Complex conductivity in strongly fluctuating layered superconductors

The time-dependent Ginzburg-Landau approach is used to calculate the complex fluctuation conductivity in layered type-II superconductor under magnetic field. Layered structure of the superconductor is accounted for by means of the Lawrence-Doniach model, while the nonlinear interaction term in dynamics is treated within self-consistent Gaussian approximation. In high-$T_{c}$ materials, large portion of the $H-T$ diagram belongs to vortex liquid phase. The expressions summing contributions of all the Landau levels are presented in explicit form which are applicable essentially to the whole phase and are compared to experimental data on high-$T_{c}$ superconductor YBa$_{2}$Cu$_{3}$O$_{7-\delta }$. Above the crossover to the "normal phase", our results agree with the previously obtained.Comment: 8 pages, 1 figur

Clinically applicable GABA receptor positive allosteric modulators promote ß-cell replication.

A key goal of diabetes research is to develop treatments to safely promote human ß-cell replication. It has recently become appreciated that activation of γ-aminobutyric acid receptors (GABA-Rs) on ß-cells can promote their survival and replication. A number of positive allosteric modulators (PAMs) that enhance GABA's actions on neuronal GABAA-Rs are in clinical use. Repurposing these GABAA-R PAMs to help treat diabetes is theoretically appealing because of their safety and potential to enhance the ability of GABA, secreted from ß-cells, or exogenously administered, to promote ß-cell replication and survival. Here, we show that clinically applicable GABAA-R PAMs can increase significantly INS-1 ß-cell replication, which is enhanced by exogenous GABA application. Furthermore, a GABAA-R PAM promoted human islet cell replication in vitro. This effect was abrogated by a GABAA-R antagonist. The combination of a PAM and low levels of exogenous GABA further increased human islet cell replication. These findings suggest that PAMs may potentiate the actions of GABA secreted by islet ß-cells on GABAA-Rs and provide a new class of drugs for diabetes treatment. Finally, our findings may explain a past clinical observation of a GABAA-R PAM reducing HbA1c levels in diabetic patients

Age and Sex Differences in Duration of Pre-Hospital Delay, Hospital Treatment Practices, and Short-Term Outcomes in Patients Hospitalized with an Acute Coronary Syndrome/Acute Myocardial Infarction: A Dissertation

BackgroundThe prompt seeking of medical care after the onset of symptoms suggestive of acute coronary syndromes (ACS)/acute myocardial infarction (AMI) is associated with the receipt of coronary reperfusion therapy, and effective cardiac medications in patients with an ACS/AMI and is crucial to reducing mortality and the risk of serious clinical complications in these patients. Despite declines in important hospital complications and short-term death rates in patients hospitalized with an ACS/AMI, several patient groups remain at increased risk for these adverse outcomes, including women and the elderly. However, recent trends in age and sex differences in extent of pre-hospital delay, hospital management practices, and short-term outcomes associated with ACS/AMI remain unexplored. The objectives of this study were to examine the overall magnitude, and changing trends therein, of age and sex differences in duration of pre-hospital delay (1986-2005), hospital management practices (1999-2007), and short-terms outcomes (1975-2005) in patients hospitalized with ACS/AMI. MethodsData from 13,663 residents of the Worcester, MA, metropolitan area hospitalized at all greater Worcester medical centers for AMI 15 biennial periods between 1975 and 2005 (Worcester Heart Attack Study), and from 50,096 patients hospitalized with an ACS in 106 medical centers in 14 countries participating in the Global Registry of Acute Coronary Events (GRACE) between 2000 and 2007 were used for this investigation. Results In comparison with men years, patients in other age-sex strata exhibited significantly longer pre-hospital delay, with the exception of women \u3c 65 years; had a significantly lower odds of receiving aspirin, angiotensin converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs), beta blockers, statins, and undergoing coronary artery bypass graft surgery (CABG) surgery or percutaneous coronary intervention (PCI), and were significantly more likely to develop atrial fibrillation, cardiogenic shock, heart failure, and to die during hospitalization and in the first 30 days after admission. There was a significant interaction between age and sex in relation to the use of several medications and the development of several of these outcomes; in patients Conclusions Our results suggest that the elderly were more likely to experience longer prehospital delay, were less likely to be treated with evidence-based treatments during hospitalization for acute coronary syndrome, and were more likely to develop adverse outcomes compared to younger persons. Younger women were less likely to be treated with effective treatments and were more likely to develop adverse outcomes compared with younger men while there was no sex difference in these outcomes. Interventions targeted at older patients, in particular, are needed to encourage these high-risk patients to seek medical care promptly to maximize the benefits of currently available treatment modalities. More targeted treatment approaches during hospitalization for ACS/AMI for younger women and older patients are needed to improve their hospital prognosis

Optimisation of transmission bandwidth for indoor cellular OWC system using a dynamic handover decision-making algorithm

In this paper, we propose a novel cellular optical wireless communications (COWC) system with four diffused cells. A dynamic handover scheme is proposed to make the link more flexible by the way of adaptive channel allocation in different environments. The simulation results show that the proposed algorithm offers almost five times of the maximum dynamic transmission bandwidth and energy efficiency compared to the worst scenarios when all base stations (BS)s are active

Homotaurine, a safe blood-brain barrier permeable GABAA-R-specific agonist, ameliorates disease in mouse models of multiple sclerosis.

There is a need for treatments that can safely promote regulatory lymphocyte responses. T cells express GABA receptors (GABAA-Rs) and GABA administration can inhibit Th1-mediated processes such as type 1 diabetes and rheumatoid arthritis in mouse models. Whether GABAA-R agonists can also inhibit Th17-driven processes such as experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis (MS), is an open question. GABA does not pass through the blood-brain barrier (BBB) making it ill-suited to inhibit the spreading of autoreactivity within the CNS. Homotaurine is a BBB-permeable amino acid that antagonizes amyloid fibril formation and was found to be safe but ineffective in long-term Alzheimer's disease clinical trials. Homotaurine also acts as GABAA-R agonist with better pharmacokinetics than that of GABA. Working with both monophasic and relapsing-remitting mouse models of EAE, we show that oral administration of homotaurine can (1) enhance CD8+CD122+PD-1+ and CD4+Foxp3+ Treg, but not Breg, responses, (2) inhibit autoreactive Th17 and Th1 responses, and (3) effectively ameliorate ongoing disease. These observations demonstrate the potential of BBB-permeable GABAA-R agonists as a new class of treatment to enhance CD8+ and CD4+ Treg responses and limit Th17 and Th1-medaited inflammation in the CNS

Combined therapy with GABA and proinsulin/alum acts synergistically to restore long-term normoglycemia by modulating T-cell autoimmunity and promoting β-cell replication in newly diabetic NOD mice.

Antigen-based therapies (ABTs) fail to restore normoglycemia in newly diabetic NOD mice, perhaps because too few β-cells remain by the time that ABT-induced regulatory responses arise and spread. We hypothesized that combining a fast-acting anti-inflammatory agent with an ABT could limit pathogenic responses while ABT-induced regulatory responses arose and spread. γ-Aminobutyric acid (GABA) administration can inhibit inflammation, enhance regulatory T-cell (Treg) responses, and promote β-cell replication in mice. We examined the effect of combining a prototypic ABT, proinsulin/alum, with GABA treatment in newly diabetic NOD mice. Proinsulin/alum monotherapy failed to correct hyperglycemia, while GABA monotherapy restored normoglycemia for a short period. Combined treatment restored normoglycemia in the long term with apparent permanent remission in some mice. Proinsulin/alum monotherapy induced interleukin (IL)-4- and IL-10-secreting T-cell responses that spread to other β-cell autoantigens. GABA monotherapy induced moderate IL-10 (but not IL-4) responses to β-cell autoantigens. Combined treatment synergistically reduced spontaneous type 1 T-helper cell responses to autoantigens, ABT-induced IL-4 and humoral responses, and insulitis, but enhanced IL-10 and Treg responses and promoted β-cell replication in the islets. Thus, combining ABT with GABA can inhibit pathogenic T-cell responses, induce Treg responses, promote β-cell replication, and effectively restore normoglycemia in newly diabetic NOD mice. Since these treatments appear safe for humans, they hold promise for type 1 diabetes intervention

Hydrodynamics of Diatom Chains and Semiflexible Fibres

Diatoms are non-motile, unicellular phytoplankton that have the ability to form colonies in the form of chains. Depending upon the species of diatoms and the linking structures that hold the cells together, these chains can be quite stiff or very flexible. Recently, the bending rigidities of some species of diatom chains have been quantified. In an effort to understand the role of flexibility in nutrient uptake and aggregate formation, we begin by developing a three-dimensional model of the coupled elastic-hydrodynamic system of a diatom chain moving in an incompressible fluid. We find that simple beam theory does a good job of describing diatom chain deformation in a parabolic flow when its ends are tethered, but does not tell the whole story of chain deformations when they are subjected to compressive stresses in shear. While motivated by the fluid dynamics of diatom chains, our computational model of semiflexible fibres illustrates features that apply widely to other systems. The use of an adaptive immersed boundary framework allows us to capture complicated buckling and recovery dynamics of long, semiflexible fibres in shear

Drosophila RecQ4 Is Directly Involved in Both DNA Replication and the Response to UV Damage in S2 Cells.

The RecQ4 protein shows homology to both the S.cerevisiae DNA replication protein Sld2 and the DNA repair related RecQ helicases. Experimental data also suggest replication and repair functions for RecQ4, but the precise details of its involvement remain to be clarified.Here we show that depletion of DmRecQ4 by dsRNA interference in S2 cells causes defects consistent with a replication function for the protein. The cells show reduced proliferation associated with an S phase block, reduced BrdU incorporation, and an increase in cells with a subG1 DNA content. At the molecular level we observe reduced chromatin association of DNA polymerase-alpha and PCNA. We also observe increased chromatin association of phosphorylated H2AvD--consistent with the presence of DNA damage and increased apoptosis.Analysis of DmRecQ4 repair function suggests a direct role in NER, as the protein shows rapid but transient nuclear localisation after UV treatment. Re-localisation is not observed after etoposide or H₂O₂ treatment, indicating that the involvement of DmRecQ4 in repair is likely to be pathway specific.Deletion analysis of DmRecQ4 suggests that the SLD2 domain was essential, but not sufficient, for replication function. In addition a DmRecQ4 N-terminal deletion could efficiently re-localise on UV treatment, suggesting that the determinants for this response are contained in the C terminus of the protein. Finally several deletions show differential rescue of dsRNA generated replication and proliferation phenotypes. These will be useful for a molecular analysis of the specific role of DmRecQ4 in different cellular pathways