Solid-State Microwave Electronics

Contains reports on six research projects.Joint Services Electronics Programs (U. S. Army, U. S. Navy, and U. S. Air Force) under Contract DAAB07-71-C-0300California Institute of Technology Contract 952568National Institutes of Health (Grant RR00317) from the Biotechnology Resources Branch, Division of Research Resource

Morbillivirus Glycoprotein Expression Induces ER Stress, Alters Ca2+ Homeostasis and Results in the Release of Vasostatin

Although the pathology of Morbillivirus in the central nervous system (CNS) is well described, the molecular basis of neurodegenerative events still remains poorly understood. As a model to explore Morbillivirus-mediated CNS dysfunctions, we used canine distemper virus (CDV) that we inoculated into two different cell systems: a monkey cell line (Vero) and rat primary hippocampal neurons. Importantly, the recombinant CDV used in these studies not only efficiently infects both cell types but recapitulates the uncommon, non-cytolytic cell-to-cell spread mediated by virulent CDVs in brain of dogs. Here, we demonstrated that both CDV surface glycoproteins (F and H) markedly accumulated in the endoplasmic reticulum (ER). This accumulation triggered an ER stress, characterized by increased expression of the ER resident chaperon calnexin and the proapoptotic transcription factor CHOP/GADD 153. The expression of calreticulin (CRT), another ER resident chaperon critically involved in the response to misfolded proteins and in Ca2+ homeostasis, was also upregulated. Transient expression of recombinant CDV F and H surface glycoproteins in Vero cells and primary hippocampal neurons further confirmed a correlation between their accumulation in the ER, CRT upregulation, ER stress and disruption of ER Ca2+ homeostasis. Furthermore, CDV infection induced CRT fragmentation with re-localisation of a CRT amino-terminal fragment, also known as vasostatin, on the surface of infected and neighbouring non-infected cells. Altogether, these results suggest that ER stress, CRT fragmentation and re-localization on the cell surface may contribute to cytotoxic effects and ensuing cell dysfunctions triggered by Morbillivirus, a mechanism that might potentially be relevant for other neurotropic viruses

Intercomparison of O3 profiles observed by SCIAMACHY and ground based microwave instruments

Ozone profiles retrieved from limb scattering measurements of the SCIAMACHY instrument based on the satellite ENVISAT are compared to ground-based low altitude resolution remote sensors. All profiles are retrieved using optimal estimation. Following the work of Rodgers and Connor (2003) the retrievals of the ground-based instruments are simulated using the SCIAMACHY retrieval. The SCIAMACHY results and the results of the ground-based microwave radiometer in Bremen and Ny A° lesund agree within the expected covariance of the intercomparison

Change in tau phosphorylation associated with neurodegeneration in the ME7 model of prion disease

Hyperphosphorylation of the microtubule-associated protein tau is a significant determinant in AD (Alzheimer's disease), where it is associated with disrupted axonal transport and probably causes synaptic dysfunction. Although less well studied, hyperphosphorylation has been observed in prion disease. We have investigated the expression of hyperphosphorylated tau in the hippocampus of mice infected with the ME7 prion agent. In ME7-infected animals, there is a selective loss of CA1 synapse, first discernable at 13 weeks of disease. There is a potential that dysfunctional axonal transport contributes to this synaptopathy. Thus investigating hyperphosphorylated tau that is dysfunctional in AD could illuminate whether and how they are significant in prion disease. We observed no differences in the levels of phosphorylated tau (using MC1, PHF-1 and CP13 antibodies) in detergent-soluble and detergent-insoluble fractions extracted from ME7- and NBH- (normal brain homogenate) treated animals across disease. In contrast, we observed an increase in phospho-tau staining for several epitopes using immunohistochemistry in ME7-infected hippocampal sections. Although the changes were not of the magnitude seen in AD tissue, clear differences for several phospho-tau species were seen in the CA1 and CA3 of ME7-treated animals (pSer(199-202)>pSer(214)>PHF-1 antibody). Temporally, these changes were restricted to animals at 20 weeks and none of the disease-related staining was associated with the axons or dendrites that hold CA1 synapses. These findings suggest that phosphorylation of tau at the epitopes examined does not underpin the early synaptic dysfunction. These data suggest that the changes in tau phosphorylation recorded here and observed by others relate to end-stage prion pathology when early dysfunctions have progressed to overt neuronal loss

Cardiovascular risk management in patients with coronary heart disease in primary care: variation across countries and practices. An observational study based on quality indicators

Contains fulltext : 110491.pdf (publisher's version ) (Open Access)ABSTRACT: BACKGROUND: Primary care has an important role in cardiovascular risk management (CVRM) and a minimum size of scale of primary care practices may be needed for efficient delivery of CVRM . We examined CVRM in patients with coronary heart disease (CHD) in primary care and explored the impact of practice size. METHODS: In an observational study in 8 countries we sampled CHD patients in primary care practices and collected data from electronic patient records. Practice samples were stratified according to practice size and urbanisation; patients were selected using coded diagnoses when available. CVRM was measured on the basis of internationally validated quality indicators. In the analyses practice size was defined in terms of number of patients registered of visiting the practice. We performed multilevel regression analyses controlling for patient age and sex. RESULTS: We included 181 practices (63% of the number targeted). Two countries included a convenience sample of practices. Data from 2960 CHD patients were available. Some countries used methods supplemental to coded diagnoses or other inclusion methods introducing potential inclusion bias. We found substantial variation on all CVRM indicators across practices and countries. We computed aggregated practice scores as percentage of patients with a positive outcome. Rates of risk factor recording varied from 55% for physical activity as the mean practice score across all practices (sd 32%) to 94% (sd 10%) for blood pressure. Rates for reaching treatment targets for systolic blood pressure, diastolic blood pressure and LDL cholesterol were 46% (sd 21%), 86% (sd 12%) and 48% (sd 22%) respectively. Rates for providing recommended cholesterol lowering and antiplatelet drugs were around 80%, and 70% received influenza vaccination. Practice size was not associated to indicator scores with one exception: in Slovenia larger practices performed better. Variation was more related to differences between practices than between countries. CONCLUSIONS: CVRM measured by quality indicators showed wide variation within and between countries and possibly leaves room for improvement in all countries involved. Few associations of performance scores with practice size were found