306 research outputs found
Vergleich zwischen elektrisch und durch fossilen Brennstoff angetriebenen Fahrkonzepten
Elektrofahrzeuge gelten als nachhaltige Alternative zu konventionellen Antriebskonzepten. Die Entscheidung für ein Konzept muss aller dings diverse Kriterien berücksichtigen. Welche dieser Technologien sind in einer kosten- und emissionsspezifischen Gegenüberstellung vorteilhaft
Randomised, double-blind, placebo-controlled trial of oral budesonide for prophylaxis of acute intestinal graft-versus-host disease after allogeneic stem cell transplantation (PROGAST)
Background Gastrointestinal graft–versus-host disease (GvHD) is a potentially
life-threatening complication after allogeneic stem cell transplantation
(SCT). Since therapeutic options are still limited, a prophylactic approach
seems to be warranted. Methods In this randomised, double-blind-phase III
trial, we evaluated the efficacy of budesonide in the prophylaxis of acute
intestinal GvHD after SCT. The trial was registered at
https://clinicaltrials.gov webcite, number NCT00180089. Patients were randomly
assigned to receive either 3 mg capsule three times daily oral budesonide or
placebo. Budesonide was applied as a capsule with pH-modified release in the
terminal ileum. Study medication was administered through day 56, follow-up
continued until 12 months after transplantation. If any clinical signs of
acute intestinal GvHD appeared, an ileocolonoscopy with biopsy specimens was
performed. Results The crude incidence of histological or clinical stage 3–4
acute intestinal GvHD until day 100 observed in 91 (n =48 budesonide, n =43
placebo) evaluable patients was 12.5% (95% CI 3-22%) under treatment with
budesonide and 14% (95% CI 4-25%) under placebo (p = 0.888). Histologic and
clinical stage 3–4 intestinal GvHD after 12 months occurred in 17% (95% CI
6-28%) of patients in the budesonide group and 19% (CI 7-32%) in the placebo
group (p = 0.853). Although budesonide was tolerated well, we observed a trend
towards a higher rate of infectious complications in the study group (47.9%
versus 30.2%, p = 0.085). The cumulative incidences at 12 months of intestinal
GvHD stage >2 with death as a competing event (budesonide 20.8% vs. placebo
32.6%, p = 0.250) and the cumulative incidence of relapse (budesonide 20.8%
vs. placebo 16.3%, p = 0.547) and non-relapse mortality (budesonide 28% (95%
CI 15-41%) vs. placebo 30% (95% CI 15-44%), showed no significant difference
within the two groups (p = 0.911). The trial closed after 94 patients were
enrolled because of slow accrual. Within the limits of the final sample size,
we were unable to show any benefit for the addition of budesonide to standard
GvHD prophylaxis. Conclusions Budesonide did not decrease the occurrence of
intestinal GvHD in this trial. These results imply most likely that
prophylactic administration of budenoside with pH-modified release in the
terminal ileum is not effective
Precise Analysis of Polymer Rotational Dynamics
Through the analysis of individual chain dynamics alongside the corresponding molecular structures under shear via nonequilibrium molecular dynamics simulations of C178H358 linear and short-chain branched polyethylene melts under shear flow, we observed that the conventional method based on the chain end-to-end vector (and/or the gyration tensor of chain) is susceptible to quantitatively inaccurate measurements and often misleading information in describing the rotational dynamics of polymers. Identifying the flaw as attributed to strong irregular Brownian fluctuations inherent to the chain ends associated with their large free volume and strong molecular collisions, we propose a simple, robust way based on the chain center-to-center vector connecting the two centers of mass of the bisected chain, which is shown to adequately describe polymer rotational dynamics without such shortcomings. We present further consideration that the proposed method can be useful in accurately measuring the overall chain structure and dynamics of polymeric materials with various molecular architectures, including branched and ring polymers.open
Decatransin, a novel natural product inhibiting protein translocation at the Sec61/SecY translocon
A new cyclic decadepsipeptide was isolated from Chaetosphaeria tulasneorum with potent bioactivity on mammalian and yeast cells. Chemogenomic profiling in S. cerevisiae indicated that the Sec61 translocon, the machinery for protein translocation and membrane insertion at the endoplasmic reticulum, is the target. The profiles were similar to those of cyclic heptadepsipeptides of a distinct chemotype (HUN-7293/cotransin) that had previously been shown to inhibit cotranslational translocation at the mammalian Sec61 translocon. Unbiased, genome-wide mutagenesis followed by full-genome sequencing in both fungal and mammalian cells identified dominant mutations in Sec61p/Sec61α1 to confer resistance. Most, but not all, of these mutations affected inhibition by both chemotypes, despite an absence of structural similarity. Biochemical analysis confirmed inhibition of protein translocation into the endoplasmic reticulum of both co- and posttranslationally translocated substrates by both chemotypes, demonstrating a mechanism independent of a translating ribosome. Most interestingly, both chemotypes were found to also inhibit SecYEG, the bacterial Sec61 homolog. We suggest "decatransin" as the name for this novel decadepsipeptide translocation inhibitor
Improving the effectiveness of sickness benefit case management through a public-private partnership? A difference-in-difference analysis in eighteen Danish municipalities
Adhesion Class GPCRs (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database
Adhesion GPCRs are structurally identified on the basis of a large extracellular region, similar to the Class B GPCR, but which is linked to the 7TM region by a GPCR autoproteolysis-inducing (GAIN) domain [8] containing a GPCR proteolytic site. The N-terminus often shares structural homology with adhesive domains (e.g. cadherins, immunolobulin, lectins) facilitating inter- and matricellular interactions and leading to the term adhesion GPCR [82, 332]. Several receptors have been suggested to function as mechanosensors [254, 234, 315, 32]. The nomenclature of these receptors was revised in 2015 as recommended by NC-IUPHAR and the Adhesion GPCR Consortium [100]
Adhesion Class GPCRs in GtoPdb v.2023.1
Adhesion GPCRs are structurally identified on the basis of a large extracellular region, similar to the Class B GPCR, but which is linked to the 7TM region by a GPCR autoproteolysis-inducing (GAIN) domain [10] containing a GPCR proteolysis site (GPS). The N-terminal extracellular region often shares structural homology with adhesive domains (e.g. cadherins, immunolobulin, lectins) facilitating inter- and matricellular interactions and leading to the term adhesion GPCR [104, 418]. Several receptors have been suggested to function as mechanosensors [320, 288, 396, 38]. Cryo-EM structures of the 7-transmembrane domain of several adhesion GPCRs have been determined recently [292, 21, 403, 212, 300, 302, 431, 293]. The nomenclature of these receptors was revised in 2015 as recommended by NC-IUPHAR and the Adhesion GPCR Consortium [125]
Adhesion Class GPCRs in GtoPdb v.2021.3
Adhesion GPCRs are structurally identified on the basis of a large extracellular region, similar to the Class B GPCR, but which is linked to the 7TM region by a GPCR autoproteolysis-inducing (GAIN) domain [9] containing a GPCR proteolytic site. The N-terminus often shares structural homology with adhesive domains (e.g. cadherins, immunolobulin, lectins) facilitating inter- and matricellular interactions and leading to the term adhesion GPCR [101, 403]. Several receptors have been suggested to function as mechanosensors [309, 280, 383, 35]. The nomenclature of these receptors was revised in 2015 as recommended by NC-IUPHAR and the Adhesion GPCR Consortium [122]
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