Population Frequencies Determined by Next-generation Sequencing Provide Strategies for Prospective HLA Epitope Matching for Transplantation

Compatibility for human leukocyte antigen (HLA) genes between transplant donors and recipients improves graft survival but prospective matching is rarely performed due to the vast heterogeneity of this gene complex. To reduce complexity, we have combined next-generation sequencing and in silico mapping to determine population frequencies and matching probabilities of 150 antibody-binding eplets across all 11 classical HLA genes in 2000 ethnically heterogeneous renal patients and donors. We show that eplets are more common and more uniformly distributed between donors and recipients than the respective HLA isoforms. Simulation of targeted eplet matching shows that a high degree of overall compatibility, and perfect identity at the clinically important HLA class II loci, can be obtained within a patient waiting list of approximately 250 subjects. Internal epitope-based allocation is thus feasible for most major renal transplant programs, while regional or national sharing may be required for other solid organs

High-throughput sequencing defines donor and recipient HLA B-cell epitope frequencies for prospective matching in transplantation

Compatibility for human leukocyte antigen (HLA) genes between transplant donors and recipients improves graft survival but prospective matching is rarely performed due to the vast heterogeneity of this gene complex. To reduce complexity, we have combined next-generation sequencing and in silico mapping to determine transplant population frequencies and matching probabilities of 150 antibody-binding eplets across all 11 classical HLA genes in 2000 ethnically heterogeneous renal patients and donors. We show that eplets are more common and uniformly distributed between donors and recipients than the respective HLA isoforms. Simulations of targeted eplet matching shows that a high degree of overall compatibility, and perfect identity at the clinically important HLA class II loci, can be obtained within a patient waiting list of approximately 250 subjects. Internal epitope-based allocation is thus feasible for most major renal transplant programs, while regional or national sharing may be required for other solid organs

Anticancer Evaluation of Adiantum venustum Don

Cancer is a malignant disease that is characterized by rapid and uncontrolled formation of abnormal cells which may mass together to form a growth or tumor, or proliferate throughout the body. Next to heart disease, cancer is a major killer of mankind. This study aims at a preliminary phytochemical screening and anticancer evaluation of Adiantum venustum Don against Ehrlich Ascites Carcinoma in animal model. The findings indicate that ethanolic extract of A. venustum Don possesses significant anticancer activity and also reduces elevated level of lipid peroxidation due to the presence of terpenoids and flavonoids. Thus, ethanolic extract of A. venustum Don could have vast therapeutic application against cancer

Global Diversity of the Stylasteridae (Cnidaria: Hydrozoa: Athecatae)

The history and rate of discovery of the 247 valid Recent stylasterid species are discussed and graphed, with emphasis on five historical pulses of species descriptions. A table listing all genera, their species numbers, and their bathymetric ranges are presented. The number of species in 19 oceanographic regions is mapped, the southwestern temperate Pacific (region including New Zealand) having the most species; species are cosmopolitan from the Arctic Circle to the Antarctic at depths from 0 to 2789 m. The current phylogenetic classification of the genera is briefly discussed. An illustrated glossary of 53 morphological characters is presented. Biological and ecological information pertaining to reproduction, development, commensals, and distribution is discussed. Aspects of stylasterid mineralogy and taxa of commercial value are discussed, concluding with suggestions for future work

The promotion of interest in the role of the physician associate as a potential career opportunity for nurses: An alternative strategy

Several frameworks are presented for understanding the development of interest in the role of the Physician Associate as a potential career opportunity for nurses. The contribution of professional role identification with nursing, medicine, and amalgamation of the two professions are explored as a basis for career choice. The usefulness of the current mobility model in health careers emphasizing differential vertical and horizontal mobility is contrasted with a classical sociological mobility model. Deficiencies are noted in both professional role identification and mobility models employing horizontal and vertical mobility as a basis for the development of interest in the role of the Physician Associate as a potential career opportunity for nurses.An examination of the factors implicit in the development of the Physician Associate in the emerging nations leads to significant understandings with regard to the development of interest in assuming some roles in those settings. Such cross cultural considerations make possible an integrated approach for understanding interest development of the Physician Associate. Attention is focused upon interest development as a function of: 1. 1. Individual competencies.2. 2. Aspirational patterns.3. 3. The structure of opportunities which are made available, as well as upon specific career strategies.Examination of these factors indicates that a major deterrent to career development by nurses in the role of Physician Associate is the pervasive psycho-sexual deference associated with current nursing practice. Attention to this factor in both training and practice setting is imperative in order to facilitate role alteration by nurses.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/33853/1/0000112.pd

Die Einführung der Kindergrundsicherung in Österreich - ein Modell der Volkshilfe

Soziale

Mutation of an L-type calcium channel gene leads to a novel primary cellular immunodeficiency in mice and humans

Human primary immunodeficiencies are inherited diseases that can provide valuable insight into our immune system. Calcium (Ca²⁺) is a vital secondary messenger in T cells that regulates a vast array of important events including maturation, homeostasis, activation, and apoptosis. The proper orchestration of Ca²⁺ signalling is essential to prevent immune related diseases. Upon antigen binding to the T cell receptor, extracellular Ca²⁺ enters the cell through CRAC, TRP and CaV channels. Here we describe a mutation in the L-type Ca²⁺ channel CaV1.4 leading to a novel immunological disorder. Three CaV1.4-deficient siblings presented with X-linked incomplete congenital stationary night blindness as well as recurrent infections, autoimmunity and pro-inflammatory cytokine production. The subjects uniformly exhibited a T cell memory phenotype and T cell exhaustion as well as chronic activation of their B cells. Moreover, their T cells but not B cells exhibited a reduced Ca²⁺ flux, compared to healthy control donors. This is the first example where the mutation of any CaV channel causes a primary immunodeficiency in humans and establishes their physiological importance in the immune system. In parallel, we detected a remarkably similar phenotype in a CaV1.4-deficient mouse model. In a separate set of experiments, a commercially available C57BL/6 mouse strain harbouring an undescribed mutation in Dock2, was introduced into our breeding stock resulting in some mice with a double deficiency of DOCK2 and CaV1.4. This provided the opportunity to assess the compound phenotype. We found that the double-deficient mouse model exhibited severe splenic cytopenia as well as chronic B cell activation but impaired BCR-induced activation / Ca²⁺ mobilization.Science, Faculty ofMicrobiology and Immunology, Department ofGraduat

Determination of the uncertainty parameters for total reflection X-ray fluorescence analysis

Arbeit an der Bibliothek noch nicht eingelangt - Daten nicht geprüftAbweichender Titel nach Übersetzung der Verfasserin/des VerfassersRöntgenfluoreszenzanalyse ist eine analytische Methode, die es erlaubt die elementare Zusammensetzung von unterschiedlichen Proben qualitativ und quantitativ zerstörungsfrei zu bestimmen. Totalreflexions-Röntgenfluoreszenzanalyse (TX- RF) ist eine energiedispersive Röntgenfluoreszenzanalyse mit einem speziellen Versuchsaufbau. Dabei wird die Probe auf einem Reflektor mit einer glatten Oberfläche platziert und der einfallende Röntgenstrahl regt diese Probe unterhalb des kritischen Winkels für Totalreflexion an. Der Detektor ist knapp über der Probe montiert und detektiert daher einen großen Raumwinkel der von der Probe emittierten Fluoreszenzstrahlung. Das führt verglichen mit konventioneller energiedispersiver Röntgenfluoreszenzanalyse zu einem deutlich besseren Signal zu Hintergrund Verhältnis. Mittels TXRF kann die elementare Zusammensetzung von flüssigen und pulverförmigen Proben qualitativ und quantitativ ermittelt werden.Am Atominstitut der TU Wien sind zwei baugleiche TXRF-Spektrometer 8030C der Firma Atomika Instruments GmbH vorhanden. Das Ziel dieser Arbeit ist die Bestimmung der Messunsicherheit für dieses Spektrometer. Dafür wurde zunächst die Sensitivity auf beiden Anlagen bestimmt. Aus den für die Bestimmung der Sensitivity gewonnen Daten wurde die Unsicherheit der Sensitivity ermittelt. Um die vollständige Messunsicherheit zu bestimmen wurde mit weiteren Messungen die Unsicherheit der Repeatability und die Unsicherheit der Probendeposition abgeschätzt. Abschließend wird die in dieser Arbeit ermittelte Messunsicherheit anhand zweier Standardreferenzmaterialien validiert. Für die Quantifizierung der Messergebnisse wurde ein Python Skript programmiert. Das Python Skript berechnet unter Verwendung des bei einer Messung erzeugten Resultfiles und anderen Eingabeparametern die vollständige Quantifizierung inklusive Messunsicherheit. Das Ergebnis wird in Form eines Excel-Files ausgegeben. Neben der Bestimmung der Messunsicherheit wurde im Laufe dieser Arbeit auch eine Reihe von pulverförmigen Nanopartikel- Proben quantifiziert.X-ray fluorescence (XRF) spectrometry is an analytical method that allows the de- termination the elemental composition of a sample both qualitatively and quantita- tively in a non-destructive way. Total reflection x-ray fluorescence (TXRF) analysis is an energy dispersive XRF analysis with a special experimental setup. The sample is placed on a reflector and is irradiated by x-rays within the critical angle of total reflection. The detector is placed just above the sample and thus can detect a great solid angle of the emitted x-ray fluorescence radiation. Compared to conventional energy dispersive XRF analysis the signal-to-noise ratio in TXRF is greatly impro- ved. Using TXRF the elemental composition of both liquid and pulverized samples can be obtained.At the Atominstitut of the TU Wien there are two TXRF-spectrometers 8030C by the company Atomika Instruments GmbH. The goal of this masters thesis is the estimation of the global measurement uncertainty of the TXRF spectrometer Atomika 8030C. First of all, the sensitivity of both spectrometers was determined. From the obtained data of the determination of the sensitivity the uncertainty of the sensitivity was estimated. To further determine the measurement uncertainty the uncertainty of the repeatability and the uncertainty of the sample deposition was estimated. Finally, the obtained uncertainty was validated using two certified standard reference materials. For the quantification of the samples a python script was programmed. This script uses the result-file obtained from a measurement and other input parameters to calculate the global uncertainty. The quantification including the uncertainty is exported to an excel-file. In addition to the estimation of the measurement uncertainty of the spectrometer a number of pulverized samples was quantified in this work.13