Blade loss transient dynamics analysis, volume 1. Task 1: Survey and perspective

An analytical technique was developed to predict the behavior of a rotor system subjected to sudden unbalance. The technique is implemented in the Turbine Engine Transient Rotor Analysis (TETRA) computer program using the component element method. The analysis was particularly aimed toward blade-loss phenomena in gas turbine engines. A dual-rotor, casing, and pylon structure can be modeled by the computer program. Blade tip rubs, Coriolis forces, and mechanical clearances are included. The analytical system was verified by modeling and simulating actual test conditions for a rig test as well as a full-engine, blade-release demonstration

Blade loss transient dynamics analysis, volume 2. Task 2: Theoretical and analytical development. Task 3: Experimental verification

The component element method was used to develop a transient dynamic analysis computer program which is essentially based on modal synthesis combined with a central, finite difference, numerical integration scheme. The methodology leads to a modular or building-block technique that is amenable to computer programming. To verify the analytical method, turbine engine transient response analysis (TETRA), was applied to two blade-out test vehicles that had been previously instrumented and tested. Comparison of the time dependent test data with those predicted by TETRA led to recommendations for refinement or extension of the analytical method to improve its accuracy and overcome its shortcomings. The development of working equations, their discretization, numerical solution scheme, the modular concept of engine modelling, the program logical structure and some illustrated results are discussed. The blade-loss test vehicles (rig full engine), the type of measured data, and the engine structural model are described

CD40 cross-linking induces migration of renal tumor cell through nuclear factor of activated T cells (NFAT) activation

CD40 crosslinking plays an important role in regulating cell migration, adhesion and proliferation in renal cell carcinoma (RCC). CD40/CD40L interaction on RCC cells activates different intracellular pathways but the molecular mechanisms leading to cell scattering are not yet clearly defined. Aim of our study was to investigate the main intracellular pathways activated by CD40 ligation and their specific involvement in RCC cell migration. CD40 ligation increased the phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun NH (2)-terminal kinase (JNK) and p38 MAPK. Furthermore, CD40 crosslinking activated different transcriptional factors on RCC cell lines: AP-1, NFkB and some members of the Nuclear Factor of Activated T cells (NFAT) family. Interestingly, the specific inhibition of NFAT factors by cyclosporine A, completely blocked RCC cell motility induced by CD40 ligation. In tumor tissue, we observed a higher expression of NFAT factors and in particular an increased activation and nuclear migration of NFATc4 on RCC tumor tissues belonging to patients that developed metastases when compared to those who did not. Moreover, CD40-CD40L interaction induced a cytoskeleton reorganization and increased the expression of integrin β1 on RCC cell lines, and this effect was reversed by cyclosporine A and NFAT inhibition. These data suggest that CD40 ligation induces the activation of different intracellular signaling pathways, in particular the NFATs factors, that could represent a potential therapeutic target in the setting of patients with metastatic RCC

Correction: Appetite disinhibition rather than hunger explains genetic effects on adult BMI trajectory

Correction to: International Journal of Obesity https://doi.org/10.1038/s41366-020-00735-9 The original version of this article unfortunately contained a mistake in the ESM. The original article has been corrected

Appetite disinhibition rather than hunger explains genetic effects on adult BMI trajectory

BACKGROUND/OBJECTIVES: The mediating role of eating behaviors in genetic susceptibility to weight gain during mid-adult life is not fully understood. This longitudinal study aims to help us understand contributions of genetic susceptibility and appetite to weight gain. SUBJECTS/METHODS: We followed the body-mass index (BMI) trajectories of 2464 adults from 45 to 65 years of age by measuring weight and height on four occasions at 5-year intervals. Genetic risk of obesity (gene risk score: GRS) was ascertained, comprising 92 BMI-associated single-nucleotide polymorphisms and split at a median (=high and low risk). At the baseline, the Eating Inventory was used to assess appetite-related traits of 'disinhibition', indicative of opportunistic eating or overeating and 'hunger' which is susceptibility to/ability to cope with the sensation of hunger. Roles of the GRS and two appetite-related scores for BMI trajectories were examined using a mixed model adjusted for the cohort effect and sex. RESULTS: Disinhibition was associated with higher BMI (β = 2.96; 95% CI: 2.66-3.25 kg/m2), and accounted for 34% of the genetically-linked BMI difference at age 45. Hunger was also associated with higher BMI (β = 1.20; 0.82-1.59 kg/m2) during mid-life and slightly steeper weight gain, but did not attenuate the effect of disinhibition. CONCLUSIONS: Appetite disinhibition is most likely to be a defining characteristic of genetic susceptibility to obesity. High levels of appetite disinhibition, rather than hunger, may underlie genetic vulnerability to obesogenic environments in two-thirds of the population of European ancestry

Clinical characteristics and outcome of dogs with presumed primary renal lymphoma

Objectives: To characterise the presentation, clinicopathologic data and outcome of 29 dogs with presumed primary renal lymphoma. Materials and methods: Retrospective analysis of medical records of dogs with suspected primary renal lymphoma from 11 institutions. Results: All dogs were substage b, and lethargy and gastrointestinal signs were common presenting complaints, as were azotaemia (n=25; 86%) and erythrocytosis (n=15; 51%) on biochemical testing. Ultrasonography typically revealed bilateral renal lesions (n=23; 79%), renomegaly (n=22; 76%) and abdominal lymphadenopathy (n=14; 48%). Chemotherapy was the only treatment in 23 dogs, of which 11 responded, all considered partial responses. For all dogs the median progression-free survival and median overall survival times were 10 days (range: 1 to 126) and 12 days (range: 1 to 212), respectively, and for dogs that responded to chemotherapy 41 days (range: 10 to 126) and 47 days (range: 10 to 212), respectively. Clinical significance: Primary renal lymphoma in dogs appears to be associated with a poor prognosis and short-lived response to chemotherapy

A phase I dose-escalation study to evaluate safety and tolerability of sorafenib combined with sirolimus in patients with advanced solid cancer

Contains fulltext : 87630.pdf (publisher's version ) (Closed access)BACKGROUND: The combination of sorafenib (vascular endothelial growth factor receptor 2 inhibitor) and sirolimus (mammalian target of rapamycin inhibitor) might work synergistically. METHODS: A phase I dose-escalation study with sorafenib twice a day (b.i.d.) and sirolimus once daily (q.d.) was performed to determine the recommended dose of the combination in patients with solid tumours. Secondary objectives were to determine the safety profile and maximum tolerated dose (MTD), and to evaluate the pharmacokinetics (PK) of the combination. RESULTS: Dose-limiting toxicities were transaminitis and cutaneous toxicity. The most frequently reported adverse events were elevated transaminases, hypophosphatemia, fatigue, anorexia, diarrhoea, nausea, rash and palmar-plantar erythrodysaesthesia. Sirolimus did not change the PK of sorafenib; in contrast, sorafenib reduced the AUC(0-96) and C(max) of sirolimus. No objective responses were observed; eight patients showed stable disease for a median of 16.3 weeks (range 8-24). The MTD of the combination was sorafenib 200 mg b.i.d. with sirolimus 1 mg q.d. CONCLUSION: The combination of sorafenib and sirolimus showed enhanced toxicity, which could not be explained by the PK of both drugs. The relative low doses at the MTD, in combination with the PK results, do not warrant further development of this combination

Autistic Spectrum Disorders in Velo-cardio Facial Syndrome (22q11.2 Deletion)

The extent to which the phenotype of children comorbid for velocardiofacial syndrome (VCFS) and autism spectrum disorders (ASD) differs from that of VCFS-only has not been studied. The sample consisted of 41 children (20 females) with VCFS, ranging in age from 6.5 years to 15.8 years. Eight children with VCFS met formal DSM-IV diagnostic criteria for autism based upon the ADI-R. These eight plus an additional nine participants met diagnostic criteria for an autistic spectrum disorder (VCFS + ASD). Ninety-four percent of the children with VCFS + ASD had a co-occurring psychiatric disorder while 60% of children with VCFS had a psychiatric disorder. Children with VCFS + ASD had larger right amygdala volumes. All other neuroanatomic regions of interest were statistically similar between the two groups