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排序方式: 共有794条查询结果,搜索用时 15 毫秒
41.
Mach UR Hackling AE Perachon S Ferry S Wermuth CG Schwartz JC Sokoloff P Stark H 《Chembiochem : a European journal of chemical biology》2004,5(4):508-518
Based on N-alkylated 1,2,3,4-tetrahydroisoquinoline derivatives, which are structurally related to the partial agonist BP 897, a series of novel, selective dopamine D3 receptor antagonists has been synthesised. Derivatisation included changes in the arylamide moiety and the tetrahydroisoquinoline substructure leading to compounds with markedly improved selectivities and affinities in the low nanomolar concentration range. From the 55 structures presented here, (E)-3-(4-iodophenyl)-N-(4-(1,2,3,4-tetrahydroisoquinolin-2-yl)butyl)acrylamide (51) has high affinity (Ki(hD3)=12 nM) and a 123-fold preference for the D3 receptor relative to the D2 receptor subtype. Its pharmacological profile offers the prospect of a novel radioligand as a tool for various dopamine D3-receptor-related in vitro and in vivo investigations. 相似文献
42.
Structural diversity of sphingomyelin microdomains 总被引:2,自引:0,他引:2
In cells plasma membrane, sphingomyelin (SM) plays a key role in the formation of a category of lipid microdomains enriched in cholesterol (Chl) often referred to as rafts. Atomic force microscopy (AFM) was used to analyze the mesoscopic topography of enriched SM microdomains in supported bilayers made of SM/dioleoylphosphatidylcholine (SM/DOPC) and SM/palmitoyl-oleoyl-phosphatidylcholine (SM/POPC) equimolar mixtures, in buffer, at room temperature. Gel–fluid phase separation occurs in both SM/DOPC and SM/POPC bilayers. The gel phase SM-enriched microdomains adopt a variety of size, shape and mesoscopic structure, from homogeneous flat domains of a few hundreds of nanometer in diameter to domains of several micrometers made of closely packed globular structures. Gel–gel phase separation in SM domains is also observed which gives rise to different structures for the diunsaturated and the mixed-saturated PC species. These differences could also extend to the interactions with Chl. This suggests that studies on rafts formation commonly performed using SM/DOPC mixture as a model should also include the physiologically more relevant POPC species. 相似文献
43.
Prevalence of Clostridium botulinum in food raw materials used in REPFEDs manufactured in France 总被引:1,自引:0,他引:1
Carlin F Broussolle V Perelle S Litman S Fach P 《International journal of food microbiology》2004,91(2):141-145
Food raw materials used in refrigerated processed foods of extended durability (REPFEDs) manufactured in France were surveyed for Clostridium botulinum types A, B and E using PCR-Enzyme-linked Immunosorbent assay (PCR-ELISA) and mouse bioassay for detection respectively of cells and toxins in enrichment broth. Portions of 25 to 50 g of food were analysed. A total of 8 out of the 102 samples of fish and shellfish, 12 out of the 143 samples of meat and poultry, 1 out of the 62 samples of aroma, sauce and gravy, 4 out of the 25 samples of thickening agents, 3 out of the 26 samples of dehydrated dairy ingredients, and none of the 65 samples of spices, herbs and dehydrated mushroom were positive for C. botulinum in PCR-ELISA, i.e., 6.6% of all the samples tested. The 28 positive samples comprised 10 type A, 10 type B, 4 with both types A and B, and 4 undetermined by PCR typing. No sample positive for type E was detected. Of the 28 samples positive in PCR-ELISA, 15 were also positive in the mouse bioassay. The MPN count was between 1 and 3 C. botulinum/kg of food, which is similar to or in the lower range of values reported in the literature. 相似文献
44.
IRSN (France) and SCK-CEN (Belgium), two institutes of research and expertise in radiation protection and nuclear safety, simultaneously organised a very similar public opinion survey in their respective countries in November 2002. The study explores subjects such as: major people's concerns, perception of environmental risks, perception of risks in general, the role of experts in decision making, opinions on nuclear matters and aspects of nuclear emergency preparedness. In each country, more than 1000 citizens representing the general public have been consulted in face-to-face interviews. The field work has been performed by professional companies (BVA in France and Research International in Belgium). The paper shows that industrial and technological risks are not perceived as one of the major public concerns, although many other risks, of different nature are considered to be high. The actions of the authorities to provide protection against the consequences of many risks or disasters are not considered to be sufficient, and many respondents claim not to believe the information they receive. There exists a large difference between the opinion of French and Belgian public, and within the different language groups in Belgium, with regard to who should be in charge of the control of the hazardous industries. Many of the "actors" within the nuclear industry are not known by the respondents. The perception of the technical competence or the truth being told shows large variations between the main actors (such as members of the nuclear industry, the government or the media). Majorities within the population believe that a disaster as serious as the Chernobyl one can happen in their country and that in case of a nuclear accident, the authorities would not be capable to protect the population adequately. 相似文献
45.
Frantisek Lopot Bohdan Nejedlý Sylvie Sulková 《Hemodialysis international. International Symposium on Home Hemodialysis》2004,8(1):39-44
Quotidian or “daily" hemodialysis (DHD) is practiced in widely differing schedules. Yet all those schedules are reported to significantly ameliorate clinical outcome of patients. It is, however, not clear what is the actual cause of this amelioration. Rational possibilities include increased overall dialysis dose and increased weekly time. Conventional mathematical approaches (Kt/Vurea concept, equivalent renal clearance) cannot be used to study those issues because they do not consider number of dialysis per week and thus ignore the issue of treatment schedule “unphysiology.” The time average concentration/time average deviation (TAC/TAD) concept may well be used to visualize impact of treatment schedule on both plasma urea profile statics (TAC) and dynamics (TAD). The concept may further help to stratify studies for elucidation of the key factors of clinical outcome improvement seen on DHD. Actual physiologic mechanisms responsible for this improvement are to be sought among those with having derivative component (i.e., reacting to the rate of a change rather than to the magnitude of the change). It should, however, be kept in mind that the TAC/TAD concept is able to assess unphysiology of a treatment schedule, not unphysiology of a single treatment session. 相似文献
46.
Sylvie Boldo Marc Daumas 《International Journal on Software Tools for Technology Transfer (STTT)》2004,5(2-3):237-246
Few designs, mostly those of Texas Instruments, continue to use twos complement floating point units. Such units are simpler to build and to validate, but they do not comply to the dominant IEEE standard for floating point arithmetic. We compare some properties of the two systems in this text. Some features are lost, but others remain unchanged. One strong example is the case of Sterbenzs theorem and our recent extension. We show in the paper that the theorem and its extension hold for the twos complement architecture. Still, users should ensure that results are large enough on circuits that do not implement gradual underflow. Theorems have been proven and validated using the Coq automatic proof checker. 相似文献
47.
48.
Zohar S Latouche A Taconnet M Chevret S 《Computer methods and programs in biomedicine》2003,72(2):117-125
The aim of dose-ranging phase I (resp. phase II) clinical trials is to rapidly identify the maximum tolerated dose (MTD) (resp., minimal effective dose (MED)) of a new drug or combination. For the conduct and analysis of such trials, Bayesian approaches such as the Continual Reassessment Method (CRM) have been proposed, based on a sequential design and analysis up to a completed fixed sample size. To optimize sample sizes, Zohar and Chevret have proposed stopping rules (Stat. Med. 20 (2001) 2827), the computation of which is not provided by available softwares. We present in this paper a user-friendly software for the design and analysis of these Bayesian Phase I (resp. phase II) dose-ranging Clinical Trials (BPCT). It allows to carry out the CRM with stopping rules or not, from the planning of the trial, with choice of model parameterization based on its operating characteristics, up to the sequential conduct and analysis of the trial, with estimation at stopping of the MTD (resp. MED) of the new drug or combination. 相似文献
49.
Pochet S Dugué L Labesse G Delepierre M Munier-Lehmann H 《Chembiochem : a European journal of chemical biology》2003,4(8):742-747
Thymidine monophosphate kinase (TMPK) from Mycobacterium tuberculosis (TMPKmt) is an attractive target for the design of specific inhibitors. This fact is the result of its key role in the thymidine pathway and of unique structural features in the active site observed by X-ray crystallography, especially in comparison to its human counterpart (TMPKh). Different 5-modified thymidine derivatives, as well as purine and pyrimidine analogues or C-nucleosides were tested on TMPKmt and TMPKh, and the results were rationalized by docking studies. 5-Halogenated 2'-deoxyuridines are the best inhibitors of TMPKmt found and present the highest selectivity indexes in favor of TMPKmt. 相似文献
50.
Opto-electronic properties of rough LP-CVD ZnO:B for use as TCO in thin-film silicon solar cells 总被引:1,自引:0,他引:1
Sylvie Faÿ Jérôme Steinhauser Nuno Oliveira Evelyne Vallat-Sauvain Christophe Ballif 《Thin solid films》2007,515(24):8558-8561
Polycrystalline Boron-doped ZnO films deposited by low pressure chemical vapor deposition technique are developed for their use as transparent contacts for thin-film silicon solar cells. The size of the columnar grains that constitute the ZnO films is related to their light scattering capability, which has a direct influence on the current generation in thin-film silicon solar cells. Furthermore, if the doping level of the ZnO films is kept below 1 × 1020 cm− 3, the electron mobility can be drastically enhanced by growing large grains, and the free carrier absorption is reduced. All these considerations have been taken in account to develop ZnO films finely optimized for the fabrication of microcrystalline thin-film silicon solar cells. These TCO allow the achievement of solar cell conversion efficiencies close to 10%. 相似文献