Miracle-dz/UniFAR-FTUs huggingface dataset:
Mitomycin C induces apoptosis in human epidural scar fibroblasts after surgical decompression for spinal cord injury

Numerous studies have shown that topical application of mitomycin C after surgical decompression effectively reduces scar adhesion. However, the underlying mechanisms remain unclear. In this study, we investigated the effect of mitomycin C on the proliferation and apoptosis of human epidural scar fibroblasts. Human epidural scar fibroblasts were treated with various concentrations of mitomycin C (1, 5, 10, 20, 40 μg/mL) for 12, 24 and 48 hours. Mitomycin C suppressed the growth of these cells in a dose- and time-dependent manner. Mitomycin C upregulated the expression levels of Fas, DR4, DR5, cleaved caspase-8/9, Bax, Bim and cleaved caspase-3 proteins, and it downregulated Bcl-2 and Bcl-xL expression. In addition, inhibitors of caspase-8 and caspase-9 (Z-IETD-FMK and Z-LEHD-FMK, respectively) did not fully inhibit mitomycin C-induced apoptosis. Furthermore, mitomycin C induced endoplasmic reticulum stress by increasing the expression of glucose-regulated protein 78, CAAT/enhancer-binding protein homologous protein (CHOP) and caspase-4 in a dose-dependent manner. Salubrinal significantly inhibited the mitomycin C-induced cell viability loss and apoptosis, and these effects were accompanied by a reduction in CHOP expression. Our results support the hypothesis that mitomycin C induces human epidural scar fibroblast apoptosis, at least in part, via the endoplasmic reticulum stress pathway.
Empirical Confirmation of Pair Programming Effectiveness in the Teaching of Computer Programming

This paper presents issues of computer programming and results of controlled experiment conducted to evaluate and understand the significance of pair programming in the teaching of programming. It involved 42 second year students attending object-oriented programming in Java, CISM 214 module as an elective at our institution. The experiment assessed the time for task completion, code correctness and quality as well as students' motivation. The results obtained were analyzed as well as hypothesis formulated and tested. The paired samples T-tests showed a statistically reliable difference between the mean number of time taken and the correctness/quality of programming task in individual and pair programming carried out by the students at a significant level of α=0.05 at 95% confidence interval. The results shows that pair programming is more effective in the teaching of programming than traditional approach and confirms several reports on pair programming in the literature. Thus, it would be advantageous to adopt pair programming as a technique for teaching computer programming for beginners.
Heart failure: mechanisms of cardiac and vascular dysfunction and the rationale for pharmacologic intervention

Congestive heart failure is a complex clinical syndrome that has its basis in an abnormality of myocardial cell function resulting in impaired ventricular performance, exercise intolerance, and ventricular arrhythmias. The functional defect in myocardial performance may be related to alterations in receptor function, in regulatory proteins, or in biochemical mechanisms. Remodeling of the left ventricle has been observed to play an important role in the natural course of heart failure. The complex interplay between cellular elongation, reactive hypertrophy, and the influence of the change from ellipsoid to spheroidal shape of the left ventricle after acute myocardial infarction are just beginning to be understood. Prevention of this remodeling effect by pharmacologic intervention is being widely explored, although the mechanisms are poorly defined. Impedance to left ventricular ejection is also an important determinant of cardiac performance in heart failure. Constriction of arteriolar resistance vessels and reduction in compliance of arterial conductance vessels is a common manifestation of heart failure and may be under the influence of neural, hormonal, endothelial, and local regulatory factors. Increased tone of venous capacitance vessels contributes to a shift of blood centrally and to an increase in ventricular preload. Vasodilator drugs by relaxing the arterial, arteriolar, and venous vasculature result in a reduction in impedance and left ventricular afterload and a decrease in cardiac filling pressure and preload. Structural changes of hypertrophy and remodeling apparently contribute to the changes in resistance, compliance, and capacitance in the vasculature. Treatment of heart failure is aimed at relieving symptoms and prolonging life. Interventions to improve left ventricular function are critical to symptom relief. Vasodilators have been most effective for this purpose, and new positive inotropic drugs are being tested for efficacy. Long‐term benefit may require interference with the myocardial and peripheral vascular remodeling processes that lead to progressive depression of ventricular performance. New insights into the cellular and subcellular mechanisms of this progression are critical to the development of innovative therapeutic strategies. — Francis, G. S. ; Cohn, J. N. Heart failure: mechanisms of cardiac and vascular dysfunction and the rationale for pharmacologic intervention. FASEB J. 4: 3068‐3075; 1990.
Dyscholesterolemia Protects Against Ischemia-Induced Ventricular Arrhythmias

Background—Hypercholesterolemia protects against ventricular fibrillation in patients with myocardial infarction. We hypothesize that hypercholesterolemia protects against ischemia-induced reentrant arrhythmias because of altered ion channel function. Methods and Results—ECGs were measured in low-density lipoprotein receptor knockout (LDLr−/−), apolipoprotein A1 knockout (ApoA1−/−), and wild-type (WT) mice. Action potentials, calcium handling, and ion currents were recorded in ventricular myocytes. Gene expression was determined by quantitative polymerase chain reaction and Western blot. In isolated perfused hearts, regional ischemia was induced and arrhythmia inducibility was tested. Serum low-density lipoprotein (LDL) cholesterol was higher in LDLr−/− mice than in WT mice (2.6 versus 0.4 mmol/L), and high-density lipoprotein cholesterol was significantly lower in ApoA1−/− mice than in WT mice (0.3 versus 1.8 mmol/L). LDLr−/− and ApoA1−/− myocytes contained more cholesterol than WT (34.4±2.8 and 36.5±2.4 versus 25.5±0.4 &mgr;mol/g protein). The major potassium currents were not different in LDLr−/− and ApoA1−/− compared with WT mice. The L-type calcium current (ICa), however, was larger in LDLr−/− and ApoA1−/− than in WT (12.1±0.7 and 12.8±0.8 versus 9.4±1.1 pA/pF). Calcium transient amplitude and fractional sarcoplasmic reticulum calcium release were larger and action potential and QTc duration longer in LDLr−/− and ApoA1−/− than in WT mice (action potential duration at 90% of repolarization: 102±4 and 106±3 versus 84±3.1 ms; QTc: 50.9±1.3 and 52.8±0.8 versus 43.5±1.2 ms). During ischemia, ventricular tachycardia/ventricular fibrillation inducibility was larger in WT than in LDLr−/− and ApoA1−/− hearts. Expression of sodium channel and Ca-handling genes were not significantly different between groups. Conclusions—Dyscholesterolemia is associated with action potential prolongation because of increased ICa and reduces occurrence of reentrant arrhythmias during ischemia.
Vesicular Glutamate Transporter Expression in Supraoptic Neurones Suggests a Glutamatergic Phenotype

Magnocellular neuroendocrine cells of the supraoptic nucleus (SON) release the peptides oxytocin (OT) and vasopressin (VP) from their dendrites and terminals. In addition to peptide‐containing large dense‐core vesicles, axon terminals from these cells contain clear microvesicles that have been shown to contain glutamate. Using multilabelling confocal microscopy, we investigated the presence of vesicular glutamate transporters (VGLUTs) in astrocytes as well as VP and OT neurones of the SON. Simultaneous probing of the SON with antibodies against VGLUT isoforms 1–3, OT, VP and glial fibrillary acidic protein (GFAP) revealed the presence of VGLUT‐2 in somata and dendrites of SON neurones. Immunoreactivity (‐ir) for VGLUT‐3 was also detected in both OT and VP neurones as well as in GFAP‐ir astrocytes and other cells of the ventral glial lamina. Colocalisation of VGLUT‐2 and VGLUT‐3 in individual SON neurones was also examined and VGLUT‐ir with both antibodies could be detected in both types of SON neurones. Although VGLUT‐1‐ir was strong lateral to the SON, only sparse labelling was apparent within the nucleus, and no colocalisation with either SON neurones or astrocytes was observed. The SON or the SON plus its surrounding perinuclear zone was probed using the reverse transcriptase‐polymerase chain reaction and the presence of mRNA for all three VGLUT isoforms was detected. These results suggest that similar arrangements of transmitters exist in SON neuronal dendrites and their neurohypophysial terminals and that magnocellular neuroendocrine somata and dendrites may be capable of glutamatergic transmission.
Gastroprotective Activity of Ethyl-4-[(3,5-di-tert-butyl-2-hydroxybenzylidene) Amino]benzoate against Ethanol-Induced Gastric Mucosal Ulcer in Rats

Background The study was carried out to determine the cytotoxic, antioxidant and gastro-protective effect of ethyl-4-[(3,5-di-tert-butyl-2-hydroxybenzylid ene)amino] benzoate (ETHAB) in rats. Methodology/Principal Findings The cytotoxic effect of ETHAB was assessed using a MTT cleavage assay on a WRL68 cell line, while its antioxidant activity was evaluated in vitro. In the anti-ulcer study, rats were divided into six groups. Group 1 and group 2 received 10% Tween 20 (vehicle). Group 3 received 20 mg/kg Omeprazole. Groups 4, 5 and 6 received ETHAB at doses of 5, 10, and 20 mg/kg, respectively. After an hour, group 1 received the vehicle. Groups 2–6 received absolute ethanol to induce gastric mucosal lesions. In the WRL68 cell line, an IC50 of more than 100 µg/mL was observed. ETHAB results showed antioxidant activity in the DPPH, FRAP, nitric oxide and metal chelating assays. There was no acute toxicity even at the highest dosage (1000 mg/kg). Microscopy showed that rats pretreated with ETHAB revealed protection of gastric mucosa as ascertained by significant increases in superoxide dismutase (SOD), pH level, mucus secretion, reduced gastric lesions, malondialdehyde (MDA) level and remarkable flattened gastric mucosa. Histologically, pretreatment with ETHAB resulted in comparatively better gastric protection, due to reduction of submucosal edema with leucocyte infiltration. PAS staining showed increased intensity in uptake of Alcian blue. In terms of immunohistochemistry, ETHAB showed down-expression of Bax proteins and over-expression of Hsp70 proteins. Conclusion/Significance The gastroprotective effect of ETHAB may be attributed to antioxidant activity, increased gastric wall mucus, pH level of gastric contents, SOD activity, decrease in MDA level, ulcer area, flattening of gastric mucosa, reduction of edema and leucocyte infiltration of the submucosal layer, increased PAS staining, up-regulation of Hsp70 protein and suppressed expression of Bax. Key words: ethyl 4-(3, 5-di-ter-butyl-2-hydroxybenzylamino) benzoate; toxicity; antioxidant; gastric-ulcer; anti-ulcer; histology; immunohistochemistry.
Infection of Human Liver Myofibroblasts by Hepatitis C Virus: A Direct Mechanism of Liver Fibrosis in Hepatitis C

Background Chronic hepatitis C is a major cause of liver fibrosis and cirrhosis. It is generally accepted that inflammation that occurs in response to hepatocyte infection by the hepatitis C virus (HCV) is the main mechanism that triggers myofibroblast differentiation and stimulation in chronic hepatitis C. The aim of this study was to determine if HCV might infect human liver myofibroblasts (HLMF) and directly stimulate their fibrogenic activities. Methods We evaluated the expression of the viral entry receptors, levels of HCV-RNA and HCV-protein and the expression of fibrosis markers in HLMF by using quantitative PCR, western blot and immunofluorescence analyses. Pseudoparticles (HCVpp) and cell culture–derived HCV (HCVcc) were used to study the ability of HLMF to support viral entry, replication and fibrosis induction. Results We showed that HLMF expressed all known molecules of the HCV receptor complex, i.e. CD81, LDL-R, scavenger receptor-BI, claudin-1 and occludin. These cells were also permissive to HCVpp entry. Inoculation with HCVcc caused short-term infection of these cells, as shown by their content in positive- and negative-strand HCV RNA, in core and NS3 viral proteins, and by their release of core protein levels in the culture supernatants. HCV infection stimulated myofibroblastic differentiation, proliferation and collagen production in these cells. In addition, evidence of in vivo infection was provided by the detection of positive- and negative-strand HCV RNA in preparations of HLMF obtained from HCV-infected patients. Conclusion These findings indicate that HCV infection of HLMF can occur and trigger extracellular matrix overproduction, thereby contributing to the development of HCV-related liver fibrosis.
Handling class imbalance in customer behavior prediction

Class imbalance is a common problem in real world applications and it affects significantly the prediction accuracy. In this study, investigation on better handling class imbalance problem in customer behavior prediction is performed. Using a more appropriate evaluation metric (AUC), we investigated the increase of performance for under-sampling and two machine learning algorithms (weight Random Forests and RUSBoost) against a benchmark case of just using Random Forests. Results show that under-sampling is the most effective way to deal with class imbalance. RUSBoost, as a specific algorithm designed to deal with class imbalance problem, is also effective but not as good as under-sampling. Weighted Random Forests, as a cost-sensitive learner, only improves the performance of appetency classification problem out of three classification problems.
Convergence Properties of the K-Means Algorithms

This paper studies the convergence properties of the well known K-Means clustering algorithm. The K-Means algorithm can be described either as a gradient descent algorithm or by slightly extending the mathematics of the EM algorithm to this hard threshold case. We show that the K-Means algorithm actually minimizes the quantization error using the very fast Newton algorithm.
Identification of a Novel Dynein Binding Domain in Nudel Essential for Spindle Pole Organization in Xenopus Egg Extract*

The nuclear distribution protein E (NudE) and nuclear distribution protein E-like (Nudel or Ndel1) interact with both lissencephaly 1 (Lis1) and dynein. These interactions are thought to be essential for dynein function. Previous studies have shown that the highly conserved N terminus of NudE/Nudel directly binds to Lis1, and such binding is critical for dynein activity. By contrast, although the C terminus of NudE/Nudel was reported to bind to dynein, the functional significance of this binding has remained unclear. Using the sperm-mediated spindle assembly assay in Xenopus egg extracts and extensive mutagenesis studies, we have identified a highly conserved dynein binding domain within the first 80 amino acids of Nudel. We further demonstrate that the dynein intermediate chain in the dynein complex is directly involved in this interaction. Importantly, we show that both the dynein and Lis1 binding domains of Nudel are required for spindle pole organization. Finally, we report that spindle defects caused by immuno-depletion of Nudel could be rescued by a 1-fold increase of Lis1 concentration in Xenopus egg extracts. This suggests that an important function of the N terminus of Nudel is to facilitate the interaction between Lis1 and dynein during spindle assembly. Together, our findings open up new avenues to further decipher the mechanism of dynein regulation by Nudel and Lis1.
Actinorhizal Alder Phytostabilization Alters Microbial Community Dynamics in Gold Mine Waste Rock from Northern Quebec: A Greenhouse Study

Phytotechnologies are rapidly replacing conventional ex-situ remediation techniques as they have the added benefit of restoring aesthetic value, important in the reclamation of mine sites. Alders are pioneer species that can tolerate and proliferate in nutrient-poor, contaminated environments, largely due to symbiotic root associations with the N2-fixing bacteria, Frankia and ectomycorrhizal (ECM) fungi. In this study, we investigated the growth of two Frankia-inoculated (actinorhizal) alder species, A. crispa and A. glutinosa, in gold mine waste rock from northern Quebec. Alder species had similar survival rates and positively impacted soil quality and physico-chemical properties in similar ways, restoring soil pH to neutrality and reducing extractable metals up to two-fold, while not hyperaccumulating them into above-ground plant biomass. A. glutinosa outperformed A. crispa in terms of growth, as estimated by the seedling volume index (SVI), and root length. Pyrosequencing of the bacterial 16S rRNA gene for bacteria and the ribosomal internal transcribed spacer (ITS) region for fungi provided a comprehensive, direct characterization of microbial communities in gold mine waste rock and fine tailings. Plant- and treatment-specific shifts in soil microbial community compositions were observed in planted mine residues. Shannon diversity and the abundance of microbes involved in key ecosystem processes such as contaminant degradation (Sphingomonas, Sphingobium and Pseudomonas), metal sequestration (Brevundimonas and Caulobacter) and N2-fixation (Azotobacter, Mesorhizobium, Rhizobium and Pseudomonas) increased over time, i.e., as plants established in mine waste rock. Acetate mineralization and most probable number (MPN) assays showed that revegetation positively stimulated both bulk and rhizosphere communities, increasing microbial density (biomass increase of 2 orders of magnitude) and mineralization (five-fold). Genomic techniques proved useful in investigating tripartite (plant-bacteria-fungi) interactions during phytostabilization, contributing to our knowledge in this field of study.
Clinical pharmacokinetics of irinotecan and its metabolites: a population analysis.

PURPOSE To build population pharmacokinetic (PK) models for irinotecan (CPT-11) and its currently identified metabolites. PATIENTS AND METHODS Seventy cancer patients (24 women and 46 men) received 90-minute intravenous infusions of CPT-11 in the dose range of 175 to 300 mg/m(2). The PK models were developed to describe plasma concentration profiles of the lactone and carboxylate forms of CPT-11 and 7-ethyl-10-hydroxycamptothecin (SN-38) and the total forms of SN-38 glucuronide (SN-38G), 7-ethyl-10-[4-N-(5-aminopentanoic acid)-1-piperidino]-carbonyloxycamptothecin (APC), and 7-ethyl-10-[4-amino-1-piperidino]-carbonyloxycamptothecin (NPC) by using NONMEM. RESULTS The interconversion between the lactone and carboxylate forms of CPT-11 was relatively rapid, with an equilibration half-life of 14 minutes in the central compartment and hydrolysis occurring at a rate five times faster than lactonization. The same interconversion also occurred in peripheral compartments. CPT-11 lactone had extensive tissue distribution (steady-state volume of distribution [Vss], 445 L) compared with the carboxylate form (Vss, 78 L, excluding peripherally formed CPT-11 carboxylate). Clearance (CL) was higher for the lactone form (74.3 L/h) compared with the carboxylate form (12.3 L/h). During metabolite data modeling, goodness of fit indicated a preference of SN-38 and NPC to be formed out of the lactone form of CPT-11, whereas APC could be modeled best by presuming formation from CPT-11 carboxylate. The interconversion between SN-38 lactone and carboxylate was slower than that of CPT-11, with the lactone form dominating at equilibrium. The CLs for SN-38 lactone and carboxylate were similar, but the lactone form had more extensive tissue distribution. CONCLUSION Plasma data of CPT-11 and metabolites could be adequately described by this compartmental model, which may be useful in predicting the time courses, including interindividual variability, of all characterized substances after intravenous administrations of CPT-11.
Distraction, not hunger, is associated with lower mood and lower perceived work performance on fast compared to non-fast days during intermittent fasting

Using a repeated measures design, 16 females recorded hunger, distraction, mood and perceived work performance on two consecutive fast days, on two earlier and on two subsequent consecutive non-fast days, during intermittent fasting. Using regression analyses, low positive mood was associated with higher distraction (β = −0.38, p < 0.01), and lower perceived work performance was associated with higher distraction (β = −0.50, p < 0.01) and lower positive mood (β = 0.59, p = 0.01). No associations were found with hunger (largest β = −0.11, p = 0.15). Associations between mood, perceived work performance and distraction but not hunger mirror those found in traditional dieting and suggest no benefit for attention from intermittent fasting-type regimes.
Sparse sets in NP-P: Exptime versus nexptime

This paper investigates the structural properties of sets in NP-P and shows that the computational difficulty of lower density sets in NP depends explicitly on the relations between higher deterministic and nondeterministic time-bounded complexity classes. The paper exploits the recently discovered upward separation method, which shows for example that there exist sparse sets in NP-Pif and only if EXPTIME @@@@ NEXPTIME. In addition, the paper uses relativization techniques to determine logical possibilities, limitations of these proof techniques, and, for the first time, to exhibit structural differences between relativized NP and CoNP.
Light power behaviour when bending plastic optical fibres

The redistribution of light power and the radiated power along a bent section of a plastic optical fibre (POF) is analysed. In this context, a theoretical approach for understanding, and hence optimising. The major factors that affect the behaviour of sensors utilising losses in fibre bends is reported. With a brief comment on the bend loss model used, an implementation of a three-dimensional analysis for bend losses is presented, and the theoretical analysis is compared with experimental results. The spatial redistribution of the optical power in the bend is also calculated.