Additive effects of HLA alleles and innate immune genes determine viral outcome in HCV infection

BACKGROUND Chronic HCV infection is a leading cause of liver-related morbidity globally. The innate and adaptive immune responses are thought to be important in determining viral outcomes. Polymorphisms associated with the IFNL3 (IL28B) gene are strongly associated with spontaneous clearance and treatment outcomes. OBJECTIVE This study investigates the importance of HLA genes in the context of genetic variation associated with the innate immune genes IFNL3 and KIR2DS3. DESIGN We assess the collective influence of HLA and innate immune genes on viral outcomes in an Irish cohort of women (n=319) who had been infected from a single source as well as a more heterogeneous cohort (Swiss Cohort, n=461). In the Irish cohort, a number of HLA alleles are associated with different outcomes, and the impact of IFNL3-linked polymorphisms is profound. RESULTS Logistic regression was performed on data from the Irish cohort, and indicates that the HLA-A*03 (OR 0.36 (0.15 to 0.89), p=0.027) -B*27 (OR 0.12 (0.03 to 0.45), p=<0.001), -DRB1*01:01 (OR 0.2 (0.07 to 0.61), p=0.005), -DRB1*04:01 (OR 0.31 (0.12 to 0.85, p=0.02) and the CC IFNL3 rs12979860 genotypes (OR 0.1 (0.04 to 0.23), p<0.001) are significantly associated with viral clearance. Furthermore, DQB1*02:01 (OR 4.2 (2.04 to 8.66), p=0.008), KIR2DS3 (OR 4.36 (1.62 to 11.74), p=0.004) and the rs12979860 IFNL3 'T' allele are associated with chronic infection. This study finds no interactive effect between IFNL3 and these Class I and II alleles in relation to viral clearance. There is a clear additive effect, however. Data from the Swiss cohort also confirms independent and additive effects of HLA Class I, II and IFNL3 genes in their prediction of viral outcome. CONCLUSIONS This data supports a critical role for the adaptive immune response in the control of HCV in concert with the innate immune response.

The positive effects of protean career attitude for self-initiated expatriates: Cultural adjustment as a mediator

Purpose – The authors sought to explain why and how protean career attitude might influence self‐initiated expatriates' (SIEs) experiences positively. A mediation model of cultural adjustment was proposed and empirically evaluated. Design/methodology/approach – Data from 132 SIEs in Germany containing measures of protean career attitude, cultural adjustment, career satisfaction, life satisfaction, and intention to stay in the host country were analysed using path analysis with a bootstrap method. Findings – Empirical results provide support for the authors' proposed model: the positive relations between protean career attitude and the three expatriation outcomes (career satisfaction, life satisfaction and intention to stay in the host country) were mediated by positive cross‐cultural adjustment of SIEs. Research limitations/implications – All data were cross‐sectional from a single source. The sample size was small and included a large portion of Chinese participants. The study should be replicated with samples in other destination countries, and longitudinal research is suggested. Practical implications – By fostering both a protean career attitude in skilled SIE employees and their cultural adjustment, corporations and receiving countries could be able to retain this international workforce better in times of talent shortage. Originality/value – This study contributes to the scarce research on the conceptual relatedness of protean career attitude and SIEs, as well as to acknowledging the cultural diversity of the SIE population.

Intra- and interlaboratory reliability of a cryopreserved trout hepatocyte assay for the prediction of chemical bioaccumulation potential

Measured rates of intrinsic clearance determined using cryopreserved trout hepatocytes can be extrapolated to the whole animal as a means of improving modeled bioaccumulation predictions for fish. To date, however, the intra- and interlaboratory reliability of this procedure has not been determined. In the present study, three laboratories determined in vitro intrinsic clearance of six reference compounds (benzo[a]pyrene, 4-nonylphenol, di-tert-butyl phenol, fenthion, methoxychlor and o-terphenyl) by conducting substrate depletion experiments with cryopreserved trout hepatocytes from a single source. O-terphenyl was excluded from the final analysis due to nonfirst-order depletion kinetics and significant loss from denatured controls. For the other five compounds, intralaboratory variability (% CV) in measured in vitro intrinsic clearance values ranged from 4.1 to 30%, while interlaboratory variability ranged from 27 to 61%. Predicted bioconcentration factors based on in vitro clearance values exhibited a reduced level of interlaboratory variability (5.3-38% CV). The results of this study demonstrate that cryopreserved trout hepatocytes can be used to reliably obtain in vitro intrinsic clearance of xenobiotics, which provides support for the application of this in vitro method in a weight-of-evidence approach to chemical bioaccumulation assessment.

Genetic composition, genetic diversity, and small-scale environmental variation matter for the experimental reintroduction of a rare plant

Aims Reintroduction has become an important tool for the management of endangered plant species. We tested the little-explored effects of small-scale environmental variation, genotypic composition (i.e. identity of genotypes), and genotypic diversity on the population survival of the regionally rare clonal plant Ranunculus reptans. For this species of periodically inundated lakeshores genetic differentiation had been reported between populations and between short-flooded and long-flooded microsites within populations.Methods We established 306 experimental test populations at a previously unoccupied lake shore, comprising either monocultures of 32 genotypes, mixtures of genotypes within populations or mixtures of genotypes between populations. In 2000, three years after planting out at the experimental site, a long-lasting flood caused the death of half of the experimental populations. In 2003, an extreme drought resulted in the lowest summer water levels ever measured.Important findings Despite these climatic extremes, 27 of the established populations survived until the end of the experiment in December 2003. The success of experimental populations largely differed between microsites. Moreover, the success of genotype monocultures depended on genotype and source population. Genetic differentiation between microsites played a minor role for the success of reintroduction. After the flood, populations planted with genotypes from different source populations increased in abundance, whereas populations with genotypes from single source populations and genotype monocultures decreased. We conclude that sources for reintroductions need to be selected carefully. Moreover, mixtures of plants from different populations appear to be the best choice for successful reintroduction, at least in unpredictably varying environments.

CHARACTERIZATION OF THE COUNT RATE PERFORMANCE AND EVALUATION OF THE EFFECTS OF HIGH COUNT RATES ON MODERN GAMMA CAMERAS

CHARACTERIZATION OF THE COUNT RATE PERFORMANCE AND EVALUATION OF THE EFFECTS OF HIGH COUNT RATES ON MODERN GAMMA CAMERAS Michael Stephen Silosky, B.S. Supervisory Professor: S. Cheenu Kappadath, Ph.D. Evaluation of count rate performance (CRP) is an integral component of gamma camera quality assurance and measurement of system dead time (τ) is important for quantitative SPECT. The CRP of three modern gamma cameras was characterized using established methods (Decay and Dual Source) under a variety of experimental conditions. For the Decay method, input count rate was plotted against observed count rate and fit to the paralyzable detector model (PDM) to estimate τ (Rates method). A novel expression for observed counts as a function of measurement time interval was derived and the observed counts were fit to this expression to estimate τ (Counts method). Correlation and Bland-Altman analysis were performed to assess agreement in estimates of τ between methods. The dependencies of τ on energy window definition and incident energy spectrum were characterized. The Dual Source method was also used to estimate τ and its agreement with the Decay method under identical conditions and the effects of total activity and the ratio of source activities were investigated. Additionally, the effects of count rate on several performance metrics were evaluated. The CRP curves for each system agreed with the PDM at low count rates but deviated substantially at high count rates. Estimates of τ for the paralyzable portion of the CRP curves using the Rates and Counts methods were highly correlated (r=0.999) but with a small (~6%) difference. No significant difference was observed between the highly correlated estimates of τ using the Decay or Dual Source methods under identical experimental conditions (r=0.996). Estimates of τ increased as a power-law function with decreasing ratio of counts in the photopeak to the total counts and linearly with decreasing spectral effective energy. Dual Source method estimates of τ varied as a quadratic with the ratio of the single source to combined source activities and linearly with total activity used across a large range. Image uniformity, spatial resolution, and energy resolution degraded linearly with count rate and image distorting effects were observed. Guidelines for CRP testing and a possible method for the correction of count rate losses for clinical images have been proposed.

Mid-Pliocene diatom and palynological assemblages north-northeast of Cape Adare, Antarctica

Microfossil assemblages in Pliocene sediments from DSDP Site 274 (68°59.81'S, 173°2564'E) provide data on the age of the sediments and suggest the presence of Nothofagus (southern beach) in Antarctica during the Pliocene. A suite of 17 samples was collected in an interval from Samples 28-274-6R-1, 83-87 cm to 28-274-11R-4, 73-77 cm (48.33-100.29 mbsf). Biostratigraphic study of the abundant diatom assemblages combined with published radiolarian data indicates that the sample interval ranges in age from 5.0 to 2.2 Ma, with an apparent unconformity between about 3.8 and 3.2 Ma. Nothofagidites (the genus for fossil pollen referable to Nothofagus) occurs throughout the interval, as well as pollen and spores with known stratigraphic ranges that unequivocally indicate reworking from older rocks. Species of Nothofagidites recovered include N. asperus, N. brachyspinulosus, N. flemingii, N. senectus, and N. sp. cf. N. lachlaniae; the latter form is previously known from the Sirius Group in the Transantarctic Mountains. Abundant palynomorphs were recovered in only three of the samples from Site 274 (Samples 28-274-9R-2,15-19 cm; 28-274-9R-2,48-52 cm; and 28-274-9R-2,65-69 cm). Based on the diatom and radiolarian biostratigraphic data, the ages of these samples range from 3.00 to 3.01 Ma. The relative abundance of N. sp. cf. N. lachlaniae in the three samples is an order of magnitude higher than relative abundances for the other species of Nothofagidites in the same samples. The signiticantly higher relative abundance of N. sp. cf. N. luchlaniae suggests that this pollen was derived from trees of Nothofugus that were living in Antarctica during the mid Pliocene. Diatom assemblages from these three samples indicate that sediments in this interval were rapidly deposited as biogenic oozes in an open-ocean setting relatively free of sea ice, thus decreasing the possibility of reworking from a single source bed rich in N. sp. cf. N. lachlaniae. Clearly, more detailed work in additional well-dated cores from around Antarctica is needed before a clear picture of the Neogene history of Antarctic terrestrial vegetation emerges.

Discription of coastal shape at Bykovsky Peninsula

This article presents a comparison of sediment input by rivers and by coastal erosion into both the Laptev Sea and the Canadian Beaufort Sea (CBS). New data on coastal erosion in the Laptev Sea, which are based on field measurements and remote sensing information, and existing data on coastal erosion in the CBS as well as riverine sediment discharge into both the Laptev Sea and the CBS are included. Strong regional differences in the percentages of coastal erosion and riverine sediment supply are observed. The CBS is dominated by the riverine sediment discharge (64.45210**6 t/a) mainly of the Mackenzie River, which is the largest single source of sediments in the Arctic. Riverine sediment discharge into the Laptev Sea amounts to 24.10210**6 t/a, more than 70% of which are related to the Lena River. In comparison with the CBS, the Laptev Sea coast on average delivers approximately twice as much sediment mass per kilometer, a result of higher erosion rates due to higher cliffs and seasonal ice melting. In the Laptev Sea sediment input by coastal erosion (58.4210**6 t/a) is therefore more important than in the CBS and the ratio between riverine and coastal sediment input amounts to 0.4. Coastal erosion supplying 5.6210**6 t/a is less significant for the sediment budget of the CBS where riverine sediment discharge exceeds coastal sediment input by a factor of ca. 10.

Chemistry of upper Eocene microtektites

Late Eocene microtektites and crystal-bearing microkrystites extracted from DSDP and ODP cores from the Atlantic, Pacific, and Indian oceans have been analyzed to address their provenance. A new analysis of Nd and Sr isotopic compositions confirms previous work and the assignment of the uppermost microtektite layer to the North American tektites, which are associated with the 35.5 Ma, 85 km diameter Chesapeake impact structure of Virginia, USA. Extensive major element and Nd and Sr isotopic analyses of the microkrystites from the lowermost layer were obtained. The melanocratic microkrystites from Sites 216 and 462 in the Indian and Pacific oceans possess major element chemistries, Sr and Nd isotopic signatures and Sm-Nd, T CHUR, model ages similar to those of tagamite melt rocks in the Popigai impact structure. They also possess Rb-Sr, T UR, model ages that are younger than the tagamite TCHUR ages by up to ~1 Ga, which require a process, as yet undefined, of Rb/Sr enrichment. These melanocratic microkrystites are consistent with a provenance from the 35.7 Ma, 100 km diameter Popigai impact structure of Siberia, Russia, while ruling out other contemporaneous structures as a source. Melanocratic microkrystites from other sites and leucocratic microkrystites from all sites possess a wide range of isotopic compositions (epsilon (143Nd) values of -16 to -27.7 and epsilon (87Sr) values of 4.1-354.0), making the association with Popigai tagamites less clear. These microkrystites may have been derived by the melting of target rocks of mixed composition, which were ejected without homogenization. Dark glass and felsic inclusions extracted from Popigai tagamites possess epsilon (143Nd) and epsilon (87Sr) values of -26.7 to -27.8 and 374.7 and 432.4, respectively, and T CHUR and T UR model ages of 1640-1870 Ma and 240-1830 Ma, respectively, which require the preservation of initially present heterogeneity in the source materials. The leucocratic microkrystites possess diverse isotopic compositions that may reflect the melting of supra-basement sedimentary rocks from Popigai, or early basement melts that were ejected prior to homogenization of the Popigai tagamites. The ejection of melt rocks with chemistries consistent with a basement provenance, rather than the surface ~1 km of sedimentary cover rocks, atypically indicates a non-surficial source to some of the ejecta. Microkrystites from two adjacent biozones possess statistically indistinguishable major element compositions, suggesting they have a single source. The occurrence of microkrystites derived from a single impact event, but in different biozones, can be explained by: (1) diachronous biozone boundaries; (2) post-accumulation sedimentary reworking; or (3) erroneous biozonation.

Age model and stable isotope record of DSDP holes 48-401 and 86-577

Early Paleogene warm climates may have been linked to different modes and sources of deepwater formation. Warm polar temperatures of the Paleocene and Eocene may have resulted from either increased atmospheric trace gases or increased heat transport through deep and intermediate waters. The possibility of increasing ocean heat transport through the production of warm saline deep waters (WSDW) in the Tethyan region has generated considerable interest. In addition, General Circulation Model results indicate that deepwater source regions may be highly sensitive to changing basin configurations. To decipher deepwater changes, we examined detailed benthic foraminiferal faunal and isotopic records of the late Paleocene through the early Eocene (~60 to 50 Ma) from two critical regions: the North Atlantic (Bay of Biscay Site 401) and the Pacific (Shatsky Rise Site 577). These records are compared with published data from the Southern Ocean (Maud Rise Site 690, Islas Orcadas Rise Site 702). During the late Paleocene, similar benthic foraminiferal delta18O values were recorded at all four sites. This indicates uniform deepwater temperatures, consistent with a single source of deep water. The highest delta13C values were recorded in the Southern Ocean and were 0.5 per mil more positive than those of the Pacific. We infer that the Southern Ocean was proximal to a source of nutrient-depleted deep water during the late Paleocene. Upper Paleocene Reflector Ab was cut on the western Bermuda Rise by cyclonically circulating bottom water, also suggesting a vigorous source of bottom water in the Southern Ocean. A dramatic negative excursion in both carbon and oxygen isotopes occurred in the latest Paleocene in the Southern Ocean. This is a short-term (<100 kyr), globally synchronous event which also is apparent in both the Atlantic and Pacific records as a carbon isotopic excursion of approximately 1 per mil. Faunal analyses from the North Atlantic and Pacific sites indicate that the largest benthic foraminiferal faunal turnover of the Cenozoic was synchronous with the isotopic excursion, lending support to the hypothesis that the extinctions were caused by a change in deepwater circulation. We speculate that the Southern Ocean deepwater source was reduced or eliminated at the time of the excursion. During the early Eocene, Southern Ocean delta13C values remained enriched relative to the North Atlantic and Pacific. However, the Southern Ocean was also enriched in delta18O relative to these basins. We interpret that these patterns indicate that although the Southern Ocean was proximal to a source of cool, nutrient-depleted water, the intermediate to upper deep water sites of the North Atlantic and Pacific were ventilated by a different source that probably originated in low latitudes, i.e., WSDW.

Modular extensions for modular (Logic) languages

We address the problem of developing mechanisms for easily implementing modular extensions to modular (logic) languages. By(language) extensions we refer to different groups of syntactic definitions and translation rules that extend a language. Our use of the concept of modularity in this context is twofold. We would like these extensions to be modular, in the sense above, i.e., we should be able to develop different extensions mostly separately. At the same time, the sources and targets for the extensions are modular languages, i.e., such extensions may take as input sepárate pieces of code and also produce sepárate pieces of code. Dealing with this double requirement involves interesting challenges to ensure that modularity is not broken: first, combinations of extensions (as if they were a single extensión) must be given a precise meaning. Also, the sepárate translation of múltiple sources (as if they were a single source) must be feasible. We present a detailed description of a code expansion-based framework that proposes novel solutions for these problems. We argüe that the approach, while implemented for Ciao, can be adapted for other Prolog-based systems and languages.

Towards modular extensions for a modular language

Modularity allows the construction of complex designs from simpler, independent units that most of the time can be developed separately. In this paper we are concerned with developing mechanisms for easily implementing modular extensions to modular (logic) languages. By (language) extensions we refer to different groups of syntactic definitions and translation rules that extend a language. Our application of the concept of modularity in this context is twofold. We would like these extensions to be modular, in the above sense, i.e., we should be able to develop different extensions mostly separately. At the same time, the sources and targets for the extensions are modular languages, i.e., such extensions may take as input separate pieces of code and also produce separate pieces of code. Dealing with this double requirement involves interesting challenges to ensure that modularity is not broken: first, combinations of extensions (as if they were a single extension) must be given a precise meaning. Also, the separate translation of multiple sources (as if they were a single source) must be feasible. We present a detailed description of a code expansion-based framework that proposes novel solutions for these problems. We argue that the approach, while implemented for Ciao, can be adapted for other languages and Prolog-based systems.

Entanglement Distribution in Quantum Metropolitan Optical Networks

The ability to generate entangled photon-pairs over a broad wavelength range opens the door to the simultaneous distribution of entanglement to multiple users of a network using a single source and wavelength-division multiplexing technologies. Here we show the design of a metropolitan optical network made of tree-type access networks where entangled photon-pairs are distributed to any pair of users, independently of their location. The resulting network improves the reach, number of users and capabilities of existing proposals. Moreover, it is made up of typical commercial components and uses the existing infrastructure, which allows for moderate deployment costs. Finally, we develop a channel plan and a network design that allow direct optical communications, quantum and classical, between any pair of users. Therefore, multiple quantum information technologies can make use of this network.

Propuesta de libro de texto: fundamentos de bases de datos, saber y hacer

Through the years, we have detected a problem in the academic program of Information and Communication Technologies of our University, a recurrent problem in the teaching learning process, accentuated with the associated paradigm to the construction of knowledge by the own pupil. We are specifically referring to the search and assimilation of content inside the book texts about Digital Databases. The work exposed in this paper represents an effort for contributing in the reduction of educational slump in areas related to good design and construction of data banks. The textbook of this research, treats all the thematical content in this area, which are studied in the whole academic program. These and another relevant subjects in the database area are retaken from a simple but fundamentally practical theorical focus, allowing the studying on acquiring a significative learning in an easier and single source way. As a result, we present the almost definitive version of the book which is been tested on pilot groups

Collecting and harvesting biological data: the GPCRDB and NucleaRDB information systems

The amount of genomic and proteomic data that is entered each day into databases and the experimental literature is outstripping the ability of experimental scientists to keep pace. While generic databases derived from automated curation efforts are useful, most biological scientists tend to focus on a class or family of molecules and their biological impact. Consequently, there is a need for molecular class-specific or other specialized databases. Such databases collect and organize data around a single topic or class of molecules. If curated well, such systems are extremely useful as they allow experimental scientists to obtain a large portion of the available data most relevant to their needs from a single source. We are involved in the development of two such databases with substantial pharmacological relevance. These are the GPCRDB and NucleaRDB information systems, which collect and disseminate data related to G protein-coupled receptors and intra-nuclear hormone receptors, respectively. The GPCRDB was a pilot project aimed at building a generic molecular class-specific database capable of dealing with highly heterogeneous data. A first version of the GPCRDB project has been completed and it is routinely used by thousands of scientists. The NucleaRDB was started recently as an application of the concept for the generalization of this technology. The GPCRDB is available via the WWW at http://www.gpcr.org/7tm/ and the NucleaRDB at http://www.receptors.org/NR/.

Guidelines for Forensic Report Writing: Helping Trainees Understand Common Pitfalls to Improve Reports

A forensic report is the primary work product of a forensic psychologist. The aim of a forensic report is to inform and influence the court. Unlike a clinical report, a forensic report influences the outcome of a legal conflict. This means that greater care must be taken in writing the report. The following errors (Grisso, 2010) were used to discuss best practices in forensic report writing: failure to answer the referral question, organization problems, language problems, mixed data and interpretation, inclusion of irrelevant data, over-reliance on a single source of data, improper psychological test use, failure to consider alternative hypotheses, and opinions without sufficient explanation. The purpose of this paper is to provide in one place all the information needed to improve forensic report writing, and to help the reader apply the literature using specific examples. Redacted report samples were collected from psychologists, graduate psychology trainees, teaching assistant experience, and clinical work. Identified errors in these samples were then corrected using the recommendations in the literature. Geared toward graduate psychology trainees, each section should serve both as a tutorial and as a brief checklist to help the reader avoid common pitfalls and assist in promoting better forensic report writing.