14,537 research outputs found

    Insertion of the CXC chemokine ligand 9 (CXCL9) into the mouse hepatitis virus genome results in protection from viral-induced encephalitis and hepatitis.

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    The role of the CXC chemokine ligand 9 (CXCL9) in host defense following infection with mouse hepatitis virus (MHV) was determined. Inoculation of the central nervous system (CNS) of CXCL9-/- mice with MHV resulted in accelerated and increased mortality compared to wild type mice supporting an important role for CXCL9 in anti-viral defense. In addition, infection of RAG1-/- or CXCL9-/- mice with a recombinant MHV expressing CXCL9 (MHV-CXCL9) resulted in protection from disease that correlated with reduced viral titers within the brain and NK cell-mediated protection in the liver. Survival in MHV-CXCL9-infected CXCL9-/- mice was associated with reduced viral burden within the brain that coincided with increased T cell infiltration. Similarly, viral clearance from the livers of MHV-CXCL9-infected mice was accelerated but independent of increased T cell or NK cell infiltration. These observations indicate that CXCL9 promotes protection from coronavirus-induced neurological and liver disease

    Measuring fitness of Kenyan children with polyparasitic infections using the 20-meter shuttle run test as a morbidity metric.

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    BACKGROUND: To date, there has been no standardized approach to the assessment of aerobic fitness among children who harbor parasites. In quantifying the disability associated with individual or multiple chronic infections, accurate measures of physical fitness are important metrics. This is because exercise intolerance, as seen with anemia and many other chronic disorders, reflects the body's inability to maintain adequate oxygen supply (VO(2) max) to the motor tissues, which is frequently linked to reduced quality-of-life in terms of physical and job performance. The objective of our study was to examine the associations between polyparasitism, anemia, and reduced fitness in a high risk Kenyan population using novel implementation of the 20-meter shuttle run test (20mSRT), a well-standardized, low-technology physical fitness test. METHODOLOGY/PRINCIPAL FINDINGS: Four villages in coastal Kenya were surveyed during 2009-2010. Children 5-18 years were tested for infection with Schistosoma haematobium (Sh), malaria, filaria, and geohelminth infections by standard methods. After anthropometric and hemoglobin testing, fitness was assessed with the 20 mSRT. The 20 mSRT proved easy to perform, requiring only minimal staff training. Parasitology revealed high prevalence of single and multiple parasitic infections in all villages, with Sh being the most common (25-62%). Anemia prevalence was 45-58%. Using multiply-adjusted linear modeling that accounted for household clustering, decreased aerobic capacity was significantly associated with anemia, stunting, and wasting, with some gender differences. CONCLUSIONS/SIGNIFICANCE: The 20 mSRT, which has excellent correlation with VO(2), is a highly feasible fitness test for low-resource settings. Our results indicate impaired fitness is common in areas endemic for parasites, where, at least in part, low fitness scores are likely to result from anemia and stunting associated with chronic infection. The 20 mSRT should be used as a common metric to quantify physical fitness and compare sub-clinical disability across many different disorders and community settings

    Slam excitation scales for a large wave piercing catamaran and the effect on structural response

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    A unique slamming process is observed on high speed wave piercing catamarans (WPCs) such as those manufactured by INCAT Tasmania (shown in Fig. 1). For conventional catamarans, wet-deck slamming constitutes a significant design load and is managed through proper design of the tunnel height for the proposed operating conditions. While methods have been developed for prediction of wet-deck slam occurrence and slam magnitude in conventional catamarans (for example Ge et al., 2005) the significant differences in geometry limit application to wave piercing catamarans. Although slamming of wave piercing catamarans may be categorised as a wet-deck slam, the INCAT Tasmania wave piercing catamarans include a forward centre bow to prevent deck diving which significantly alters the water entry and slamming characteristics

    The Epstein-Barr Virus Episome Maneuvers between Nuclear Chromatin Compartments during Reactivation.

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    The human genome is structurally organized in three-dimensional space to facilitate functional partitioning of transcription. We learned that the latent episome of the human Epstein-Barr virus (EBV) preferentially associates with gene-poor chromosomes and avoids gene-rich chromosomes. Kaposi's sarcoma-associated herpesvirus behaves similarly, but human papillomavirus does not. Contacts on the EBV side localize to OriP, the latent origin of replication. This genetic element and the EBNA1 protein that binds there are sufficient to reconstitute chromosome association preferences of the entire episome. Contacts on the human side localize to gene-poor and AT-rich regions of chromatin distant from transcription start sites. Upon reactivation from latency, however, the episome moves away from repressive heterochromatin and toward active euchromatin. Our work adds three-dimensional relocalization to the molecular events that occur during reactivation. Involvement of myriad interchromosomal associations also suggests a role for this type of long-range association in gene regulation.IMPORTANCE The human genome is structurally organized in three-dimensional space, and this structure functionally affects transcriptional activity. We set out to investigate whether a double-stranded DNA virus, Epstein-Barr virus (EBV), uses mechanisms similar to those of the human genome to regulate transcription. We found that the EBV genome associates with repressive compartments of the nucleus during latency and with active compartments during reactivation. This study advances our knowledge of the EBV life cycle, adding three-dimensional relocalization as a novel component to the molecular events that occur during reactivation. Furthermore, the data add to our understanding of nuclear compartments, showing that disperse interchromosomal interactions may be important for regulating transcription

    Effect of Slam Force Duration on the Vibratory Response of a Lightweight High-Speed Wave-Piercing Catamaran

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    When the surface of a ship meets the water surface at an acute angle with a high relative velocity, significant short-duration forces can act on the hull plating. Such an event is referred to as a slam. Slam loads imparted on ships are generally considered to be of an impulsive nature. As such, slam loads induce vibration in the global hull structure that has implications for both hull girder bending strength and fatigue life of a vessel. A modal method is often used for structural analysis whereby higher order modes are neglected to reduce computational effort. The effect of the slam load temporal distribution on the whipping response and vertical bending moment are investigated here by using a continuous beam model with application to a 112 m INCAT wave-piercing catamaran and correlation to full-scale and model-scale experimental data. Experimental studies have indicated that the vertical bending moment is dominated by the fundamental longitudinal bending mode of the structure. However, it is shown here that although the fundamental mode is dominant in the global structural response, the higher order modes play a significant role in the early stages of the response and may not be readily identifiable if measurements are not taken sufficiently close to the slam location. A relationship between the slam duration and the relative modal response magnitudes is found, which is useful in determining the appropriate truncation of a modal solution

    Patient-Specific Prosthetic Fingers by Remote Collaboration - A Case Study

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    The concealment of amputation through prosthesis usage can shield an amputee from social stigma and help improve the emotional healing process especially at the early stages of hand or finger loss. However, the traditional techniques in prosthesis fabrication defy this as the patients need numerous visits to the clinics for measurements, fitting and follow-ups. This paper presents a method for constructing a prosthetic finger through online collaboration with the designer. The main input from the amputee comes from the Computer Tomography (CT) data in the region of the affected and the non-affected fingers. These data are sent over the internet and the prosthesis is constructed using visualization, computer-aided design and manufacturing tools. The finished product is then shipped to the patient. A case study with a single patient having an amputated ring finger at the proximal interphalangeal joint shows that the proposed method has a potential to address the patient's psychosocial concerns and minimize the exposure of the finger loss to the public.Comment: Open Access articl

    Historic landmarks in clinical transplantation: Conclusions from the consensus conference at the University of California, Los Angeles

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    The transplantation of organs, cells, and tissues has burgeoned during the last quarter century, with the development of multiple new specialty fields. However, the basic principles that made this possible were established over a three-decade period, beginning during World War II and ending in 1974. At the historical consensus conference held at UCLA in March 1999, 11 early workers in the basic science or clinical practice of transplantation (or both) reached agreement on the most significant contribution of this era that ultimately made transplantation the robust clinical discipline it is today. These discoveries and achievements are summarized here is six tables and annotated with references

    Baryon-Baryon Interactions

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    After a short survey of some topics of interest in the study of baryon-baryon scattering, the recent Nijmegen energy dependent partial wave analysis (PWA) of the nucleon-nucleon data is reviewed. In this PWA the energy range for both pp and np is now 0 < Tlab < 350 MeV and a chi^2_{d.o.f.}=1.08 was reached. The implications for the pion-nucleon coupling constants are discussed. Comments are made with respect to recent discussions around this coupling constant in the literature. In the second part, we briefly sketch the picture of the baryon in several, more or less QCD-based, quark-models that have been rather prominent in the literature. Inspired by these pictures we constructed a new soft-core model for the nucleon-nucleon interaction and present the first results of this model in a chi^2 -fit to the new multi-energy Nijmegen PWA. With this new model we succeeded in narrowing the gap between theory and experiment at low energies. For the energies Tlab = 25-320 MeV we reached a record low chi^2_{p.d.p.} = 1.16. We finish the paper with some conclusions and an outlook describing the extension of the new model to baryon-baryon scattering.Comment: 12 pages LaTeX and one postscript figure included. Invited talk presented at the XIVth European Conference of Few-Body Problems in Physics, Amsterdam, August 23-28, 199

    The effect of hip joint angle on isometric midthigh pull kinetics

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    The aim of this study were to compare isometric midthigh pull (IMTP) peak force (PF), time-specific force values (100-, 150-, and 200 ms), rate of force development (RFD) at predetermined time bands (0–100, 0–150, and 0–200 ms) and net forces between 2 commonly adopted hip joint angles (145°[hip145] and 175°[hip175]) with a 145° standardized knee angle. Twenty-eight collegiate athletes (age: 21.7 ± 1.5 years, height: 1.75 ± 0.08 m, mass: 81.5 ± 8.4 kg) performed 2 IMTP trials at each hip joint angle in a randomized counterbalanced order. A subgroup (n = 10) performed the IMTP testing 7 days later to establish the between-session reliability. Intraclass correlation coefficients (ICCs) and coefficient of variation (CV) demonstrated high within-session reliability and acceptable variability for all IMTP kinetics at each posture (ICC ≥ 0.86, CV ≤ 13.7%), excluding hip175 RFD 0–100 ms and net force at 100 ms which demonstrated greater variability (CV = 18.1–18.5%). High between-session reliability and acceptable variability were observed for all IMTP kinetics at each posture (ICC = 0.72–0.97, CV = 4.5–12.8%), excluding RFD 0–100 ms which demonstrated greater variability for both postures. Hip145 produced significantly greater time-specific force values (p ≤ 0.025, g = 0.25–0.28), RFD at predetermined time bands (p ≤ 0.001, g = 0.59–0.78), and net forces (p ≤ 0.001, g = 0.57–0.74) compared with hip175. Trivial nonsignificant differences were demonstrated between postures for PF and force at 100 ms (p > 0.05, g ≤ 0.14). Significantly greater body weights (weighing period force) were observed with hip175 compared with hip145 (p < 0.001, g = 0.74). Coaches should consider administering a hip145 for IMTP testing as greater IMTP kinetics and lower levels of pretension during the weighing period are achieved with this posture
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