Genetic fixity in the human major histocompatibility complex and block size diversity in the class I region including HLA-E

BACKGROUND: The definition of human MHC class I haplotypes through association of HLA-A, HLA-Cw and HLA-B has been used to analyze ethnicity, population migrations and disease association. RESULTS: Here, we present HLA-E allele haplotype association and population linkage disequilibrium (LD) analysis within the ~1.3 Mb bounded by HLA-B/Cw and HLA-A to increase the resolution of identified class I haplotypes. Through local breakdown of LD, we inferred ancestral recombination points both upstream and downstream of HLA-E contributing to alternative block structures within previously identified haplotypes. Through single nucleotide polymorphism (SNP) analysis of the MHC region, we also confirmed the essential genetic fixity, previously inferred by MHC allele analysis, of three conserved extended haplotypes (CEHs), and we demonstrated that commercially-available SNP analysis can be used in the MHC to help define CEHs and CEH fragments. CONCLUSION: We conclude that to generate high-resolution maps for relating MHC haplotypes to disease susceptibility, both SNP and MHC allele analysis must be conducted as complementary techniques

Evolution and Phylogenetic Analysis of Full-Length VP3 Genes of Eastern Mediterranean Bluetongue Virus Isolates

Bluetongue virus (BTV) is the ‘type’ species of the genus Orbivirus within the family Reoviridae. The BTV genome is composed of ten linear segments of double-stranded RNA (dsRNA), each of which codes for one of ten distinct viral proteins. Previous phylogenetic comparisons have evaluated variations in genome segment 3 (Seg-3) nucleotide sequence as way to identify the geographical origin (different topotypes) of BTV isolates. The full-length nucleotide sequence of genome Seg-3 was determined for thirty BTV isolates recovered in the eastern Mediterranean region, the Balkans and other geographic areas (Spain, India, Malaysia and Africa). These data were compared, based on molecular variability, positive-selection-analysis and maximum-likelihood phylogenetic reconstructions (using appropriate substitution models) to 24 previously published sequences, revealing their evolutionary relationships. These analyses indicate that negative selection is a major force in the evolution of BTV, restricting nucleotide variability, reducing the evolutionary rate of Seg-3 and potentially of other regions of the BTV genome. Phylogenetic analysis of the BTV-4 strains isolated over a relatively long time interval (1979–2000), in a single geographic area (Greece), showed a low level of nucleotide diversity, indicating that the virus can circulate almost unchanged for many years. These analyses also show that the recent incursions into south-eastern Europe were caused by BTV strains belonging to two different major-lineages: representing an ‘eastern’ (BTV-9, -16 and -1) and a ‘western’ (BTV-4) group/topotype. Epidemiological and phylogenetic analyses indicate that these viruses originated from a geographic area to the east and southeast of Greece (including Cyprus and the Middle East), which appears to represent an important ecological niche for the virus that is likely to represent a continuing source of future BTV incursions into Europe

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Interaction of NK inhibitory receptor genes with HLA-C and MHC class II alleles in Hepatitis C virus infection outcome

ABOUT THE TEST REPORT AND USE OF THE DATA The test data contained in this report are a tabulation of the results of a series of tests. Due to the restricted format of these pages, only a limited amount of data and not all of the tractor specifications are included. The full OECD report contains usually about 30 pages of data and specifications. The test data were obtained for each tractor under similar conditions and therefore, provide a means of comparison of performance based on a limited set of reported data. EXPLANATION OF THE TEST PROCEDURES Purpose The purpose of the tests in this booklet, and available test reports is to provide users with data for comparisons of performance among tractor models. General Tractors are tested at the University of Nebraska according to test procedures of the OECD (Organization of Economic Cooperation and Development), the SAE (Society of Automotive Engineers) International and the ASABE (American Society of Agricultural and Biological Engineers). The three codes are technically equivalent, but do differ slightly. For the past 10 years, the majority of tests have been performed according to the OECD codes. The manufacturer selects the tractor to be tested from its production line, provides the specifications, and certifies that the tractor is a stock model. Each tractor is equipped with the common energy consuming accessories (power steering, PTO, implement lifts, etc.). Any power consuming accessory may be disconnected when the means for doing so can be reached from the operator position. A manufacturer\u27s representative is present during the tests to as certain that the tractor gives its optimum performance. Weight can be added to the tractor to improve drawbar performance in certain tests. Static tire loads and inflation pressures must conform to the specifications of the Tire and Rim Association or to weight limits set by the manufacturer. Specifications All manufacturers provide the Laboratory with detailed specifications which are required for the tests. The Nebraska Tractor Test report provides only a limited amount of data due to space constraints. Preparation for Test The tractor is required to have been limbered up by the manufacturer for a sufficient number of hours; if this was not done, this limber- up is performed at the Tractor Test Lab. Adjustments are permitted during this period. After the start of the official test, no adjustments can be made. Any adjustments. repairs, alterations or replacements are mentioned in the final Nebraska Tractor Test report. At this time, instrumentation for measuring engine rpm, fan speed, temperatures and pressures is installed on the tractor. The tractor is also provided with connections to the Lab\u27s fuel supply. PTO Performance The tractor PTO is connected to a dynamometer, which is a device for putting a load on the tractor and measuring the power generated by the tractor. During the preliminary runs, the manufacturer is allowed to make some adjustments to optimize the performance. These adjustments, which include the injection pump volume and timing and the high idle set within the specified range, will remain during the whole test program and must be settings guaranteed by the manufacturer. The tests are performed while maintaining an ambient temperature of 75°F (24°C) and at a barometer reading above 28.5 inches Hg (96.6 kPa). Data are taken at intervals after the tractor performance has stabilized. Inlet fuel temperatures are also maintained at a predetermined level. The throttle being set for maximum no-load rpm (High Idle), an increasing load is applied to the PTO by the dynamometer along the operating curve of the engine. The full test report will show the torque, rpm, power and fuel consumption data obtained at Rated Engine speed, Standard PTO speed (either 1000 or 540 rpm), the maximum power on the curve and the torque rise. Drawbar Performance Tests are performed in all gears between one gear below the one at Which 15% slip occurs and a maximum speed of 10 mph (16.1 km/h). In each gear, the throttle is set for maximum speed (High Idle) and the drawbar load increased until maximum drawbar power is obtained. The drawbar load is created by towing load units behind the test-and- measurement vehicle which, itself, is hitched to the tested tractor\u27s drawbar. For each load, measurements and calculations are made to determine drawbar pull, speed, drawbar power, slip and fuel consumption. All measurements are recorded at intervals after the tractor\u27s condition is stabilized. No operational limits set by the manufacturer can be exceeded. A second test series investigates the part loads at 75% and 50% of the drawbar load at Rated Engine Speed in a gear close to 4.6 mph (7.5 km/h) and in the gear where maximum drawbar power was obtained. Sound Measurement Sound measurement is made on the test track in two locations-at the driver\u27s ear and in a location representing bystander noise. The tests at the driver\u27s ear are performed in several gears and under a number of conditions, but only the maximum level is reported. The bystander sound test is performed with the microphone located at 25 ft (7.5 m) from the centerline of the tractor which is accelerating from a lower speed to full speed in its top gear. The OECD procedure differs. The SAE/ASABE procedures and only the numbers for the same gears and same load conditions can be compared. The SAE/ASABE procedure measures sound in only one gear under different load conditions, whereas the GECD procedure measures sound in different gears between High Idle and Rated Engine speed. For tractors with Mechanical Front Wheel Drive, operator- ear measurements are made with the front-wheel drive engaged and disengaged. Hydraulic Lift Capacity and Flow Hydraulic lift capacity is measured in a special test stand. A frame is fitted to the three-point hitch lift links. Measurements of lift capacity are taken at the hitch points and at a point 24 (610 mm) behind the hitch points when the lower links are horizontal. The load is applied with a hydraulic cylinder and the arms move stepwise through the lift range. The number which is reported is 90% of the load which can be carried throughout the lift range. The booklet reports the lift capacity at 24 (610 mm) behind the hitch points. A second test determines the pressure/flow relationship and performance of the hydraulic system for supplying power to external hydraulic cylinders or hydraulic motors. The Nebraska report provides data on delivery rate, pressure and available powe

Virtual Sonography Through the Internet: Volume Compression Issues

BACKGROUND: Three-dimensional ultrasound images allow virtual sonography even at a distance. However, the size of final 3-D files limits their transmission through slow networks such as the Internet. OBJECTIVE: To analyze compression techniques that transform ultrasound images into small 3-D volumes that can be transmitted through the Internet without loss of relevant medical information. METHODS: Samples were selected from ultrasound examinations performed during, 1999-2000, in the Obstetrics and Gynecology Department at the University Hospital in La Laguna, Canary Islands, Spain. The conventional ultrasound video output was recorded at 25 fps (frames per second) on a PC, producing 100- to 120-MB files (for from 500 to 550 frames). Processing to obtain 3-D images progressively reduced file size. RESULTS: The original frames passed through different compression stages: selecting the region of interest, rendering techniques, and compression for storage. Final 3-D volumes reached 1:25 compression rates (1.5- to 2-MB files). Those volumes need 7 to 8 minutes to be transmitted through the Internet at a mean data throughput of 6.6 Kbytes per second. At the receiving site, virtual sonography is possible using orthogonal projections or oblique cuts. CONCLUSIONS: Modern volume-rendering techniques allowed distant virtual sonography through the Internet. This is the result of their efficient data compression that maintains its attractiveness as a main criterion for distant diagnosis

Nanoengineering properties through porous alumina

Trabajo presentado en el Nanospain, celebrado en San Sebastian (España), del 7 al 10 de marzo de 2017The understanding of how the properties of the materials, such as thermal conductivity and electrical conductivity, can be tailored by growing nano-scale structures that affect them, is the main aim of this work. The fabrication of nanowires with diameters down to 12 nm and the recent development of threedimensional nanostructured networks based on the controlled pulsed anodization of aluminum [1] open the possibility of tailoring the properties in a certain range. A review of ways of tailoring different properties of materials through nanostructuration with the aid of porous alumina templates will be presented. For instance, in the case of the thermal conductivity, it has been demonstrated how this parameter can be experimentally changed and measured [2]. Moreover, the understanding of the reasons behind this change and how to control from a theoretical point of view has been also pursued. In the case of electrical conductivity, the effect of topological insulating appears in different materials when they are structured at the nano-scale [3].Peer reviewe