A collaborative community approach to homeless care

Myxoma virus is a leporipoxvirus of New World rabbits (Sylvilagus sp.) that induces a rapidly lethal infection known as myxomatosis in the European rabbit (Oryctolagus cuniculus). Like all poxviruses, myxoma virus encodes a plethora of proteins to circumvent or inhibit a variety of host antiviral immune mechanisms. M-T7, the most abundantly secreted protein of myxoma virus-infected cells, was originally identified as an interferon-gamma receptor homolog (Upton, Mossman, and McFadden, Science 258, 1369-1372, 1992). Here, we demonstrate that M-T7 is dispensable for virus replication in cultured cells but is a critical virulence factor for virus pathogenesis in European rabbits. Disruption of both copies of the M-T7 gene in myxoma virus was achieved by the deletion of 372 bp of M-T7 coding sequences, replacement with a selectable marker, p7.5Ecogpt, and selection of a recombinant virus (vMyxlac-T7gpt) resistant to mycophenolic acid. vMyxlac-T7gpt expressed no detectable M-T7 protein and infected cells supernatants were devoid of any detectable interferon-gamma binding activities. Immunohistochemical staining with anti-beta-galactosidase and anti-CD43 antibodies demonstrated that in vMyxlac-T7gpt-infected rabbits the loss of M-T7 not only caused a dramatic reduction in disease symptoms and viral dissemination to secondary sites, but also dramatically influenced host leukocyte behavior. Notably, primary lesions in wild-type virus infections were generally underlayed by large masses of inflammatory cells that did not effectively migrate into the dermal sites of viral replication, whereas in vMyxlac-T7gpt infections this apparent block to leukocyte influx was relieved. A second major phenotypic distinction noted for the M-T7 knockout virus was the extensive activation of lymphocytes in secondary immune organs, particularly the spleen and lymph nodes, by Day 4 of the infection. This is in stark contrast to infection by wild-type myxoma virus, which results in relatively little, if any, cellular activation of germinal centers of spleen and lymph node by Day 4. We conclude that M-T7 functions early in infection to (1) retard inflammatory cell migration into infected tissues and (2) disrupt the communication between sentinel immune cells at the site of primary virus infection in the subdermis and lymphocytes in the secondary lymphoid organs, thereby disabling the host from mounting an effective cellular immune response. To summarize, in addition to neutralizing host interferon-gamma at infected sites, we propose that M-T7 protein also modifies leukocyte traffic in the vicinity of virus lesions, thus effectively severing the link between antigen presenting cells of the infected tissue and the effector lymphocytes of the peripheral immune organs.     

Antioxidant effects of propofol in human hepatic microsomes: concentration effects and clinical relevance

Parvoviruses of rodents are endowed with oncosuppressive properties. In particular, parvoviral infections protect host animals from spontaneous and chemical- or virus-induced tumour initiation in laboratory animals. The present study was undertaken to substantiate the capacity of parvovirus H-1 to inhibit therapeutically the growth of established tumours originating from human carcinoma cells implanted in recipient mice. To this end, quickly growing s.c. carcinomas were established by injection of human cervical carcinoma cells (HeLa) into immunodeficient (SCID) mice. Tumour-bearing mice subsequently were inoculated with H-1 at various multiplicities of infection. H-1 virus infection led to regression of tumours, the onset and efficiency of which were dose-dependent.     

The rapidly deployable radio network

The rapidly deployable radio network (RDRN) is an architecture and experimental system to develop and evaluate hardware and software components suitable for implementing mobile, rapidly deployable, and adaptive wireless communications systems. The driving application for the RDRN is the need to quickly establish a communications infrastructure following a natural disaster, during a law enforcement activity, or rapid deployment of military force. The RDRN project incorporates digitally controlled antenna beams, programmable radios, adaptive protocols at the link layer, and mobile node management. This paper describes the architecture for the RDRN and a prototype system built to evaluate key system components     

Large-signal dynamic behavior of distributed-feedback lasersincluding lateral effects

The large-signal behavior of DFB lasers is analyzed, including lateral as well as longitudinal variations in carrier density, photon density, and refractive index. The effective index method and other approximations are used to reduce the complex three-dimensional problem to one dimension. The coupled wave and carrier rate equations are then solved in a self-consistent manner. Lateral spatial carrier hole burning and lateral diffusion are found to affect the relaxation oscillation frequency and damping rate of DFB lasers, depending on their detailed structure. The effective time-averaged linewidth enhancement factor is also affected. In symmetric AR-coated λ/4 phase-shifted lasers the side mode suppression ratio can be deteriorated significantly by lateral spatial hole burning when kL is large     

Text revision: Detection and correction of errors.

Examined independent measures of detection and correction of text errors in 2 experiments. In Session 1, Ss tried to detect spelling, grammatical, and meaning errors in a text; in Session 2, Ss tried to correct the same errors in workbooklike exercises. Errors were classified according to whether they were detected in Session 1 and whether they were corrected in Session 2. With the exception of spelling errors, knowledge of how to correct an error was necessary but not sufficient for detection. For spelling error detection, knowledge of how to correct may be both necessary and sufficient. In Exp 2, detection of meaning errors was manipulated by having Ss answer comprehension questions, surface questions, or no questions. Both question groups detected nearly twice as many meaning errors as the no-question group. Questioning had no effects on detection of spelling or grammatical errors. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

DRYING OF POROUS MATERIALS AT LOW MOISTURE CONTENT

Drying experiments were conducted using packed beds of glass beads with initial moisture content near or slightly above the irreducible moisture content. The objective was to validate the vapor phase diffusion coefficient determined in earlier experiments and to quantify the effect of temperature gradient on vapor phase diffusion in the presence of irreducible saturation. The resulls indicate that for isothermal drying the enhancement factor, β, which is the ratio of the diffusion coefficient in the packed bed to that in free space, is slightly less than unity. This is consistent with previous results. However, the results for non-isothermal drying show little effect of temperature gradient for temperature gradients either assisting the concentration gradient or opposing the concentration gradient. This is contrary to the traditional thinking about enhanced vapor diffusion originally proposed by Philip and deVries (1957).     

Statistical heterospectroscopy, an approach to the integrated analysis of NMR and UPLC-MS data sets: application in metabonomic toxicology studies

Statistical heterospectroscopy (SHY) is a new statistical paradigm for the coanalysis of multispectroscopic data sets acquired on multiple samples. This method operates through the analysis of the intrinsic covariance between signal intensities in the same and related molecules measured by different techniques across cohorts of samples. The potential of SHY is illustrated using both 600-MHz 1H NMR and UPLC-TOFMS data obtained from control rat urine samples (n = 54) and from a corresponding hydrazine-treated group (n = 58). We show that direct cross-correlation of spectral parameters, viz. chemical shifts from NMR and m/z data from MS, is readily achievable for a variety of metabolites, which leads to improved efficiency of molecular biomarker identification. In addition to structure, higher level biological information can be obtained on metabolic pathway activity and connectivities by examination of different levels of the NMR to MS correlation and anticorrelation matrixes. The SHY approach is of general applicability to complex mixture analysis, if two or more independent spectroscopic data sets are available for any sample cohort. Biological applications of SHY as demonstrated here show promise as a new systems biology tool for biomarker recovery.     

Dihydroimidazophenanthridinium (DIP)-based DNA binding agents with tuneable structures and biological activity

We have synthesised a library of dihydroimidazophenanthridinium cations (DIPs) with large structural diversity (1-29) using a "one-pot" approach. The DNA binding constants of DIPs range from 2x10(4) to 1.3x10(5) M(-1), and the free energies for binding range from -5.9 to -6.40 kcal mol(-1). Viscosity measurements demonstrated that the binding of the compounds caused DNA lengthening, thus signifying binding by intercalation. The cytotoxicities of the compounds were determined by tetrazolium dye-based microtitration assays and showed a large range of values (0.09-11.7 microM). Preliminary molecular modelling studies of the DNA-DIP interactions suggested that the DIP moieties can interact with DNA by intercalation, and some R groups might facilitate binding by minor-groove binding. The results provide insight into how to design biologically active DNA binding agents that can interact in these ways.