172 research outputs found

    Automated generation of constructive ordering heuristics for educational timetabling

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    Construction heuristics play an important role in solving combinatorial optimization problems. These heuristics are usually used to create an initial solution to the problem which is improved using optimization techniques such as metaheuristics. For examination timetabling and university course timetabling problems essentially graph colouring heuristics have been used for this purpose. The process of deriving heuristics manually for educational timetabling is a time consuming task. Furthermore, according to the no free lunch theorem different heuristics will perform well for different problems and problem instances. Hence, automating the induction of construction heuristics will reduce the man hours involved in creating such heuristics, allow for the derivation of problem specific heuristics and possibly result in the derivation of heuristics that humans have not thought of. This paper presents generation construction hyper-heuristics for educational timetabling. The study investigates the automatic induction of two types of construction heuristics, namely, arithmetic heuristics and hierarchical heuristics. Genetic programming is used to evolve arithmetic heuristics. Genetic programming, genetic algorithms and the generation of random heuristic combinations is examined for the generation of hierarchical heuristics. The hyper-heuristics generating both types of heuristics are applied to the examination timetabling and the curriculum based university course timetabling problems. The evolved heuristics were found to perform much better than the existing graph colouring heuristics used for this domain. Furthermore, it was found that the while the arithmetic heuristics were more effective for the examination timetabling problem, the hierarchical heuristics produced better results than the arithmetic heuristics for the curriculum based course timetabling problem. Genetic algorithms proved to be the most effective at inducing hierarchical heuristics

    Archiving multi-epoch data and the discovery of variables in the near infrared

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    We present a description of the design and usage of a new synoptic pipeline and database model for time series photometry in the VISTA Data Flow System (VDFS). All UKIRT-WFCAM data and most of the VISTA main survey data will be processed and archived by the VDFS. Much of these data are multi-epoch, useful for finding moving and variable objects. Our new database design allows the users to easily find rare objects of these types amongst the huge volume of data being produced by modern survey telescopes. Its effectiveness is demonstrated through examples using Data Release 5 of the UKIDSS Deep Extragalactic Survey (DXS) and the WFCAM standard star data. The synoptic pipeline provides additional quality control and calibration to these data in the process of generating accurate light-curves. We find that 0.6+-0.1% of stars and 2.3+-0.6% of galaxies in the UKIDSS-DXS with K<15 mag are variable with amplitudes \Delta K>0.015 magComment: 30 pages, 31 figures, MNRAS, in press Minor changes from previous version due to refereeing and proof-readin

    Minor intron splicing is critical for survival of lethal prostate cancer.

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    The evolutionarily conserved minor spliceosome (MiS) is required for protein expression of ∼714 minor intron-containing genes (MIGs) crucial for cell-cycle regulation, DNA repair, and MAP-kinase signaling. We explored the role of MIGs and MiS in cancer, taking prostate cancer (PCa) as an exemplar. Both androgen receptor signaling and elevated levels of U6atac, a MiS small nuclear RNA, regulate MiS activity, which is highest in advanced metastatic PCa. siU6atac-mediated MiS inhibition in PCa in vitro model systems resulted in aberrant minor intron splicing leading to cell-cycle G1 arrest. Small interfering RNA knocking down U6atac was ∼50% more efficient in lowering tumor burden in models of advanced therapy-resistant PCa compared with standard antiandrogen therapy. In lethal PCa, siU6atac disrupted the splicing of a crucial lineage dependency factor, the RE1-silencing factor (REST). Taken together, we have nominated MiS as a vulnerability for lethal PCa and potentially other cancers

    Inter-Relationship between Testicular Dysgenesis and Leydig Cell Function in the Masculinization Programming Window in the Rat

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    The testicular dysgenesis syndrome (TDS) hypothesis proposes that maldevelopment of the testis, irrespective of cause, leads to malfunction of the somatic (Leydig, Sertoli) cells and consequent downstream TDS disorders. Studies in rats exposed in utero to di(n-butyl) phthalate (DBP) have strongly supported the TDS concept, but so far no direct evidence has been produced that links dysgenesis per se to somatic cell dysfunction, in particular to androgen production/action during the ‘masculinization programming window’ (MPW; e15.5–e18.5). Normal reproductive tract development and anogenital distance (AGD) are programmed within the MPW, and TDS disorders arise because of deficiencies in this programming. However, DBP-induced focal testicular dysgenesis (Leydig cell aggregation, ectopic Sertoli cells, malformed seminiferous cords) is not evident until after the MPW. Therefore, we used AGD as a read-out of androgen exposure in the MPW, and investigated if this measure was related to objectively quantified dysgenesis (Leydig cell aggregation) at e21.5 in male fetuses exposed to vehicle, DBP (500 or 750 mg/kg/day) or the synthetic glucocorticoid dexamethasone (Dex; alone or plus DBP-500) from e15.5–e18.5 (MPW), e13.5–e20.5 or e19.5–e20.5 (late window). Dysgenesis was found only in animals exposed to DBP during the MPW, and was negatively correlated (R2 = −0.5) with AGD at e21.5 and at postnatal day 8, irrespective of treatment period. Dysgenesis was also negatively correlated (R2 = –0.5) with intratesticular testosterone (ITT) at e21.5, but only when treatments in short windows (MPW, late window) were excluded; the same was true for correlation between AGD and ITT. We conclude that AGD, reflecting Leydig cell function solely within the MPW, is strongly related to focal dysgenesis. Our results point to this occurring because of a common early mechanism, targeted by DBP that determines both dysgenesis and early (during the MPW) fetal Leydig cell dysfunction. The findings provide strong validation of the TDS hypothesis

    Metabolic variability in seafloor brines revealed by carbon and sulphur dynamics

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    Brine fluids that upwell from deep, hot reservoirs below the sea bed supply the sea floor with energy-rich substrates and nutrients that are used by diverse microbial ecosystems. Contemporary hypersaline environments formed by brine seeps may provide insights into the metabolism and distribution of microorganisms on the early Earth or on extraterrestrial bodies. Here we use geochemical and genetic analyses to characterize microbial community composition and metabolism in two seafloor brines in the Gulf of Mexico: an active mud volcano and a quiescent brine pool. Both brine environments are anoxic and hypersaline. However, rates of sulphate reduction and acetate production are much higher in the brine pool, whereas the mud volcano supports much higher rates of methane production. We find no evidence of anaerobic oxidation of methane, despite high methane fluxes at both sites. We conclude that the contrasting microbial community compositions and metabolisms are linked to differences in dissolved-organic-matter input from the deep subsurface and different fluid advection rates between the two sites. DOI: 10.1038/NGEO47

    The Role of Environmental Transmission in Recurrent Avian Influenza Epidemics

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    Avian influenza virus (AIV) persists in North American wild waterfowl, exhibiting major outbreaks every 2–4 years. Attempts to explain the patterns of periodicity and persistence using simple direct transmission models are unsuccessful. Motivated by empirical evidence, we examine the contribution of an overlooked AIV transmission mode: environmental transmission. It is known that infectious birds shed large concentrations of virions in the environment, where virions may persist for a long time. We thus propose that, in addition to direct fecal/oral transmission, birds may become infected by ingesting virions that have long persisted in the environment. We design a new host–pathogen model that combines within-season transmission dynamics, between-season migration and reproduction, and environmental variation. Analysis of the model yields three major results. First, environmental transmission provides a persistence mechanism within small communities where epidemics cannot be sustained by direct transmission only (i.e., communities smaller than the critical community size). Second, environmental transmission offers a parsimonious explanation of the 2–4 year periodicity of avian influenza epidemics. Third, very low levels of environmental transmission (i.e., few cases per year) are sufficient for avian influenza to persist in populations where it would otherwise vanish

    Motivational component profiles in university students learning histology: a comparative study between genders and different health science curricula

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    Background: The students' motivation to learn basic sciences in health science curricula is poorly understood. The purpose of this study was to investigate the influence of different components of motivation (intrinsic motivation, self-determination, self-efficacy and extrinsic -career and grade-motivation) on learning human histology in health science curricula and their relationship with the final performance of the students in histology. Methods: Glynn Science Motivation Questionnaire II was used to compare students' motivation components to learn histology in 367 first-year male and female undergraduate students enrolled in medical, dentistry and pharmacy degree programs. Results: For intrinsic motivation, career motivation and self-efficacy, the highest values corresponded to medical students, whereas dentistry students showed the highest values for self-determination and grade motivation. Genders differences were found for career motivation in medicine, self-efficacy in dentistry, and intrinsic motivation, self-determination and grade motivation in pharmacy. Career motivation and self-efficacy components correlated with final performance in histology of the students corresponding to the three curricula. Conclusions: Our results show that the overall motivational profile for learning histology differs among medical, dentistry and pharmacy students. This finding is potentially useful to foster their learning process, because if they are metacognitively aware of their motivation they will be better equipped to self-regulate their science-learning behavior in histology. This information could be useful for instructors and education policy makers to enhance curricula not only on the cognitive component of learning but also to integrate students' levels and types of motivation into the processes of planning, delivery and evaluation of medical education.This research was supported by the Unidad de Innovación Docente, University of Granada, Spain through grants UGR11-294 and UGR11-303

    Comorbid substance abuse and brain morphology in recent-onset psychosis

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    The aim of the presented study was to compare schizophrenia and schizoaffective patients early in the course of the disease with and without comorbid substance abuse disorder (SUD vs. NSUD) with regard to brain morphology. In a prospective design 41 patients (20 SUD vs. 21 NSUD) diagnosed as recent-onset schizophrenia or schizoaffective disorder consecutively admitted to hospital received standardized psychopathological evaluation (BPRS, SANS, MADRS, CGI, GAF) and MRI scanning with volumetric measurement of superior temporal gyrus (STG), amygdala-hippocampal complex, and cingulum. Patients with SUD (primarily cannabis) were significantly younger, predominantly male and had a lower socioeconomic status. Despite less attentional impairment (SANS subscore) and elevated anxiety/depression (BPRS subscore) in patients with SUD compared to NSUD, no other psychopathological differences could be detected. There were no differences in the assessed temporolimbic brain morphology between the two subgroups. In conclusion, in this study substance abuse in recent-onset psychosis had no effect on brain morphology and the earlier onset of psychosis in patients with comorbid SUD could not be explained by supposed accentuated brain abnormalities in temporolimbic regions

    Cinnamomum cassia Bark in Two Herbal Formulas Increases Life Span in Caenorhabditis elegans via Insulin Signaling and Stress Response Pathways

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    Background: Proving the efficacy and corresponding mode of action of herbal supplements is a difficult challenge for evidence-based herbal therapy. A major hurdle is the complexity of herbal preparations, many of which combine multiple herbs, particularly when the combination is assumed to be vitally important to the effectiveness of the herbal therapy. This issue may be addressed through the use of contemporary methodology and validated animal models. Methods and Principal Findings: In this study, two commonly used traditional herbal formulas, Shi Quan Da Bu Tang (SQDB) and Huo Luo Xiao Ling Dan (HLXL) were evaluated using a survival assay and oxidative stress biomarkers in a well-established C. elegans model of aging. HLXL is an eleven herb formula modified from a top-selling traditional herbal formula for the treatment of arthritic joint pain. SQDB consists of ten herbs often used for fatigue and energy, particularly in the aged. We demonstrate here that SQDB significantly extend life span in a C. elegans model of aging. Among all individual herbs tested, two herbs Cinnamomum cassia bark (Chinese pharmaceutical name: Cinnamomi Cortex, CIN) and Panax ginseng root (Chinese pharmaceutical name: Ginseng Radix, GS) significantly extended life span in C. elegans. CIN in both SQDB and HLXL formula extended life span via modulation of multiple longevity assurance genes, including genes involved in insulin signaling and stress response pathways. All the life-span-extending herbs (SQDB, CIN and GS) also attenuated levels of H2O2 and enhanced small heat shock protein expression. Furthermore, the life spanextending herbs significantly delayed human amyloid beta (Aβ)-induced toxicity in transgenic C. elegans expressing human Aβ. Conclusion/Significance:These results validate an invertebrate model for rapid, systematic evaluation of commonly used Chinese herbal formulations and may provide insight for designing future evidence-based herbal therapy(s). Copyright: © 2010 Yu et al.published_or_final_versio
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