53,922 research outputs found
Opern Ausw / 5 Wohlfeile Ausgabe von W. A. Mozart's sämmtlichen Opern
KV 384Bibliograph. Nachweis: RISM A/I: M 4256 ; Höft, Ein Mannheimer Musikverleger als Wegbereiter des klassischen Erbes, S. 167Textverf. ermitteltVorlageform des Erscheinungsvermerks: Mannheim bei Karl Ferdinand Heckel ; Druckerey von K. F Heckel. W: T: ; Sub. Pr. f 4. Lad. Pr. f 6LithographieText dt. u. ital
Molecular Epidemiology of Hepatitis B Virus Variants in Nonhuman Primates
ABSTRACT
We characterized hepatitis B virus (HBV) isolates from sera of 21 hepatitis B virus surface antigen-positive apes, members of the families
Pongidae
and
Hylobatidae
(19 gibbon spp., 1 chimpanzee, and 1 gorilla). Sera originate from German, French, Thai, and Vietnamese primate-keeping institutions. To estimate the phylogenetic relationships, we sequenced two genomic regions, one located within the pre-S1/pre-S2 region and one including parts of the polymerase and the X protein open reading frames. By comparison with published human and ape HBV isolates, the sequences could be classified into six genomic groups. Four of these represented new genomic groups of gibbon HBV variants. The gorilla HBV isolate was distantly related to the chimpanzee isolate described previously. To confirm these findings, the complete HBV genome from representatives of each genomic group was sequenced. The HBV isolates from gibbons living in different regions of Thailand and Vietnam could be classified into four different phylogenetically distinct genomic groups. The same genomic groups were found in animals from European zoos. Therefore, the HBV infections of these apes might have been introduced into European primate-keeping facilities by direct import of already infected animals from different regions in Thailand. Taken together, our data suggest that HBV infections are indigenous in the different apes. One event involving transmission between human and nonhuman primates in the Old World of a common ancestor of human HBV genotypes A to E and the ape HBV variants might have occurred.
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The Bowen–Conradi syndrome protein Nep1 (Emg1) has a dual role in eukaryotic ribosome biogenesis, as an essential assembly factor and in the methylation of Psi1191 in yeast 18S rRNA
The Nep1 (Emg1) SPOUT-class methyltransferase is an essential ribosome assembly factor and the human Bowen–Conradi syndrome (BCS) is caused by a specific Nep1D86G mutation. We recently showed in vitro that Methanocaldococcus jannaschii Nep1 is a sequence-specific pseudouridine-N1-methyltransferase. Here, we show that in yeast the in vivo target site for Nep1-catalyzed methylation is located within loop 35 of the 18S rRNA that contains the unique hypermodification of U1191 to 1-methyl-3-(3-amino-3-carboxypropyl)-pseudouri-dine (m1acp3Psi). Specific 14C-methionine labelling of 18S rRNA in yeast mutants showed that Nep1 is not required for acp-modification but suggested a function in Psi1191 methylation. ESI MS analysis of acp-modified Psi-nucleosides in a DeltaNep1-mutant showed that Nep1 catalyzes the Psi1191 methylation in vivo. Remarkably, the restored growth of a nep1-1ts mutant upon addition of S-adenosylmethionine was even observed after preventing U1191 methylation in a deltasnr35 mutant. This strongly suggests a dual Nep1 function, as Psi1191-methyltransferase and ribosome assembly factor. Interestingly, the Nep1 methyltransferase activity is not affected upon introduction of the BCS mutation. Instead, the mutated protein shows enhanced dimerization propensity and increased affinity for its RNA-target in vitro. Furthermore, the BCS mutation prevents nucleolar accumulation of Nep1, which could be the reason for reduced growth in yeast and the Bowen-Conradi syndrome
Acoustic radiation due to scattering of T-S wave by the mean-flow distortion induced by steady local suction
Substantial sound waves can be generated by boundary-layer instability modes when the latter are scattered by a rapid mean-flow distortion. This is a rather generic mechanism and operates when an oncoming T-S wave is scattered by a steady local suction slot. This paper focuses on this problem by extending a recently developed Local Scattering Theory (Wu & Dong, J. Fluid Mech. submitted), where a so-called transmission coefficient, defined as the ratio of the T-S wave amplitude downstream of the scatter to that upstream, is introduced to characterize the effect of a local scatter on boundary-layer instability and transition. As in the earlier work, the mathematical formulation is based on triple-deck formulism, but in order to accommodate the acoustic far field, which was not considered in the paper mentioned, the unsteady terms in the upper deck, which play a leading-order role in radiation, are retained, and the influence of the radiated sound on the near-wall perturbation is included. The upper deck equation for the pressure is the Helmholtz equation rather than the Laplace equation. This leads to a modified pressure-displacement relation, which is coupled with the linearized boundary-layer equations in the lower deck. Discretization of the whole system formulates a generalized eigenvalue problem, which is solved numerically. It is found that suction suppresses oncoming T-S waves, and this effect increases with the suction velocity and the slot width. The directivity is ndependent of the flow parameters only when the Mach number is low. The intensity of the radiated sound in general increases with the frequency, the suction velocity and the width of the suction slot. Interestingly, for O(1) suction velocities, the radiated sound is very weak, indicating that the gain of stabilizing effect does not cause aeroacoustic penalty
Pharmaceutical powder compressibility - a science-based approach
Background:
The compressibility is a crucial property of powder formulations. For being able to compress a powder mixture to tablets with satisfactory pharmacocinetical behaviour, its compressibility has to be within a certain range.
Especially nowadays, where powder formulations for tablets can contain a big number of different compounds, a reliable determination and monitoring of the compressibility is very important.
Objective:
Investigation of three methods to determine powder compressibility (Heckel-Plot, modified Heckel-Plot, Leuenberger equation) with focus on their scientific reliability and their ability to show the influence of small composition adjustments to the compressibility of the formulation.
Development of a method to determine and monitor powder compressibility and additional quality aspects by scanning the final tablet with Near-Infrared Spectroscopy.
Materials and Methods:
Binary mixtures of poorly compressible API and well-compressible excipient were compressed to tablets within a range of relative densities. The compaction pressure, the relative density of the tablet and its tensile strength were used to calculate the compressibility value of the formulation. In a second step, the API of the formulation was increased to detect and investigate the change of the compressibility values.
An investigation with compaction and analysis of the final compacts was performed with 12 different powder formulations. Relative density and tensile strength were the main investigation targets since these elements are used to establish the powder compressibility with the chosen approaches.
One part of the final compacts was tested for relative density and tensile strength with the traditional method, while another part of the tablet collection was investigated with Near-Infrared Spectroscopy. These research steps led to a development of a method for compressibility determination with Near-Infrared Spectroscopy.
Results and Discussion:
The results of the investigated binary mixtures showed the values for compressibility to be really individual for the three different approaches. Additionally, it could be shown that the change of the compressibility value with increase of the poorly-compressible API led to individually different changes in compressibility values for the three different plots.
The developed NIR-method showed really similar results in comparison to the traditional method for the compressibility values, calculated with the Heckel-Plot and the modified Heckel-Plot. Additionally the values of relative density and tensile strength could be detected in a reliable way with the established method.
Conclusion:
The importance of a reliable compressibility determination and all the challenges associated with it could be shown clearly with the research work of this thesis. Especially the sensitivity of the chosen method to small variations within the formulation could be identified and shown.
The developed NIR-method showed promising results and underlined its usability for online monitoring of the tablet production and of the final compact quality
Measuring industry-science links through inventor-author relations: A profiling method
In this pilot study we examine the performance of text-based profiling in recovering a set of validated inventor-author links. In a first step we match patents and publications solely based on their similarity in content. Next, we compare inventor and author names on the highest ranked matches for the occurrence of name matches. Finally, we compare these candidate matches with the names listed in a validated set of inventor-author names. Our text-based profile methodology performs significantly better than a random matching of patents and publications, suggesting that text-based profiling is a valuable complementary tool to the name searches used in previous studies.innovation; industry-science links; text-based profiling;
The maternal immune system during pregnancy and its influence on fetal development
The maternal immune system plays a critical role in the establishment, maintenance, and completion of a healthy pregnancy. However, the specific mechanisms utilized to achieve these goals are not well understood. Various cells and molecules of the immune system are key players in the development and function of the placenta and the fetus. Effector cells of the immune system act to promote and yet limit placental development. The T helper 1 (Th1)/T helper 2 (Th2) immune shift during pregnancy is well established. A fine balance between proinflammatory and anti-inflammatory influences is required. We herein review the evidence regarding maternal tolerance of fetal tissues and the underlying cell-mediated immune and humoral (hormones and cytokines) mechanisms. We also note the many unanswered questions in our understanding of these mechanisms. In addition, we summarize the clinical manifestations of an altered maternal immune system during pregnancy related to susceptibility to common viral, bacterial, and parasitic infections, as well as to autoimmune diseases.Peer reviewe
Comparison of terminally ill cancer- vs. non-cancer patients in specialized palliative home care in Germany – a single service analysis
Stiel S, Heckel M, Seifert A, Frauendorf T, Hanke RM, Ostgathe C. Comparison of terminally ill cancer- vs. non-cancer patients in specialized palliative home care in Germany – a single service analysis. BMC Palliative Care. 2015;14(1): 14
S-heterocyclic carbene with a disilane backbone
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Heterogeneous and tissue-specific regulation of effector T cell responses by IFN-gamma during Plasmodium berghei ANKA infection.
IFN-γ and T cells are both required for the development of experimental cerebral malaria during Plasmodium berghei ANKA infection. Surprisingly, however, the role of IFN-γ in shaping the effector CD4(+) and CD8(+) T cell response during this infection has not been examined in detail. To address this, we have compared the effector T cell responses in wild-type and IFN-γ(-/-) mice during P. berghei ANKA infection. The expansion of splenic CD4(+) and CD8(+) T cells during P. berghei ANKA infection was unaffected by the absence of IFN-γ, but the contraction phase of the T cell response was significantly attenuated. Splenic T cell activation and effector function were essentially normal in IFN-γ(-/-) mice; however, the migration to, and accumulation of, effector CD4(+) and CD8(+) T cells in the lung, liver, and brain was altered in IFN-γ(-/-) mice. Interestingly, activation and accumulation of T cells in various nonlymphoid organs was differently affected by lack of IFN-γ, suggesting that IFN-γ influences T cell effector function to varying levels in different anatomical locations. Importantly, control of splenic T cell numbers during P. berghei ANKA infection depended on active IFN-γ-dependent environmental signals--leading to T cell apoptosis--rather than upon intrinsic alterations in T cell programming. To our knowledge, this is the first study to fully investigate the role of IFN-γ in modulating T cell function during P. berghei ANKA infection and reveals that IFN-γ is required for efficient contraction of the pool of activated T cells
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