Method of Reducing Internal Stress in Materials

Methods are provided for adjusting and controlling the stress between layers of material in a multilayer structure. A first stress is configured in a region of stress on the substrate material. A second material is then deposited over the substrate. A second stress results between the substrate and the second material such that a net stress results where the net stress is a function of said first and second stresses. As such, the first stress can be configured to achieve a predetermined, desired net stress. For example, the first stress can be configured to cancel out the second stress such that the net stress is substantially zero

Effect of Soil Treatment on the Dynamic Response of Machine Foundations

Improvement of foundation soils using existing treatment techniques such as chemical, compaction and jet grouting can significantly enhance the general load bearing capacity of foundations. This paper describes the effect of soil treatment on the dynamic response of a rigid foundation subjected to steady-state, lCM-amplitude high-frequency vibrations, such as those encountered in machine foundation problems. Dynamic finite element analysis were performed to evaluate the effect of soil treatment as a function of treatment type and geometry. The treatment of foundation soil significantly reduced the amplitude of vibration of the foundation with the reduction being highly dependent on the type and geometry (i.e., width and depth) of the treated zone

PySCIPOpt: Mathematical Programming in Python with the SCIP Optimization Suite

This is the author accepted manuscript. The final version is available frpm Springer Verlag via the DOI in this record5th International Congress on Mathematical Software (ICMS 2016), 11-14 July 2016, Berlin, GermanySCIP is a solver for a wide variety of mathematical optimization problems. It is written in C and extendable due to its plug-in based design. However, dealing with all C specifics when extending SCIP can be detrimental to development and testing of new ideas. This paper attempts to provide a remedy by introducing PySCIPOpt, a Python interface to SCIP that enables users to write new SCIP code entirely in Python. We demonstrate how to intuitively model mixed-integer linear and quadratic optimization problems and moreover provide examples on how new Python plug-ins can be added to SCIP.German Federal Ministry of Education and Researc

Meta-analysis of effect of nintedanib on reducing FVC decline across interstitial lung diseases

INTRODUCTION: The effect of nintedanib on slowing the rate of decline in forced vital capacity (FVC) has been investigated in randomized placebo-controlled trials in subjects with idiopathic pulmonary fibrosis (IPF), other progressive fibrosing interstitial lung diseases (ILDs), and ILD associated with systemic sclerosis (SSc-ILD). We assessed the consistency of the effect of nintedanib on the rate of decline in FVC over 52 weeks across four placebo-controlled phase III trials. METHODS: We used data on FVC decline from the INPULSIS-1 and INPULSIS-2 trials in subjects with IPF, the INBUILD trial in subjects with progressing fibrosing ILDs other than IPF, and the SENSCIS trial in subjects with SSc-ILD. In each trial, the primary endpoint was the annual rate of decline in FVC (mL/year) assessed over 52 weeks. We performed fixed effect and random effects meta-analyses based on the relative treatment effect of nintedanib versus placebo on the rate of decline in FVC (mL/year) over 52 weeks. Heterogeneity of the relative treatment effect of nintedanib across populations was assessed using the I2 statistic, τ2 and corresponding p value from a Q test for heterogeneity. RESULTS: The combined analysis comprised 1257 subjects treated with nintedanib and 1042 subjects who received placebo. Nintedanib reduced the rate of decline in FVC (mL/year) over 52 weeks by 51.0% (95% CI 39.1, 63.0) compared with placebo. The relative effect (95% CI) was the same using the fixed effect and random effects models. There was no evidence of heterogeneity in the relative treatment effect of nintedanib across the populations studied (I2 = 0%, τ2 = 0, p = 0.93). CONCLUSIONS: A meta-analysis of data from four placebo-controlled trials demonstrated that nintedanib approximately halved the rate of decline in FVC over 52 weeks across subjects with different forms of pulmonary fibrosis, with no evidence of heterogeneity in its relative treatment effect across patient populations

Mutation analysis of HIF prolyl hydroxylases (PHD/EGLN) in individuals with features of phaeochromocytoma and renal cell carcinoma susceptibility

Germline mutations in the von Hippel–Lindau disease (VHL) and succinate dehydrogenase subunit B (SDHB) genes can cause inherited phaeochromocytoma and/or renal cell carcinoma(RCC). Dysregulation of the hypoxia-inducible factor (HIF) transcription factors has been linked to VHL and SDHB-related RCC; both HIF dysregulation and disordered function of a prolyl hydroxylase domain isoform 3 (PHD3/EGLN3)-related pathway of neuronal apoptosis have been linked to the development of phaeochromocytoma. The 2-oxoglutarate-dependent prolyl hydroxylase enzymes PHD1 (EGLN2), PHD2 (EGLN1) and PHD3 (EGLN3) have a key role in regulating the stability of HIF-a subunits (and hence expression of the HIF-a transcription factors). A germline PHD2 mutation has been reported in association with congenital erythrocytosis and recurrent extra-adrenal phaeochromocytoma. We undertook mutation analysis of PHD1, PHD2 and PHD3 in two cohorts of patients with features of inherited phaeochromocytoma (nZ82) and inherited RCC (nZ64) and no evidence of germline mutations in known susceptibility genes. No confirmed pathogenic mutations were detected suggesting that mutations in these genes are not a frequent cause of inherited phaeochromocytoma or RCC

Renal Autotransplant and Celiac Artery Bypass for Aneurysmal Degeneration Related to Neurofibromatosis Type 1

We present a case of an 18-year-old female with neurofibromatosis type 1 who presented with abdominal pain and weight loss secondary to chronic mesenteric ischemia due to celiac axis occlusion and was subsequently found to have multiple visceral artery aneurysms. Of clinical significance, 2 aneurysms of the right renal artery were noted at the hilum, with the larger one having a diameter of 2.4 cm. After initial endovascular treatment with stenting of a concurrent pancreaticoduodenal artery pseudoaneurysm, staged aorto-hepatic bypass and right nephrectomy with renal autotransplantation after back table resection of the aneurysmal segments were successfully completed

Printing in three dimensions with graphene

Responsive graphene oxide sheets form non‐covalent networks with optimum rheological properties for 3D printing. These networks have shear thinning behavior and sufficiently high elastic shear modulus (G′) to build self‐supporting 3D structures by direct write assembly. Drying and thermal reduction leads to ultra‐light graphene‐only structures with restored conductivity and elastomeric behavior

Exploration of a potent PI3 kinase/mTOR inhibitor as a novel anti-fibrotic agent in IPF

© 2016 BMJ Publishing Group Ltd & British Thoracic Society.Rationale Idiopathic pulmonary fibrosis (IPF) is the most rapidly progressive and fatal of all fibrotic conditions with no curative therapies. Common pathomechanisms between IPF and cancer are increasingly recognised, including dysfunctional pan-PI3 kinase (PI3K) signalling as a driver of aberrant proliferative responses. GSK2126458 is a novel, potent, PI3K/mammalian target of rapamycin (mTOR) inhibitor which has recently completed phase I trials in the oncology setting. Our aim was to establish a scientific and dosing framework for PI3K inhibition with this agent in IPF at a clinically developable dose. Methods We explored evidence for pathway signalling in IPF lung tissue and examined the potency of GSK2126458 in fibroblast functional assays and precision-cut IPF lung tissue. We further explored the potential of IPF patient-derived bronchoalveolar lavage (BAL) cells to serve as pharmacodynamic biosensors to monitor GSK2126458 target engagement within the lung. Results We provide evidence for PI3K pathway activation in fibrotic foci, the cardinal lesions in IPF. GSK2126458 inhibited PI3K signalling and functional responses in IPF-derived lung fibroblasts, inhibiting Akt phosphorylation in IPF lung tissue and BAL derived cells with comparable potency. Integration of these data with GSK2126458 pharmacokinetic data from clinical trials in cancer enabled modelling of an optimal dosing regimen for patients with IPF. Conclusions Our data define PI3K as a promising therapeutic target in IPF and provide a scientific and dosing framework for progressing GSK2126458 to clinical testing in this disease setting. A proof-ofmechanism trial of this agent is currently underway. Trial registration number NCT01725139, pre-clinical

Synthesis of some new spirothiazolidinone and spiroazetidinone derivatives incorporated with quinazoline

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Perturbations of a Universe Filled with Dust and Radiation

A first-order perturbation approach to $k=0$ Friedmann cosmologies filled with dust and radiation is developed. Adopting the coordinate gauge comoving with the perturbed matter, and neglecting the vorticity of the radiation, a pair of coupled equations is obtained for the trace $h$ of the metric perturbations and for the velocity potential $v$. A power series solution with upwards cutoff exists such that the leading terms for large values of the dimensionless time $\xi$ agree with the relatively growing terms of the dust solution of Sachs and Wolfe.Comment: 9 pp, typeset in late