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61.
    
The parasitic disease schistosomiasis is the cause of more than 200 000 human deaths per year. Although the disease is treatable, there is one major shortcoming: praziquantel has been the only drug used to combat these parasites since 1977. The risk of the emergence of resistant schistosomes is known to be increasing, as a reduced sensitivity of these parasites toward praziquantel has been observed. We developed a new class of substances, which are derived from inhibitors of human aldose reductase, and which showed promising activity against Schistosoma mansoni couples in vitro. Further optimisation of the compounds led to an increase in anti-schistosomal activity with observed phenotypes such as reduced egg production, vitality, and motility as well as tegumental damage and gut dilatation. Here, we performed structure–activity relationship studies on the carboxylic acid moiety of biarylalkyl carboxylic acids. Out of 82 carboxylic acid amides, we identified 10 compounds that are active against S. mansoni at 25 μm . The best five compounds showed an anti-schistosomal activity up to 10 μm and induced severe phenotypes. Cytotoxicity tests in human cell lines showed that two derivatives had no cytotoxicity at 50 or 100 μm . These compounds are promising candidates for further optimisation toward the new anti-schistosomal agents.  相似文献   
62.
    
The combination of III/V semiconductors with Si is very attractive, since it allows the fabrication of high efficient optoelectronic devices like solar cells, lasers or the integration of III/V transistors on Si substrates. However, the growth of polar III/V materials on nonpolar Si holds several challenges. The different valences of group III and group V atoms as well as Si possibly give rise to the formation of charged defects, i.e., antiphase boundaries, as well as to charge accumulation at the interface between the different materials. Accordingly, the interfaces present, i.e., the ones between antiphase and main phase and the one between III/V and Si, eventually limit any device's performance. Electron microscopy, in particular transmission electron microscopy, has proven to be a valuable tool to acquire quantitative information from III/V–Si heterostructures. Among this information are defect densities as well as the structure of the involved interfaces at spatial resolutions down to the atomic level. Moreover, information on charge distribution can be retrieved. In this review, the authors collocate the results gained for the model system GaP on Si utilizing various electron microscopy related techniques.  相似文献   
63.
The magnetron-plasma-enhanced chemical vapor deposition (magPECVD) provides silicon-organic thin films for optical, electrically insulating or diffusion barrier coating applications. With process pressures of ≤ 1 Pa this technology is well adapted to the sputtering process of optical interference coatings and also facilitates an inline-process implementation. This paper describes the deposition process for scratch resistant coatings on polycarbonate (PC) and allyl diglycol carbonate substrates. Based on the optical, chemical and mechanical characterization of single magPECVD thin films of varied chemical composition, several types of layer stacks (e.g. of gradient or alternating hardness distribution) were deposited with varied total thickness on PC substrates. Abrasion test results indicate two main effects: the resistance against scratches of high load abrasion (50 N) mainly depends on the total coating thickness. The durability against scratches of low load abrasion (5 N) shows a clear advantage for the multilayer design in contrast to homogeneous single layers even of higher thickness. Finally a 5-layer antireflective system was reactively sputtered onto the magPECVD coating and successfully passed adhesion and environmental tests.  相似文献   
64.
Tantalum oxynitride powder with a baddeleyite crystal structure was synthesized and densified by hot pressing in Ar and under high pressure using a belt-type high-pressure apparatus. The tantalum oxynitride powder could not be densified completely under hot-pressing conditions at 1400°C. The use of high pressure resulted in dense materials. The samples showed a hardness of 16–17 GPa and a fracture toughness of 3–4 MPa·m1/2. The hardness is higher compared with that of ZrO2 and HfO2 ceramics. The fracture toughness corresponds to the value of fully stabilized ZrO2 due to the absence of any transformation toughening mechanism.  相似文献   
65.
Bulk and quantum well GaAs1?xBix/GaAs layers with Bi mole fractions from 0.02 to 0.10 are grown by molecular-beam epitaxy at temperatures ranging from 280 to 320?°C. The samples are characterized using temperature and pump-power dependent photoluminescence measurements covering 8–300?K and 1–250?mW (7–1,800?W/cm2), respectively. The results indicate that there is strong reduction in bandgap energy with the incorporation of small amounts of Bi and that GaAsBi most likely forms a weak type-I band alignment with GaAs.  相似文献   
66.
67.
    
X-chromosomal retinitis pigmentosa (RP) frequently is caused by mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene. We evaluated the potential of PTC124 (Ataluren, TranslamaTM) treatment to promote ribosomal read-through of premature termination codons (PTC) in RPGR. Expression constructs in HEK293T cells showed that the efficacy of read-through reagents is higher for UGA than UAA PTCs. We identified the novel hemizygous nonsense mutation c.1154T > A, p.Leu385* ({\"type\":\"entrez-nucleotide\",\"attrs\":{\"text\":\"NM_000328.3\",\"term_id\":\"1677500221\"}}NM_000328.3) causing a UAA PTC in RPGR and generated patient-derived fibroblasts. Immunocytochemistry of serum-starved control fibroblasts showed the RPGR protein in a dot-like expression pattern along the primary cilium. In contrast, RPGR was no longer detectable at the primary cilium in patient-derived cells. Applying PTC124 restored RPGR at the cilium in approximately 8% of patient-derived cells. RT-PCR and Western blot assays verified the pathogenic mechanisms underlying the nonsense variant. Immunofluorescence stainings confirmed the successful PTC124 treatment. Our results showed for the first time that PTC124 induces read-through of PTCs in RPGR and restores the localization of the RPGR protein at the primary cilium in patient-derived cells. These results may provide a promising new treatment option for patients suffering from nonsense mutations in RPGR or other genetic diseases.  相似文献   
68.
    
Inflammatory processes are triggered by the fibrinolytic enzyme plasmin. Tissue-type plasminogen activator, which cleaves plasminogen to plasmin, can be activated by the cross-β-structure of misfolded proteins. Misfolded protein aggregates also represent substrates for plasmin, promoting their degradation, and are potent platelet agonists. However, the regulation of plasmin-mediated platelet activation by misfolded proteins and vice versa is incompletely understood. In this study, we hypothesize that plasmin acts as potent agonist of human platelets in vitro after short-term incubation at room temperature, and that the response to thrombospondin-1 and the bona fide misfolded proteins Eap and SCN-denatured IgG interfere with plasmin, thereby modulating platelet activation. Plasmin dose-dependently induced CD62P surface expression on, and binding of fibrinogen to, human platelets in the absence/presence of plasma and in citrated whole blood, as analyzed by flow cytometry. Thrombospondin-1 pre-incubated with plasmin enhanced these plasmin-induced platelet responses at low concentration and diminished them at higher dose. Platelet fibrinogen binding was dose-dependently induced by the C-terminal thrombospondin-1 peptide RFYVVMWK, Eap or NaSCN-treated IgG, but diminished in the presence of plasmin. Blocking enzymatically catalyzed thiol-isomerization decreased plasmin-induced platelet responses, suggesting that plasmin activates platelets in a thiol-dependent manner. Thrombospondin-1, depending on the concentration, may act as cofactor or inhibitor of plasmin-induced platelet activation, and plasmin blocks platelet activation induced by misfolded proteins and vice versa, which might be of clinical relevance.  相似文献   
69.
B6O is a possible candidate of superhard materials with a hardness of 45 GPa measured on single crystals. Up to now, densification of these materials was only possible at high pressure. However, recently it was found that Al2O3 can be utilized as an effective sintering additive, similar to the addition of Y2O3/Al2O3 that was used in this work. The densification behavior of the material as a function of applied pressure, its microstructure evolution, and the resulting mechanical properties were investigated. A strong dependence of the densification with increasing pressure was found. The material revealed characteristic triple junctions filled with amorphous residue composed of B2O3, Al2O3, and Y2O3, while no amorphous grain-boundary films were observed along internal interfaces. Mechanical testing revealed on average a hardness of 33 GPa, a fracture toughness of 4 MPa·m1/2, and a strength value of 520 MPa.  相似文献   
70.
Larval insect herbivores feeding externally on leaves are vulnerable to numerous and varied enemies. Larvae of the Neotropical herbivore, Chelymorpha alternans (Chrysomelidae:Cassidinae), possess shields made of cast skins and feces, which can be aimed and waved at attacking enemies. Prior work with C. alternans feeding on Merremia umbellata (Convolvulaceae) showed that shields offered protection from generalist predators, and polar compounds were implicated. This study used a ubiquitous ant predator, Azteca lacrymosa, in field bioassays to determine the chemical constitution of the defense. We confirmed that intact shields do protect larvae and that methanol-water leaching significantly reduced shield effectiveness. Liquid chromatography-mass spectrometry (LC-MS) of the methanolic shield extract revealed two peaks at 20.18 min and 21.97 min, both with a molecular ion at m/z 593.4, and a strong UV absorption around 409 nm, suggesting a porphyrin-type compound. LC-MS analysis of a commercial standard confirmed pheophorbide a (Pha) identity. C. alternans shields contained more than 100 μg Pha per shield. Shields leached with methanol-water did not deter ants. Methanol-water-leached shields enhanced with 3 μg of Pha were more deterrent than larvae with solvent-leached shields, while those with 5 μg additional Pha provided slightly less deterrence than larvae with intact shields. Solvent-leached shields with 10 μg added Pha were comparable to intact shields, even though the Pha concentration was less than 10% of its natural concentration. Our findings are the first to assign an ecological role for a chlorophyll catabolite as a deterrent in an insect defense.  相似文献   
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