Search results for "SIMULATION"
showing 10 items of 5095 documents
Molecular mechanism of T-cell protein tyrosine phosphatase (TCPTP) activation by mitoxantrone.
2013
T-cell protein tyrosine phosphatase (TCPTP) is a ubiquitously expressed non-receptor protein tyrosine phosphatase. It is involved in the negative regulation of many cellular signaling pathways. Thus, activation of TCPTP could have important therapeutic applications in diseases such as cancer and inflammation. We have previously shown that the α-cytoplasmic tail of integrin α1β1 directly binds and activates TCPTP. In addition, we have identified in a large-scale high-throughput screen six small molecules that activate TCPTP. These small molecule activators include mitoxantrone and spermidine. In this study, we have investigated the molecular mechanism behind agonist-induced TCPTP activation.…
Performance potential for simulating spin models on GPU
2012
Graphics processing units (GPUs) are recently being used to an increasing degree for general computational purposes. This development is motivated by their theoretical peak performance, which significantly exceeds that of broadly available CPUs. For practical purposes, however, it is far from clear how much of this theoretical performance can be realized in actual scientific applications. As is discussed here for the case of studying classical spin models of statistical mechanics by Monte Carlo simulations, only an explicit tailoring of the involved algorithms to the specific architecture under consideration allows to harvest the computational power of GPU systems. A number of examples, ran…
Nonlinear dependence on temperature and field of electron spin depolarization in GaAs semiconductors
2009
In this work the influence of temperature and drift conditions on the electron spin relaxation in lightly doped n-type GaAs bulk semiconductors is investigated. The electron transport, including the evolution of the spin polarization vector, is simulated by a Monte Carlo procedure which keeps into account all the possible scattering phenomena of the hot electrons in the medium. Electron-spin states in semiconductor structures relax by scattering with imperfections, other carriers and phonons. Spin relaxation lengths and times are computed through the D'yakonov-Perel process since this is the more relevant spin relaxation mechanism in the regime of interest (10 < T < 300 K). The decay of the…
Doping dependence of spin lifetime of drifting electrons in GaAs bulks
2010
We study the effect of the impurity density on lifetimes and relaxation lengths of electron spins in the presence of a static electric field in a n-type GaAs bulk. The transport of electrons and the spin dynamics are simulated by using a semiclassical Monte Carlo approach, which takes into account the intravalley scattering mechanisms of warm electrons in the semiconductor material. Spin relaxation is considered through the D'yakonov-Perel mechanism, which is the dominant mechanism in III-V semiconductors. The evolution of spin polarization is analyzed by computing the lifetimes and depolarization lengths as a function of the doping density in the range 10^{13} - 10^{16} cm^{-3}, for differ…
First-order and tricritical wetting transitions in the two-dimensional Ising model caused by interfacial pinning at a defect line
2014
We present a study of the critical behavior of the Blume-Capel model with three spin states (S=±1,0) confined between parallel walls separated by a distance L where competitive surface magnetic fields act. By properly choosing the crystal field (D), which regulates the density of nonmagnetic species (S=0), such that those impurities are excluded from the bulk (where D=) except in the middle of the sample [where DM(L/2)≠], we are able to control the presence of a defect line in the middle of the sample and study its influence on the interface between domains of different spin orientations. So essentially we study an Ising model with a defect line but, unlike previous work where defect lines …
Investigating the Molecular Mechanism of H3B-8800: A Splicing Modulator Inducing Preferential Lethality in Spliceosome-Mutant Cancers.
2021
The SF3B1 protein, part of the SF3b complex, recognizes the intron branch point sequence of precursor messenger RNA (pre-mRNA), thus contributing to splicing fidelity. SF3B1 is frequently mutated in cancer and is the target of distinct families of splicing modulators (SMs). Among these, H3B-8800 is of particular interest, as it induces preferential lethality in cancer cells bearing the frequent and highly pathogenic K700E SF3B1 mutation. Despite the potential of H3B-8800 to treat myeloid leukemia and other cancer types hallmarked by SF3B1 mutations, the molecular mechanism underlying its preferential lethality towards spliceosome-mutant cancer cells remains elusive. Here, microsecond-long a…
Low density lipoproteins and human serum albumin as the carriers of squalenoylated drugs: insights from molecular simulations
2018
We have studied the interaction of three clinically promising squalenoylated drugs (gemcitabine-squalene, adenine-squalene, and doxorubicin-squalene) with low-density lipoproteins (LDL) by means of atomistic molecular dynamics simulations. It is shown that all studied squalenoylated drugs accumulate inside the LDL particles. This effect is promoted by the squalene moiety, which acts as an anchor and drives the hydrophilic drugs into the hydrophobic core of the LDL lipid droplet. Our data suggest that LDL particles could be a universal carriers of squalenoylated drugs in the bloodstream. Interaction of gemcitabine-squalene with human serum albumin (HSA) was also studied by ensemble of dockin…
New stage-discharge relationship for inclined non-rectangular weirs
2018
Abstract In this paper, the outflow process of inclined non-rectangular weirs is studied applying the dimensional analysis and the incomplete self-similarity theory. At first, a new stage-discharge equation, applicable for the non-rectangular weirs having a different geometrical shape (parabolic, semicircular, inverted semicircular), is theoretically deduced using a characteristic width. Then, this power stage-discharge relationship (Eq. (17) ) is calibrated and tested using measurements carried out by Raiknar for parabolic, semicircular and inverted semicircular weirs having different inclination respect to the vertical (10°, 20°, 30°, 40° and 45°). For each geometrical shape, the analysis…
Pyrrolomycins as antimicrobial agents. Microwave-assisted organic synthesis and insights into their antimicrobial mechanism of action
2019
Abstract New compounds able to counteract staphylococcal biofilm formation are needed. In this study we investigate the mechanism of action of pyrrolomycins, whose potential as antimicrobial agents has been demonstrated. We performed a new efficient and easy method to use microwave organic synthesis suitable for obtaining pyrrolomycins in good yields and in suitable amount for their in vitro in-depth investigation. We evaluate the inhibitory activity towards Sortase A (SrtA), a transpeptidase responsible for covalent anchoring in Gram-positive peptidoglycan of many surface proteins involved in adhesion and in biofilm formation. All compounds show a good inhibitory activity toward SrtA, havi…
Discovery and structure-activity relationship studies of irreversible benzisothiazolinone-based inhibitors against Staphylococcus aureus sortase A tr…
2014
Gram-positive bacteria, in general, and staphylococci, in particular, are the widespread cause of nosocomial and community-acquired infections. The rapid evolvement of strains resistant to antibiotics currently in use is a serious challenge. Novel antimicrobial compounds have to be developed to fight these resistant bacteria, and sortase A, a bacterial cell wall enzyme, is a promising target for novel therapies. As a transpeptidase that covalently attaches various virulence factors to the cell surface, this enzyme plays a crucial role in the ability of bacteria to invade the host's tissues and to escape the immune response. In this study we have screened a small molecule library against rec…