Miracle-dz/UniFAR-FTUs huggingface dataset:
Dynorphin A (1–13) Neurotoxicity in Vitro: Opioid and Non-Opioid Mechanisms in Mouse Spinal Cord Neurons

Dynorphin A is an endogenous opioid peptide that preferentially activates kappa-opioid receptors and is antinociceptive at physiological concentrations. Levels of dynorphin A and a major metabolite, dynorphin A (1-13), increase significantly following spinal cord trauma and reportedly contribute to neurodegeneration associated with secondary injury. Interestingly, both kappa-opioid and N-methyl-D-aspartate (NMDA) receptor antagonists can modulate dynorphin toxicity, suggesting that dynorphin is acting (directly or indirectly) through kappa-opioid and/or NMDA receptor types. Despite these findings, few studies have systematically explored dynorphin toxicity at the cellular level in defined populations of neurons coexpressing kappa-opioid and NMDA receptors. To address this question, we isolated populations of neurons enriched in both kappa-opioid and NMDA receptors from embryonic mouse spinal cord and examined the effects of dynorphin A (1-13) on intracellular calcium concentration ([Ca2+]i) and neuronal survival in vitro. Time-lapse photography was used to repeatedly follow the same neurons before and during experimental treatments. At micromolar concentrations, dynorphin A (1-13) elevated [Ca2+]i and caused a significant loss of neurons. The excitotoxic effects were prevented by MK-801 (Dizocilpine) (10 microM), 2-amino-5-phosphopentanoic acid (100 microM), or 7-chlorokynurenic acid (100 microM)--suggesting that dynorphin A (1-13) was acting (directly or indirectly) through NMDA receptors. In contrast, cotreatment with (-)-naloxone (3 microM), or the more selective kappa-opioid receptor antagonist nor-binaltorphimine (3 microM), exacerbated dynorphin A (1-13)-induced neuronal loss; however, cell losses were not enhanced by the inactive stereoisomer (+)-naloxone (3 microM). Neuronal losses were not seen with exposure to the opioid antagonists alone (10 microM). Thus, opioid receptor blockade significantly increased toxicity, but only in the presence of excitotoxic levels of dynorphin. This provided indirect evidence that dynorphin also stimulates kappa-opioid receptors and suggests that kappa receptor activation may be moderately neuroprotective in the presence of an excitotoxic insult. Our findings suggest that dynorphin A (1-13) can have paradoxical effects on neuronal viability through both opioid and non-opioid (glutamatergic) receptor-mediated actions. Therefore, dynorphin A potentially modulates secondary neurodegeneration in the spinal cord through complex interactions involving multiple receptors and signaling pathways.
The Effects of Instruction on Science Students' Socio-Cultural Attitudes and Achievement

ABSTRACT This study investigated whether instruction through the socio-cultural mode had any effect on students' attitude towards and achievement in science. The sample consisted of 600 students (442 boys, 158 girls) at the Senior Year One level from 15 selected secondary schools in Nigeria. The Socio-Cultural Environment Scale (SCES) and a Biology Achievement Test (BAT) were used to measure attitudes and achievement in biology during a six-week instructional treatment. The results indicated that instruction in science which deliberately encompassed the discussion of socio-cultural views about science concepts engendered achievement in science. The instructional method was equally effective for boys and girls in terms of the socio-cultural attitudes, but boys benefited more than girls from the treatment in terms of achievement. The findings also suggest that a harmonious coexistence could be found for both the anthropomorphic and mechanistic views in such a way as to promote positive attitude towards the .
Methylene blue adsorption on graphene oxide

In this study, graphene oxide (GO), produced using the simple Hummer’s method, was used as adsorbent to remove methylene blue (MB) from aqueous solution. Characterizations using transmission electron microscope (TEM) and Fourier transform infrared (FTIR) spectroscopy were carried out on the GO before the MB adsorption experiments. The adsorption kinetics and isotherm studies were conducted under different conditions (pH = 3-7 and MB concentration = 100-400 mg/L) to examine the adsorption efficiency of the GO towards MB in aqueous solution. The adsorption kinetics data were analyzed using different kinetic models to investigate the adsorption behavior of MB on GO. The obtained results showed that the maximum adsorption capacity of the GO towards MB can achieve up to ~700 mg/g for the adsorption at 300 mg/L MB. The adsorption kinetic data were found to fit pseudo-second order model as compared with pseudo-first-order model. The intraparticle diffusion model suggested that the adsorption process of GO towards MB was dominated by the external mass transfer of MB molecules to the surface of GO.
Glycerol Production in a Triose Phosphate Isomerase Deficient Mutant of Saccharomyces cerevisiae

Interesting challenges from metabolically engineered Saccharomyces cerevisiae cells arise from the opportunity to obtain yeast strains useful for the production of chemicals. In this paper, we show that engineered yeast cells deficient in the triose phosphate isomerase activity are able to produce glycerol without the use of steering agents. High yields of conversion of glucose into glycerol (80−90% of the theoretical yield) and productivity (1.5 g L−1 h−1) have been obtained by a bioconversion process carried out in a poor and clean medium. We obtained indications that the growth phase at which the biomass was collected affect the process. The best results were obtained using cells collected at the end of exponential phase of growth. In perspective, the strategies and the information about the physiology of the cells described here could be useful for the developing of new biotechnological processes for glycerol production, outflanking the problems related to the use of high level of steering agents.
An Investigation of Alcohol Dependent Respondents' Attributions for Their Own and “Others” Relapses

In this study the attributions made by alcohol dependent respondents for their “own” and “others” relapses were examined. Seventy alcohol dependent inpatients participated. Each respondent completed a research questionnaire which assessed demographic details, drinking history, alcohol dependence and included an attribution scale on which respondents rated their own last relapse, and four relapse scenarios of “other” people, in terms of locus of causality (external/internal), personal control, external control, stability and globality. There were significant differences in the attributions made by alcohol dependent respondents for their “own” relapses as against the relapses of “others”. The relapses of “others” were seen as being significantly different; having greater internal locus of causality, lower external control and higher personal control attributions. No differences were found on the dimensions of globality and stability. The existence of such differences suggest that attribution theory is of relevance to any model of relapse that is based on client self report. It is also possible that the current emphasis in clinical work on the identification and management of high risk external situations as pre-cipitants of relapse, may be a consequence of the attribution process rather than the “real” cause of relapse.
IL28B: relevance extended to hepatitis B virus or limited to interferon‐based therapies in hepatitis C virus?

The three top single-nucleotide polymorphism (SNPs) rs12979860, rs12980275 and rs8099917 were recently related to treatment-induced hepatitis C virus (HCV) clearance. Thio and Thomas (1) elegantly reviewed that rs8099917 is likely irrelevant in the setting of African American patients. Furthermore, several studies confirmed that rs12979860 seems to be the most dominant SNP in Caucasian populations (2). In contrast, in an Asian population, rs8099917 has been superior to rs12979860 for predicting HCV treatment response or spontaneous clearance in some (3, 4) but not all studies (5).
Development of Infants of Drug Dependent Mothers

Infants of mothers who used methadone, heroin, cocaine and other drugs during pregnancy were compared with a group of control infants over the first 30 months of life. Results of repeated examinations with the Bayley Scales of Infant Development showed a difference between the groups in mental development. No differences were found in a non-verbal version of the mental scale, but infants of drug dependent mothers seem to have specific difficulties in early language development. In psychomotor development, in behaviour during testing and on a questionnaire on activity, infants of drug dependent mothers did not differ from the comparison children.
Know Thyself: Examining Factors That Influence the Activation of Organizational Identity Concepts in Top Managers’ Minds

This article addresses how top managers activate their organizational identity concepts during strategic decision making. It integrates the social cognition and strategic management literature by employing the accessibility principle in strategic management processes. Data were gathered through interviews and case scenario—based questionnaires from top managers in four Indonesian pharmaceutical companies. Analysis suggests that cognitive associations that are achieved through decision integration, desired future image, and information sharing are keys in making identity dimensions accessible, thus enabling the activation of organizational identity concepts in these top managers’ minds. Results also indicate an association between perception of control and top managers’ ability to activate concepts of organizational identity. The article discusses the theoretical and practical implications of findings.
Autophagy Inhibition Promotes 5-Fluorouraci-Induced Apoptosis by Stimulating ROS Formation in Human Non-Small Cell Lung Cancer A549 Cells

Chemotherapy is an important option for the treatment of various cancers including lung cancer. However, tumor resistance towards cytotoxic chemotherapy has become more common. It has been reported that autophagy is one of the processes contributing to this resistance. In the present study, we found that the anti-cancer drug 5-fluorouraci(5-FU) could induce autophagy in A549 cells. 5-FU treatment could lead to the conversion of LC3 I/II, the up-regulation of Beclin-1, the down-regulation of p62 and the formation of acidic vesicular organelles (AVOs) in A549 cells. Pre-treatment of cancer cells with 3-MA or siAtg7 could enhance 5-FU-induced apoptosis through the activation of caspases, and the caspase inhibitor z-VAD-fmk rescued the cell viability reduction. Furthermore, the inhibition of autophagy also stimulated ROS formation and scavenging of ROS by antioxidant NAC inhibited caspase-3 activity, prevented the release of cyt-c from mitochondria and eventually rescued cancer cells from 5-FU-mediated apoptosis. These results suggest that 5-FU-elicited autophagic response plays a protective role against cell apoptosis and the inhibition of autophagy could sensitize them to 5-FU-induced caspase-dependent apoptosis through the stimulation of ROS formation.
Macroscopic Fluid Models with Localized Kinetic Upscaling Effects

This paper presents a general methodology to design macroscopic fluid models that take into account localized kinetic upscaling effects. The fluid models are solved in the whole domain together with a localized kinetic upscaling that corrects the fluid model wherever it is necessary. This upscaling is obtained by solving a kinetic equation on the nonequilibrium part of the distribution function. This equation is solved only locally and is related to the fluid equation through a downscaling effect. The method does not need to find an interface condition as do usual domain decomposition methods to match fluid and kinetic representations. We show our approach applies to problems that have a hydrodynamic time scale as well as to problems with diffusion time scale. Simple numerical schemes are proposed to discretize our models, and several numerical examples are used to validate the method.
Analysis of polarization in QM/MM modelling of biologically relevant hydrogen bonds

Combined quantum mechanics/molecular mechanics (QM/MM) methods are increasingly important for the study of chemical reactions and systems in condensed phases. Here, we have tested the accuracy of a density functional theory-based QM/MM implementation (B3LYP/6-311+G(d,p)/CHARMM27) on a set of biologically relevant interactions by comparison with full QM calculations. Intermolecular charge transfer due to hydrogen bond formation is studied to assess the severity of spurious polarization of QM atoms by MM point charges close to the QM/MM boundary. The changes in total electron density and natural bond orbital atomic charges due to hydrogen bond formation in selected complexes obtained at the QM/MM level are compared with full QM results. It is found that charge leakage from the QM atoms to MM atomic point charges close to the QM/MM boundary is not a serious problem, at least with limited basis sets. The results are encouraging in showing that important properties of key biomolecular interactions can be treated well at the QM/MM level employing good-quality levels of QM theory.
Trauma in the childhood stories of people who have injected drugs

Abstract Aim: To document childhood trauma in the life stories of people who have injected drugs. Method: Fifty-five participants (38 m, 17 f) recruited via Scottish recovery networks, who had injected drugs in the previous five years, were interviewed by peer researchers using the Life Story method. Results: Remembered childhood trauma included persistent violence, repeated sexual abuse, neglect and traumatic bereavements. Many traumas were related to adult alcohol use. Few participants told of no trauma, some of severe trauma contributing to subsequent drug problems, some recounted stories including traumatic events, but not linked to later drug problems. A few told of initial severe behavioural problems leading to trauma for the child and to drug problems. Drug problems followed trauma by various routes, without straightforward cause and effect: direct use of drugs as avoidant coping; juvenile heavy recreational use that escalated; forming relationships in mid to late teens with criminals. For men, this involved enmeshment in drug dealing, crime and prison. Some women formed relationships with men who injected drugs, who often introduced them to drugs, and some of whom were violently abusive. Heroin injecting was an effective means of blotting out distressing thoughts and feelings. Although, childhood stories also contained positive memories, factors that might have promoted resilience were rarely mentioned. Conclusions: Severe childhood trauma was common and gravitated people towards problem drug use via various pathways. Participants had often normalised the problems and did not remember adult help. Parental alcohol use contributed to trauma. Addiction services need to be more trauma minded.
Using Formal Methods to Reason about Architectural Standards

Abstract : We present a study in which we used formal methods to reason precisely about aspects of a widely used software architectural standard, namely Microsoft's Component Object Model (COM). We developed a formal theory of COM to help us reason about a proposed compositional architectural style based on COM, intended for use in a novel commercial multimedia authoring system. The style combined COM objects, integration mediators, and the COM reuse mechanism of aggregation. Our use of formal methods averted an architectural disaster by revealing essential but subtle and counterintuitive properties of COM. We partially validated our theory by subjecting it to review by the designers of COM and by testing it against other available data. The theory has good evidential support.
PD-L1 Expression, Tumor-infiltrating Lymphocytes, and Clinical Outcome in Patients With Surgically Resected Esophageal Cancer

Objectives: To examine the prognostic impact of the programmed death ligand 1 (PD-L1) expression, tumor-infiltrating lymphocyte (TIL) status, and their combination in esophageal cancer. Summary Background Data: PD-L1 has garnered much attention for its roles in tumor immunology and as an immune-based therapeutic target. To ensure a response to PD-L1 checkpoint inhibitor, a new framework based on PD-L1 expression and the presence or absence of TILs is required. Methods: Using a nonbiased database of 305 curatively resected esophageal cancers, we evaluated PD-L1 expression and TIL status (cluster of differentiation 8 (CD8) expression) by immunohistochemical analysis. The Cox proportional hazard model was used to compute the hazard ratio (HR) for mortality. Results: Compared with PD-L1 negative cases (n=252), PD-L1 positive cases (n = 53) showed significantly worse overall survival [log-rank P = 0.016; HR: 1.71; 95% confidence interval: 1.08–2.61; P = 0.024; multivariate HR: 1.69; 95% confidence interval: 1.05–2.67; P = 0.033]. TIL positivity was significantly correlated with longer overall survival (log-rank P < 0.0001) and high CD8 expression (P < 0.0001). A stratification based on PD-L1 expression and TIL status was also significantly associated with overall survival (log rank P < 0.0001). Conclusions: PD-L1 expression was associated with an unfavorable clinical outcome in esophageal cancer, supporting its role as a prognostic biomarker. In addition, the combination with TIL status enabled further classification patients according to clinical outcome. PD-L1 expression and TIL status may serve as predictive tissue biomarkers and can be used for patient selection in clinical trials of drugs targeting the PD-1/PD-L1 pathways.
Childhood and Coress model of carcinogenesis.

INTRODUCTION In the last fifty years the incidence of gastric cancer in developed countries is a constant trend, but mortality in all countries remains at the same level and ranks second behind lung cancer. In the case of gastric cancer has a far more important the role the early diagnosis compared to prevention. MATERIAL AND METHODS The sample included 200 subjects aged 7-18 years treated at the Pediatric Clinic, University Clinic Tuzla and Pediatric Clinic and the Clinic for Child Surgery of Clinical Center of Sarajevo University who had endoscopic and histologically verified gastritis. The method of processing the tissue preparations of histologic sections of paraffin-fixed and paraffin tissue by hematoxylin-eosin method and Helicobacter pylori, using Giemsa. RESULTS AND DISCUSSION Pathological analysis of the sample of patients with gastritis found that in 91% of patients had chronic superficial gastritis, while in 9% of patients were found atrophic changes, with or without intestinal metaplasia. Atrophic changes with or without intestinal metaplasia was found in 10.2% of H. pylori-positive patients with gastritis. The same analysis in a significant percentage of 5.7% of H. pylori-negative patients was atrophic changes, with or without intestinal metaplasia. Analysis of activity of the inflammatory process, we have found that the symptoms matched a statistically significant percentage (86.5%) with the active phase of the disease, which speaks against thinking that H. pylori infection is asymptomatic condition, which is often cited in the literature. CONCLUSION Gastric mucosal lesion caused H. pylori infection is a reversible process and the eradication of this infection not only stops the activity of the inflammatory process, but also restores the mucous membranes. Eradication leads to a significant drop in the incidence of recurrence of gastritis and peptic ulcer disease, and can lead to prevention of malignant disease in 70-80% of cases, even, and perhaps more.
Inbreeding depression of sperm traits in the zebra finch Taeniopygia guttata

Abstract Inbreeding depression, or the reduction in fitness due to mating between close relatives, is a key issue in biology today. Inbreeding negatively affects many fitness‐related traits, including survival and reproductive success. Despite this, very few studies have quantified the effects of inbreeding on vertebrate gamete traits under controlled breeding conditions using a full‐sib mating approach. Here, we provide comprehensive evidence for the negative effect of inbreeding on sperm traits in a bird, the zebra finch Taeniopygia guttata. We compared sperm characteristics of both inbred (pedigree F = 0.25) and outbred (pedigree F = 0) individuals from two captive populations, one domesticated and one recently wild‐derived, raised under standardized conditions. As normal spermatozoa morphology did not differ consistently between inbred and outbred individuals, our study confirms the hypothesis that sperm morphology is not particularly susceptible to inbreeding depression. Inbreeding did, however, lead to significantly lower sperm motility and a substantially higher percentage of abnormal spermatozoa in ejaculate. These results were consistent across both study populations, confirming the generality and reliability of our findings.
Postural and respiratory functions of the pelvic floor muscles

Due to their contribution to modulation of intra‐abdominal pressure (IAP) and stiffness of the sacroiliac joints, the pelvic floor muscles (PFM) have been argued to provide a contribution to control of the lumbar spine and pelvis. Furthermore, as IAP is modulated during respiration this is likely to be accompanied by changes in PFM activity.
Effect of Cell Cycle Inhibition on Cisplatin-Induced Cytotoxicity

Pharmacological inhibitors of cyclin-dependent kinase (CDK)2 are currently in preclinical and clinical development. The purpose of our work was to evaluate a series of guanine derivatives for their ability to inhibit CDK2, affect cell cycle progression, and enhance the cytotoxic and apoptotic effects of cisplatin. A panel of guanine derivatives, including O6-benzylguanine (O6-BG), S6-benzyl-6-thioguanine (S6-BG), S6-[(cyclohexyl)methyl]-6-thioguanine (S6-CMG), O6-[(cyclohexyl)methyl]guanine (O6-CMG), O6-benzyl-9-methylguanine (9-CH3-BG), O6-[(cyclohexyl)methyl]-9-methyl-guanine (9-CH3-CMG), and 7-benzylguanine (N7-BG), exhibited varying degrees of CDK2 inhibition with O6-CMG being the most potent and 9-CH3-BG, 9-CH3-CMG, and N7-BG the least potent compounds. Treatment with S6-CMG and O6-CMG significantly decreased the percentage of cells in S phase. In SQ20b and SCC61 head and neck cancer cell lines, the most potent CDK2 inhibitor, O6-CMG, was also the most effective at enhancing cisplatin-induced cytotoxicity and apoptosis. Cisplatin-induced DNA platination increased in SQ20b cells pretreated with S6-BG, S6-CMG, and O6-CMG. Treatment with both O6-BG and trichostatin A, an indirect cell cycle inhibitor, demonstrated additive effects on cisplatin-induced cytotoxicity. In summary, we have identified a group of guanine derivatives that were effective modulators of cisplatin-induced cytotoxicity and apoptosis.
Inpatient Course and Length of Hospital Stay in Patients with Brain Disorders in South Korea: A Population-based Registry Study

Objective To describe inpatient course and length of hospital stay (LOS) for people who sustain brain disorders nationwide. Method We interviewed 1,903 randomly selected community-dwelling patients registered as 'disabled by brain disorders' in 28 regions of South Korea. Results Seventy-seven percent were initially admitted to a Western medicine hospital, and 18% were admitted to a traditional Oriental medicine hospital. Forty-three percent were admitted to two or more hospitals. Mean LOS was 192 days. Most patients stayed in one hospital for more than 4 weeks. The transfer rate to other hospitals was 30-40%. Repeated admissions and increased LOS were related to younger onset age, higher education, non-family caregiver employment, smaller families, and more severe disability. Conclusion Korean patients with brain disorders showed significantly prolonged LOS and repeated admissions. Factors increasing burden of care influenced LOS significantly.