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731.
The genotoxic impurities (GIs) are carcinogenic hence its management during synthesis of pharmaceuticals is very important to be detected even in trace level for the safe use of the drugs. The presence of drug substance/drug product DNA-reactive impurities poses a significant problem for drug regulators as well as industry. There are several regulatory guidelines and position papers focused on controlling the amount of impurities within the specified limits. The present compilation gives an account of updated information about GIs and reviews the regulatory aspects for GIs in active pharmaceutical ingredients/drug formulations. A detailed discussion about control strategies in the context of GIs is also described precisely. The analysis of GIs is a challenging and complex aspect of the drug development process. Control and determination of these impurities at ppm or ppb levels are significant challenges for analysts, therefore the approaches for the analysis of GIs have also been discussed. 相似文献
732.
Purvi Gupta 《Journal of Geometric Analysis》2017,27(2):1029-1064
In convex geometry, the Blaschke surface area measure on the boundary of a convex domain can be interpreted in terms of the complexity of approximating polyhedra. This approach is formulated in the holomorphic setting to establish an alternate interpretation of Fefferman’s hypersurface measure on boundaries of strongly pseudoconvex domains in \(\mathbb {C}^2\). In particular, it is shown that Fefferman’s measure can be recovered from the Bergman kernel of the domain. 相似文献
733.
Dr. Samuel M. Meier M. Sc. Dominique Kreutz Dr. Lilli Winter M. Sc. Matthias H. M. Klose M. Sc. Klaudia Cseh M. Sc. Tamara Weiss Dr. Andrea Bileck M. Sc. Beatrix Alte Dr. Johanna C. Mader M. Sc. Samir Jana Dr. Annesha Chatterjee Dr. Arindam Bhattacharyya Michaela Hejl Dr. Michael A. Jakupec Priv.-Doz. Dr. Petra Heffeter Prof. Dr. Walter Berger Prof. Dr. Christian G. Hartinger Prof. Dr. Bernhard K. Keppler Prof. Dr. Gerhard Wiche Prof. Dr. Christopher Gerner 《Angewandte Chemie (International ed. in English)》2017,56(28):8267-8271
Organometallic metal(arene) anticancer agents require ligand exchange for their anticancer activity and this is generally believed to confer low selectivity for potential cellular targets. However, using an integrated proteomics-based target-response profiling approach as a potent hypothesis-generating procedure, we found an unexpected target selectivity of a ruthenium(arene) pyridinecarbothioamide (plecstatin) for plectin, a scaffold protein and cytolinker, which was validated in a plectin knock-out model in vitro. Plectin targeting shows potential as a strategy to inhibit tumor invasiveness as shown in cultured tumor spheroids while oral administration of plecstatin-1 to mice reduces tumor growth more efficiently in the invasive B16 melanoma than in the CT26 colon tumor model. 相似文献
734.
735.
We investigate the invariant rings of two classes of finite groups G ≤ GL(n, F q) which are generated by a number of generalized transvections with an invariant subspace H over a finite field F q in the modular case. We name these groups generalized transvection groups. One class is concerned with a given invariant subspace which involves roots of unity. Constructing quotient groups and tensors, we deduce the invariant rings and study their Cohen-Macaulay and Gorenstein properties. The other is concerned with different invariant subspaces which have the same dimension. We provide a explicit classification of these groups and calculate their invariant rings. 相似文献
736.
An elastic wave transmitting system (e.g. a nonuniform elastic rod) consisting of an input section with constant impedance, a joint with variable impedance, and an output section with constant impedance is considered. The efficiency of energy transmission (the ratio of transmitted to incident elastic wave energy) is determined and the following optimization problem is solved for two sample cases: Given the properties of the wave transmitting system and a limited duration of the incident wave, determine the shape of this wave such that the efficiency of energy transmission is maximized. In the first case (a joint with constant impedance) the optimization problem leads to a matrix eigenvalue problem. In the second case (a joint with concentrated mass) it leads to an eigenvalue problem for an integral equation. The efficiencies obtained for the optimum incident waves are compared with those obtained for rectagular incident waves an it is found that the differences are generally small. The results, which are discussed with particular reference to the transmission of elastic wave energy through drill rod joints, can also be interpreted for e.g. shallow water waves and electromagnetic waves in a transmission line. 相似文献
737.
Summary The development of a compressible boundary layer over a wedge impulsively set into motion is studied in this paper. The initial motion is independent of the leading edge effect and the solutions are those of a Rayleigh-type problem. The motion tends to an ultimate steady state of Falkner-Skan type. The equations governing the transient boundary layer from the initial steady state to the terminal steady-state change their character after certain time due to the leading edge effect and thereafter solution depends on both the end conditions. Numerical solutions are obtained through the second-order accuracy upwind scheme. The effects of the Falkner-Skan parameter and the surface temperature on the transient flow and heat transfer are also studied. It has been found that the flow separation does not occur form–0.0707 when
w
= 1.5 (hot wall), andm–0.118 when
0.5
(cold wall). 相似文献
738.
A spinline-type extensional viscometer is described in which an innovative method of tensile stress measurement is employed. A limited amount of liquid flows through a vertical capillary at a constant flow rate under the influence of a constant pressure head. The drainage time decreases when the liquid stream leaving the capillary is stretched by the application of vacuum. These drainage times are measured in a manner similar to that used for intrinsic viscosity measurements. The measured difference in drainage times, with and without stretching, is trivially related to the extensional stress at the capillary exit, and this provides a very simple method of accurately determining fluid stretching forces having a magnitude as low as 10-4 N; stresses at other axial locations in the stretched liquid jet are obtained by means of a force balance in the usual manner. The validity of the proposed technique is demonstrated by obtaining the expected results for a Newtonian oil having a shear viscosity of 56.2 mPa-s. Also presented are preliminary data on polyethylene oxide-in-water solutions having an even lower shear viscosity. 相似文献
739.
An analysis is made of the steady two-dimensional stagnation-point flow of an incompressible viscoelastic fluid over a flat deformable surface when the surface is stretched in its own plane with a velocity proportional to the distance from the stagnation-point. It is shown that for a viscoelastic fluid of short memory (obeying Walters’ B′ model), a boundary layer is formed when the stretching velocity of the surface is less than the inviscid free-stream velocity and velocity at a point increases with increase in the elasticity of the fluid. On the other hand, an inverted boundary layer is formed when the surface stretching velocity exceeds the velocity of the free stream and the velocity decreases with increase in the elasticity of the fluid. A novel result of the analysis is that the flow near the stretching surface is that corresponding to an inviscid stagnation-point flow when the surface stretching velocity is equal to the velocity of the free stream. Temperature distribution in the boundary layer is found when the surface is held at constant temperature and surface heat flux is determined. It is found that temperature at a point decreases with increase in the elasticity of the fluid. 相似文献
740.
Introducing fractional operators in the adaptive control loop, and especially in Model Reference Adaptive Control (MRAC),
has proven to be a good mean for improving the plant dynamics with respect to response time and disturbance rejection. The
idea of introducing fractional operators in adaptation algorithms is very recent and needs to be more established, that is
why many research teams are working on the subject. Previously, some authors have introduced a fractional model reference
in the adaptation scheme, and then fractional integration has been used to deal directly with the control rule. Our original
contribution in this paper is the use of a fractional derivative feedback of the plant output, showing that this scheme is
equivalent to the fractional integration, one with a certain benefit action on the system dynamical behaviour and a good robustness
effect. Numerical simulations are presented to show the effectiveness of the proposed fractional adaptive schemes. 相似文献