Miracle-dz/UniFAR-FTUs huggingface dataset:
Multi-Objective Mapping for Mesh-Based NoC Architectures

In this paper we present an approach to multi-objective exploration of the mapping space of a mesh-based network-on-chip architecture. Based on evolutionary computing techniques, the approach is an efficient and accurate way to obtain the Pareto mappings that optimize performance and power consumption. Integration of the approach in an exploration framework with a kernel based on an event-driven trace-based simulator makes it possible to take account of important dynamic effects that have a great impact on mapping. Validation on both synthesized traffic and real applications (an MPEG-2 encoder/decoder system) confirms theefficiency, accuracy and scalability of the approach.
Assessment of medication adherence and responsible use of isotretinoin and contraception through Belgian community pharmacies by using pharmacy refill data

Purpose The aims of the study were to evaluate medication adherence and the influencing factors for isotretinoin and contraception (oral, patches, and rings) and to evaluate the concomitant use of contraception and isotretinoin. Methods Reimbursed prescription data from January 2012 to August 2015 of all patients in Belgium were received from Pharmanet–National Institute for Health and Disability Insurance. Medication adherence was measured according to the medication possession ratio. The influence of gender and age was analyzed using the Mann–Whitney test and the Spearman coefficient correlation. The independence between adherence to contraception and adherence to isotretinoin was analyzed using the Pearson chi-square test of independence. Persistence was defined as the number of days between initiation and presumed end of treatment. The Kaplan–Meier method was used to plot the medication persistence curves, and the log-rank test was used to compare the curves. The concomitant use of contraception and isotretinoin was analyzed using descriptive statistics. Results The medication possession ratio was ≥0.8 for 46.1% of patients receiving isotretinoin and for 74.0% of women using contraception. For isotretinoin, this percentage decreased as the number of attempts increased (29.8% for the second attempt and 19.8% for more than two attempts). Men seemed more adherent than women, and a weak negative correlation between adherence and age was observed. The adherence data of isotretinoin and contraception were independent. The median persistence for isotretinoin treatment was 139 days (interquartile range 71–209) and was higher for men. Among women between 12 and 21 years old taking isotretinoin, 63.8% received at least one contraceptive prescription. However, 15.7% of women taking isotretinoin adhered to the use of contraception 1 month before, during, and 1 month after treatment. Conclusion Medication adherence to isotretinoin and contraception and compliance with the isotretinoin safety recommendation could be improved. Health service interventions, using pharmacy refill data, should be delivered to ensure patient safety and strict adherence to contraception when under isotretinoin treatment.
Uncoupling Protein 2, in Vivo Distribution, Induction upon Oxidative Stress, and Evidence for Translational Regulation*

Uncoupling protein 2 (UCP2) belongs to the mitochondrial anion carrier family and partially uncouples respiration from ATP synthesis when expressed in recombinant yeast mitochondria. We generated a highly sensitive polyclonal antibody against human UCP2. Its reactivity toward mitochondrial proteins was compared between wild type and ucp2(−/−) mice, leading to non-ambiguous identification of UCP2. We detected UCP2 in spleen, lung, stomach, and white adipose tissue. No UCP2 was detected in heart, skeletal muscle, liver, and brown adipose tissue. The level of UCP2 in spleen mitochondria is less than 1% of the level of UCP1 in brown adipose tissue mitochondria. Starvation and LPS treatments increase UCP2 level up to 12 times in lung and stomach, which supports the hypothesis that UCP2 responds to oxidative stress situations. Stimulation of the UCP2 expression occurs without any change in UCP2 mRNA levels. This is explained by translational regulation of the UCP2 mRNA. We have shown that an upstream open reading frame located in exon two of theucp2 gene strongly inhibits the expression of the protein. This further level of regulation of the ucp2 gene provides a mechanism by which expression can be strongly and rapidly induced under stress conditions.
Double-blind, controlled phase II study of a 5-HT6 receptor antagonist, SB-742457, in Alzheimer's disease.

BACKGROUND This randomized, double-blind, placebo-controlled study investigated the efficacy and tolerability of the 5-HT6 receptor antagonist, SB-742457, in subjects with mild-to-moderate probable Alzheimer's disease (AD). METHODS Participating subjects had a Mini-Mental State Examination (MMSE) score of 12 to 26 after a 4-week, single-blind, placebo run-in phase, and were randomized (2:1:1:2) to receive placebo, SB-742457 5 mg, 15 mg, or 35 mg once daily for 24 weeks. Coprimary efficacy endpoints were the Clinician's Interview-Based Impression of Change with caregiver input (CIBIC+) score and change from baseline in Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) score at Week 24, in the intent-to-treat (ITT) population. A model-based design provided 90% power to detect a linear trend in treatment response across increasing doses and > or =90% power to compare SB-742457 35 mg with placebo. RESULTS 371 subjects were randomized. In the ITT population (n=357), linear trend analysis at Week 24 suggested a dose response for CIBIC+ with a mean slope of -0.05 points/5-mg dose increase (95% confidence interval [CI]: -0.09, -0.01; p=0.016). The dose response slope for change from baseline in ADAS-Cog was -0.22 points/5-mg dose increase (95% CI: -0.45, 0.01; p=0.059). The adjusted mean treatment difference from placebo at Week 24 for SB-742457 35 mg (-0.31) was significant on CIBIC+ (95% CI: -0.62, -0.00; p=0.047) but non-significant on ADAS-Cog (-1.28 [95% CI: -2.96, 0.40]; p=0.135). Adverse events occurred in 24-37% in the SB-742457 groups vs 29% for placebo; 11-16% discontinued SB-742457 vs 15% for placebo. COMMENTS SB-742457 was generally safe and well tolerated and may be efficacious in AD.
concentric and eccentric cycle exercise Comparison of oxygen uptake kinetics during

[PDF] [Full Text] [Abstract] , April 1, 2003; 94 (4): 1501-1507. J Appl Physiol J. S. M. Pringle, J. H. Doust, H. Carter, K. Tolfrey and A. M. Jones heavy-cycle exercise Effect of pedal rate on primary and slow-component oxygen uptake responses during [PDF] [Full Text] [Abstract] , January 1, 2006; 91 (1): 179-189. Exp Physiol M. A Osborne and D. A Schneider uptake kinetics during heavy exercise Muscle glycogen reduction in man: relationship between surface EMG activity and oxygen [PDF] [Full Text] [Abstract] , May 1, 2006; 35 (3): 291-297. Age Ageing A. F. Vallejo, E. T. Schroeder, L. Zheng, N. E. Jensky and F. R. Sattler Cardiopulmonary responses to eccentric and concentric resistance exercise in older adults
A Review of Green IS Research and Directions for Future Studies

As practitioners become more interested in green information systems, the IS academic community requires direction in how to examine this important phenomenon. We conduct a systematic and comprehensive review of the academic literature surrounding green IS and compares the results with those from the practical literature. Through this review, we identify the main categories in the literature and assess the current state of research into green IS. We discuss some limitations of the current literature, posit research directions for future scholars, and address the gaps in the current research on green IS.
Cereal lipids

Composition and distribution Cereal lipids are complex (Morrison, 1977; Nechaev & Sander, 1975; Weber, 1973), but for nutritional purposes they can be regarded as consisting of glycerides containing six fatty acids, plus tocopherols, carotenoids and other unsaponifiable matter. The principal fatty acids are 16:0, 16:1(n-7), 18:0, 18:1(n-9), 18:2(n-6) and 18:3(n-3), and the two essential fatty acids usually comprise about half of the total (Table I). Linoleate (18:2, n-6) is formed by oxidative desaturation of oleate (I 8 :I , n-), and there is often an inverse relationship between the percentages of these two acids when fatty acid composition is altered genetically or by changed growing conditions (de la Roche, Alexander & Weber, 1971; Flora & Wiley, 1972; Jellum, 1970; Poneleit & Baumann, 1970; Thompson, Jellum & Young, 1973). Increased quantities of linolenic acid (18:3, n-3) in the growing embryonic axis of germinating grain are found in cereals during vernalization and development of cold hardiness (de la Roche, Andrews, Pomeroy, Weinberger & Kates, 1972; de la Roche, Pomeroy & Andrews, 1975; de Silva, Weinberger, Kates & de la Roche, 1975; Farkas, Deri-Hadlacsky 8z Adonis, 1975; Redshaw & Zalik, 1968).
Improving the In Silico Assessment of Proarrhythmia Risk by Combining hERG (Human Ether-à-go-go-Related Gene) Channel–Drug Binding Kinetics and Multichannel Pharmacology

Background— The current proarrhythmia safety testing paradigm, although highly efficient in preventing new torsadogenic drugs from entering the market, has important limitations that can restrict the development and use of valuable new therapeutics. The CiPA (Comprehensive in vitro Proarrhythmia Assay) proposes to overcome these limitations by evaluating drug effects on multiple cardiac ion channels in vitro and using these data in a predictive in silico model of the adult human ventricular myocyte. A set of drugs with known clinical torsade de pointes risk was selected to develop and calibrate the in silico model. Methods and Results— Manual patch-clamp data assessing drug effects on expressed cardiac ion channels were integrated into the O’Hara–Rudy myocyte model modified to include dynamic drug–hERG channel (human Ether-à-go-go-Related Gene) interactions. Together with multichannel pharmacology data, this model predicts that compounds with high torsadogenic risk are more likely to be trapped within the hERG channel and show stronger reverse use dependency of action potential prolongation. Furthermore, drug-induced changes in the amount of electronic charge carried by the late sodium and L-type calcium currents was evaluated as a potential metric for assigning torsadogenic risk. Conclusions— Modeling dynamic drug–hERG channel interactions and multi-ion channel pharmacology improves the prediction of torsadogenic risk. With further development, these methods have the potential to improve the regulatory assessment of drug safety models under the CiPA paradigm.
Obesity Associated Modulation of miRNA and Co-Regulated Target Transcripts in Human Adipose Tissue of Non-Diabetic Subjects

Objective: Micro RNAs (miRNAs) are a class of non-coding regulatory RNAs. We performed a transcriptome-wide analysis of subcutaneous adipose tissue and in vitro studies to identify miRNAs and co-regulated target transcripts associated with insulin sensitivity (SI) and obesity in human. Methods: We selected 20 insulin-resistant (IR, SI=2.0±0.7) and 20 insulin-sensitive (IS, SI=7.2±2.3) subjects from a cohort of 117 metabolically characterized non-diabetic Caucasians for comparison. Results: After global profiling, 3 miRNAs had marginally different expressions between IR and IS subjects. A total of 14 miRNAs were significantly correlated with %fat mass, body mass index (BMI), or SI. The qRT-PCR validated the correlation of miR-148a-3p with BMI (r=-0.70, P=2.73X10-6). MiRNA target filtering analysis identified DNA methyltransferase 1 (DNMT1) as one of the target genes of miR-148a-3p. DNMT1 expression in adipose tissue was positively correlated with BMI (r=0.47, p=8.42X10-7) and was inversely correlated with miR-148a-3p (r=-0.34). Differentiation of SGBS preadipocytes showed up-regulation of miR-148a-3p and down-regulation of DNMT1 in differentiated adipocytes. After transfecting miR-148a-3p mimics into HeLa-S3 cells, DNMT1 was down-regulated, while transfection of adipose stem cells with miR-148a-3p inhibitor up-regulated DNMT1. Conclusions: Our results indicate that miR-148a-3p-mediated regulation of DNMT1 expression may play a mechanistic role in obesity.
Treatment interruptions predict resistance in HIV-positive individuals purchasing fixed-dose combination antiretroviral therapy in Kampala, Uganda

Objective:To evaluate adherence, treatment interruptions, and outcomes in patients purchasing antiretroviral fixed-dose combination (FDC) therapy. Design:Ninety-seven participants were recruited into a prospective 24-week observational cohort study of HIV-positive, antiretroviral-naive individuals initiating self-pay Triomune or Maxivir therapy in Kampala, Uganda. Adherence was measured by monthly structured interview, unannounced home pill count, and electronic medication monitors (EMM). Treatment interruptions were measured as continuous intervals greater than 48 h without opening the EMM. The primary outcomes were survival with viral suppression below 400 copies/ml, CD4 cell increases, and genotypic drug resistance at 24 weeks. Results:The median baseline CD4 cell count was 56 cells/μl and median log10 copies RNA/ml was 5.54; mean adherence ranged from 82 to 95% for all measures but declined significantly over time. In an intent-to-treat analysis, 70 (72%) patients had an undetectable plasma HIV-RNA level at week 24. Sixty-two of 95 (65%) individuals with continuous EMM data had a treatment interruption of greater than 48 h. Treatment interruptions accounted for 90% of missed doses. None of 33 participants who did not interrupt treatment for over 48 h had drug resistance, whereas eight of 62 (13%) participants who did interrupt therapy experienced drug resistance. Antiretroviral resistance was seen in 8% of individuals and overall mortality was 10% at 24 weeks. Conclusion:HIV-positive individuals purchasing generic FDC antiretroviral therapy have high rates of adherence and viral suppression, low rates of antiretroviral resistance, and robust CD4 cell responses. Adherence is an important predictor of survival with full viral suppression. Treatment interruptions are an important predictor of drug resistance.
Experimental Allergic Uveiris Investigotions of Retinol Autoimmunity ond the Immunopothologic Responses Evoked

Waldon D. Uveitis is an inflammatory condition of the eye that is generally of unknown etiology. Although it may occur in association with systemic disorders, it most often occurs alone as a specific organ disease. It usually runs a chronic relapsing course that is difficult to manage clinically and may result in blindness. Infective agents as a cause have been established in only a few cases. However, diverse immunologic studies over the past century suggested that allergy or autoimmunity may be a factor in many instances. Historically, the main thrust for a role of autoimmunity in the pathogenesis of uveitis was provided by Elschnig in 1910, who proposed autoimmunity to uveal antigens as a mechanism of sympathetic ophthalmia. This appealing concept focused attention on the uvea as the source of antigens that might produce the disease experimentally. Few of the many attempts over the ensuing decades to produce an animal model of autoimmune uveitis were successful. With the aid of Freund's adjuvant, Collins in 1949 reported production of autoimmune uveitis in guinea pigs immu-
Regulation of T‐helper cell responses to inhalant allergen during early childhood

Recent evidence suggests that preschool children manifest patterns of allergen‐specific skin prick test (SPT) reactivity and in vitro T‐cell cytokine production which are similar to that of either atopic or nonatopic adults. However, published studies on this age group involve small sample sizes and a restricted number of cytokines, usually in response to polyclonal stimuli.
Association of melanocortin-4 receptor gene polymorphisms with obesity-related parameters in Malaysian Malays

Background: Melanocortin-4 receptor (MC4R) is an important regulator of body weight and energy intake. Genetic polymorphisms of the MC4R gene have been found to be linked to obesity in many recent studies across the globe. Aim: This study aimed to examine the effects of MC4R polymorphisms on obesity parameters, Linkage disequilibrium (LD) pattern and haplotypes in Malaysian Malays. Methods: The study subjects were 652 Malaysian Malays. Genomic DNA was extracted from buccal swabs. Genotyping was performed using Sequenom MassARRAY® iPLEX platform. Anthropometric and blood lipid profiles were measured. Results: MC4R rs571312 SNP was associated with logBMI (p = 0.008) and systolic blood pressure (p = 0.005), while MC4R rs2229616 SNP was associated with total cholesterol (TC) levels (p = 0.016). The MC4R rs7227255 SNP did not show any association with obesity parameters. Conclusions: The strength of LD of the MC4R gene region is low and the haplotypes were not associated with obesity in Malaysian Malays.
Promising immunotherapy for prostate cancer

ABSTRACT Introduction: Sipuleucel-T is the only currently approved immunotherapy for the management of prostate cancer. However, other immunotherapy agents have recently shown activity in prostate cancer and are being developed alone or in combination with other agents. Areas covered: This article provides a review of positive or encouraging clinical trials of agents under development including vaccines, monoclonal antibodies, immune modulators, gene-mediated cytotoxic immunotherapy and chimeric antigen receptor-modified ‘designer’ T cells in patients with prostate cancer. Expert opinion: Personalized peptide vaccines have been associated with improvements in overall survival in early phase clinical trials of patients with prostate cancer, which may lead to their future adoption into management. While single agent, monoclonal antibody-based immunotherapy trials and PSA-TRICOM’s phase III trial have not demonstrated statistically significant improvements in overall survival, combinations of these agents with complementary agents have demonstrated encouraging activity. To improve the development and targeting of these therapies, agent and patient selection/modification needs to occur in the context of a rational model of the immune system’s interaction with prostate cancer. In addition, some traditional surrogates of efficacy may need to be reconsidered as multiple trials of immunotherapy in prostate cancer have had conflicting results between progression-free survival and overall survival.
Cardiovascular disease in rheumatoid arthritis: state of the art and future perspectives

Rheumatoid arthritis is associated with an increased risk for cardiovascular events, such as myocardial infarction and stroke. Epidemiological evidence suggests that classic cardiovascular risk factors, such as hypertension, dyslipidaemia, insulin resistance and body composition alterations are important but not sufficient to explain all of the excess risk. High-grade systemic inflammation and its interplay with classic risk factors may also contribute. Some associations between classic risk factors and cardiovascular risk in people with rheumatoid arthritis appear counterintuitive but may be explained on the basis of biological alterations. More research is necessary to uncover the exact mechanisms responsible for this phenomenon, develop accurate systems used to identify patients at high risk, design and assess prevention strategies specific to this population of patients.
S100A9 and EGFR gene signatures predict disease progression in muscle invasive bladder cancer patients after chemotherapy.

BACKGROUND In our previous gene expression profile analysis, IL1B, S100A8, S100A9, and EGFR were shown to be important mediators of muscle invasive bladder cancer (MIBC) progression. The aim of the present study was to investigate the ability of these gene signatures to predict disease progression after chemotherapy in patients with locally recurrent or metastatic MIBC. PATIENTS AND METHODS Patients with locally advanced MIBC who received chemotherapy were enrolled. The expression signatures of four genes were measured and carried out further functional analysis to confirm our findings. RESULTS Two of the four genes, S100A9 and EGFR, were determined to significantly influence disease progression (P = 0.023, 0.045, respectively). Based on a receiver operating characteristic curve, a cut-off value for disease progression was determined. Patients with the good-prognostic signature group had a significantly longer time to progression and cancer-specific survival time than those with the poor-prognostic signature group (P < 0.001, 0.042, respectively). In the multivariate Cox regression analysis, gene signature was the only factor that significantly influenced disease progression [hazard ratio: 4.726, confidence interval: 1.623-13.763, P = 0.004]. In immunohistochemical analysis, S100A9 and EGFR positivity were associated with disease progression after chemotherapy. Protein expression of S100A9/EGFR showed modest correlation with gene expression of S100A9/EGFR (r = 0.395, P = 0.014 and r = 0.453, P = 0.004). Our functional analysis provided the evidence demonstrating that expression of S100A9 and EGFR closely associated chemoresistance, and that inhibition of S100A9 and EGFR may sensitize bladder tumor cells to the cisplatin-based chemotherapy. CONCLUSIONS The S100A9/EGFR level is a novel prognostic marker to predict the chemoresponsiveness of patients with locally recurrent or metastatic MIBC.
Effects of treatment with glucagon-like peptide-2 on bone resorption in colectomized patients with distal ileostomy or jejunostomy and short-bowel syndrome

Objective. The gut hormone GLP-2 (glucagon-like peptide-2) seems to be involved in the circadian pattern of bone resorption, whereas parathyroid hormone (PTH) is an established key hormone in bone turnover. Endogenous GLP-2 secretion is lacking in colectomized patients with short-bowel syndrome (SBS) and they have reduced bone mineral density (BMD). The aim of the study was to investigate the anti-resorptive effect (assessed by s-CTX) of 14 days of GLP-2 treatment in these patients and to determine whether 56 days of treatment would improve BMD. PTH secretion in response to GLP-2 was also investigated in colectomized SBS patients and colectomized controls (with ileostomy). Material and methods. Eight SBS patients and 13 patients with ileostomy were treated with subcutaneous injections of 1600 µg GLP-2 at bedtime for 56 and 14 consecutive days, respectively. BMD was determined at days 1 and 56 in SBS patients. On days 1 and 14, measurements of CTX, P1NP and PTH were taken 4 h after the GLP-2 injection. Results. Patients with ileostomy showed a significant reduction in bone resorption after GLP-2 injections at days 1 and 14. In contrast, there was no change in s-CTX after 1 and 14 days in the SBS patients, and after 56 days of GLP-2 treatment there was no improvement in BMD. A significant reduction in PTH secretion in response to GLP-2 was observed only in patients with ileostomy. Conclusions. The decreased bone resorption in response to GLP-2 injections cannot be elicited in SBS patients and therefore precludes treatment of their osteopenia with GLP-2. The anti-resorptive response to GLP-2 seems to require an intact small intestine and may involve suppression of PTH secretion.
Cysticercosis as a Major Risk Factor for Epilepsy in Burundi, East Africa

Summary: Purpose: Human cysticercosis is a direct consequence of infection by Taenia solium larvae (Cysticercus cellulosae). Results of studies on the impact of neurocysticercosis on epilepsy in Africa are inconsistent. The objective was to evaluate the role of cysticercosis in epilepsy in Burundi.