98 research outputs found

    GEOMORPHIC CONSTRAINS ON THE EVOLUTION OF THE AGGITIS RIVER BASIN NORTHERN GREECE (A PRELIMINARY REPORT)

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    Στην παρούσα εργασία αναλύουμε την γεωμορφολογική εξέλιξη της κοιλάδας του Αγγίτη ποταμού και παρουσιάζουμε τον συσχετισμό των μορφολογικών χαρακτηριστικών από το σπήλαιο του Μααρά (Σπήλαιο πηγών Αγγίτη) με τις διάφορες γεωμορφές στην κοιλάδα του ποταμού. Παράλληλα, επιχειρούμε να θέσουμε ένα γενικό χρονολογικό πλαίσιο για την εξέλιξη της κοιλάδας. Για τον σκοπό αυτό μελετήσαμε το σπήλαιο και τις γεωμορφές στο εσωτερικό του ενώ παράλληλα μελετήθηκε και η επιφανειακή μορφολογία. Η τρισδιάστατη χαρτογράφηση του σπηλαίου έδειξε ότι η οροφή του σπηλαίου έχει κυματοειδές σχήμα ενώ το δάπεδό του παρουσιάζει μικρή κλίση και είναι καλυμμένο με κλαστικές αποθέσεις μεγάλου πάχους. Η γεωμορφολογική χαρτογράφηση έδειξε πως στο νότιο τμήμα της κοιλάδας υπάρχουν δύο windgaps. Αξιολογώντας τα αποτελέσματα καταλήγουμε στο συμπέρασμα ότι τέσσερα εξελεκτικά στάδια διαμόρφωσαν την κοιλάδα του Αγγίτη ποταμού κατά την περίοδο από το Νεογενές ως το Τεταρτογενές.In this paper we discuss the landscape evolution of the Aggitis River basin by correlating the morphological characteristics of the Maaras Cave (Aggitis River spring) with the main geomorphological features of the Aggitis fluvial valley. We combine the various morphological features that are hidden inside the Maaras Cave with the surface geomorphology of the river valley in order to trace the imprint of the different evolutionary stages on the landscape. Also, we provide a relative chronological framework for the evolution of the area. The 3D survey of the Maaras Cave shows that the roof of the cave is looping-like shaped in contrast to the floor of the cave that shows low slopes and holds thick clastic sediment deposits. Furthermore, the geomorphological mapping of the Aggitis River valley shows two prominent windgaps at the southern part of the basin that formed as the result of river capture. Our results suggest that the Aggitis River basin suffered four major evolutionary stages from the Neogene until the Quaternary

    Complexity of Discrete Energy Minimization Problems

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    Discrete energy minimization is widely-used in computer vision and machine learning for problems such as MAP inference in graphical models. The problem, in general, is notoriously intractable, and finding the global optimal solution is known to be NP-hard. However, is it possible to approximate this problem with a reasonable ratio bound on the solution quality in polynomial time? We show in this paper that the answer is no. Specifically, we show that general energy minimization, even in the 2-label pairwise case, and planar energy minimization with three or more labels are exp-APX-complete. This finding rules out the existence of any approximation algorithm with a sub-exponential approximation ratio in the input size for these two problems, including constant factor approximations. Moreover, we collect and review the computational complexity of several subclass problems and arrange them on a complexity scale consisting of three major complexity classes -- PO, APX, and exp-APX, corresponding to problems that are solvable, approximable, and inapproximable in polynomial time. Problems in the first two complexity classes can serve as alternative tractable formulations to the inapproximable ones. This paper can help vision researchers to select an appropriate model for an application or guide them in designing new algorithms.Comment: ECCV'16 accepte

    Studies of CTNNBL1 and FDFT1 variants and measures of obesity: analyses of quantitative traits and case-control studies in 18,014 Danes

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    <p>Abstract</p> <p>Background</p> <p>A genome-wide scan in unrelated US Caucasians identified rs7001819 upstream of farnesyl-diphosphate farnesyltransferase 1 (<it>FDFT1</it>) and multiple variants within catenin (cadherin-associated protein), β-like 1 (<it>CTNNBL1</it>) to associate strongly with body mass index (BMI). The most significantly associating variants within <it>CTNNBL1 </it>including rs6013029 and rs6020846 were additionally confirmed to associate with morbid obesity in a French Caucasian case-control sample. The aim of this study was to investigate the impact of these three variants on obesity, through analyses of obesity-related quantitative traits, and case-control studies in large study samples of Danes.</p> <p>Methods</p> <p>The <it>FDFT1 </it>rs7001819, <it>CTNNBL1 </it>rs6013029 and rs6020846 were genotyped, using TaqMan allelic discrimination, in a combined study sample comprising 18,014 participants ascertained from; the population-based Inter99 cohort (<it>n </it>= 6,514), the ADDITION Denmark screening study cohort (<it>n </it>= 8,662), and a population-based sample (<it>n </it>= 680) and a type 2 diabetic patients group (<it>n </it>= 2,158) from Steno Diabetes Center.</p> <p>Results</p> <p>Both <it>CTNNBL1 </it>variants associated with body weight and height with per allele effect sizes of 1.0 [0.3–0.8] kg and 0.6 [0.2–0.9] cm, respectively, for the rs6020846 G-allele. No association was observed with BMI and waist circumference. In case-control studies neither of the <it>CTNNBL1 </it>variants showed association with overweight, obesity or morbid obesity (rs6013029: Odds Ratio (OR)<sub>overweight </sub>= 1.02 [0.90–1.16], OR<sub>obesity </sub>= 1.09 [0.95–1.25], OR<sub>morbidobesity </sub>= 1.26 [0.91–1.74]; rs6020846: OR<sub>overweight </sub>= 1.05 [0.93–1.18], OR<sub>obesity</sub>= 1.13 [1.00–1.28], OR<sub>morbidobesity </sub>= 1.17 [0.86–1.61]). However, in meta-analyses of the present and the previous study, both the rs6013029 T-allele and the rs6020846 G-allele increased the risk of developing morbid obesity (rs6013029: OR<sub>combined </sub>= 1.36 [1.12–1.64], <it>p </it>= 0.002; rs6020846: OR<sub>combined </sub>= 1.26 [1.06–1.51], <it>p </it>= 0.01), and obesity (rs6013029: OR<sub>combined </sub>= 1.17 [1.04–1.31], <it>p </it>= 0.007; rs6020846: OR<sub>combined </sub>= 1.17 [1.05–1.30], <it>p </it>= 0.004).</p> <p>The <it>FDFT1 </it>rs7001819 C-allele showed no association with obesity-related quantitative measures or dichotomous measures of overweight, obesity and morbid obesity.</p> <p>Conclusion</p> <p><it>CTNNBL1 </it>variants associated with body weight and height, and confer the risk of developing obesity in meta-analyses combining the present and a previous study. <it>FDFT1 </it>rs7001819 showed no association with obesity, neither when analysing quantitative traits nor when performing case-control studies of obesity.</p

    Studies of Metabolic Phenotypic Correlates of 15 Obesity Associated Gene Variants

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    Genome-wide association studies have identified novel BMI/obesity associated susceptibility loci. The purpose of this study is to determine associations with overweight, obesity, morbid obesity and/or general adiposity in a Danish population. Moreover, we want to investigate if these loci associate with type 2 diabetes and to elucidate potential underlying metabolic mechanisms.15 gene variants in 14 loci including TMEM18 (rs7561317), SH2B1 (rs7498665), KCTD15 (rs29941), NEGR1 (rs2568958), ETV5 (rs7647305), BDNF (rs4923461, rs925946), SEC16B (rs10913469), FAIM2 (rs7138803), GNPDA2 (rs10938397), MTCH2 (rs10838738), BAT2 (rs2260000), NPC1 (rs1805081), MAF (rs1424233), and PTER (rs10508503) were genotyped in 18,014 middle-aged Danes.Five of the 15 gene variants associated with overweight, obesity and/or morbid obesity. Per allele ORs ranged from 1.15-1.20 for overweight, 1.10-1.25 for obesity, and 1.41-1.46 for morbid obesity. Five of the 15 variants moreover associated with increased measures of adiposity. BDNF rs4923461 displayed a borderline BMI-dependent protective effect on type 2 diabetes (0.87 (0.78-0.96, p = 0.008)), whereas SH2B1 rs7498665 associated with nominally BMI-independent increased risk of type 2 diabetes (1.16 (1.07-1.27, p = 7.8×10(-4))).Associations with overweight and/or obesity and measures of obesity were confirmed for seven out of the 15 gene variants. The obesity risk allele of BDNF rs4923461 protected against type 2 diabetes, which could suggest neuronal and peripheral distinctive ways of actions for the protein. SH2B1 rs7498665 associated with type 2 diabetes independently of BMI

    Cochlin, Intraocular Pressure Regulation and Mechanosensing

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    Fluid shear modulates many biological properties. How shear mechanosensing occurs in the extracellular matrix (ECM) and is transduced into cytoskeletal change remains unknown. Cochlin is an ECM protein of unknown function. Our investigation using a comprehensive spectrum of cutting-edge techniques has resulted in following major findings: (1) over-expression and down-regulation of cochlin increase and decrease intraocular pressure (IOP), respectively. The overexpression was achieved in DBA/2J-Gpnmb+/SjJ using lentiviral vectors, down-regulation was achieved in glaucomatous DBA/2J mice using targeted disruption (cochlin-null mice) and also using lentiviral vector mediated shRNA against cochlin coding region; (2) reintroduction of cochlin in cochlin-null mice increases IOP; (3) injection of exogenous cochlin also increased IOP; (4) increasing perfusion rates increased cochlin multimerization, which reduced the rate of cochlin proteolysis by trypsin and proteinase K; The cochlin multimerization in response to shear stress suggests its potential mechanosensing. Taken together with previous studies, we show cochlin is involved in regulation of intraocular pressure in DBA/2J potentially through mechanosensing of the shear stress

    A pig model of acute Staphylococcus aureus induced pyemia

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    <p>Abstract</p> <p>Background</p> <p>Sepsis caused by <it>Staphylococcus aureus </it>constitutes an important cause of morbidity and mortality in humans, and the incidence of this disease-entity is increasing. In this paper we describe the initial microbial dynamics and lesions in pigs experimentally infected with <it>S. aureus</it>, with the aim of mimicking human sepsis and pyemia.</p> <p>Methods</p> <p>The study was conducted in anaesthetized and intravenously inoculated pigs, and was based on bacteriological examination of blood and testing of blood for IL-6 and C-reactive protein. Following killing of the animals and necropsy bacteriological and histological examinations of different organs were performed 4, 5 or 6 h after inoculation.</p> <p>Results</p> <p>Clearance of bacteria from the blood was completed within the first 2 h in some of the pigs and the highest bacterial load was recorded in the lungs as compared to the spleen, liver and bones. This probably was a consequence of both the intravenous route of inoculation and the presence of pulmonary intravascular macrophages. Inoculation of bacteria induced formation of acute microabscesses in the lungs, spleen and liver, but not in the kidneys or bones. No generalized inflammatory response was recorded, i.e. IL-6 was not detected in the blood and C-reactive protein did not increase, probably because of the short time course of the study.</p> <p>Conclusion</p> <p>This study demonstrates the successful induction of acute pyemia (microabscesses), and forms a basis for future experiments that should include inoculation with strains of <it>S. aureus </it>isolated from man and an extension of the timeframe aiming at inducing sepsis, severe sepsis and septic shock.</p

    MC EMiNEM Maps the Interaction Landscape of the Mediator

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    The Mediator is a highly conserved, large multiprotein complex that is involved essentially in the regulation of eukaryotic mRNA transcription. It acts as a general transcription factor by integrating regulatory signals from gene-specific activators or repressors to the RNA Polymerase II. The internal network of interactions between Mediator subunits that conveys these signals is largely unknown. Here, we introduce MC EMiNEM, a novel method for the retrieval of functional dependencies between proteins that have pleiotropic effects on mRNA transcription. MC EMiNEM is based on Nested Effects Models (NEMs), a class of probabilistic graphical models that extends the idea of hierarchical clustering. It combines mode-hopping Monte Carlo (MC) sampling with an Expectation-Maximization (EM) algorithm for NEMs to increase sensitivity compared to existing methods. A meta-analysis of four Mediator perturbation studies in Saccharomyces cerevisiae, three of which are unpublished, provides new insight into the Mediator signaling network. In addition to the known modular organization of the Mediator subunits, MC EMiNEM reveals a hierarchical ordering of its internal information flow, which is putatively transmitted through structural changes within the complex. We identify the N-terminus of Med7 as a peripheral entity, entailing only local structural changes upon perturbation, while the C-terminus of Med7 and Med19 appear to play a central role. MC EMiNEM associates Mediator subunits to most directly affected genes, which, in conjunction with gene set enrichment analysis, allows us to construct an interaction map of Mediator subunits and transcription factors

    Natural Selection Affects Multiple Aspects of Genetic Variation at Putatively Neutral Sites across the Human Genome

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    A major question in evolutionary biology is how natural selection has shaped patterns of genetic variation across the human genome. Previous work has documented a reduction in genetic diversity in regions of the genome with low recombination rates. However, it is unclear whether other summaries of genetic variation, like allele frequencies, are also correlated with recombination rate and whether these correlations can be explained solely by negative selection against deleterious mutations or whether positive selection acting on favorable alleles is also required. Here we attempt to address these questions by analyzing three different genome-wide resequencing datasets from European individuals. We document several significant correlations between different genomic features. In particular, we find that average minor allele frequency and diversity are reduced in regions of low recombination and that human diversity, human-chimp divergence, and average minor allele frequency are reduced near genes. Population genetic simulations show that either positive natural selection acting on favorable mutations or negative natural selection acting against deleterious mutations can explain these correlations. However, models with strong positive selection on nonsynonymous mutations and little negative selection predict a stronger negative correlation between neutral diversity and nonsynonymous divergence than observed in the actual data, supporting the importance of negative, rather than positive, selection throughout the genome. Further, we show that the widespread presence of weakly deleterious alleles, rather than a small number of strongly positively selected mutations, is responsible for the correlation between neutral genetic diversity and recombination rate. This work suggests that natural selection has affected multiple aspects of linked neutral variation throughout the human genome and that positive selection is not required to explain these observations
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