On design criteria for a disconnectable FPSO mooring system associated with expected lifecycle cost

Some floating production, storage and offloading units (FPSOs) possess disconnectable systems to avoid harsh environments. According to a literature survey, the practice is based on perceptions and experiences of operators to judge disconnection; however, this paper offers a rational approach. A life-cycle cost model is proposed to optimise (1) the disconnection criteria and (2) the design of mooring lines under reliability format. Relevant ultimate limit states are considered in association with hull, moorings and green water failure. Effects of future failure costs are considered (downtime, environmental damage, reputation, etc.). Disconnection criteria are then formulated in terms of significant wave height and wind speed limits. Because a permanent mooring system may exhibit excessive resistance, it is possible to reduce the lines’ thickness until the cost is optimised for non-permanent service. Results for an example in the Gulf of Mexico show that important savings can be achieved by implementing the proposed optimisations

A life-cycle cost model for the reliability-based design of disconnectable FPSO mooring lines

Floating production, storage, and offloading units (FPSOs) are widely used to develop offshore oil fields from shallow to ultra-deep waters, and some possess fast disconnection systems to avoid harsh environmental conditions. According to a literature survey, the current industry practice is based on the perceptions and experiences of operators to judge the disconnection of these units during cyclonic storms. However, systematic criteria should be established to judge whether disconnection is needed, and the downtime costs and safety issues associated with life-cycle costs should be considered. In this paper, a life-cycle cost model is proposed to optimize (1) the disconnection criteria of FPSOs and (2) the design of their mooring system. Relevant ultimate limit states and reliabilities are considered in association with hull collapse, mooring system failure, and green water impact failure. Effects of downtime costs (deferred production costs), mobilization, and other failure costs are considered. Disconnection criteria are then formulated in terms of the significant wave height and wind speed limits. Because a permanent mooring system may exhibit excessive resistance, it is possible to further optimize the life-cycle cost by reducing the system’s resistance until an optimum reliability is obtained, minimizing the costs for non-permanent service. An FPSO in the Gulf of Mexico is selected as an example to illustrate the application of the developed model. The results of this study show that important savings for an overall FPSO project can be achieved by implementing the proposed optimizations

Synthetic Lethality of Chk1 Inhibition Combined with p53 and/or p21 Loss During a DNA Damage Response in Normal and Tumor Cells

Cell cycle checkpoints ensure genome integrity and are frequently compromised in human cancers. A therapeutic strategy being explored takes advantage of checkpoint defects in p53-deficient tumors in order to sensitize them to DNA-damaging agents by eliminating Chk1-mediated checkpoint responses. Using mouse models, we demonstrated that p21 is a key determinant of how cells respond to the combination of DNA damage and Chk1 inhibition (combination therapy) in normal cells as well as in tumors. Loss of p21 sensitized normal cells to the combination therapy much more than did p53 loss and the enhanced lethality was partially blocked by CDK inhibition. In addition, basal pools of p21 (p53 independent) provided p53 null cells with protection from the combination therapy. Our results uncover a novel p53-independent function for p21 in protecting cells from the lethal effects of DNA damage followed by Chk1 inhibition. As p21 levels are low in a significant fraction of colorectal tumors, they are predicted to be particularly sensitive to the combination therapy. Results reported in this study support this prediction

Phage typing or CRISPR typing for epidemiological surveillance of Salmonella Typhimurium?

Objective: Salmonella Typhimurium is the most dominant Salmonella serovar around the world. It is associated with foodborne gastroenteritis outbreaks but has recently been associated with invasive illness and deaths. Characterization of S. Typhimurium is therefore very crucial for epidemiological surveillance. Phage typing has been used for decades for subtyping of S. Typhimurium to determine the epidemiological relation among isolates. Recent studies however have suggested that high throughput clustered regular interspaced short palindromic repeats (CRISPR) typing has the potential to replace phage typing. This study aimed to determine the efficacy of highthroughput CRISPR typing over conventional phage typing in epidemiological surveillance and outbreak investigation of S. Typhimurium. Results: In silico analysis of whole genome sequences (WGS) of well-documented phage types of S. Typhimurium reveals the presence of different CRISPR type among strains belong to the same phage type. Furthermore, different phage types of S. Typhimurium share identical CRISPR type. Interestingly, identical spacers were detected among outbreak and non-outbreak associated DT8 strains of S. Typhimurium. Therefore, CRISPR typing is not useful for the epidemiological surveillance and outbreak investigation of S. Typhimurium and phage typing, until it is replaced by WGS, is still the gold standard method for epidemiological surveillance of S. Typhimurium

Mathematical modeling of the dynamic storage of iron in ferritin

<p>Abstract</p> <p>Background</p> <p>Iron is essential for the maintenance of basic cellular processes. In the regulation of its cellular levels, ferritin acts as the main intracellular iron storage protein. In this work we present a mathematical model for the dynamics of iron storage in ferritin during the process of intestinal iron absorption. A set of differential equations were established considering kinetic expressions for the main reactions and mass balances for ferritin, iron and a discrete population of ferritin species defined by their respective iron content.</p> <p>Results</p> <p>Simulation results showing the evolution of ferritin iron content following a pulse of iron were compared with experimental data for ferritin iron distribution obtained with purified ferritin incubated <it>in vitro </it>with different iron levels. Distinctive features observed experimentally were successfully captured by the model, namely the distribution pattern of iron into ferritin protein nanocages with different iron content and the role of ferritin as a controller of the cytosolic labile iron pool (cLIP). Ferritin stabilizes the cLIP for a wide range of total intracellular iron concentrations, but the model predicts an exponential increment of the cLIP at an iron content > 2,500 Fe/ferritin protein cage, when the storage capacity of ferritin is exceeded.</p> <p>Conclusions</p> <p>The results presented support the role of ferritin as an iron buffer in a cellular system. Moreover, the model predicts desirable characteristics for a buffer protein such as effective removal of excess iron, which keeps intracellular cLIP levels approximately constant even when large perturbations are introduced, and a freely available source of iron under iron starvation. In addition, the simulated dynamics of the iron removal process are extremely fast, with ferritin acting as a first defense against dangerous iron fluctuations and providing the time required by the cell to activate slower transcriptional regulation mechanisms and adapt to iron stress conditions. In summary, the model captures the complexity of the iron-ferritin equilibrium, and can be used for further theoretical exploration of the role of ferritin in the regulation of intracellular labile iron levels and, in particular, as a relevant regulator of transepithelial iron transport during the process of intestinal iron absorption.</p

Optimization of Control Strategies for Non-Domiciliated Triatoma dimidiata, Chagas Disease Vector in the Yucatán Peninsula, Mexico

Chagas disease is the most important vector-borne disease in Latin America. Residual insecticide spraying has been used successfully for the elimination of domestic vectors in many regions. However, some vectors of non-domestic origin are able to invade houses, and they are now a key challenge for further disease control. We developed a mathematical model to predict the temporal variations in abundance of non-domiciliated vectors inside houses, based on triatomine demographic parameters. The reliability of the predictions was demonstrated by comparing these with different sets of insect collection data from the Yucatan peninsula, Mexico. We then simulated vector control strategies based on insecticide spraying, insect, screens and bednets to evaluate their efficacy at reducing triatomine abundance in the houses. An optimum reduction in bug abundance by at least 80% could be obtained by insecticide application only when doses of at least 50 mg/m2 were applied every year within a two-month period matching the house invasion season by bugs. Alternatively, the use of insect screens consistently reduced bug abundance in the houses and offers a sustainable alternative. Such screens may be part of novel interventions for the integrated control of various vector-borne diseases

Analyzing musculoskeletal neck pain, measured as present pain and periods of pain, with three different regression models: a cohort study

<p>Abstract</p> <p>Background</p> <p>In the literature there are discussions on the choice of outcome and the need for more longitudinal studies of musculoskeletal disorders. The general aim of this longitudinal study was to analyze musculoskeletal neck pain, in a group of young adults. Specific aims were to determine whether psychosocial factors, computer use, high work/study demands, and lifestyle are long-term or short-term factors for musculoskeletal neck pain, and whether these factors are important for developing or ongoing musculoskeletal neck pain.</p> <p>Methods</p> <p>Three regression models were used to analyze the different outcomes. Pain at present was analyzed with a marginal logistic model, for number of years with pain a Poisson regression model was used and for developing and ongoing pain a logistic model was used. Presented results are odds ratios and proportion ratios (logistic models) and rate ratios (Poisson model). The material consisted of web-based questionnaires answered by 1204 Swedish university students from a prospective cohort recruited in 2002.</p> <p>Results</p> <p>Perceived stress was a risk factor for pain at present (PR = 1.6), for developing pain (PR = 1.7) and for number of years with pain (RR = 1.3). High work/study demands was associated with pain at present (PR = 1.6); and with number of years with pain when the demands negatively affect home life (RR = 1.3). Computer use pattern (number of times/week with a computer session ≥ 4 h, without break) was a risk factor for developing pain (PR = 1.7), but also associated with pain at present (PR = 1.4) and number of years with pain (RR = 1.2). Among life style factors smoking (PR = 1.8) was found to be associated to pain at present. The difference between men and women in prevalence of musculoskeletal pain was confirmed in this study. It was smallest for the outcome ongoing pain (PR = 1.4) compared to pain at present (PR = 2.4) and developing pain (PR = 2.5).</p> <p>Conclusion</p> <p>By using different regression models different aspects of neck pain pattern could be addressed and the risk factors impact on pain pattern was identified. Short-term risk factors were perceived stress, high work/study demands and computer use pattern (break pattern). Those were also long-term risk factors. For developing pain perceived stress and computer use pattern were risk factors.</p

Self-esteem in adolescent patients with attention-deficit/hyperactivity disorder during open-label atomoxetine treatment: psychometric evaluation of the Rosenberg Self-Esteem Scale and clinical findings

To report on (1) psychometric properties of the Rosenberg Self-Esteem Scale (SES) studied in adolescents with ADHD, (2) correlations of SES with ADHD scale scores, and (3) change in patient-reported self-esteem with atomoxetine treatment. ADHD patients (12–17 years), treated in an open-label study for 24 weeks. Secondary analyses on ADHD symptoms (assessed with ADHD-RS, CGI, GIPD scales) and self-esteem (SES) were performed. One hundred and fifty-nine patients were treated. A dichotomous structure of the SES could be confirmed. Reliability and internal consistency were moderate to excellent. Highest coefficients were found for the correlation between SES and GIPD scores. Self-esteem significantly increased over time, accompanied by an improvement of ADHD symptoms and related perceived difficulties. The Rosenberg SES was shown to be internally consistent, reliable, and sensitive to treatment-related changes of self-esteem. According to these findings, self-esteem may be an important individual patient outcome beyond the core symptoms of ADHD

A fluorogenic cyclic peptide for imaging and quantification of drug-induced apoptosis

Programmed cell death or apoptosis is a central biological process that is dysregulated in many diseases, including inflammatory conditions and cancer. The detection and quantification of apoptotic cells in vivo is hampered by the need for fixatives or washing steps for non-fluorogenic reagents, and by the low levels of free calcium in diseased tissues that restrict the use of annexins. In this manuscript, we report the rational design of a highly stable fluorogenic peptide (termed Apo-15) that selectively stains apoptotic cells in vitro and in vivo in a calcium-independent manner and under wash-free conditions. Furthermore, using a combination of chemical and biophysical methods, we identify phosphatidylserine as a molecular target of Apo-15. We demonstrate that Apo-15 can be used for the quantification and imaging of drug-induced apoptosis in preclinical mouse models, thus creating opportunities for assessing the in vivo efficacy of anti-inflammatory and anti-cancer therapeutics