Global convergence of a primal-dual interior-point method for nonlinear programming

Many recent convergence results obtained for primal-dual interior-point methods for nonlinear programming, use assumptions of the boundedness of generated iterates. In this paper we replace such assumptions by new assumptions on the NLP problem, develop a modification of a primal-dual interior-point method implemented in software package LOQO and analyze convergence of the new method from any initial guess

Relationships among Bone Metabolic Markers, Body Fat Composition and Carotid Intima–Media Thickness in Premenopausal Obese Women

Osteocalcin (OC) is inversely related to body fat distribution and fasting glucose levels. We sought to observe the effect of OC on fat distribution and subclinical atherosclerosis as measured by carotid intima-media thickness (CIMT) in premenopausal obese women. In this prospective observational study, totally, 73 premenopausal obese women (aged 17-55 years) and 53 healthy women (aged 20-50 years) with normal weight were included as controls. Anthropometric measurements, total fat and fat ratio, insulin, fasting blood glucose, and OC levels were estimated. Ultrasonography was used to assess fat distribution, and fat thickness was measured in 4 regions. Subcutaneous fat (SCF), visceral fat (VF), and preperitoneal fat (PPF) thicknesses were considerably higher in obese subjects (p<0.01) than healthy controls, while OC levels were significantly lower. No correlation was observed between OC levels and SCF, VF, or PPF. In a multiple regression analysis, OC was significantly positively associated with SCF (p=0.04, Beta=0.284). No associations were observed between OC levels and VF, PPF, or CIMT. A significant association was observed between parathyroid hormone (PTH) and VF (p=0.021, Beta=0.284), and vitamin D levels were inversely associated with VF (p=0.002, r=−0.366). OC levels were lower in premenopausal obese women than normal-weight healthy controls, but OC exhibited no correlation with VF or PPF, and only a weak positive association with SCF. Additionally, VF was positively correlated with PTH and inversely correlated with vitamin D. These results suggest that OC may be an early indicator of lipid accumulation in te subcutaneous area and development of atherosclerosis

Not an innocent bystander: case series of tranexamic acid induced cortical necrosis

Acute cortical necrosis accounts for &lt;2% of all acute kidney injuries. Pregnancy complications, viperine snake bites, haemolytic uremic syndrome, shock, and severe pancreatitis are all linked to it. There are relatively few case reports of acute cortical necrosis secondary to tranexamic acid, which is utilised in the treatment of acute bleeding because of its antifibrinolytic actions. Acute cortical necrosis is very infrequently brought on by medicines. Here, we present a group of three instances, each of which experienced the onset of oligo-anuria soon after receiving tranexamic acid. Cortical necrosis was demonstrated by contrast computed tomography (CT) and renal biopsy. While the third patient had patchy cortical necrosis and had partially recovered renal functions, the other two patients both had total acute cortical necrosis and are still reliant on dialysis. This case series demonstrates the need for clinicians to be cautious while using tranexamic acid and to be aware of the possibility of abrupt renal cortical necrosis following its administration

MyD88 and TRIF mediate the cyclic adenosine monophosphate (cAMP) induced corticotropin releasing hormone (CRH) expression in JEG3 choriocarcinoma cell line

Background: Classically protein kinase A (PKA) and transcription factor activator protein 1 (AP-1) mediate the cyclic AMP (cAMP) induced-corticotrophin releasing hormone (CRH) expression in the placenta. However enteric Gram (-) bacterial cell wall component lipopolysaccharide (LPS) may also induce-CRH expression via Toll like receptor (TLR)4 and its adaptor molecule Myd88. Here we investigated the role of MyD88, TRIF and IRAK2 on cAMP-induced CRH promoter activation in JEG3 cells in the absence of LPS/TLR4 stimulation. Methods: JEG3 cells were transfected with CRH-luciferase and Beta-galactosidase expression vectors and either empty or dominant-negative (DN)-MyD88, DN-TRIF or DN-IRAK2 vectors using Fugene6 (Roche). cAMP-induced CRH promoter activation was examined by using a luminometer and luciferase assay. Calorimetric Beta-galactosidase assays were performed to correct for transfection efficiency. Luciferase expression vectors of cAMP-downstream molecules, CRE and AP-1, were used to further examine the signaling cascades. Results: cAMP stimulation induced AP-1 and CRE promoter expression and led to dose-dependent CRH promoter activation in JEG3 cells. Inhibition of MyD88 signaling blocked cAMP-induced CRE and CRH promoter activation. Inhibition of TRIF signaling blocked cAMP-induced CRH but not CRE expression, while inhibition of IRAK2 did not have an effect on cAMP-induced CRH expression. Conclusion: MyD88 and TRIF exert direct regulatory effect on cAMP-induced CRH promoter activation in JEG3 cells in the absence of infection. MyD88 most likely interacts with molecules upstream of IRAK2 to regulate cAMP-induced CRH expression

Impact of Early Coronary Revascularization on Long-Term Outcomes in Patients With Myocardial Ischemia on Dobutamine Stress Echocardiography

The role of early coronary revascularization in the management of stable coronary artery disease remains controversial. The aim of this study was to evaluate the impact of early coronary revascularization on long-term outcomes (>10 years) after an ischemic dobutamine stress echocardiography (DSE) in patients with known or suspected coronary artery disease. Patients without stress-induced ischemia on DSE and those who underwent late coronary revascularization (>90 days after DSE) were excluded. The final study cohort consisted of 905 patients. A DSE with a peak wall motion score index of 1.1 to 1.7 was considered mild

Thymoquinone Induces Telomere Shortening, DNA Damage and Apoptosis in Human Glioblastoma Cells

Background: A major concern of cancer chemotherapy is the side effects caused by the non-specific targeting of both normal and cancerous cells by therapeutic drugs. Much emphasis has been placed on discovering new compounds that target tumour cells more efficiently and selectively with minimal toxic effects on normal cells. Methodology/Principal Findings: The cytotoxic effect of thymoquinone, a component derived from the plant Nigella sativa, was tested on human glioblastoma and normal cells. Our findings demonstrated that glioblastoma cells were more sensitive to thymoquinone-induced antiproliferative effects. Thymoquinone induced DNA damage, cell cycle arrest and apoptosis in the glioblastoma cells. It was also observed that thymoquinone facilitated telomere attrition by inhibiting the activity of telomerase. In addition to these, we investigated the role of DNA-PKcs on thymoquinone mediated changes in telomere length. Telomeres in glioblastoma cells with DNA-PKcs were more sensitive to thymoquinone mediated effects as compared to those cells deficient in DNA-PKcs. Conclusions/Significance: Our results indicate that thymoquinone induces DNA damage, telomere attrition by inhibiting telomerase and cell death in glioblastoma cells. Telomere shortening was found to be dependent on the status of DNA-PKcs. Collectively, these data suggest that thymoquinone could be useful as a potential chemotherapeutic agent in th

Telomere-Mediated Chromosomal Instability Triggers TLR4 Induced Inflammation and Death in Mice

BACKGROUND: Telomeres are essential to maintain chromosomal stability. Cells derived from mice lacking telomerase RNA component (mTERC-/- mice) display elevated telomere-mediated chromosome instability. Age-dependent telomere shortening and associated chromosome instability reduce the capacity to respond to cellular stress occurring during inflammation and cancer. Inflammation is one of the important risk factors in cancer progression. Controlled innate immune responses mediated by Toll-like receptors (TLR) are required for host defense against infection. Our aim was to understand the role of chromosome/genome instability in the initiation and maintenance of inflammation. METHODOLOGY/PRINCIPAL FINDINGS: We examined the function of TLR4 in telomerase deficient mTERC-/- mice harbouring chromosome instability which did not develop any overt immunological disorder in pathogen-free condition or any form of cancers at this stage. Chromosome instability was measured in metaphase spreads prepared from wildtype (mTERC+/+), mTERC+/- and mTERC-/- mouse splenocytes. Peritoneal and/or bone marrow-derived macrophages were used to examine the responses of TLR4 by their ability to produce inflammatory mediators TNFalpha and IL6. Our results demonstrate that TLR4 is highly up-regulated in the immune cells derived from telomerase-null (mTERC-/-) mice and lipopolysaccharide, a natural ligand for TLR4 stabilises NF-kappaB binding to its promoter by down-regulating ATF-3 in mTERC-/- macrophages. CONCLUSIONS/SIGNIFICANCE: Our findings implied that background chromosome instability in the cellular level stabilises the action of TLR4-induced NF-kappaB action and sensitises cells to produce excess pro-inflammatory mediators. Chromosome/genomic instability data raises optimism for controlling inflammation by non-toxic TLR antagonists among high-risk groups

Development of a Selective Wet-Chemical Etchant for 3D Structuring of Silicon via Nonlinear Laser Lithography

Recently-demonstrated high-quality three-dimensional (3D) subsurface laser processing inside crystalline silicon (c-Si) wafers opens a door to a wide range of novel applications in multidisciplinary research areas. Using this technique, a novel maskless micro-pillars with precise control on the surface reflection and coverage are successfully fabricated by etching the laser processed region of c-Si wafer. To achieve this, a particular selective wet chemical etching is developed to follow subsurface laser processing of c-Si to reveal the desired 3D structures with smooth surfaces. Here, we report the development of a novel chromium-free chemical etching recipe based on copper nitrate, which yields substantially smooth surfaces at high etch rate and selectivity on the both laser-processed Si surface and subsurface, i.e., without significant etching of the unmodified Si. Our results show that the etch rate and surface morphology are interrelated and strongly influenced by the composition of the adopted etching solution. After an extensive compositional study performed at room temperature, we identify an etchant with a selectivity of over 1600 times for laser-modified Si with respect to unmodified Si. We also support our findings using density functional theory calculations of HF and Cu adsorption energies, indicating significant diversity on the c-Si and laser-modified surfaces