Force decomposition

Parallel Molecular Dynamics Using Force Decomposition... 

The force decomposition algorithm maps all possible interactions to processors and does not require inter-processor communication during the force calculation phase of MD simulation. However, to obtain the net force on each particle for the update phase would need global communication. In this section, we will present parallel algorithms based on force decomposition. 

The fifth and final chapter, on Parallel Force Field Evaluation, takes account of the fact that the bulk of CPU time spent in MD simulations is required for evaluation of the force field. In the first paper, BOARD and his coworkers present a comparison of the performance of various parallel implementations of Ewald and multipole summations together with recommendations for their application. The second paper, by Phillips et AL., addresses the special problems associated with the design of parallel MD programs. Conflicting issues that shape the design of such codes are identified and the use of features such as multiple threads and message-driven execution is described. The final paper, by Okunbor Murty, compares three force decomposition techniques (the checkerboard partitioning method. 

At times the solubility of a drug in water is insufficient at room temperature to allow a meaningful kinetic study, in which case it can, at times, be carried out at elevated temperature [58]. If done at several different temperatures, it may be possible to estimate the stability at room temperature by extrapolation. Frequently, a broad screen of stability is performed on the initial small sample used for initial performulation this is frequently referred to as forced decomposition studies [59], in which the drug is exposed to acid degradation, base degradation, aqueous degradation, drug powder... 

Stress testing is conducted to provide data on forced decomposition products and decomposition mechanisms for the drug substance. 

The easiest way to perform specificity for any HPLC method is to perform this test in conjunction with a forced decomposition study. The utilization of mass spectrometry (MS) detector (in series) after a Photo Diode Array (PDA) detector to obtain more information is encouraged (in terms of mass-to-charge ratio of parent ions, initial fragmentation pattern, and peak purity). 

Even if the same drug substance HPLC method is used for the drug product, forced decomposition studies must be performed again for the drug product to confirm the resolution of potential degradation products from the API. In addition, forced decomposition studies must also be performed for different dosage forms (capsule, tablet, suspension, injectable, etc.) of the same drug substance. 

The guidance on forced degradation is available, as stated above however, the details of the investigations are left up to the pharmaceutical researcher. Forced decomposition testing within the pharmaceutical industry varies tremendously this was demonstrated by Baertschi [22], who surveyed 20 pharmaceutical companies on the practices of forced decomposition studies. 

The following four steps have been proposed by Bakshi and Singh for a development of a SIM [34] (1) critical study of an API to assess the likely decomposition route(s), (2) collection of information on physicochemical properties, (3) stress (forced decomposition) studies, and (4) preliminary separation studies on stressed samples. 

Each processor is assigned a predetermined set of force computations, involving a force decomposition of the workload that remains in effect during the simulation. 

Two categories of force decomposition algorithm have appeared in the literature those that systolically cycle atom data around a ring, and those based on the force-matrix formalism discussed by Plimpton.i o A variety of systolic loop methods have been implemented on both and... 

In spatial decomposition, or geometric methods,249 tjjg physical simulation domain is subdivided into small three-dimensional boxes, one for each processor. Each processor computes forces on and updates the positions and velocities of all atoms within its box at each time step, with atoms reassigned to new processors as they move through the physical domain. Because a processor can compute forces on its atoms knowing only the positions of atoms in nearby boxes, the communication required in the spatial decomposition is local, in contrast to the global communications required in the atom and force decomposition methods. 

Force decomposition algorithms based on a block decomposition of the force matrix reduce the memory and communication costs by a factor of /P versus the atom decomposition algorithms. In the LJ benchmark, the force decomposition algorithm continued to speed up, even when hundreds of processors were used. 

For the approval of a drug, it is necessary to know the results of elementary analysis, the structural formula, ultraviolet cind infrared absorption. X-ray diffraction and the other physicochemical properties of the substance. The test results on the forced decomposition, decomposition mechanism, etc., of bulk drugs are to be part of b-2 (Notification No. 43 of the PAB in 1992). The contents of the standards and test methods in the application form for new drugs should follow the guidelines on the standards and test methods for new drugs (Notification No. 586 of the PAB in 1994). 

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