200 research outputs found

    Switching from oil to gas production in a depleting field

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    Author's accepted version (post-print).Available from 26/05/2020.We derive an optimal decision rule with regards to making an irreversible switch from oil to gas production. The approach can be used by petroleum field operators to maximize the value creation from a petroleum field with diminishing oil production and remaining gas reserves. Assuming that both the oil and gas prices follow a geometric Brownian motion we derive an analytical solution for the exercise threshold. We also propose an explicit solution for the option value that is new to the literature. Numerical examples are used to demonstrate the threshold and option value for a generic petroleum field. Both the threshold and option value solutions are relevant for application to other real options cases with similar features (e.g. other types of switching options or a perpetual spread option).acceptedVersio

    Single-Molecule Fluorescence Meets DNA Origami

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    Pattern of joint damage in persons with knee osteoarthritis and concomitant ACL tears.

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    OBJECTIVE: The aim of this study was to evaluate the morphological changes of the lateral meniscus in end-stage lateral compartment osteoarthritis (OA) of the knee. METHODS: One hundred fifty-eight knee joints from 133 patients that subsequently underwent total knee joint arthroplasty from January 2008 to December 2009 were enrolled. There were 26 men and 107 women. Their ages ranged from 56 to 81 (mean 67.4 + 6.5 years). All study participants had complete obliteration of the lateral joint space identified by weight-bearing radiography. Meniscal position was assessed by measuring meniscal subluxation and meniscal height. The meniscal morphology was assessed using a modification of the whole-organ magnetic resonance imaging score (WORMS). The frequency of different meniscal morphology and their respective positions was calculated. RESULTS: The predominant type (42.4%, 53.8% and 52.5% in the anterior horn, mid-body and posterior horn, respectively) of abnormal meniscal morphology was a complete maceration/destruction or complete resection. The anterior horn of non-macerated lateral meniscus was more subluxed than that of the non-macerated medial meniscus in patients with lateral OA. CONCLUSION: This study suggests that the lateral meniscus in persons with end-stage lateral OA are mostly macerated or destroyed. Also, unlike isolated end-staged medial compartment OA, the anterior horn of the lateral meniscus in isolated end-stage lateral OA is commonly affected. Copyright 2011 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved

    Pattern of joint damage in persons with knee osteoarthritis and concomitant ACL tears.

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    OBJECTIVE: The aim of this study was to evaluate the morphological changes of the lateral meniscus in end-stage lateral compartment osteoarthritis (OA) of the knee. METHODS: One hundred fifty-eight knee joints from 133 patients that subsequently underwent total knee joint arthroplasty from January 2008 to December 2009 were enrolled. There were 26 men and 107 women. Their ages ranged from 56 to 81 (mean 67.4 + 6.5 years). All study participants had complete obliteration of the lateral joint space identified by weight-bearing radiography. Meniscal position was assessed by measuring meniscal subluxation and meniscal height. The meniscal morphology was assessed using a modification of the whole-organ magnetic resonance imaging score (WORMS). The frequency of different meniscal morphology and their respective positions was calculated. RESULTS: The predominant type (42.4%, 53.8% and 52.5% in the anterior horn, mid-body and posterior horn, respectively) of abnormal meniscal morphology was a complete maceration/destruction or complete resection. The anterior horn of non-macerated lateral meniscus was more subluxed than that of the non-macerated medial meniscus in patients with lateral OA. CONCLUSION: This study suggests that the lateral meniscus in persons with end-stage lateral OA are mostly macerated or destroyed. Also, unlike isolated end-staged medial compartment OA, the anterior horn of the lateral meniscus in isolated end-stage lateral OA is commonly affected. Copyright 2011 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved

    Association between TAS2R38 gene polymorphisms and colorectal cancer risk

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    Molecular sensing in the lingual mucosa and in the gastro-intestinal tract play a role in the detection of ingested harmful drugs and toxins. Therefore, genetic polymorphisms affecting the capability of initiating these responses may be critical for the subsequent efficiency of avoiding and/or eliminating possible threats to the organism. By using a tagging approach in the region of Taste Receptor 2R38 (TAS2R38) gene, we investigated all the common genetic variation of this gene region in relation to colorectal cancer risk with a case-control study in a German population (709 controls and 602 cases) and in a Czech population (623 controls and 601 cases). We found that there were no significant associations between individual SNPs of the TAS2R38 gene and colorectal cancer in the Czech or in the German population, nor in the joint analysis. However, when we analyzed the diplotypes and the phenotypes we found that the non-taster group had an increased risk of colorectal cancer in comparison to the taster group. This association was borderline significant in the Czech population, (OR = 1.28, 95% CI 0.99-1.67; P(value) = 0.058) and statistically significant in the German population (OR = 1.36, 95% CI 1.06-1.75; P(value) = 0.016) and in the joint analysis (OR = 1.34, 95% CI 1.12-1.61; P(value) = 0.001). In conclusion, we found a suggestive association between the human bitter tasting phenotype and the risk of CRC in two different populations of Caucasian origin

    Interaction of developmental factors and ordinary stressful life events on brain structure in adults

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    An interplay of early environmental and genetic risk factors with recent stressful life events (SLEs) in adulthood increases the risk for adverse mental health outcomes. The interaction of early risk and current SLEs on brain structure has hardly been investigated. Whole brain voxel-based morphometry analysis was performed in N = 786 (64.6% female, mean age = 33.39) healthy subjects to identify correlations of brain clusters with commonplace recent SLEs. Genetic and early environmental risk factors, operationalized as those for severe psychopathology (i.e., polygenic scores for neuroticism, childhood maltreatment, urban upbringing and paternal age) were assessed as modulators of the impact of SLEs on the brain. SLEs were negatively correlated with grey matter volume in the left medial orbitofrontal cortex (mOFC, FWE p = 0.003). This association was present for both, positive and negative, life events. Cognitive-emotional variables, i.e., neuroticism, perceived stress, trait anxiety, intelligence, and current depressive symptoms did not account for the SLE-mOFC association. Further, genetic and environmental risk factors were not correlated with grey matter volume in the left mOFC cluster and did not affect the association between SLEs and left mOFC grey matter volume. The orbitofrontal cortex has been implicated in stress-related psychopathology, particularly major depression in previous studies. We find that SLEs are associated with this area. Important early life risk factors do not interact with current SLEs on brain morphology in healthy subjects

    Severity of current depression and remission status are associated with structural connectome alterations in major depressive disorder

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    Major depressive disorder (MDD) is associated to affected brain wiring. Little is known whether these changes are stable over time and hence might represent a biological predisposition, or whether these are state markers of current disease severity and recovery after a depressive episode. Human white matter network ("connectome") analysis via network science is a suitable tool to investigate the association between affected brain connectivity and MDD. This study examines structural connectome topology in 464 MDD patients (mean age: 36.6 years) and 432 healthy controls (35.6 years). MDD patients were stratified categorially by current disease status (acute vs. partial remission vs. full remission) based on DSM-IV criteria. Current symptom severity was assessed continuously via the Hamilton Depression Rating Scale (HAMD). Connectome matrices were created via a combination of T1-weighted magnetic resonance imaging (MRI) and tractography methods based on diffusion-weighted imaging. Global tract-based metrics were not found to show significant differences between disease status groups, suggesting conserved global brain connectivity in MDD. In contrast, reduced global fractional anisotropy (FA) was observed specifically in acute depressed patients compared to fully remitted patients and healthy controls. Within the MDD patients, FA in a subnetwork including frontal, temporal, insular, and parietal nodes was negatively associated with HAMD, an effect remaining when correcting for lifetime disease severity. Therefore, our findings provide new evidence of MDD to be associated with structural, yet dynamic, state-dependent connectome alterations, which covary with current disease severity and remission status after a depressive episode

    In vivo function of the lipid raft protein flotillin-1 during cd8+ t cell–mediated host surveillance

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    Flotillin-1 (Flot1) is an evolutionary conserved, ubiquitously expressed lipid raft– associated scaffolding protein. Migration of Flot1-deficient neutrophils is impaired because of a decrease in myosin II–mediated contractility. Flot1 also accumulates in the uropod of polarized T cells, suggesting an analogous role in T cell migration. In this study, we analyzed morphology and migration parameters of murine wild-type and Flot1−/− CD8+ T cells using in vitro assays and intravital two-photon microscopy of lymphoid and nonlymphoid tissues. Flot1−/− CD8+ T cells displayed significant alterations in cell shape and motility parameters in vivo but showed comparable homing to lymphoid organs and intact in vitro migration to chemokines. Furthermore, their clonal expansion and infiltration into nonlymphoid tissues during primary and secondary antiviral immune responses was comparable to wild-type CD8+ T cells. Taken together, Flot1 plays a detectable but unexpectedly minor role for CD8+ T cell behavior under physiological conditions

    The serotonin receptor 3E variant is a risk factor for female IBS-D

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    Irritable bowel syndrome (IBS) is a gut-brain disorder of multifactorial origin. Evidence of disturbed serotonergic function in IBS accumulated for the 5-HT3 receptor family. 5-HT3Rs are encoded by HTR3 genes and control GI function, and peristalsis and secretion, in particular. Moreover, 5-HT3R antagonists are beneficial in the treatment of diarrhea predominant IBS (IBS-D). We previously reported on functionally relevant SNPs in HTR3A c.-42C > T (rs1062613), HTR3C p.N163K (rs6766410), and HTR3E c.*76G > A (rs56109847 = rs62625044) being associated with IBS-D, and the HTR3B variant p.Y129S (rs1176744) was also described within the context of IBS. We performed a multi-center study to validate previous results and provide further evidence for the relevance of HTR3 genes in IBS pathogenesis. Therefore, genotype data of 2682 IBS patients and 9650 controls from 14 cohorts (Chile, Germany (2), Greece, Ireland, Spain, Sweden (2), the UK (3), and the USA (3)) were taken into account. Subsequent meta-analysis confirmed HTR3E c.*76G > A (rs56109847 = rs62625044) to be associated with female IBS-D (OR = 1.58; 95% CI (1.18, 2.12)). Complementary expression studies of four GI regions (jejunum, ileum, colon, sigmoid colon) of 66 IBS patients and 42 controls revealed only HTR3E to be robustly expressed. On top, HTR3E transcript levels were significantly reduced in the sigma of IBS patients (p = 0.0187); more specifically, in those diagnosed with IBS-D (p = 0.0145). In conclusion, meta-analysis confirmed rs56109847 = rs62625044 as a risk factor for female IBS-D. Expression analysis revealed reduced HTR3E levels in the sigmoid colon of IBS-D patients, which underlines the relevance of HTR3E in the pathogenesis of IBS-D
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