Calibration of Traffic Simulation Models using SPSA

Εθνικό Μετσόβιο Πολυτεχνείο--Μεταπτυχιακή Εργασία. Διεπιστημονικό-Διατμηματικό Πρόγραμμα Μεταπτυχιακών Σπουδών (Δ.Π.Μ.Σ.) “Γεωπληροφορική

Subtidal macrozoobenthos communities from northern Chile during and post El Niño 1997–1998

Despite a large amount of climatic and oceanographic information dealing with the recurring climate phenomenon El Niño (EN) and its well known impact on diversity of marine benthic communities, most published data are rather descriptive and consequently our understanding of the underlying mechanisms and processes that drive community structure during EN are still very scarce. In this study, we address two questions on the effects of EN on macrozoobenthic communities: (1) how does EN affect species diversity of the communities in northern Chile? and (2) is EN a phenomenon that restarts community assembling processes by affecting species interactions in northern Chile? To answer these questions, we compared species diversity and co-occurrence patterns of soft-bottoms macrozoobenthos communities from the continental shelf off northern Chile during (March 1998) and after (September 1998) the strong EN event 1997–1998. The methods used varied from species diversity and species co-occurrence analyses to multivariate ordination methods. Our results indicate that EN positively affects diversity of macrozoobenthos communities in the study area, increasing the species richness and diversity and decreasing the species dominance. EN represents a strong disturbance that affects species interactions that rule the species assembling processes in shallow-water, sea-bottom environments

The health care setting rather than medical speciality impacts on physicians adherence to guideline-conform anticoagulation in outpatients with non-valvular atrial fibrillation: a cross sectional survey

BACKGROUND: In patients with non-valvular atrial fibrillation (NVAF) at high risk for stroke guidelines consistently recommend long-term oral anticoagulation (OAC) with a vitamin K antagonist. However recommendations remain ambiguous in respect to the precise OAC initiation regimens. Based on the clinical observation, that the initiation of OAC for NVAF varies considerably in daily practice, we aimed to assess the current practice in Switzerland. METHODS: Cross-sectional survey of randomly selected general practitioners, internists and cardiologists from different health care settings in an urban Swiss region that covers 1.4 million inhabitants. The main outcome measures were the preferred antithrombotic initiation regimen and long-term treatment in patients with newly diagnosed NVAF at high risk for stroke. RESULTS: We received 226 out of 388 (58.2%) surveys. Compared to physicians working in a hospital setting (33.6% of respondents) physicians in ambulatory care reported more years of experience and claimed lower-use (never or seldom) of guidelines in general (47.6 vs. 12.2%). Regarding long-term thromboembolic prophylaxis 93.7% of all responders followed current recommendation by choosing an OAC. When focussing on guideline-consistent correct OAC initiation (either low-dose initial OAC or a combination of LMWH and OAC) adherence dropped to 60.6% with hospital physicians demonstrating a significantly higher use of guideline-conform OAC regimens (79.7 vs. 51.0%). Medical speciality in non-hospital physicians was not related to correct guideline-use. Hospital setting remained independently associated with a guideline-conform OAC initiation regimen (OR 2.8, p = 0.023) when controlled for medical speciality, physicians' characteristics and clinical experience. Problems when starting an anticoagulation treatment were seldom reported (never or seldom accounting for 94.1% of all responses). CONCLUSIONS: The guideline adherence with respect to OAC initiation regimens in NVAF was significantly lower when compared to long-term treatment and health care setting rather than medical speciality explained guideline-conform OAC initiation. The majority of the physicians did not consider the initiation of anticoagulation to be a major obstacle in outpatient care

Mutability and mutational spectrum of chromosome transmission fidelity genes

It has been more than two decades since the original chromosome transmission fidelity (Ctf) screen of Saccharomyces cerevisiae was published. Since that time the spectrum of mutations known to cause Ctf and, more generally, chromosome instability (CIN) has expanded dramatically as a result of systematic screens across yeast mutant arrays. Here we describe a comprehensive summary of the original Ctf genetic screen and the cloning of the remaining complementation groups as efforts to expand our knowledge of the CIN gene repertoire and its mutability in a model eukaryote. At the time of the original screen, it was impossible to predict either the genes and processes that would be overrepresented in a pool of random mutants displaying a Ctf phenotype or what the entire set of genes potentially mutable to Ctf would be. We show that in a collection of 136 randomly selected Ctf mutants, >65% of mutants map to 13 genes, 12 of which are involved in sister chromatid cohesion and/or kinetochore function. Extensive screening of systematic mutant collections has shown that ~350 genes with functions as diverse as RNA processing and proteasomal activity mutate to cause a Ctf phenotype and at least 692 genes are required for faithful chromosome segregation. The enrichment of random Ctf alleles in only 13 of ~350 possible Ctf genes suggests that these genes are more easily mutable to cause genome instability than the others. These observations inform our understanding of recurring CIN mutations in human cancers where presumably random mutations are responsible for initiating the frequently observed CIN phenotype of tumors

Population-based laboratory surveillance for Giardia sp. and Cryptosporidium sp. infections in a large Canadian health region

BACKGROUND: Giardia lamblia (intestinalis) and Cryptosporidium parvum are the two most important intestinal parasites infecting North Americans but there is a paucity of active population-based surveillance data from Canada. This study determined the incidence of and demographic risk factors for developing Giardia sp. and Cryptosporidium sp. infections in a general Canadian population. METHODS: Population-based laboratory surveillance was conducted among all residents of the Calgary Health Region (CHR; population ≅ 1 million) during May 1, 1999 and April 30, 2002. RESULTS: Giardia sp. infection occurred at a rate of 19.6 per 100,000 populations per year. Although the yearly incidence was stable, a significant seasonal variation was observed with a peak in late summer to early fall. Males were at higher risk for development of this infection as compared to females (21.2 vs. 17.9 per 100,000/yr; relative risk (RR) 1.19; 95% confidence interval (CI), 1.00–1.40, p = 0.047), and there was a significant decrease in risk associated with an increasing age. Cryptosporidium sp. infection occurred at an overall rate of 6.0 per 100,000 populations per year although a large outbreak of Cryptosporidium sp. infections occurred in the second half of the summer of 2001. During August and September of 2001, the incidence of cryptosporidiosis was 55.1 per 100,000 per year as compared to 3.1 per 100,000 per year for the remainder of the surveillance period (p < 0.0001). Cryptosporidiosis was largely a disease of children with an incidence of 17.8 per 100,000 per year occurring among those aged < 20 years of age compared to 1.25 per 100,000 per year for adults ≥ 20 years of age (RR 14.19; 95% CI, 9.77–21.11; p < 0.0001). CONCLUSION: This study provides important information on the occurrence and demographic risk groups for acquisition of giardiasis and cryptosporidiosis in a non-selected Canadian population

Karyotypic Determinants of Chromosome Instability in Aneuploid Budding Yeast

Recent studies in cancer cells and budding yeast demonstrated that aneuploidy, the state of having abnormal chromosome numbers, correlates with elevated chromosome instability (CIN), i.e. the propensity of gaining and losing chromosomes at a high frequency. Here we have investigated ploidy- and chromosome-specific determinants underlying aneuploidy-induced CIN by observing karyotype dynamics in fully isogenic aneuploid yeast strains with ploidies between 1N and 2N obtained through a random meiotic process. The aneuploid strains exhibited various levels of whole-chromosome instability (i.e. chromosome gains and losses). CIN correlates with cellular ploidy in an unexpected way: cells with a chromosomal content close to the haploid state are significantly more stable than cells displaying an apparent ploidy between 1.5 and 2N. We propose that the capacity for accurate chromosome segregation by the mitotic system does not scale continuously with an increasing number of chromosomes, but may occur via discrete steps each time a full set of chromosomes is added to the genome. On top of such general ploidy-related effect, CIN is also associated with the presence of specific aneuploid chromosomes as well as dosage imbalance between specific chromosome pairs. Our findings potentially help reconcile the divide between gene-centric versus genome-centric theories in cancer evolution

Relationship between human tumour angiogenic profile and combretastatin-induced vascular shutdown: an exploratory study

Combretastatin-A4-phosphate (CA4P) acts most effectively against immature tumour vasculature. We investigated whether histological angiogenic profile can explain the differential sensitivity of human tumours to CA4P, by correlating the kinetic changes demonstrated by dynamic MRI (DCE-MRI) in response to CA4P, with tumour immunohistochemical angiogenic markers. Tissue was received from 24 patients (mean age 59, range 32–73, 18 women, 6 men). An angiogenic profile was performed using standard immunohistochemical techniques. Dynamic MRI data were obtained for the same patients before and 4 h after CA4P. Three patients showed a statistically significant fall in Ktrans following CA4P, and one a statistically significant fall in IAUGC60. No statistically significant correlations were seen between the continuous or categorical variables and the DCE-MRI kinetic parameters other than between ang-2 and Ktrans (P=0.044). In conclusion, we found no strong relationships between changes in DCE-MRI kinetic variables following CA4P and the immunohistochemical angiogenic profile

Metagenomics reveals sediment microbial community response to Deepwater Horizon oil spill

The Deepwater Horizon (DWH) oil spill in the spring of 2010 resulted in an input of ∼4.1 million barrels of oil to the Gulf of Mexico; >22% of this oil is unaccounted for, with unknown environmental consequences. Here we investigated the impact of oil deposition on microbial communities in surface sediments collected at 64 sites by targeted sequencing of 16S rRNA genes, shotgun metagenomic sequencing of 14 of these samples and mineralization experiments using (14)C-labeled model substrates. The 16S rRNA gene data indicated that the most heavily oil-impacted sediments were enriched in an uncultured Gammaproteobacterium and a Colwellia species, both of which were highly similar to sequences in the DWH deep-sea hydrocarbon plume. The primary drivers in structuring the microbial community were nitrogen and hydrocarbons. Annotation of unassembled metagenomic data revealed the most abundant hydrocarbon degradation pathway encoded genes involved in degrading aliphatic and simple aromatics via butane monooxygenase. The activity of key hydrocarbon degradation pathways by sediment microbes was confirmed by determining the mineralization of (14)C-labeled model substrates in the following order: propylene glycol, dodecane, toluene and phenanthrene. Further, analysis of metagenomic sequence data revealed an increase in abundance of genes involved in denitrification pathways in samples that exceeded the Environmental Protection Agency (EPA)'s benchmarks for polycyclic aromatic hydrocarbons (PAHs) compared with those that did not. Importantly, these data demonstrate that the indigenous sediment microbiota contributed an important ecosystem service for remediation of oil in the Gulf. However, PAHs were more recalcitrant to degradation, and their persistence could have deleterious impacts on the sediment ecosystem

Absence of Ataxin-3 Leads to Enhanced Stress Response in C. elegans

Ataxin-3, the protein involved in Machado-Joseph disease, is able to bind ubiquitylated substrates and act as a deubiquitylating enzyme in vitro, and it has been involved in the modulation of protein degradation by the ubiquitin-proteasome pathway. C. elegans and mouse ataxin-3 knockout models are viable and without any obvious phenotype in a basal condition however their phenotype in stress situations has never been described

Genetic and Physical Interactions between Tel2 and the Med15 Mediator Subunit in Saccharomyces cerevisiae

International audienceBACKGROUND: In budding yeast, the highly conserved Tel2 protein is part of several complexes and its main function is now believed to be in the biogenesis of phosphatidyl inositol 3-kinase related kinases. PRINCIPAL FINDINGS: To uncover potentially novel functions of Tel2, we set out to isolate temperature-sensitive (ts) mutant alleles of TEL2 in order to perform genetic screenings. MED15/GAL11, a subunit of Mediator, a general regulator of transcription, was isolated as a suppressor of these mutants. The isolated tel2 mutants exhibited a short telomere phenotype that was partially rescued by MED15/GAL11 overexpression. The tel2-15 mutant was markedly deficient in the transcription of EST2, coding for the catalytic subunit of telomerase, potentially explaining the short telomere phenotype of this mutant. In parallel, a two-hybrid screen identified an association between Tel2 and Rvb2, a highly conserved member of the AAA+ family of ATPases further found by in vivo co-immunoprecipitation to be tight and constitutive. Transiently overproduced Tel2 and Med15/Gal11 associated together, suggesting a potential role for Tel2 in transcription. Other Mediator subunits, as well as SUA7/TFIIB, also rescued the tel2-ts mutants. SIGNIFICANCE: Altogether, the present data suggest the existence of a novel role for Tel2, namely in transcription, possibly in cooperation with Rvb2 and involving the existence of physical interactions with the Med15/Gal11 Mediator subunit