University of Alabama at Birmingham

About: University of Alabama at Birmingham is a education organization based out in Birmingham, Alabama, United States. It is known for research contribution in the topics: Population & Poison control. The organization has 38523 authors who have published 86775 publications receiving 3930642 citations. The organization is also known as: UAB & The University of Alabama at Birmingham.

Invited review: cGMP-dependent protein kinase signaling mechanisms in smooth muscle: from the regulation of tone to gene expression.

Abstract: cGMP is a second messenger that produces its effects by interacting with intracellular receptor proteins. In smooth muscle cells, one of the major receptors for cGMP is the serine/threonine protein kinase, cGMP-dependent protein kinase (PKG). PKG has been shown to catalyze the phosphorylation of a number of physiologically relevant proteins whose function it is to regulate the contractile activity of the smooth muscle cell. These include proteins that regulate free intracellular calcium levels, the cytoskeleton, and the phosphorylation state of the regulatory light chain of smooth muscle myosin. Other studies have shown that vascular smooth muscle cells (VSMCs) that are cultured in vitro may cease to express PKG and will, coincidentally, acquire a noncontractile, synthetic phenotype. The restoration of PKG expression to the synthetic phenotype VSMC results in the cells acquiring a more contractile phenotype. These more recent studies suggest that PKG controls VSMC gene expression that, in turn, regulates phenotypic modulation of the cells. Therefore, the regulation of PKG gene expression appears to be linked to phenotypic modulation of VSMC. Because several vascular disorders are related to the accumulation of synthetic, fibroproliferative VSMC in the vessel wall, it is likely that changes in the activity of the nitric oxide/cGMP/PKG pathway is involved the development of these diseases.

Management of thyroid nodules detected at US: Society of Radiologists in Ultrasound consensus conference statement

Abstract: The Society of Radiologists in Ultrasound convened a panel of specialists from a variety of medical disciplines to come to a consensus on the management of thyroid nodules identified with thyroid ultrasonography (US), with particular focus on which nodules should be subjected to US-guided fine needle aspiration and which thyroid nodules need not be subjected to fine-needle aspiration. The panel met in Washington, DC, October 26-27, 2004, and created this consensus statement. The recommendations in this consensus statement, which are based on analysis of the current literature and common practice strategies, are thought to represent a reasonable approach to thyroid nodular disease.

Ceramic Matrix Composites

Abstract: Ceramic materials in general have a very attractive package of properties: high strength and high stiffness at very high temperatures, chemical inertness, low density, and so on. This attractive package is marred by one deadly flaw, namely, an utter lack of toughness. They are prone to catastrophic failures in the presence of flaws (surface or internal). They are extremely susceptible to thermal shock and are easily damaged during fabrication and/or service. It is therefore understandable that an overriding consideration in ceramic matrix composites (CMCs) is to toughen the ceramics by incorporating fibers in them and thus exploit the attractive high-temperature strength and environmental resistance of ceramic materials without risking a catastrophic failure. It is worth pointing out at the very outset that there are certain basic differences between CMCs and other composites. The general philosophy in nonceramic matrix composites is to have the fiber bear a greater proportion of the applied load. This load partitioning depends on the ratio of fiber and matrix elastic moduli, Ef/Em. In nonceramic matrix composites, this ratio can be very high, while in CMCs, it is rather low and can be as low as unity; think of alumina fiber reinforced alumina matrix composite. Another distinctive point regarding CMCs is that because of limited matrix ductility and generally high fabrication temperature, thermal mismatch between components has a very important bearing on CMC performance. The problem of chemical compatibility between components in CMCs has ramifications similar to those in, say, MMCs. We first describe some of the processing techniques for CMCs, followed by a description of some salient characteristics of CMCs regarding interface and mechanical properties and, in particular, the various possible toughness mechanisms, and finally a description of some applications of CMCs.

Avelumab, an anti-PD-L1 antibody, in patients with locally advanced or metastatic breast cancer: a phase 1b JAVELIN Solid Tumor study.

Abstract: Agents targeting programmed death receptor 1 (PD-1) or its ligand (PD-L1) have shown antitumor activity in the treatment of metastatic breast cancer (MBC). The aim of this study was to assess the activity of avelumab, a PD-L1 inhibitor, in patients with MBC. In a phase 1 trial (JAVELIN Solid Tumor; NCT01772004), patients with MBC refractory to or progressing after standard-of-care therapy received avelumab intravenously 10 mg/kg every 2 weeks. Tumors were assessed every 6 weeks by RECIST v1.1. Adverse events (AEs) were graded by NCI-CTCAE v4.0. Membrane PD-L1 expression was assessed by immunohistochemistry (Dako PD-L1 IHC 73-10 pharmDx). A total of 168 patients with MBC, including 58 patients with triple-negative breast cancer (TNBC), were treated with avelumab for 2–50 weeks and followed for 6–15 months. Patients were heavily pretreated with a median of three prior therapies for metastatic or locally advanced disease. Grade ≥ 3 treatment-related AEs occurred in 13.7% of patients, including two treatment-related deaths. The confirmed objective response rate (ORR) was 3.0% overall (one complete response and four partial responses) and 5.2% in patients with TNBC. A trend toward a higher ORR was seen in patients with PD-L1+ versus PD-L1− tumor-associated immune cells in the overall population (16.7% vs. 1.6%) and in the TNBC subgroup (22.2% vs. 2.6%). Avelumab showed an acceptable safety profile and clinical activity in a subset of patients with MBC. PD-L1 expression in tumor-associated immune cells may be associated with a higher probability of clinical response to avelumab in MBC.