The Synthesis and Antiviral Properties of 8- Amino-3- [(2 hydroxyethoxy)methyl]-1,2,4-triazolo- [4,3-a ]pyrazine

The preparation of 8-amino-3-[(2-hydroxyethoxy)methyl]-1,2,4- triazolo[4,3-a]pyrazine (IV) as an analogue of 9-[(2-hydroxyethoxy) methyl]guanine and 9-(S)-(2,3-dihydroxypropyl)adenine is described from the reaction of 3-chloro-2-hydrazinopyrazine (V) and ethyl 2-(2-acetoxyethoxy)thioacetimidate (IXg) followed by treatment with ammonia. Compound IV was found to lack antiviral properties towards herpes simplex I and II, vaccinia virus, vesicular stomatitis virus, measles, reovirus type 1, parainfluenza virus type 3, Sindbis virus, Coxsackie type B4 virus, and poliovirus type

Stationäre Kinder- und Jugendpsychiatrie: Umsetzung des neuen Kindes- und Erwachsenenschutzrechts

Mit dem neuen Kindes- und Erwachsenenschutzrecht wollte der Gesetzgeber die Behandlung einer psychischen Störung von urteilsunfähigen Erwachsenen vereinheitlichen. Die Behandlung von psychischen Störungen von Kindern und Jugendlichen wurde allerdings nicht so klar geregelt

Bacterial contamination of anesthesia machines’ internal breathing-circuit-systems

Background: Bacterial contamination of anesthesia breathing machines and their potential hazard for pulmonary infection and cross-infection among anesthetized patients has been an infection control issue since the 1950s. Disposable equipment and bacterial filters have been introduced to minimize this risk. However, the machines’ internal breathing-circuit-system has been considered to be free of micro-organisms without providing adequate data supporting this view. The aim of the study was to investigate if any micro-organisms can be yielded from used internal machines’ breathing-circuit-system. Based on such results objective reprocessing intervals could be defined

Plectin 1f scaffolding at the sarcolemma of dystrophic (mdx) muscle fibers through multiple interactions with β-dystroglycan

In skeletal muscle, the cytolinker plectin is prominently expressed at Z-disks and the sarcolemma. Alternative splicing of plectin transcripts gives rise to more than eight protein isoforms differing only in small N-terminal sequences (5–180 residues), four of which (plectins 1, 1b, 1d, and 1f) are found at substantial levels in muscle tissue. Using plectin isoform–specific antibodies and isoform expression constructs, we show the differential regulation of plectin isoforms during myotube differentiation and their localization to different compartments of muscle fibers, identifying plectins 1 and 1f as sarcolemma-associated isoforms, whereas plectin 1d localizes exclusively to Z-disks. Coimmunoprecipitation and in vitro binding assays using recombinant protein fragments revealed the direct binding of plectin to dystrophin (utrophin) and β-dystroglycan, the key components of the dystrophin–glycoprotein complex. We propose a model in which plectin acts as a universal mediator of desmin intermediate filament anchorage at the sarcolemma and Z-disks. It also explains the plectin phenotype observed in dystrophic skeletal muscle of mdx mice and Duchenne muscular dystrophy patients

Sex and the Single Gametophyte: Revising the Homosporous Vascular Plant Life Cycle in Light of Contemporary Research

Homosporous vascular plants are typically depicted as extreme inbreeders, with bisexual gametophytes that produce strictly homozygous sporophytes. This view is promulgated in textbook life cycles despite ample evidence that natural populations of most species regularly outcross. We review research on a variety of mechanisms, including genetic load, asynchronous production of eggs and sperm, and pheromonal control of gamete production, that actively promote heterozygosity in ferns and lycophytes. Evolution of the land plants cannot be reconstructed without accurate depictions of the unique life cycle that has helped make ferns the second most diverse lineage of vascular plants on Earth. With revised illustrations and definitions, we provide scientists, educators, and students with a contemporary understanding of fern and lycophyte reproduction, revealing them as evolutionarily dynamic and exploiting a wide range of mating systems

Results of UBV Photoelectric Observations of the Early-Type Eclipsing Binary System XZ Cep

Results of the three-colour photoelectric observation of the close binary system XZ Cep, obtained at the Abastumani Astrophysical observatory, are presented.Comment: 23 pages, 3 figures, 1 tebl

Understanding the UK hospital supply chain in an era of patient choice

Author Posting © Westburn Publishers Ltd, 2011. This is a post-peer-review, pre-copy-edit version of an article which has been published in its definitive form in the Journal of Marketing Management, and has been posted by permission of Westburn Publishers Ltd for personal use, not for redistribution. The article was published in Journal of Marketing Management, 27(3-4), 401 - 423, doi:10.1080/0267257X.2011.547084 http://dx.doi.org/10.1080/0267257X.2011.547084The purpose of this paper is to investigate the UK hospital supply chain in light of recent government policy reform where patients will have, inter alia, greater choice of hospital for elective surgery. Subsequently, the hospital system should become far more competitive with supply chains having to react to these changes as patient demand becomes less predictable. Using a qualitative case study methodology, hospital managers are interviewed on a range of issues. Views on the development of the hospital supply chain in different phases are derived, and are used to develop a map of the current hospital chain. The findings show hospital managers anticipating some significant changes to the hospital supply chain and its workings as Patient Choice expands. The research also maps the various aspects of the hospital supply chain as it moves through different operational phases and highlights underlying challenges and complexities. The hospital supply chain, as discussed and mapped in this research, is original work given there are no examples in the literature that provide holistic representations of hospital activity. At the end, specific recommendations are provided that will be of interest to service to managers, researchers, and policymakers

Development of a New Tacaribe Arenavirus Infection Model and Its Use to Explore Antiviral Activity of a Novel Aristeromycin Analog

Background A growing number of arenaviruses can cause a devastating viral hemorrhagic fever (VHF) syndrome. They pose a public health threat as emerging viruses and because of their potential use as bioterror agents. All of the highly pathogenic New World arenaviruses (NWA) phylogenetically segregate into clade B and require maximum biosafety containment facilities for their study. Tacaribe virus (TCRV) is a nonpathogenic member of clade B that is closely related to the VHF arenaviruses at the amino acid level. Despite this relatedness, TCRV lacks the ability to antagonize the host interferon (IFN) response, which likely contributes to its inability to cause disease in animals other than newborn mice. Methodology/Principal Findings Here we describe a new mouse model based on TCRV challenge of AG129 IFN-α/β and -γ receptor-deficient mice. Titration of the virus by intraperitoneal (i.p.) challenge of AG129 mice resulted in an LD50 of ∼100 fifty percent cell culture infectious doses. Virus replication was evident in the serum, liver, lung, spleen, and brain 4–8 days after inoculation. MY-24, an aristeromycin derivative active against TCRV in cell culture at 0.9 µM, administered i.p. once daily for 7 days, offered highly significant (P\u3c0.001) protection against mortality in the AG129 mouse TCRV infection model, without appreciably reducing viral burden. In contrast, in a hamster model of arenaviral hemorrhagic fever based on challenge with clade A Pichinde arenavirus, MY-24 did not offer significant protection against mortality. Conclusions/Significance MY-24 is believed to act as an inhibitor of S-adenosyl-L-homocysteine hydrolase, but our findings suggest that it may ameliorate disease by blunting the effects of the host response that play a role in disease pathogenesis. The new AG129 mouse TCRV infection model provides a safe and cost-effective means to conduct early-stage pre-clinical evaluations of candidate antiviral therapies that target clade B arenaviruses