Using the nonhuman primate model of HCMV to guide vaccine development.

The natural history of human cytomegalovirus (HCMV) is inextricably associated with mucosal surfaces. The vast preponderance of primary infections occur following mucosal exposure to infectious virions, and the high seroprevalence of HCMV throughout the world is due to long-term excretion of HCMV in bodily fluids from multiple mucosal sites. Accumulating evidence presents a model where the earliest virus-host interactions following infection dictate the long-term pattern of infection, alter innate immune responses that skew adaptive responses to enable persistence within an immune host, and are essential for reinfection of a host with prior immunity. HCMV has evolved a complex repertoire of viral functions fine-tuned to manipulate the immune environment both locally at the sites of infection and systemically within an infected host. Collectively, viral immune modulation represents a significant impediment for an HCMV vaccine. As HCMV can disseminate beyond mucosal surfaces to reinfect immune hosts, it may not matter whether prior immunity results from prior infection or immunization. A better understanding of the earliest virus-hosts interactions at mucosal surfaces may identify elements of the viral proteome that are especially susceptible to vaccine-mediated disruption and prevent challenge virus from disseminating to distal sites, particularly the maternal-fetal interface

Current assumptions for quantitative microbial risk assessment (QMRA) of Norovirus contamination of drinking water catchments due to recreational activities: an update

Contamination of drinking water from Norovirus (NoV) and other waterborne viruses is a major public health concern globally. Increasingly, quantitative microbial risk assessment (QMRA) is being used to assess the various risks from waterborne pathogens and evaluate control strategies. As urban populations grow and expand, there is increasing demand for recreational activities in drinking water catchments. QMRA relies on context-specific data to map out the pathways by which viruses can enter water and be transferred to drinking water consumers and identify risk factors and appropriate controls. This review examines the current evidence base and assumptions for QMRA analysis of NoV and other waterborne viral pathogens and recommends numerical values based on the most recent evidence to better understand the health risks associated with recreators in Australian drinking water sources; these are broadly applicable to all drinking water sources where recreational access is allowed. Key issues include the lack of an agreed upon data and dose-response models for human infectious NoV genotypes, faecal shedding by bathers, the extent of NoV infectivity and aggregation, resistance (secretor status) to NoV and the extent of secondary transmission

Analysis of multiply spliced transcripts in lymphoid tissue reservoirs of rhesus macaques infected with RT-SHIV during HAART.

Highly active antiretroviral therapy (HAART) can reduce levels of human immunodeficiency virus type 1 (HIV-1) to undetectable levels in infected individuals, but the virus is not eradicated. The mechanisms of viral persistence during HAART are poorly defined, but some reservoirs have been identified, such as latently infected resting memory CD4⁺ T cells. During latency, in addition to blocks at the initiation and elongation steps of viral transcription, there is a block in the export of viral RNA (vRNA), leading to the accumulation of multiply-spliced transcripts in the nucleus. Two of the genes encoded by the multiply-spliced transcripts are Tat and Rev, which are essential early in the viral replication cycle and might indicate the state of infection in a given population of cells. Here, the levels of multiply-spliced transcripts were compared to the levels of gag-containing RNA in tissue samples from RT-SHIV-infected rhesus macaques treated with HAART. Splice site sequence variation was identified during development of a TaqMan PCR assay. Multiply-spliced transcripts were detected in gastrointestinal and lymphatic tissues, but not the thymus. Levels of multiply-spliced transcripts were lower than levels of gag RNA, and both correlated with plasma virus loads. The ratio of multiply-spliced to gag RNA was greatest in the gastrointestinal samples from macaques with plasma virus loads <50 vRNA copies per mL at necropsy. Levels of gag RNA and multiply-spliced mRNA in tissues from RT-SHIV-infected macaques correlate with plasma virus load

Computational Study of an Axisymmetric Dual Throat Fluidic Thrust Vectoring Nozzle for a Supersonic Aircraft Application

A computational investigation of an axisymmetric Dual Throat Nozzle concept has been conducted. This fluidic thrust-vectoring nozzle was designed with a recessed cavity to enhance the throat shifting technique for improved thrust vectoring. The structured-grid, unsteady Reynolds- Averaged Navier-Stokes flow solver PAB3D was used to guide the nozzle design and analyze performance. Nozzle design variables included extent of circumferential injection, cavity divergence angle, cavity length, and cavity convergence angle. Internal nozzle performance (wind-off conditions) and thrust vector angles were computed for several configurations over a range of nozzle pressure ratios from 1.89 to 10, with the fluidic injection flow rate equal to zero and up to 4 percent of the primary flow rate. The effect of a variable expansion ratio on nozzle performance over a range of freestream Mach numbers up to 2 was investigated. Results indicated that a 60 circumferential injection was a good compromise between large thrust vector angles and efficient internal nozzle performance. A cavity divergence angle greater than 10 was detrimental to thrust vector angle. Shortening the cavity length improved internal nozzle performance with a small penalty to thrust vector angle. Contrary to expectations, a variable expansion ratio did not improve thrust efficiency at the flight conditions investigated

A Computational Study of a New Dual Throat Fluidic Thrust Vectoring Nozzle Concept

A computational investigation of a two-dimensional nozzle was completed to assess the use of fluidic injection to manipulate flow separation and cause thrust vectoring of the primary jet thrust. The nozzle was designed with a recessed cavity to enhance the throat shifting method of fluidic thrust vectoring. Several design cycles with the structured-grid, computational fluid dynamics code PAB3D and with experiments in the NASA Langley Research Center Jet Exit Test Facility have been completed to guide the nozzle design and analyze performance. This paper presents computational results on potential design improvements for best experimental configuration tested to date. Nozzle design variables included cavity divergence angle, cavity convergence angle and upstream throat height. Pulsed fluidic injection was also investigated for its ability to decrease mass flow requirements. Internal nozzle performance (wind-off conditions) and thrust vector angles were computed for several configurations over a range of nozzle pressure ratios from 2 to 7, with the fluidic injection flow rate equal to 3 percent of the primary flow rate. Computational results indicate that increasing cavity divergence angle beyond 10 is detrimental to thrust vectoring efficiency, while increasing cavity convergence angle from 20 to 30 improves thrust vectoring efficiency at nozzle pressure ratios greater than 2, albeit at the expense of discharge coefficient. Pulsed injection was no more efficient than steady injection for the Dual Throat Nozzle concept

Experimental Study of an Axisymmetric Dual Throat Fluidic Thrust Vectoring Nozzle for Supersonic Aircraft Application

An axisymmetric version of the Dual Throat Nozzle concept with a variable expansion ratio has been studied to determine the impacts on thrust vectoring and nozzle performance. The nozzle design, applicable to a supersonic aircraft, was guided using the unsteady Reynolds-averaged Navier-Stokes computational fluid dynamics code, PAB3D. The axisymmetric Dual Throat Nozzle concept was tested statically in the Jet Exit Test Facility at the NASA Langley Research Center. The nozzle geometric design variables included circumferential span of injection, cavity length, cavity convergence angle, and nozzle expansion ratio for conditions corresponding to take-off and landing, mid climb and cruise. Internal nozzle performance and thrust vectoring performance was determined for nozzle pressure ratios up to 10 with secondary injection rates up to 10 percent of the primary flow rate. The 60 degree span of injection generally performed better than the 90 degree span of injection using an equivalent injection area and number of holes, in agreement with computational results. For injection rates less than 7 percent, thrust vector angle for the 60 degree span of injection was 1.5 to 2 degrees higher than the 90 degree span of injection. Decreasing cavity length improved thrust ratio and discharge coefficient, but decreased thrust vector angle and thrust vectoring efficiency. Increasing cavity convergence angle from 20 to 30 degrees increased thrust vector angle by 1 degree over the range of injection rates tested, but adversely affected system thrust ratio and discharge coefficient. The dual throat nozzle concept generated the best thrust vectoring performance with an expansion ratio of 1.0 (a cavity in between two equal minimum areas). The variable expansion ratio geometry did not provide the expected improvements in discharge coefficient and system thrust ratio throughout the flight envelope of typical a supersonic aircraft. At mid-climb and cruise conditions, the variable geometry design compromised thrust vector angle achieved, but some thrust vector control would be available, potentially for aircraft trim. The fixed area, expansion ratio of 1.0, Dual Throat Nozzle provided the best overall compromise for thrust vectoring and nozzle internal performance over the range of NPR tested compared to the variable geometry Dual Throat Nozzle

Motor Competence in Early Childhood Is Positively Associated with Bone Strength in Late Adolescence

The onset of walking in early childhood results in exposure of the lower limb to substantial forces from weight bearing activity that ultimately contribute to adult bone strength. Relationships between gross motor score (GMS), at 18 months and bone outcomes measured at age 17 years were examined in 2327 participants in the Avon Longitudinal Study of Parents and Children (ALSPAC). Higher GMS indicated greater motor competence in weight‐bearing activities. Total hip bone mineral density (BMD) and hip cross‐sectional moment of inertia (CSMI) were assessed from dual‐energy X‐ray absorptiometry (DXA). Bone measures including cortical bone mineral content (BMC), periosteal circumference (PC), cortical thickness (CT), cortical bone area (CBA), cortical BMD (BMD(C)) and cross‐sectional moment of inertia (CSMI) were assessed by peripheral quantitative computed tomography (pQCT) at 50% distal‐proximal length. Before adjustment, GMS was associated with hip BMD, CSMI, and tibia BMC, PC, CT, CBA and CSMI (all p < 0.001) but not BMD(C) (p > 0.25). Strongest associations (standardized regression coefficients with 95% CI) were between GMS and hip BMD (0.086; 95% CI, 0.067 to 0.105) and tibia BMC (0.105; 95% CI, 0.089 to 0.121). With the exception of hip BMD, larger regression coefficients were observed in males (gender interactions all p < 0.05). Adjustment for lean mass resulted in substantial attenuation of regression coefficients, suggesting associations between impaired motor competence and subsequent bone development are partly mediated by alterations in body composition. In conclusion, impaired motor competence in childhood is associated with lower adolescent bone strength, and may represent a risk factor for subsequent osteoporosis. © 2015 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research (ASBMR)

CFD Predictions for Transonic Performance of the ERA Hybrid Wing-Body Configuration

A computational study was performed for a Hybrid Wing Body configuration that was focused at transonic cruise performance conditions. In the absence of experimental data, two fully independent computational fluid dynamics analyses were conducted to add confidence to the estimated transonic performance predictions. The primary analysis was performed by Boeing with the structured overset-mesh code OVERFLOW. The secondary analysis was performed by NASA Langley Research Center with the unstructured-mesh code USM3D. Both analyses were performed at full-scale flight conditions and included three configurations customary to drag buildup and interference analysis: a powered complete configuration, the configuration with the nacelle/pylon removed, and the powered nacelle in isolation. The results in this paper are focused primarily on transonic performance up to cruise and through drag rise. Comparisons between the CFD results were very good despite some minor geometric differences in the two analyses

Design Enhancements of the Two-Dimensional, Dual Throat Fluidic Thrust Vectoring Nozzle Concept

A Dual Throat Nozzle fluidic thrust vectoring technique that achieves higher thrust-vectoring efficiencies than other fluidic techniques, without sacrificing thrust efficiency has been developed at NASA Langley Research Center. The nozzle concept was designed with the aid of the structured-grid, Reynolds-averaged Navier-Stokes computational fluidic dynamics code PAB3D. This new concept combines the thrust efficiency of sonic-plane skewing with increased thrust-vectoring efficiencies obtained by maximizing pressure differentials in a separated cavity located downstream of the nozzle throat. By injecting secondary flow asymmetrically at the upstream minimum area, a new aerodynamic minimum area is formed downstream of the geometric minimum and the sonic line is skewed, thus vectoring the exhaust flow. The nozzle was tested in the NASA Langley Research Center Jet Exit Test Facility. Internal nozzle performance characteristics were defined for nozzle pressure ratios up to 10, with a range of secondary injection flow rates up to 10 percent of the primary flow rate. Most of the data included in this paper shows the effect of secondary injection rate at a nozzle pressure ratio of 4. The effects of modifying cavity divergence angle, convergence angle and cavity shape on internal nozzle performance were investigated, as were effects of injection geometry, hole or slot. In agreement with computationally predicted data, experimental data verified that decreasing cavity divergence angle had a negative impact and increasing cavity convergence angle had a positive impact on thrust vector angle and thrust efficiency. A curved cavity apex provided improved thrust ratios at some injection rates. However, overall nozzle performance suffered with no secondary injection. Injection holes were more efficient than the injection slot over the range of injection rates, but the slot generated larger thrust vector angles for injection rates less than 4 percent of the primary flow rate

On-Road Development of John Deere 6081 Natural Gas Engine: Final Technical Report, July 1999 - January 2001

Report that discusses John Deere's field development of a heavy-duty natural gas engine. As part of the field development project, Waste Management of Orange County, California refitted four existing trash packers with John Deere's prototype spark ignited 280-hp 8.1 L CNG engines. This report describes the project and also contains information about engine performance, emissions, and driveability