the level found in vertical segments by pre-soaking the tissue in a 1 mm solution of the metabolic inhibitor sodium fluoride for 2 hours. The inhibitor has no effect on lateral movement of (14)C in vertical anaerobic segments. E) In air, sodium fluoride has no effect on the lateral movement of (14)C in either vertical or horizontal segments.On the assumption that the movement of (14)C reflects the movement of IAA, these results show that the enhanced polarized lateral movement of IAA observed in horizontal corn coleoptile segments is totally abolished only when both aerobic and anaerobic metabolism are arrested. In addition, there appears to be a small metabolically dependent component in the lateral movement of IAA in vertical segments supplied with an asymmetric donor in air.
EXPONENTIAL DISPERSION MODELS AND THE GAUSS‐NEWTON ALGORITHM

It is known that the Fisher scoring iteration for generalized linear models has the same form as the Gauss‐Newton algorithm for normal regression. This note shows that exponential dispersion models are the most general families to preserve this form for the scoring iteration. Therefore exponential dispersion models are the most general extension of generalized linear models for which the analogy with normal regression is preserved. The multinomial distribution is used as an example.