1,144 research outputs found
Evaluation of the Wellspring Model for Improving Nursing Home Quality
Examines how successfully the Wellspring model improved the quality of care for residents of eleven nonprofit nursing homes in Wisconsin. Looks at staff turnover, and evaluates the impact on facilities, employees, residents, and cost
Staatsbürgerschaftsregime im Wandel: oder: Die Gleichberechtigung wird zu Markte getragen Das Beispiel Kanada
The article presents a conceptualisation of 'citizenship regime' created out of a neo-institutionalist approach to political economy and then uses the concept to examine changes in the Canadian citizenship regime over time. The basic proposition is that if the postwar years were marked by regimelike discursive and practical coherence in a wide range of institutional connections between state and citizens, states' and citizens' responses to the economic and political conditions of the late 20th century are dismantling and reconstituting citizenship, so that the postwar regime exists no more
Amino acid substitutions within the heptad repeat domain 1 of murine coronavirus spike protein restrict viral antigen spread in the central nervous system.
Targeted recombination was carried out to select mouse hepatitis viruses (MHVs) in a defined genetic background, containing an MHV-JHM spike gene encoding either three heptad repeat 1 (HR1) substitutions (Q1067H, Q1094H, and L1114R) or L1114R alone. The recombinant virus, which expresses spike with the three substitutions, was nonfusogenic at neutral pH. Its replication was significantly inhibited by lysosomotropic agents, and it was highly neuroattenuated in vivo. In contrast, the recombinant expressing spike with L1114R alone mediated cell-to-cell fusion at neutral pH and replicated efficiently despite the presence of lysosomotropic agents; however, it still caused only subclinical morbidity and no mortality in animals. Thus, both recombinant viruses were highly attenuated and expressed viral antigen which was restricted to the olfactory bulbs and was markedly absent from other regions of the brains at 5 days postinfection. These data demonstrate that amino acid substitutions, in particular L1114R, within HR1 of the JHM spike reduced the ability of MHV to spread in the central nervous system. Furthermore, the requirements for low pH for fusion and viral entry are not prerequisites for the highly attenuated phenotype
The nsp1, nsp13, and M Proteins Contribute to the Hepatotropism of Murine Coronavirus JHM.WU
ABSTRACT Mouse hepatitis virus (MHV) isolates JHM.WU and JHM.SD promote severe central nervous system disease. However, while JHM.WU replicates robustly and induces hepatitis, JHM.SD fails to replicate or induce pathology in the liver. These two JHM variants encode homologous proteins with few polymorphisms, and little is known about which viral proteins(s) is responsible for the liver tropism of JHM.WU. We constructed reverse genetic systems for JHM.SD and JHM.WU and, utilizing these full-length cDNA clones, constructed chimeric viruses and mapped the virulence factors involved in liver tropism. Exchanging the spike proteins of the two viruses neither increased replication of JHM.SD in the liver nor attenuated JHM.WU. By further mapping, we found that polymorphisms in JHM.WU structural protein M and nonstructural replicase proteins nsp1 and nsp13 are essential for liver pathogenesis. M protein and nsp13, the helicase, of JHM.WU are required for efficient replication in vitro and in the liver in vivo . The JHM.SD nsp1 protein contains a K194R substitution of Lys194, a residue conserved among all other MHV strains. The K194R polymorphism has no effect on in vitro replication but influences hepatotropism, and introduction of R194K into JHM.SD promotes replication in the liver. Conversely, a K194R substitution in nsp1 of JHM.WU or A59, another hepatotropic strain, significantly attenuates replication of each strain in the liver and increases IFN-β expression in macrophages in culture. Our data indicate that both structural and nonstructural proteins contribute to MHV liver pathogenesis and support previous reports that nsp1 is a Betacoronavirus virulence factor. IMPORTANCE The Betacoronavirus genus includes human pathogens, some of which cause severe respiratory disease. The spread of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) into human populations demonstrates the zoonotic potential of emerging coronaviruses, and there are currently no vaccines or effective antivirals for human coronaviruses. Thus, it is important to understand the virus-host interaction that regulates coronavirus pathogenesis. Murine coronavirus infection of mice provides a useful model for the study of coronavirus-host interactions, including the determinants of tropism and virulence. We found that very small changes in coronavirus proteins can profoundly affect tropism and virulence. Furthermore, the hepatotropism of MHV-JHM depends not on the spike protein and viral entry but rather on a combination of the structural protein M and nonstructural replicase-associated proteins nsp1 and nsp13, which are conserved among betacoronaviruses. Understanding virulence determinants will aid in the design of vaccines and antiviral strategies
Response of the mantle to flat slab evolution: Insights from local splitting beneath Peru
The dynamics of flat subduction, particularly the interaction between a flat slab and the overriding plate, are poorly understood. Here we study the (seismically) anisotropic properties and deformational regime of the mantle directly above the Peruvian flat slab. We analyze shear wave splitting from 370 local S events at 49 stations across southern Peru. We find that the mantle above the flat slab appears to be anisotropic, with modest average delay times (~0.28?s) that are consistent with ~4% anisotropy in a ~30?km thick mantle layer. The most likely mechanism is the lattice-preferred orientation of olivine, which suggests that the observed splitting pattern preserves information about the mantle deformation. We observe a pronounced change in anisotropy along strike, with predominately trench-parallel fast directions in the north and more variable orientations in the south, which we attribute to the ongoing migration of the Nazca Ridge through the flat slab system
High-Alpha Research Vehicle (HARV) longitudinal controller: Design, analyses, and simulation resultss
This paper describes the design, analysis, and nonlinear simulation results (batch and piloted) for a longitudinal controller which is scheduled to be flight-tested on the High-Alpha Research Vehicle (HARV). The HARV is an F-18 airplane modified for and equipped with multi-axis thrust vectoring. The paper includes a description of the facilities, a detailed review of the feedback controller design, linear analysis results of the feedback controller, a description of the feed-forward controller design, nonlinear batch simulation results, and piloted simulation results. Batch simulation results include maximum pitch stick agility responses, angle of attack alpha captures, and alpha regulation for full lateral stick rolls at several alpha's. Piloted simulation results include task descriptions for several types of maneuvers, task guidelines, the corresponding Cooper-Harper ratings from three test pilots, and some pilot comments. The ratings show that desirable criteria are achieved for almost all of the piloted simulation tasks
- …