Energy transfer in multi-collision environments; an experimental test of theory: LiH (10;2) in H2(0;0)

We report separate experimental and theoretical studies that follow the equilibration of highly excited LiH (v=10;J=2) in H2 at 680K. Experiments that follow the time evolution of state-tostate population transfer in multi-collision conditions were carried out by Shen and co-workers at Xinjiang University and East China Institute of Science and Technology with µs resolution. At the same time, theoretical computations on the relaxation of this gas mixture were undertaken by McCaffery and co-workers at Sussex University. Rapid, near-resonant, vibration-vibration energy exchange is a marked feature of the initial relaxation process. However, at later stages of ensemble evolution, slower vibration-rotation transfer processes form the dominant relaxation mechanism. The physics of the decay process are complex and, as demonstrated experimentally here, a single exponential expression is unlikely to capture the form of this decay with any accuracy. When these separate studies were complete, the evolution of modal temperatures from the Sussex calculations were compared with experimental measurements of these same quantities from Shanghai and Urumqui. The two sets of data were found to be identical to within experimental and computational error. This constitutes an important experimental validation of the theoretical/computational model developed by the Sussex group and a significant experimental advance by the group of Shen et.al

Towards modifying the genetic predisposition for glaucoma: An overview of the contribution and interaction of genetic and environmental factors

Glaucoma, the leading cause of irreversible blindness worldwide, is a complex human disease, with both genetic and environmental determinants. The availability of large-scale, population-based cohorts and biobanks, combining genotyping and detailed phenotyping, has greatly accelerated research into the aetiology of glaucoma in recent years. Hypothesis-free genome-wide association studies have furthered our understanding of the complex genetic architecture underpinning the disease, while epidemiological studies have provided advances in the identification and characterisation of environmental risk factors. It is increasingly recognised that the combined effects of genetic and environmental factors may confer a disease risk that reflects a departure from the simple additive effect of the two. These gene-environment interactions have been implicated in a host of complex human diseases, including glaucoma, and have several important diagnostic and therapeutic implications for future clinical practice. Importantly, the ability to modify the risk associated with a particular genetic makeup promises to lead to personalised recommendations for glaucoma prevention, as well as novel treatment approaches in years to come. Here we provide an overview of genetic and environmental risk factors for glaucoma, as well as reviewing the evidence and discussing the implications of gene-environment interactions for the disease

The Linkage of Innate to Adaptive Immunity via Maturing Dendritic Cells In Vivo Requires CD40 Ligation in Addition to Antigen Presentation and CD80/86 Costimulation

Dendritic cell (DC) maturation is an innate response that leads to adaptive immunity to coadministered proteins. To begin to identify underlying mechanisms in intact lymphoid tissues, we studied α-galactosylceramide. This glycolipid activates innate Vα14+ natural killer T cell (NKT) lymphocytes, which drive DC maturation and T cell responses to ovalbumin antigen. Hours after giving glycolipid i.v., tumor necrosis factor (TNF)–α and interferon (IFN)-γ were released primarily by DCs. These cytokines induced rapid surface remodeling of DCs, including increased CD80/86 costimulatory molecules. Surprisingly, DCs from CD40−/− and CD40L−/− mice did not elicit CD4+ and CD8+ T cell immunity, even though the DCs exhibited presented ovalbumin on major histocompatibility complex class I and II products and expressed high levels of CD80/86. Likewise, an injection of TNF-α up-regulated CD80/86 on DCs, but CD40 was required for immunity. CD40 was needed for DC interleukin (IL)-12 production, but IL-12p40−/− mice generated normal ovalbumin-specific responses. Therefore, the link between innate and adaptive immunity via splenic DCs and innate NKT cells has several components under distinct controls: antigen presentation in the steady state, increases in costimulatory molecules dependent on inflammatory cytokines, and a distinct CD40/CD40L signal that functions together with antigen presentation (“signal one”) and costimulation (“signal two”) to generate functioning CD4+ T helper cell 1 and CD8+ cytolytic T lymphocytes

Effects of anti-triadin antibody on Ca2+ release from sarcoplasmic reticulum

AbstractThe monoclonal antibody, mAb GE 4.90, raised against triadin, a 95 kDa protein of sarcoplasmic reticulum (SR), inhibits the slow phase of Ca2+ release from SR following depolarization of the T-tubule moiety of the triad. The antibody has virtually no effect on the fast phase of depolarization-induced Ca2+ release nor on caffeine-induced Ca2+ release. Since the slow phase of depolarization-induced Ca2+ release is also inhibited by dihydropyridines (DHP), these results suggest that triadin may be involved in the functional coupling between the DHP receptor and the SR Ca2+ channel

Systemwide Clinical Ultrasound Program Development: An Expert Consensus Model.

Clinical ultrasound (CUS) is integral to the practice of an increasing number of medical specialties. Guidelines are needed to ensure effective CUS utilization across health systems. Such guidelines should address all aspects of CUS within a hospital or health system. These include leadership, training, competency, credentialing, quality assurance and improvement, documentation, archiving, workflow, equipment, and infrastructure issues relating to communication and information technology. To meet this need, a group of CUS subject matter experts, who have been involved in institution- and/or systemwide clinical ultrasound (SWCUS) program development convened. The purpose of this paper was to create a model for SWCUS development and implementation

Influence of steps on the tilting and adsorption dynamics of ordered Pn films on vicinal Ag(111) surfaces

Here we present a structural study of pentacene (Pn) thin films on vicinal Ag(111) surfaces by He atom diffraction measurements and density functional theory (DFT) calculations supplemented with van der Waals (vdW) interactions. Our He atom diffraction results suggest initial adsorption at the step edges evidenced by initial slow specular reflection intensity decay rate as a function of Pn deposition time. In parallel with the experimental findings, our DFT+vdW calculations predict the step edges as the most stable adsorption site on the surface. An isolated molecule adsorbs as tilted on the step edge with a binding energy of 1.4 eV. In addition, a complete monolayer (ML) with pentacenes flat on the terraces and tilted only at the step edges is found to be more stable than one with all lying flat or tilted molecules, which in turn influences multilayers. Hence our results suggest that step edges can trap Pn molecules and act as nucleation sites for the growth of ordered thin films with a crystal structure similar to that of bulk Pn.Comment: 4 pages, 4 figures, 1 tabl

Gastrin Induces Nuclear Export and Proteasomal Degradation of Menin in Enteric Glial Cells

Background & aims: The multiple endocrine neoplasia, type 1 (MEN1) locus encodes the nuclear protein and tumor suppressor menin. MEN1 mutations frequently cause neuroendocrine tumors such as gastrinomas, characterized by their predominant duodenal location and local metastasis at time of diagnosis. Diffuse gastrin cell hyperplasia precedes the appearance of MEN1 gastrinomas, which develop within submucosal Brunner\u27s glands. We investigated how menin regulates expression of the gastrin gene and induces generation of submucosal gastrin-expressing cell hyperplasia. Methods: Primary enteric glial cultures were generated from the VillinCre:Men1FL/FL:Sst-/- mice or C57BL/6 mice (controls), with or without inhibition of gastric acid by omeprazole. Primary enteric glial cells from C57BL/6 mice were incubated with gastrin and separated into nuclear and cytoplasmic fractions. Cells were incubated with forskolin and H89 to activate or inhibit protein kinase A (a family of enzymes whose activity depends on cellular levels of cyclic AMP). Gastrin was measured in blood, tissue, and cell cultures using an ELISA. Immunoprecipitation with menin or ubiquitin was used to demonstrate post-translational modification of menin. Primary glial cells were incubated with leptomycin b and MG132 to block nuclear export and proteasome activity, respectively. We obtained human duodenal, lymph node, and pancreatic gastrinoma samples, collected from patients who underwent surgery from 1996 through 2007 in the United States or the United Kingdom. Results: Enteric glial cells that stained positive for glial fibrillary acidic protein (GFAP+) expressed gastrin de novo through a mechanism that required PKA. Gastrin-induced nuclear export of menin via cholecystokinin B receptor (CCKBR)-mediated activation of PKA. Once exported from the nucleus, menin was ubiquitinated and degraded by the proteasome. GFAP and other markers of enteric glial cells (eg, p75 and S100B), colocalized with gastrin in human duodenal gastrinomas. Conclusions: MEN1-associated gastrinomas, which develop in the submucosa, might arise from enteric glial cells through hormone-dependent PKA signaling. This pathway disrupts nuclear menin function, leading to hypergastrinemia and associated sequelae

Reversible Cardiomyopathies

Cardiomyopathy includes a diverse and heterogeneous group of disorders affecting the myocardium and eventually leading to cardiac dysfunction. Cardiomyopathy is the leading cause of hospitalization in patients older than 65 years of age and it is an important cause for enormous healthcare expenditure. All reversible cardiomyopathies can be associated with cardiomegaly, systolic heart failure, structural changes, and an increase in mortality, but when the offensive agent is identified and stopped, these conditions tend to stop their progression and reverse. The prognosis of reversible nonischemic cardiomyopathies is better than ischemic or other nonreversible cardiomyopathies. Additionally, it is important to diagnose etiology of HF early and precisely to determine prognosis and effective treatment. Most patients with reversible cardiomyopathy present with clinical picture similar to that of systolic heart failure. Here in this book chapter, we discuss about different types of reversible cardiomyopathy including pathogenesis, clinical picture, diagnosis and treatment

Staphylococcus aureus Protein A Disrupts Immunity Mediated by Long-Lived Plasma Cells

Infection with Staphylococcus aureus does not induce long-lived protective immunity for reasons that are not completely understood. Human and murine vaccine studies support a role for antibodies in protecting against recurring infections, but S. aureus modulates the B cell response through expression of Staphylococcal Protein A (SpA), a surface protein that drives polyclonal B cell expansion and induces cell death in the absence of co-stimulation. In this murine study, we show that SpA altered the fate of plasmablasts and plasma cells (PCs) by enhancing the short-lived extrafollicular response and reducing the pool of bone marrow (BM)-resident long-lived PCs (LLPCs). The absence of LLPCs was associated with a rapid decline in antigen-specific, class-switched antibody. In contrast, when previously inoculated mice were challenged with isogenic Δspa S. aureus, cells proliferated in the BM survival niches and sustained long-term antibody titers. The effects of SpA on PC fate were limited to the secondary response, as antibody levels and the formation of B cell memory occurred normally during the primary response in mice inoculated with either WT or Δspa S. aureus. Thus, failure to establish long-term protective antibody titers against S. aureus was not a consequence of diminished formation of B cell memory; instead, SpA reduced the proliferative capacity of PCs that entered the BM, diminishing the number of cells in the long-lived pool