Search results for " Simulation"
showing 10 items of 4034 documents
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…
Consistent shakedown theorems for materials with temperature dependent yield functions
2000
The (elastic) shakedown problem for structures subjected to loads and temperature variations is addressed in the hypothesis of elastic-plastic rate-independent associative material models with temperature-dependent yield functions. Assuming the yield functions convex in the stress/temperature space, a thermodynamically consistent small-deformation thermo-plasticity theory is provided, in which the set of state and evolutive variables includes the temperature and the plastic entropy rate. Within the latter theory the known static (Prager's) and kinematic (König's) shakedown theorems - which hold for yield functions convex in the stress space - are restated in an appropriate consistent format…
A Space-Vector State Dynamic Model of the Synchronous Reluctance Motor Including Self and Cross-Saturation Effects and its Parameters Estimation
2018
This paper proposes a space-vector dynamic model of the Synchronous Reluctance Motor (SynRM) including both self-saturation and cross-saturation effects and selecting as state variables the stator currents. The proposed dynamic model is based on an original function between the stator flux and stator current components, and relies on 8 coefficients (fewer than other models in the scientific literature), presenting an interesting physical interpretation. Starting from this approach, both the static and dynamic inductances expressions of the model have been analytically developed, so that the reciprocity conditions for the cross saturation is satisfied. This paper presents also a technique fo…
A comparison of simplex and simulated annealing for optimization of a new rear underrun protective device
2012
In this paper, two optimization approaches to improve the product design process have been analysed. Through the analysis of a case study, concerning the designing of a new High Energy Absorption Rear Underrun Protective Device (HEARUPD), two different optimization approaches (simplex and simulated annealing) have been compared. In the implemented optimization processes, the crash between an economy car and the rear part of a truck has been simulated by dynamic numerical (FEM) analyses. Moreover, authors have proposed the use of a suitable linear function of four variables with the purpose of reducing the multi-objective optimization processes to mono-objective ones. That has been made to s…
Modelling unilateral damage effect in strongly anisotropic materials by the introduction of the loading mode in damage mechanics
1999
Abstract Damage weakens the mechanical characteristics of materials. But this weakening can disappear if the cracks close again: this is called the unilateral effect of damage. We propose a model of this phenomenon using damage mechanics in the case of a diffuse network of identical microcracks. The microcracks state is defined with two internal state variables. These two variables are control parameters of the geometry of the microcracks. They also define the loading mode in damage mechanics as in fracture mechanics. In order to limit the anisotropy induced by the microcracks, hence by the loading, we suppose that the geometry of damage spreads into preferential directions. Therefore, this…