Recombinant modified vaccinia virus Ankara-simian immunodeficiency virus gag pol elicits cytotoxic T lymphocytes in rhesus monkeys detected by a major histocompatibility complex class I/peptide tetramer

The utility of modified vaccinia virus Ankara (MVA) as a vector for eliciting AIDS virus-specific cytotoxic T lymphocytes (CTL) was explored in the simian immunodeficiency virus (SIV)/rhesus monkey model. After two intramuscular immunizations with recombinant MVA-SIVSM gag pol, the monkeys developed a Gag epitope-specific CTL response readily detected in peripheral blood lymphocytes by using a functional killing assay. Moreover, those immunizations also elicited a population of CD8+ T lymphocytes in the peripheral blood that bound a specific major histocompatibility complex class I/peptide tetramer. These Gag epitope-specific CD8+ T lymphocytes also were demonstrated by using both functional and tetramer-binding assays in lymph nodes of the immunized monkeys. These observations suggest that MVA may prove a useful vector for an HIV-1 vaccine. They also suggest that tetramer staining may be a useful technology for monitoring CTL generation in vaccine trials in nonhuman primates and in humans.     

Untersuchungen im Dreistoffsystem Eisen (II)-oxid–Chrom(III)-oxid–Tonerde

Schrifttumsübersicht über die beteiligten Randsysteme. Klärung der Frage, welche Fassung des Zustandsschaubildes Eisen(II)-oxid–Tonerde zutreffend ist, mit Hilfe von Schmelzen im Tonerdetiegel. Ermittlung des Schmelzpunktes des Hercynits. Sättigungsisothermen eisen(II)-oxidreicher Schlacken an Hercynit. Untersuchung des quasibinären Schnittes Hercynit–Chromit mit Röntgenfeinstruktur- und Mikrosondenmessungen. Entwurf des Zustandsschaubildes FeO–Cr₂O₃–Al₂O₃.     

Deep desulfurization of diesel oil: kinetic studies and process-improvement by the use of a two-phase reactor with pre-saturator

Desulfurization of liquid fuels is usually obtained by heterogeneous catalyzed hydrodesulfurization (HDS). Improvement of this process is needed, particularly with respect to future low residual S-contents of about . Up to now HDS of diesel oil is performed in a trickle bed reactor equipped with an expensive H₂-recycle, although the H₂-supply is far beyond the amount chemically consumed, at least for deep HDS of an already hydrotreated feed. In addition, scale up of trickle bed reactors is in general problematic. In this work kinetic studies and above all a new HDS-concept using a two-phase reactor is presented. Thereby the oil is externally pre-saturated with H₂ and only the liquid phase is passed over the catalytic fixed bed. The H₂-recycle is then redundant, the intrinsic reaction rate can be utilized, and scale-up problems do not occur. In addition, this concept can also be used for HDS of oils with a higher content of sulfur and/or unsaturated hydrocarbons by installing a liquid recycle.     

Changes of physicochemical indicators during mastitis and the effects of milk ejection on their sensitivity

We examined the relationship between physicochemical indicators and somatic cells in the milk of dairy cows during experimentally induced mastitis and their significance as indicators for use in controlling udder health. We were concerned particularly with the effect of alveolar milk ejection on the sensitivity of these indicators. In Expt 1, Escherichia coli lipopolysaccharide (Esch. coli LPS) was injected into the left rear quarter to induce an inflammatory reaction in one quarter in each of six cows. The contralateral control quarter was injected with a solution of NaCl (9 g/l). Nine milk samples were taken from both quarters until 60 h after injection. In Expt 2, repeated milk samples were taken every 20 s from one quarter during a 120-s teat stimulation in 20 cows with different somatic cell counts (SCC). Quarters were clustered for low (<5.0 log cells/ml), mid (5.0-5.7 log cells/ml) and high (>5.7 log cells/ml) SCC of the sample taken at t=0 s. Samples were analysed for SCC, electrical conductivity (EC) and Na+ and Cl- concentrations. During the experimental inflammation SCC, EC, Na+ and Cl- peaked at 12 h from LPS administration and values in treated quarters (T) at this time were elevated to 7900, 157, 501 and 169% of the values in untreated quarters, respectively. In Expt 2, SCC, EC, Na+ and Cl- in high SCC quarters were 2520, 121, 283 and 141% of low SCC quarters at the start of stimulation (t=0 s), respectively. Highly significant (P<0.001) differences in EC, Na+ and Cl- between high and low SCC quarters disappeared owing to the onset of alveolar milk ejection 100 s after the first contact with the teat. In conclusion, SCC in cows' milk provided the strongest amplitude in the case of an intramammary inflammation. EC, Na+ or Cl- were useful tools only if the measurements were performed in cisternal milk before the start of alveolar milk ejection.     

An improved transitive closure algorithm

Several efficient transitive closure algorithms operate on the strongly connected components of a digraph, some of them using Tarjan's algorithm [17]. Exploiting facts from graph theory and the special properties of Tarjan's algorithm we develop a new, improved algorithm. The transitive reduction of a digraph defined in [1] may be obtained as a byproduct.     

KlROM2 encodes an essential GEF homologue in Kluyveromyces lactis

Cellular integrity in yeasts is ensured by a rigid cell wall whose synthesis is controlled by a MAP kinase signal transduction cascade. In Saccharomyces cerevisiae upstream regulatory components of this MAP kinase pathway involve a single protein kinase C, which is regulated in part by interaction with the small GTPase Rho1p. This small G protein is in turn rendered inactive (GDP-bound) or is activated (GTP-bound) by the influence of GTPase activating proteins (GAPs) and the GDP/GTP exchange factors (GEFs), respectively. We report here on the isolation of a gene from Kluyveromyces lactis, KlROM2, which encodes a member of the latter protein family. The nucleotide sequence contains an open reading frame of 1227 amino acids, with an overall identity of 57% to the Rom2 protein of S. cerevisiae. Four conserved sequence motifs could be identified: a RhoGEF domain, a DEP sequence, a CNH domain and a less conserved pleckstrin homology (PH) sequence. Klrom2 null mutants show a lethal phenotype, which indicates that the gene may encode the only functional GEF regulating the cellular integrity pathway in K. lactis. Conditional genomic expression of KlROM2 resulted in sensitivity towards caffeine and Calcofluor white as typical phenotypes of mutants defective in this pathway. Overexpression of KIROM2 from multicopy plasmids under the control of the ScGAL1 promoter severely impaired growth in both S. cerevisiae and in K. lactis. The fact that the lethal phenotype was not prevented in mpk1 deletion mutants indicates that growth inhibition is not simply caused by hyperactivation of the Pkc1p signal transduction pathway.     

Molecular mechanisms of death-receptor-mediated apoptosis

Apoptosis, also called "programmed cell death", can be induced by a variety of stimuli including activation of death receptors by the corresponding death ligands. Death receptors are a subgroup of the tumor necrosis factor (TNF)/nerve growth factor (NGF) receptor superfamily and are characterized by a death domain, which is required for signal transduction. Upon apoptosis induction, caspases, a family of aspartyl-specific cysteine proteases, are activated, which are the main executioners of apoptosis. Finally, specific death substrates are cleaved, resulting in the morphologic features of apoptosis. Depending on the cell type, activation of mitochondria is of central significance for apoptosis induction. This signaling pathway can be modulated by different pro- and anti-apoptotic proteins such as Bax and Bcl-2, which are localized at the mitochondria. Furthermore, apoptosis initiation can be prevented at the death receptor level by FLICE (caspase-8)-inhibitory proteins (FLIPs). Deregulation of apoptosis is associated with diseases like cancer, autoimmunity, and AIDS. Therefore, the elucidation of cell death pathways and the identification of modulators of apoptosis have many therapeutic implications.     

Contingency management and levodopa-carbidopa for cocaine treatment: A comparison of three behavioral targets.

New data support use of levodopa pharmacotherapy with behavioral contingency management (CM) as one efficacious combination in cocaine dependence disorder treatment. A potential mechanism of the combined treatment effects may be related to dopamine-induced enhancement of the saliency of contingently delivered reinforcers. Evidence to support this mechanism was sought by evaluating levodopa-enhancing effects across distinct CM conditions that varied in behavioral targets. A total of 136 treatment-seeking, cocaine dependent subjects participated in this 12-week, randomized, placebo-controlled trial of levodopa (vs. placebo) administered in combination with one of three behavioral CM conditions. In the CM-URINE condition, subjects received cash-valued vouchers contingent on cocaine-negative urine toxicology results. In the CM-ATTEND condition, the same voucher schedule was contingent on attending thrice weekly clinic visits. In the CM-MEDICATION condition, the same voucher schedule was contingent on Medication Event Monitoring Systems- and riboflavin-based evidence of pill-taking behavior. Primary outcomes associated with each CM target behavior were analyzed using generalized linear mixed models for repeated outcomes. CM responding in the CM-ATTEND and CM-MEDICATION conditions showed orderly effects, with each condition producing corresponding changes in targeted behaviors, regardless of medication condition. In contrast, CM responding in the CM-URINE condition was moderated by medication, with levodopa-treated subjects more likely to submit cocaine-negative urines. These findings specify the optimal target behavior for CM when used in combination with levodopa pharmacotherapy. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

German developments in the ultrasonic examination of pressure vessels

The scene in non-destructive evaluation in the nuclear industry is characterized by the following keywords: basic safety due to optimized layout, design and fabrication; improved reliability of fracture mechanics; steadily increasing experience in in-service inspection; international round robins to demonstrate and compare already used and new testing techniques; significant improvements in testing techniques; new quantitative testing procedures and systems in ultrasonics, eddy current and radiography. Progress to date in ultrasonic developments will be described in terms of detectability of defects, quantitative reconstruction, and localization and classification (imaging) of defects. In addition the common background behind these methods will be explained.