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排序方式: 共有7971条查询结果,搜索用时 15 毫秒
1.
M. R. Thompson 《Drug development and industrial pharmacy》2015,41(8):1223-1231
Twin screw granulation (TSG) is a new process of interest to the pharmaceutical community that can continuously wet granulate powders, doing so at lower liquid concentrations and with better product consistency than found by a high shear batch mixer. A considerable body of research has evolved over the short time since this process was introduced but generally with little comparison of results. A certain degree of confidence has been developed through these studies related to how process variables and many attributes of machinery configuration will affect granulation but some major challenges still lay ahead related to scalability, variations in the processing regimes related to degree of channel fill and the impact of wetting and granulation of complex powder formulations. This review examines the current literature for wet granulation processes studied in twin screw extrusion machinery, summarizing the influences of operational and system parameters affecting granule properties as well as strives to provide some practical observations to newly interested users of the technique. 相似文献
2.
3.
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
4.
Dr. Li Di Prof. Per Artursson Dr. Alex Avdeef Prof. Leslie Z. Benet Prof. J. Brian Houston Dr. Manfred Kansy Edward H. Kerns Prof. Hans Lennernäs Dr. Dennis A. Smith Prof. Kiyohiko Sugano 《ChemMedChem》2020,15(20):1862-1874
Passive permeability is a key property in drug disposition and delivery. It is critical for gastrointestinal absorption, brain penetration, renal reabsorption, defining clearance mechanisms and drug-drug interactions. Passive diffusion rate is translatable across tissues and animal species, while the extent of absorption is dependent on drug properties, as well as in vivo physiology/pathophysiology. Design principles have been developed to guide medicinal chemistry to enhance absorption, which combine the balance of aqueous solubility, permeability and the sometimes unfavorable compound characteristic demanded by the target. Permeability assays have been implemented that enable rapid development of structure-permeability relationships for absorption improvement. Future advances in assay development to reduce nonspecific binding and improve mass balance will enable more accurately measurement of passive permeability. Design principles that integrate potency, selectivity, passive permeability and other ADMET properties facilitate rapid advancement of successful drug candidates to patients. 相似文献
5.
M. J. O’Sullivan C. G. Walker M. L. O’Sullivan T. D. Thompson A. B. Philpott 《Telecommunication Systems》2006,33(4):353-376
The problem of designing fibre-optic networks for local-access telecommunications generates (at least) three non-trivial subproblems.
In the first of these subproblems one must determine how many fibre-optic cables (fibres) are required at either end of a
street. In the next subproblem a minimum-cost network must be designed to support the fibres. The network must also provide
distinct paths from either end of the street to the central exchange(s). Finally, the fibre-optic cables must be placed in
protective covers. These covers are available in a number of different sizes, allowing some flexibility when covering each
section of the network. In this paper we describe a dynamic programming (DP) formulation for finding a minimum-cost (protective)
covering for the network (the third of the subproblems). This problem is a generalised set covering problem with side constraints
and is further complicated by the introduction of fixed and variable welding costs. The DP formulation selects covers along
each arc (in the network), but cannot exactly model the fixed costs and so does not guarantee optimality. We also describe
an integer programming (IP) formulation for assessing the quality of the DP solutions. The cost of the networks constructed
by the IP model is less than those designed using the DP model, but the saving is not significant for the problems examined
(less than 0.1%). This indicates that the DP model will generally give very good solutions. Furthermore, as the problem dimensions
grow, DP gives significantly better solution times than IP. 相似文献
6.
B. Ma P.I. Djurovich S. Garon B. Alleyne M.E. Thompson 《Advanced functional materials》2006,16(18):2438-2446
Efficient blue‐, green‐, and red‐light‐emitting organic diodes are fabricated using binuclear platinum complexes as phosphorescent dopants. The series of complexes used here have pyrazolate bridging ligands and the general formula C∧NPt(μ‐pz)2PtC∧N (where C∧N = 2‐(4′,6′‐difluorophenyl)pyridinato‐N,C2′, pz = pyrazole ( 1 ), 3‐methyl‐5‐tert‐butylpyrazole ( 2 ), and 3,5‐bis(tert‐butyl)pyrazole ( 3 )). The Pt–Pt distance in the complexes, which decreases in the order 1 > 2 > 3 , solely determines the electroluminescence color of the organic light‐emitting diodes (OLEDs). Blue OLEDs fabricated using 8 % 1 doped into a 3,5‐bis(N‐carbazolyl)benzene (mCP) host have a quantum efficiency of 4.3 % at 120 Cd m–2, a brightness of 3900 Cd m–2 at 12 V, and Commission Internationale de L'Eclairage (CIE) coordinates of (0.11, 0.24). Green and red OLEDs fabricated with 2 and 3 , respectively, also give high quantum efficiencies (~ 6.7 %), with CIE coordinates of (0.31, 0.63) and (0.59, 0.46), respectively. The current‐density–voltage characteristics of devices made using dopants 2 and 3 indicate that hole trapping is enhanced by short Pt–Pt distances (< 3.1 Å). Blue electrophosphorescence is achieved by taking advantage of the binuclear molecular geometry in order to suppress dopant intermolecular interactions. No evidence of low‐energy emission from aggregate states is observed in OLEDs made with 50 % 1 doped into mCP. OLEDs made using 100 % 1 as an emissive layer display red luminescence, which is believed to originate from distorted complexes with compressed Pt–Pt separations located in defect sites within the neat film. White OLEDs are fabricated using 1 and 3 in three different device architectures, either with one or two dopants in dual emissive layers or both dopants in a single emissive layer. All the white OLEDs have high quantum efficiency (~ 5 %) and brightness (~ 600 Cd m–2 at 10 V). 相似文献
7.
Using an integrated process of data and modeling in HRA 总被引:1,自引:0,他引:1
John Wreathall Dennis Bley Emilie Roth Jordan Multer Thomas Raslear 《Reliability Engineering & System Safety》2004,83(2):221
The paper describes an approach taken to estimate the probabilities of failure associated with various railroad tasks to prevent accidents (principally collisions and derailments). These probabilities were estimated using an expert elicitation process that used partially relevant data available from a variety of databases and that were filtered and scaled to make them more directly relevant to the analyses being performed. Extensive qualitative studies were performed prior to the elicitation process to identify relevant contexts under which the tasks can be performed. 相似文献
8.
Hyungtak Kim Thompson R.M. Tilak V. Prunty T.R. Shealy J.R. Eastman L.F. 《Electron Device Letters, IEEE》2003,24(7):421-423
The authors report on the effects of silicon nitride (SiN) surface passivation and high-electric field stress (hot electron stress) on the degradation of undoped AlGaN-GaN power HFETs. Stressed devices demonstrated a decrease in the drain current and maximum transconductance and an increase in the parasitic drain series resistance, gate leakage, and subthreshold current. The unpassivated devices showed more significant degradation than SiN passivated devices. Gate lag phenomenon was observed from unpassivated devices and removed by SiN passivation. However, SiN passivated devices also showed gate lag phenomena after high-electric field stress, which suggests possible changes in surface trap profiles occurred during high-electric field stress test. 相似文献
9.
The planimetric shifts in channel location of large alluvial rivers are a critical component in the creation of diverse structures and functions in riverine habitats. Engineered management schemes must also compensate for this type of channel change to protect resources and maintain navigation channels. The stability of the Lower Mississippi River channel was assessed through an analysis of historical records of channel position produced and archived by the United States Army Corps of Engineers. Channel location was recorded for the years 1765, 1820, 1881, 1915, 1930, 1937, 1960 and 1970. Channel stability was measured by two introduced metrics on a cell‐by‐cell basis: (1) the standard deviation of Euclidean distance to a channel cell for the entire period of record, and (2) the rate of Euclidean distance change between years in the period of record. At a coarse spatial scale, channel instability increased in the downstream direction. The variability of channel stability also increased in the downstream direction. Analysis of this variability identified alternating areas of high and low stability occurring with greater frequency as distance downstream increased. These findings are validated by past studies of channel stability along the Lower Mississippi River. As a result, the proposed metrics provide a consistent, quantitative, efficient and cost‐effective means of identifying areas of channel instability at several spatial scales. Copyright © 2006 John Wiley & Sons, Ltd. 相似文献
10.
Life is pleasant--and memory helps to keep it that way! 总被引:1,自引:0,他引:1
Walker W. Richard; Skowronski John J.; Thompson Charles P. 《Canadian Metallurgical Quarterly》2003,7(2):203
People's recollections of the past are often positively biased. This bias has 2 causes. The 1st cause lies in people's perceptions of events. The authors review the results of several studies and present several new comparative analyses of these studies, all of which indicate that people perceive events in their lives to more often be pleasant than unpleasant. A 2nd cause is the fading affect bias: The affect associated with unpleasant events fades faster than the affect associated with pleasant events. The authors review the results of several studies documenting this bias and present evidence indicating that dysphoria (mild depression) disrupts such bias. Taken together, this evidence suggests that autobiographical memory represents an important exception to the theoretical claim that bad is stronger than good. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献