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91.
    
Inhibition of PSD-95 has emerged as a promising strategy for the treatment of ischemic stroke, as shown with peptide-based compounds that target the PDZ domains of PSD-95. In contrast, developing potent and drug-like small molecules against the PSD-95 PDZ domains has so far been unsuccessful. Here, we explore the druggability of the PSD-95 PDZ1-2 domain and use fragment screening to investigate if this protein is prone to binding small molecules. We screened 2500 fragments by fluorescence polarization (FP) and validated the hits by surface plasmon resonance (SPR), including an inhibition counter-test, and found four promising fragments. Three ligand efficient fragments were shown by 1H,15N HSQC NMR to bind in the small hydrophobic P0 pockets of PDZ1-2, and one of them underwent structure-activity relationship (SAR) studies. Overall, we demonstrate that fragment screening can successfully be applied to PDZ1-2 of PSD-95 and disclose novel fragments that can serve as starting points for optimization towards small-molecule PDZ domain inhibitors.  相似文献   
92.
93.
The demand for instruments that are suitable for the separation of fine particles and biological cells is steadily increasing. Various innovative particles have already implemented in bulk products and many others are close to commercial availability. Tubular bowl centrifuges offer high centrifugal forces at reasonable throughputs. There is a high potential for the optimisation of existing processes and in the design of new tubular centrifuges especially for the separation of nanoscale materials. The separation of fine particulates and biological cells in a semibatch tubular bowl centrifuge at high rotational speeds is described in this work. Furthermore, the influence of the sediment on the process outcome and possibilities to enhance the separation efficiency were investigated. A boundary layer flow was indirectly detected. Structures inside the rotor of the centrifuge cause defined liquid flow patterns, which influence the separation efficiency. A comparison of the separation behaviour with an unimpaired flow and the redirected flow yielded conclusions about the actual flow patterns.  相似文献   
94.
A water tunnel in Candida antarctica lipase B that provides the active site with substrate water is hypothesized. A small, focused library created in order to prevent water from entering the active site through the tunnel was screened for increased transacylation over hydrolysis activity. A single mutant, S47L, in which the inner part of the tunnel was blocked, catalysed the transacylation of vinyl butyrate to 20 mM butanol 14 times faster than hydrolysis. The single mutant Q46A, which has a more open outer end of the tunnel, showed an increased hydrolysis rate and a decreased hydrolysis to transacylation ratio compared to the wild‐type lipase. Mutants with a blocked tunnel could be very useful in applications in which hydrolysis is unwanted, such as the acylation of highly hydrophilic compounds in the presence of water.  相似文献   
95.

Background  

Food pattern analyses are popular tools in the study of associations between diet and health. However, there is a need for further evaluation of this methodology. The aim of the present cross-sectional study was to evaluate the relationship between food pattern groups (FPG) and existing health, and to identify factors influencing this relationship.  相似文献   
96.
Co, Mo, NiMo and CoMo catalysts supported on alumina, fishbone and platelet carbon nanofibers (CNFs) have been prepared. The dispersion of the oxide phases was qualitatively studied and compared using X-ray diffraction (XRD) and transmission electron microscopy (TEM). The reducibility of the catalysts was studied by temperature programmed reduction (TPR). Hydrodesulfurization (HDS) of thiophene was used as a model reaction to compare the activity of different catalysts. The activity tests showed that the alumina supported catalysts exhibited higher activity compared to the corresponding CNF supported catalysts, and the NiMo catalysts were more active than the corresponding CoMo catalysts. The thiophene HDS activity was correlated with the dispersion of the molybdenum species and the reducibility of different catalysts. Interestingly, the CNF supported Co catalysts have higher thiophene HDS activity than the CNF supported Co(Ni)Mo catalysts.  相似文献   
97.
The sulfiding of Mo/Al2O3 in H2S/Ar versus in H2S/H2 has been studied by temperature-programmed sulfiding (TPS), X-ray photon electron spectroscopy (XPS), extended X-ray absorption fine structure (EXAFS), and temperature-programmed desorption of NO (NO-TPD). All the applied techniques agree on the sulfur content in the sulfided catalysts and the findings are in accord with a model for the H2S production reaction. The nucleation and growth of well-ordered MoS2 clusters are probed by XPS during sulfiding with and without the presence of hydrogen. The resulting dispersion of the MoS2 phase is evaluated on the basis of XPS, EXAFS, and NO-TPD, and is found to be highest when the sulfiding occurs in the presence of hydrogen.  相似文献   
98.
Cerebral palsy (CP) is a perinatally acquired nonprogressive brain damage resulting in motor impairment affecting mobility and posture. Early identification of infants with CP is desired to target early interventions and follow-up. During early infancy, distinct motion patterns occur which are highly predictive for later disability. These motor patterns can be observed and recorded. In this paper, a method to predict later CP based on early video recordings of the infants' spontaneous movements, applying optical flow and statistical pattern recognition, is presented. We extract motion information from video recordings of young infants using a total variation related optical flow method. By using wavelet analysis features from motion trajectories of points initiated on a regular grid were extracted and classified using a support vector machine.  相似文献   
99.
The addition of sodium fluoride to poly (methyl-methacrylate) (PMMA) bone cement may theoretically improve the fixation of joint replacement. This hypothesis was tested in an animal model using nine mature healthy lop-eared rabbits. A femoral prosthesis was inserted in both knees to resurface the patellofemoral articulation. The same acrylic cement, with and without sodium fluoride, was randomised between the two sides for prosthetic fixation. Two screw shaped implants machined from cured rods of either cement were also inserted bilaterally into the proximal tibia. Qualitative and quantitative histomorphometry of the bone tissue response surrounding the cement in the femur and the intact tibial implants revealed similar results regardless of sodium fluoride addition. Six weeks after surgery removal, torque did not significantly differ between the two sides. Our findings indicate that addition of sodium fluoride to PMMA has little effect on implant stability and bone remodeling in rabbits in the short-term.  相似文献   
100.
阿尔伯茨隆德区位于丹麦哥本哈根以西20公里,1965-1975年间,该区的人口增加了10倍。该区在政治上将供暖视为重要的基础设施,并且将区域供热做为供暖的基础,这样一来就能保证拥有廉价而环境友好的供热形式,在燃料选择上有了明显的灵活性,在能源供应上有了很高的安全性。30年来阿尔伯茨隆德区政府一直将环境与资源消耗列为议事日程,目前仍然在雄心勃勃地推出一些计划。  相似文献   
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