Off-design performances of an organic Rankine cycle for waste heat recovery from gas turbines

This paper presents an off-design analysis of a gas turbine Organic Rankine Cycle (ORC) combined cycle. Combustion turbine performances are significantly affected by fluctuations in ambient conditions, leading to relevant variations in the exhaust gases’ mass flow rate and temperature. The effects of the variation of ambient air temperature have been considered in the simulation of the topper cycle and of the condenser in the bottomer one. Analyses have been performed for different working fluids (toluene, benzene and cyclopentane) and control systems have been introduced on critical parameters, such as oil temperature and air mass flow rate at the condenser fan. Results have highlighted similar power outputs for cycles based on benzene and toluene, while differences as high as 34% have been found for cyclopentane. The power output trend with ambient temperature has been found to be influenced by slope discontinuities in gas turbine exhaust mass flow rate and temperature and by the upper limit imposed on the air mass flow rate at the condenser as well, suggesting the importance of a correct sizing of the component in the design phase. Overall, benzene-based cycle power output has been found to vary between 4518 kW and 3346 kW in the ambient air temperature range considered

Metacognition, Social Cognition, and Mentalizing In Psychosis: Are These Distinct Constructs When It Comes To Subjective Experience Or Are We Just Splitting Hairs?

Research using the integrated model of metacognition has suggested that the construct of metacognition could quantify the spectrum of activities that, if impaired, might cause many of the subjective disturbances found in psychosis. Research on social cognition and mentalizing in psychosis, however, has also pointed to underlying deficits in how persons make sense of their experience of themselves and others. To explore the question of whether metacognitive research in psychosis offers unique insight in the midst of these other two emerging fields, we have offered a review of the constructs and research from each field. Following that summary, we discuss ways in which research on metacognition may be distinguished from research on social cognition and mentalizing in three broad categories: (1) experimental procedures, (2) theoretical advances, and (3) clinical applications or indicated interventions. In terms of its research methods, we will describe how metacognition makes a unique contribution to understanding disturbances in how persons make sense of and interpret their own experiences within the flow of life. We will next discuss how metacognitive research in psychosis uniquely describes an architecture which when compromised – as often occurs in psychosis – results in the loss of persons’ sense of purpose, possibilities, place in the world and cohesiveness of self. Turning to clinical issues, we explore how metacognitive research offers an operational model of the architecture which if repaired or restored should promote the recovery of a coherent sense of self and others in psychosis. Finally, we discuss the concrete implications of this for recovery-oriented treatment for psychosis as well as the need for further research on the commonalities of these approaches

Light microscopy with a differential staining technique for the characterization and discrimination of insects versus marine arthropods in processed animal proteins

The aim of this study was to evaluate the use of light microscopy with a differential staining technique for the discrimination of insect material from marine arthropods - classified as fishmeal. Specifically, three samples of single species insect material, Hermetia illucens (HI), Bombyx mori (BM) and Tenebrio molitor (TM) and two samples of marine arthropods, shrimp material and krill, have been analysed and compared after staining by two reagents to enhance fragment identification. Alizarin Red (AR) and Chlorazol black (CB), which react respectively with calcium salts and chitin, were tested for their potential efficacy in distinguishing between insect and marine materials. Results indicated that AR failed to stain HI, BM and TM materials. By contrast, the three insect species materials tested (HI, BM and TM) were stained by CB. When shrimp fragments and krill were considered, AR and CB stained marine materials reddish-pink and light blue to black, respectively. By combining these results it can be suggested that CB staining may efficiently be used to mark insect materials; AR does stain shrimp fragments but does not stain the tested insect material, indicating a possible approach for discriminating between insects and marine arthropods. However, since the present study has only been done on pure materials and on a small set of samples, possible implementation of this technique still needs to be confirmed in complex matrices such as compound feed

The tyrosine phosphatase CD148 is an essential positive regulator of platelet activation and thrombosis

Platelets play a fundamental role in hemostasis and thrombosis. They are also involved in pathologic conditions resulting from blocked blood vessels, including myocardial infarction and ischemic stroke. Platelet adhesion, activation, and aggregation at sites of vascular injury are regulated by a diverse repertoire of tyrosine kinase–linked and G protein–coupled receptors. Src family kinases (SFKs) play a central role in initiating and propagating signaling from several platelet surface receptors; however, the underlying mechanism of how SFK activity is regulated in platelets remains unclear. CD148 is the only receptor-like protein tyrosine phosphatase identified in platelets to date. In the present study, we show that mutant mice lacking CD148 exhibited a bleeding tendency and defective arterial thrombosis. Basal SFK activity was found to be markedly reduced in CD148-deficient platelets, resulting in a global hyporesponsiveness to agonists that signal through SFKs, including collagen and fibrinogen. G protein–coupled receptor responses to thrombin and other agonists were also marginally reduced. These results highlight CD148 as a global regulator of platelet activation and a novel antithrombotic drug targe

Pharmacokinetics and pharmacogenetics of SSRIs during pregnancy : An observational study

Background: An involvement of selective serotonin reuptake inhibitors (SSRIs) in increasing the risk of malformations, neonatal withdrawal syndrome, has been suggested recently. Here, we aimed to investigate the contribution of individual pharmacogenetics of SSRI on infants' outcome. We also estimated the umbilical/maternal plasma SSRI concentration ratio in the pregnant women still on SSRI therapy at the time of delivery. Methods: Thirty-four pregnant women, referred to our hospital from January 2011 to July 2015, who were given SSRIs in the third trimester, and related children, were considered. The umbilical/maternal plasma SSRI concentration ratio was estimated in 15 mothers still on SSRI therapy at the time of delivery. For patients with pharmacokinetic analyses, blood samples were collected for pharmacogenetic analyses. Results: Nineteen newborns presented clinical signs possibly related to drug toxicity. A high umbilical/maternal plasma ratio of SSRI was observed in 10 of the 15 evaluated newborns. Five mothers were intermediate metabolizers and 1 a poor metabolizer for the major CYP enzyme involved in pharmacokinetic pathway. Conclusions: Individualized psychopharmacologic treatment that takes into account the mother's exposure to SSRI concentrations and eventually her genetic background may become the standard of care to maximize drug benefit and minimize risks to the newborn

Autophagy as a new therapeutic target in Duchenne muscular dystrophy

A resolutive therapy for Duchene muscular dystrophy, a severe degenerative disease of the skeletal muscle, is still lacking. Because autophagy has been shown to be crucial in clearing dysfunctional organelles and in preventing tissue damage, we investigated its pathogenic role and its suitability as a target for new therapeutic interventions in Duchenne muscular dystrophy (DMD). Here we demonstrate that autophagy is severely impaired in muscles from patients affected by DMD and mdx mice, a model of the disease, with accumulation of damaged organelles. The defect in autophagy was accompanied by persistent activation via phosphorylation of Akt, mammalian target of rapamycin (mTOR) and of the autophagy-inhibiting pathways dependent on them, including the translation-initiation factor 4E-binding protein 1 and the ribosomal protein S6, and downregulation of the autophagy-inducing genes LC3, Atg12, Gabarapl1 and Bnip3. The defective autophagy was rescued in mdx mice by long-term exposure to a low-protein diet. The treatment led to normalisation of Akt and mTOR signalling; it also reduced significantly muscle inflammation, fibrosis and myofibre damage, leading to recovery of muscle function. This study highlights novel pathogenic aspects of DMD and suggests autophagy as a new effective therapeutic target. The treatment we propose can be safely applied and immediately tested for efficacy in humans

Clinical utility of serum HER2/neu in monitoring and prediction of progression-free survival in metastatic breast cancer patients treated with trastuzumab-based therapies

INTRODUCTION: The purpose of this retrospective study was to determine the clinical utility of serum HER2/neu in monitoring metastatic breast cancer patients undergoing trastuzumab-based therapy and to compare these results with those obtained using cancer antigen (CA) 15-3. We also sought to determine whether early changes in serum HER2/neu concentrations could be a predictor of progression-free survival. METHODS: Sera were obtained retrospectively from 103 women at four medical institutions. Patients eligible for participation were women with metastatic breast cancer who had HER2/neu tissue overexpression and were scheduled to be treated with trastuzumab with or without additional therapies as per the established practices of the treating physicians. A baseline serum sample for each patient was taken before trastuzumab-based therapy was started. Patients were subsequently monitored over 12 to 20 months and serum samples were taken at the time of clinical assessment and tested with Bayer's HER2/neu and CA15-3 assays. RESULTS: Concordance between clinical status in patients undergoing trastuzumab-based treatment and HER2/neu and CA15-3 used as single tests was 0.793 and 0.627, respectively, and increased to 0.829 when the tests were used in combination. Progression-free survival times did not differ significantly in patients with elevated baseline HER2/neu concentrations (≥ 15 ng/mL) and those with normal concentrations (<15 ng/mL). However, progression-free survival differed significantly (P = 0.043) according to whether the patient's HER2/neu concentration at 2 to 4 weeks after the start of therapy was >77% or ≤ 77% of her baseline concentration. The median progression-free survival times for these two groups were 217 and 587 days, respectively. A similar trend was observed for a subcohort of patients treated specifically with a combination of trastuzumab and taxane. CONCLUSION: These findings indicate that serum HER2/neu testing is clinically valuable in monitoring metastatic breast cancer patients undergoing trastuzumab-based treatment and provides additional value over the commonly used CA15-3 test. The percentage of baseline HER2/neu concentrations in the early weeks after the start of therapy may be an early predictor of progression-free-survival

Gene profiling of the erythro- and megakaryoblastic leukaemias induced by the Graffi murine retrovirus

<p>Abstract</p> <p>Background</p> <p>Acute erythro- and megakaryoblastic leukaemias are associated with very poor prognoses and the mechanism of blastic transformation is insufficiently elucidated. The murine Graffi leukaemia retrovirus induces erythro- and megakaryoblastic leukaemias when inoculated into NFS mice and represents a good model to study these leukaemias.</p> <p>Methods</p> <p>To expand our understanding of genes specific to these leukaemias, we compared gene expression profiles, measured by microarray and RT-PCR, of all leukaemia types induced by this virus.</p> <p>Results</p> <p>The transcriptome level changes, present between the different leukaemias, led to the identification of specific cancerous signatures. We reported numerous genes that may be potential oncogenes, may have a function related to erythropoiesis or megakaryopoiesis or have a poorly elucidated physiological role. The expression pattern of these genes has been further tested by RT-PCR in different samples, in a Friend erythroleukaemic model and in human leukaemic cell lines.</p> <p>We also screened the megakaryoblastic leukaemias for viral integrations and identified genes targeted by these integrations and potentially implicated in the onset of the disease.</p> <p>Conclusions</p> <p>Taken as a whole, the data obtained from this global gene profiling experiment have provided a detailed characterization of Graffi virus induced erythro- and megakaryoblastic leukaemias with many genes reported specific to the transcriptome of these leukaemias for the first time.</p