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排序方式: 共有2408条查询结果,搜索用时 31 毫秒
1.
Bilal Alashkar Alhamwe Daniel P. Potaczek Sarah Miethe Fahd Alhamdan Lukas Hintz Arslan Magomedov Holger Garn 《International journal of molecular sciences》2021,22(9)
Extracellular vesicles (EVs) are membranous structures, which are secreted by almost every cell type analyzed so far. In addition to their importance for cell-cell communication under physiological conditions, EVs are also released during pathogenesis and mechanistically contribute to this process. Here we summarize their functional relevance in asthma, one of the most common chronic non-communicable diseases. Asthma is a complex persistent inflammatory disorder of the airways characterized by reversible airflow obstruction and, from a long-term perspective, airway remodeling. Overall, mechanistic studies summarized here indicate the importance of different subtypes of EVs and their variable cargoes in the functioning of the pathways underlying asthma, and show some interesting potential for the development of future therapeutic interventions. Association studies in turn demonstrate a good diagnostic potential of EVs in asthma. 相似文献
2.
Steffen Vojacek Lukas Schulig Nathalie Wössner Norman Geist Prof. Dr. Walter Langel Prof. Dr. Manfred Jung Prof. Dr. Dennis Schade Prof. Dr. Andreas Link 《ChemMedChem》2019,14(8):853-864
Indoles are privileged structures in medicinal and bioorganic chemistry that are particularly well suited to serve as platforms for diversity. Among many other therapeutic areas, the indole scaffold has been used to design aromatic compounds useful to interfere with enzymes engaged in the regulation of substrate acylation status, such as sirtuins. However, the planarity of the indole ring is not necessarily optimal for all target enzymes, especially when functionalization with aromatic side chains is required. Replacement of flat scaffolds by nonplanar molecular cores dominated by sp3 hybridization is a common strategy to avoid the disadvantages associated with poor solubility and high promiscuity, while covering less-well-explored areas of chemical space. Thus, we synthesized fragment-like tetrahydroindoles suitable for fragment-based drug discovery as well as a well-characterized small library intended as multipurpose screening compounds. For proof of principle, these compounds were screened against sirtuins 1–3, enzymes known to be addressable by indoles. We found that 2,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-1H-indole-3-carboxamides are potent and selective SIRT2 inhibitors. Compound 16 t displayed an IC50 value of 0.98 μm and could serve as exquisite starting point for hit-to-lead profiling. 相似文献
3.
Pavel Strunz Debashis Mukherji Přemysl Beran Ralph Gilles Lukas Karge Michael Hofmann Markus Hoelzel Joachim Rösler Gergely Farkas 《Metals and Materials International》2018,24(5):934-944
An addition of boron largely increases the ductility in polycrystalline high-temperature Co–Re alloys. Therefore, the effect of boron on the alloy structural characteristics is of high importance for the stability of the matrix at operational temperatures. Volume fractions of ε (hexagonal close-packed—hcp), γ (face-centered cubic—fcc) and σ (Cr2Re3 type) phases were measured at ambient and high temperatures (up to 1500 °C) for a boron-containing Co–17Re–23Cr alloy using neutron diffraction. The matrix phase undergoes an allotropic transformation from ε to γ structure at high temperatures, similar to pure cobalt and to the previously investigated, more complex Co–17Re–23Cr–1.2Ta–2.6C alloy. It was determined in this study that the transformation temperature depends on the boron content (0–1000 wt. ppm). Nevertheless, the transformation temperature did not change monotonically with the increase in the boron content but reached a minimum at approximately 200 ppm of boron. A probable reason is the interplay between the amount of boron in the matrix and the amount of σ phase, which binds hcp-stabilizing elements (Cr and Re). Moreover, borides were identified in alloys with high boron content. 相似文献
4.
I. Ansia H.H. Stein C. Brøkner C.A. Hayes J.K. Drackley 《Journal of dairy science》2021,104(3):2979-2995
The aims of this experiment were (1) to compare the effects of a soybean meal with an enzymatic treatment (ESBM) to reduce the concentration of antinutritional factors versus a standard soybean meal (SBM) on foregut and small intestine digestion in weaned dairy calves and (2) to estimate the endogenous losses of crude protein (CP) in the small intestine. Our hypothesis was that a diet containing ESBM instead of SBM would improve ruminal and small intestine digestion and absorption of nutrients. A T-cannula was placed in the duodenum, and a second T-cannula was installed in the distal ileum of 12 Holstein calves at approximately 3 wk of age. Calves were weaned on d 42, and on d 50 they were assigned randomly to a quadruplicated 3 × 3 Latin square with 10-d periods. Digesta samples were collected on d 7 and 8 from the ileum and d 9 and 10 from the duodenum. The diets were fed for ad libitum intake and consisted of a calf starter (CS) of 20% CP with SBM as the main source of protein (CTRL), and an isonitrogenous CS with an ESBM instead of SBM (ENZT). A third diet with a low content of CP (10%) and no soy protein was fed to estimate endogenous N losses and digestibilities of test ingredients. Flows and digestibilities of nutrients were compared between CTRL and ENZT and their test ingredients (SBM vs. ESBM, respectively). Duodenal net flows of CP and total AA as well as ruminal microbial protein synthesis per kilogram of digested CP were greater, and flow of nonprotein N and CP true (corrected by endogenous and microbial flows) foregut digestibility were lower with ENZT than CTRL. The apparent small intestine digestibilities of CP and total AA were greater for ESBM than SBM, but there were no differences between the CTRL and ENZT diets. We observed no differences in digestibilities at the duodenum or ileum of starch or NDF, but true small intestine digestibilities of CP and all AA were greater with ENZT than CTRL. Total endogenous protein losses in the small intestine estimated from calves fed the low-CP with no soy protein diet were 37 ± 1.5 g of CP and 29 ± 1.4 g of AA/kg of DMI. These values may be considered the basal endogenous losses as they are similar to values obtained with the regression method, which estimates N losses when dietary N is null. Our results indicated that the inclusion of an ESBM improved the efficiency of ruminal microbial protein synthesis per digested kilogram of organic matter and CP, and increased CP and AA absorption in the small intestine despite a greater proportion of undigested dietary protein entering the duodenum. 相似文献
5.
In this article, we describe a knowledge-based controlled platform using program supervision techniques. This platform eases
the creation and the configuration of video surveillance systems. Several issues need to be addressed to provide a correct
system configuration: (1) to choose, among a library of programs, those which are best satisfying a given user request, (2)
to assign a correct value for each program parameter, (3) to evaluate performances and to guarantee a performance rate which
is satisfactory regarding end-user requirements. This platform is composed of three main components: the library of programs,
the knowledge base and the control component. The knowledge is either given by experts or learnt by the system. The control
is generic in the sense that it is independent of any application. To validate this platform, we have built and evaluated
six video surveillance systems which are featured with three properties: adaptability, reliability and real-time processing. 相似文献
6.
Modeling mechatronic multibody systems requires the same type of methodology as for designing and prototyping mechatronic
devices: a unified and integrated engineering approach. Various formulations are currently proposed to deal with multiphysics
modeling, e.g., graph theories, equational approaches, co-simulation techniques. Recent works have pointed out their relative
advantages and drawbacks, depending on the application to deal with: model size, model complexity, degree of coupling, frequency
range, etc. This paper is the result of a close collaboration between three laboratories, and aims at showing that for “non-academic”
mechatronic applications (i.e., issuing from real industrial issues), multibody dynamics formulations can be generalized to
mechatronic systems, for the model generation as well as for the numerical analysis phases. Model portability being also an
important aspect of the work, they must be easily interfaced with control design and optimization programs. A global “demonstrator”,
based on an industrial case, is discussed: multiphysics modeling and mathematical optimization are carried out to illustrate
the consistency and the efficiency of the proposed approaches. 相似文献
7.
Summary Small oscillations of a rotating elasticum with a mass at the free end are investigated with Poincaré-Lindstedt series. It is shown that the mass moves on a figure-eight shaped curve in a direction determined by the sign of the angular velocity and hence that the Coriolis force influences the motion. 相似文献
8.
Characterization of the epidermal growth factor receptor in pig oviduct and endometrium 总被引:1,自引:0,他引:1
K Wollenhaupt U Tiemann R Einspanier F Schneider W Kanitz KP Brüssow 《Canadian Metallurgical Quarterly》1997,111(2):173-181
Two different plaque variants of Japanese encephalitis virus were selected from a wild-type Taiwanese isolate using Vero cells. One variant was found to exhibit small plaque morphology with retarded virus replication kinetics in Vero cells, and was demonstrated to be resistant to monoclonal antibody (mAb) E3.3 neutralization. The other variant showed large plaque morphology, was sensitive to mAb E3.3 neutralization, and manifested reduced virulence in mice on both intracranial and intraperitoneal inoculations. These two variants propagated in Vero cells retained high levels of infectivity but had relatively low HA titers as compared with the parent strain. The envelope sequences of these two variants showed four amino acid differences at residues E-85 (Glu/Arg), E-306 (Glu/Gly), E-331 (Ser/Arg), and E-387 (Met/Arg). Our results indicated the neutralizing epitope of Japanese encephalitis virus did not overlap with virus virulence determinant. 相似文献
9.
Antigen-induced arthritis in guinea pigs was used as a model to investigate the pathogenic mechanisms responsible for cartilage destruction in chronic joint inflammation. The activation of macrophages, their effects on cartilage metabolism, and the development of autoimmunity to cartilage constituents were studied during the progression of arthritis. The results show that in arthritic animals the macrophages are systemically activated, with a peak in the early phase of inflammation. Interleukin 1, produced by the activated cells, suppresses the proteoglycan synthesis in cartilage explants and cultured chondrocytes and increases the proliferation of the cells in vitro. During the progression of arthritis humoral and cell-mediated immune responses to collagen type II and cartilage proteoglycans occur correlating with the severity of arthritis. It is concluded that different immunological mechanisms may be involved in cartilage destruction during antigen-induced arthritis. Mediator-induced metabolic reactions dominate in the early phase, whereas autoimmunity to cartilage might play an essential role in later phases of arthritis. 相似文献
10.
Analysis of electrocardiograms during atrial fibrillation 总被引:1,自引:0,他引:1
Vincent Jacquemet Adriaan van Oosterom Jean-Marc Vesin Lukas Kappenberger 《IEEE engineering in medicine and biology magazine》2006,25(6):79-88
The research discussed in this article is motivated by the search for an optimal classification of the different types of atrial fibrillation (AF) on the basis of recorded atrial signals. This would facilitate the selection of an optimal therapy. This article focuses on the biophysical models of the genesis of ECG waveforms during AF. The model of the electric activity of the atria was found to have sufficient realism to be used to describe the electric sources during AF. The inclusion of the volume conduction model resulted in electrocardiographic signals that are in all aspects similar to those observed clinically. The model is currently applied to solve various problems related to optimal signal preprocessing and extraction of features in AF signals for the classification of AF abnormalities. The biophysical model of the atrial activity is an essential element in this research, since it is capable of describing the electric source specifications derived from different hypotheses relating to the etiology of AF 相似文献