Accelerated in vivo proliferation of memory phenotype CD4+ T-cells in human HIV-1 infection irrespective of viral chemokine co-receptor tropism.

CD4(+) T-cell loss is the hallmark of HIV-1 infection. CD4 counts fall more rapidly in advanced disease when CCR5-tropic viral strains tend to be replaced by X4-tropic viruses. We hypothesized: (i) that the early dominance of CCR5-tropic viruses results from faster turnover rates of CCR5(+) cells, and (ii) that X4-tropic strains exert greater pathogenicity by preferentially increasing turnover rates within the CXCR4(+) compartment. To test these hypotheses we measured in vivo turnover rates of CD4(+) T-cell subpopulations sorted by chemokine receptor expression, using in vivo deuterium-glucose labeling. Deuterium enrichment was modeled to derive in vivo proliferation (p) and disappearance (d*) rates which were related to viral tropism data. 13 healthy controls and 13 treatment-naive HIV-1-infected subjects (CD4 143-569 cells/ul) participated. CCR5-expression defined a CD4(+) subpopulation of predominantly CD45R0(+) memory cells with accelerated in vivo proliferation (p = 2.50 vs 1.60%/d, CCR5(+) vs CCR5(-); healthy controls; P<0.01). Conversely, CXCR4 expression defined CD4(+) T-cells (predominantly CD45RA(+) naive cells) with low turnover rates. The dominant effect of HIV infection was accelerated turnover of CCR5(+)CD45R0(+)CD4(+) memory T-cells (p = 5.16 vs 2.50%/d, HIV vs controls; P<0.05), naïve cells being relatively unaffected. Similar patterns were observed whether the dominant circulating HIV-1 strain was R5-tropic (n = 9) or X4-tropic (n = 4). Although numbers were small, X4-tropic viruses did not appear to specifically drive turnover of CXCR4-expressing cells (p = 0.54 vs 0.72 vs 0.44%/d in control, R5-tropic, and X4-tropic groups respectively). Our data are most consistent with models in which CD4(+) T-cell loss is primarily driven by non-specific immune activation

Population genomic analysis of base composition evolution in Drosophila melanogaster.

The relative importance of mutation, selection, and biased gene conversion to patterns of base composition variation in Drosophila melanogaster, and to a lesser extent, D. simulans, has been investigated for many years. However, genomic data from sufficiently large samples to thoroughly characterize patterns of base composition polymorphism within species have been lacking. Here, we report a genome-wide analysis of coding and noncoding polymorphism in a large sample of inbred D. melanogaster strains from Raleigh, North Carolina. Consistent with previous results, we observed that AT mutations fix more frequently than GC mutations in D. melanogaster. Contrary to predictions of previous models of codon usage in D. melanogaster, we found that synonymous sites segregating for derived AT polymorphisms were less skewed toward low frequencies compared with sites segregating a derived GC polymorphism. However, no such pattern was observed for comparable base composition polymorphisms in noncoding DNA. These results suggest that AT-ending codons could currently be favored by natural selection in the D. melanogaster lineage

Reliability Assessment of a Packaging Automatic Machine by Accelerated Life Testing Approach

Industrial competitiveness in innovation, the time of the market introduction of new machines and the level of reliability requested implies that the strategies for the development of products must be more and more efficient. In particular, researchers and practitioners are looking for methods to evaluate the reliability, as cheap as possible, knowing that systems are more and more reliable. This paper presents a reliability assessment procedure applied to a mechanical component of an automatic machine for packaging using the accelerated test approach. The general log-linear (GLL) model is combined based on a relationship between a number strains, in particular mechanical and time based. The complete Accelerated Life Testing - ALT approach is presented by using Weibull distribution and Maximum Likelihood verifying method. A test plan is proposed to estimate the unknown parameters of accelerated life models. Using the proposed ALT model, the reliability function of the component is evaluated and then compared with data from the field collected by customers referring to 8 years of real work on a fleet of automatic packaging machines. The results confirm that the assessment method through ALT is effective for lifetime prediction with shorter test times, and for the same reason it can improve the design process of automatic packaging machines

Expert Elicitation for Reliable System Design

This paper reviews the role of expert judgement to support reliability assessments within the systems engineering design process. Generic design processes are described to give the context and a discussion is given about the nature of the reliability assessments required in the different systems engineering phases. It is argued that, as far as meeting reliability requirements is concerned, the whole design process is more akin to a statistical control process than to a straightforward statistical problem of assessing an unknown distribution. This leads to features of the expert judgement problem in the design context which are substantially different from those seen, for example, in risk assessment. In particular, the role of experts in problem structuring and in developing failure mitigation options is much more prominent, and there is a need to take into account the reliability potential for future mitigation measures downstream in the system life cycle. An overview is given of the stakeholders typically involved in large scale systems engineering design projects, and this is used to argue the need for methods that expose potential judgemental biases in order to generate analyses that can be said to provide rational consensus about uncertainties. Finally, a number of key points are developed with the aim of moving toward a framework that provides a holistic method for tracking reliability assessment through the design process.Comment: This paper commented in: [arXiv:0708.0285], [arXiv:0708.0287], [arXiv:0708.0288]. Rejoinder in [arXiv:0708.0293]. Published at http://dx.doi.org/10.1214/088342306000000510 in the Statistical Science (http://www.imstat.org/sts/) by the Institute of Mathematical Statistics (http://www.imstat.org

Encapsulant selection and durability testing experience

The Flat Plate Solar Array Project (FSA) has established technically challenging cost and service life goals for photovoltaic modules. These goals are a cost of $70 sq m and an expected 30 years of service life in an outdoor weathering environment. out of the cost goal,$14 sq m is allocated for encapsulation materials, which includes the cost of a structural panel. At FSA's inception in 1975, the cumulative cost of encapsulation materials in popular use, such as room temperature vulcanized (RTV) silicones, aluminum panels, etc., greatly exceeded $14/sq m. Accordingly, it became necessary to identify and/or develop new materials and new material technologies to achieve the goals. Many of these new materials are low cost polymers that satisfy module engineering and encapsulation processing requirements but unfortunately are not intrinsically weather stable. This necessitates identifying lifetime and/or weathering deficiencies inherent in these low cost materials and developing specific approaches to enhancing weather stability

Aerospace nickel-cadmium cell separator qualifications program

The present space qualified nylon separator, Pellon 2505 ML, is no longer available for aerospace nickel-cadmium (NiCd) cells. As a result of this anticipated unavailability, a joint Government program between the Air Force Space Division and the Naval Research Laboratory was established. Four cell types were procured with both the old qualified and the new unqualified separators. Acceptance, characterization, and life cycling tests are to be performed at the Naval Weapons Support Center, Crane, Ind. (NWSC/Crane). The scheduling and current status of this program are discussed and the progress of testing and available results are projected

Development of an ontology supporting failure analysis of surface safety valves used in Oil & Gas applications

Treball desenvolupat dins el marc del programa 'European Project Semester'.The project describes how to apply Root Cause Analysis (RCA) in the form of a Failure Mode Effect and Criticality Analysis (FMECA) on hydraulically actuated Surface Safety Valves (SSVs) of Xmas trees in oil and gas applications, in order to be able to predict the occurrence of failures and implement preventive measures such as Condition and Performance Monitoring (CPM) to improve the life-span of a valve and decrease maintenance downtime. In the oil and gas industry, valves account for 52% of failures in the system. If these failures happen unexpectedly it can cause a lot of problems. Downtime of the oil well quickly becomes an expensive problem, unscheduled maintenance takes a lot of extra time and the lead-time for replacement parts can be up to 6 months. This is why being able to predict these failures beforehand is something that can bring a lot of benefits to a company. To determine the best course of action to take in order to be able to predict failures, a FMECA report is created. This is an analysis where all possible failures of all components are catalogued and given a Risk Priority Number (RPN), which has three variables: severity, detectability and occurrence. Each of these is given a rating between 0 and 10 and then the variables are multiplied with each other, resulting in the RPN. The components with an RPN above an acceptable risk level are then further investigated to see how to be able to detect them beforehand and how to mitigate the risk that they pose. Applying FMECA to the SSV mean breaking the system down into its components and determining the function, dependency and possible failures. To this end, the SSV is broken up into three sub-systems: the valve, the actuator and the hydraulic system. The hydraulic system is the sub-system of the SSV responsible for containing, transporting and pressurizing of the hydraulic fluid and in turn, the actuator. It also contains all the safety features, such as pressure pilots, and a trip system in case a problem is detected in the oil line. The actuator is, as the name implies, the sub-system which opens and closes the valve. It is made up of a number of parts such as a cylinder, a piston and a spring. These parts are interconnected in a number of ways to allow the actuator to successfully perform its function. The valve is the actual part of the system which interacts with the oil line by opening and closing. Like the actuator, this sub-system is broken down into a number of parts which work together to perform its function. After breaking down and defining each subsystem on a functional level, a model was created using a functional block diagram. Each component also allows for the defining of dependencies and interactions between the different components and a failure diagram for each component. This model integrates the three sub-systems back into one, creating a complete picture of the entire system which can then be used to determine the effects of different failures in components to the rest of the system. With this model completed we created a comprehensive FMECA report and test the different possible CPM solutions to mitigate the largest risks

Long-life mission reliability for outer planet atmospheric entry probes

The results of a literature analysis on the effects of prolonged exposure to deep space environment on the properties of outer planet atmospheric entry probe components are presented. Materials considered included elastomers and plastics, pyrotechnic devices, thermal control components, metal springs and electronic components. The rates of degradation of each component were determined and extrapolation techniques were used to predict the effects of exposure for up to eight years to deep space. Pyrotechnic devices were aged under accelerated conditions to an equivalent of eight years in space and functionally tested. Results of the literature analysis of the selected components and testing of the devices indicated that no severe degradation should be expected during an eight year space mission