Computational Analysis of the Solid-State and Solvation Properties of Carbamazepine in Relation to its Polymorphism

The solvent-dependent polymorphism of the active pharmaceutical ingredient (API) carbamazepine is interpreted from calculations of the solid-state and API-solvent intermolecular interactions. These simulations suggested that apolar solute-solute interactions could be disrupted by apolar solvents. In contrast, the polar solute-solute interactions were found to be easily disrupted by polar and protic solvents. This is consistent with experimental observations that the crystallization of the metastable form II is more dominant in apolar solvents. The Mercury program remains the gold standard in terms of usability; however, further expansion into more complex simulation techniques could make this package of even greater use in pharmaceutical manufacturing workflows.     

Clarification of linear low‐density polyethylene using Bis‐oxalamide compounds

The clarifying effect of using bis‐oxalamide compounds on linear low density polyethylene (LLDPE) has been investigated for the first time. It was demonstrated that the haze of a commercial LLDPE resin, DOWLEX? 2045G, can be reduced up to 50% by adding 0.2 wt % of a bis‐oxalamide clarifying agent. The investigations on the crystalline morphology revealed that the density of spherulite cores increased with increasing concentration of bis‐oxalamide N5. Through an investigation of structure‐property relationships based on the tunable bis‐oxalamide structure, it was demonstrated that the combination of linear alkyl core and cyclohexyl pendant groups showed the best clarification. The interactions of clarifying molecules were simulated using dynamic molecular simulation. The simulation suggested that the rigidity of the core functionality played a role on the hydrogen bonding in the intermolecular network, which may contribute to the macroscopic clarification performance. POLYM. ENG. SCI., 58:142–149, 2018. © 2017 Society of Plastics Engineers     

CELLULAR AUTOMATA MODELLING OF GRAIN COARSENING DURING REHEATING AND VALIDATION WITH THE EXPERIMENTAL RESULTS

1. IntroductionG rain coarsening isthe processby w hich the m ean grain size ofan aggregate ofcrystalsincreases.A n understanding ofgrain coarsening isoffundam entalim portance forpredicting the average grain sizeand grain size distribution,w hich are dir…     

Multiscale physical characterization of an outdoor-exposed polymeric coating system

Surface topography and gloss are two related properties affecting the appearance of a polymeric coating system. Upon exposure to ultraviolet (UV) radiation, the surface topography of a coating becomes more pronounced and, correspondingly, its gloss generally decreases. However, the surface factors affecting gloss and appearance are difficult to ascertain. In this article, atomic force microscopy (AFM) and laser scanning confocal microscopy (LSCM) measurements have been performed on an amine-cured epoxy coating system exposed to outdoor environments in Gaithersburg, Maryland. The formation of the protuberances is observed at the early degradation stages, followed by the appearance of circular pits as exposure continues. At long exposure times, the circular features enlarge and deepen, resulting in a rough surface topography and crack formation. Fourier Transform Infrared Spectroscopy (FTIR) study indicates that the oxidation and chain scission reactions are likely the origins of the surface morphological changes. The relationship between changes in surface roughness and gloss has been analyzed. The root mean square (RMS) roughness of the coating is related to nanoscale and microscale morphological changes in the surface of the coating as well as to the gloss retention. A near-linear dependence of RMS roughness with the measurement length scale (L) is found on a double logarithmic scale, i.e., RMS ∼ L ^f. The scaling factor, f, decreases with exposure time. The relationship between surface topography, on nano- to microscales, and the macroscale optical properties such as gloss retention is discussed. Moreover, a recent development in using an angle-resolved light scattering technique for the measurement of the specular and off-specular reflectance of the UV-exposed specimens is also demonstrated, and the optical scattering data are compared to the gloss and the roughness results.

Cell surface markers in colorectal cancer prognosis

The classification of colorectal cancers (CRC) is currently based largely on histologically determined tumour characteristics, such as differentiation status and tumour stage, i.e., depth of tumour invasion, involvement of regional lymph nodes and the occurrence of metastatic spread to other organs. These are the conventional prognostic factors for patient survival and often determine the requirement for adjuvant therapy after surgical resection of the primary tumour. However, patients with the same CRC stage can have very different disease-related outcomes. For some, surgical removal of early-stage tumours leads to full recovery, while for others, disease recurrence and metastasis may occur regardless of adjuvant therapy. It is therefore important to understand the molecular processes that lead to disease progression and metastasis and to find more reliable prognostic markers and novel targets for therapy. This review focuses on cell surface proteins that correlate with tumour progression, metastasis and patient outcome, and discusses some of the challenges in finding prognostic protein markers in CRC.     

Separating stress and time dependent effects in the temperature dependent creep of polyethylene nanocomposites

The nonlinear time dependent creep of linear‐low density polyethylene (LLDPE) reinforced with montmorillonite layered silicate was investigated. A previous study related the time/stress dependence of creep compliance of the material at room temperature using the Burger and Kohlrausch‐Williams‐Watts models. Using both the creep and recovery compliance curves, we employ the Schapery formulation to study the relationship between deformation, time, stress, and temperature of LLDPE nanocomposites. Smooth mastercurves are constructed using time–temperature–stress superposition principles. The stress and temperature‐related creep constants and shift factors were determined for the material using the Schapery nonlinear viscoelastic equation. The prediction results confirm the enhanced creep resistance of nanofillers even at extended time scales and low temperatures. POLYM. ENG. SCI., 50:1646–1657, 2010. © 2010 Society of Plastics Engineers     

Cardiac Oxidative Signaling and Physiological Hypertrophy in the Na/K-ATPase α1s/sα2s/s Mouse Model of High Affinity for Cardiotonic Steroids

The Na/K-ATPase is the specific receptor for cardiotonic steroids (CTS) such as ouabain and digoxin. At pharmacological concentrations used in the treatment of cardiac conditions, CTS inhibit the ion-pumping function of Na/K-ATPase. At much lower concentrations, in the range of those reported for endogenous CTS in the blood, they stimulate hypertrophic growth of cultured cardiac myocytes through initiation of a Na/K-ATPase-mediated and reactive oxygen species (ROS)-dependent signaling. To examine a possible effect of endogenous concentrations of CTS on cardiac structure and function in vivo, we compared mice expressing the naturally resistant Na/K-ATPase α1 and age-matched mice genetically engineered to express a mutated Na/K-ATPase α1 with high affinity for CTS. In this model, total cardiac Na/K-ATPase activity, α1, α2, and β1 protein content remained unchanged, and the cardiac Na/K-ATPase dose–response curve to ouabain shifted to the left as expected. In males aged 3–6 months, increased α1 sensitivity to CTS resulted in a significant increase in cardiac carbonylated protein content, suggesting that ROS production was elevated. A moderate but significant increase of about 15% of the heart-weight-to-tibia-length ratio accompanied by an increase in the myocyte cross-sectional area was detected. Echocardiographic analyses did not reveal any change in cardiac function, and there was no fibrosis or re-expression of the fetal gene program. RNA sequencing analysis indicated that pathways related to energy metabolism were upregulated, while those related to extracellular matrix organization were downregulated. Consistent with a functional role of the latter, an angiotensin-II challenge that triggered fibrosis in the α1^r/rα2^s/s mouse failed to do so in the α1^s/sα2^s/s. Taken together, these results are indicative of a link between circulating CTS, Na/K-ATPase α1, ROS, and physiological cardiac hypertrophy in mice under baseline laboratory conditions.     

Comparison of interwell connectivity predictions using percolation, geometrical, and Monte Carlo models

Reservoir connectivity is often an important consideration for reservoir management. For example, connectivity controls waterflood sweep efficiency and it affects decisions concerning well placement and spacing. The uncertainty of sandbody distributions, however, can make interwell connectivity prediction extremely difficult. Percolation models are a useful tool to simulate sandbody connectivity behavior to estimate interwell connectivity.This study applies a percolation method to estimate interwell connectivity. Using results derived by Andrade, King, and others for fluid travel time between locations in a percolation model, we develop a method to estimate interwell connectivity. Four parameters are needed to use this approach: the net-to-gross ratio p_sand, the typical sandbody size, reservoir length and well spacing. To evaluate this new percolation method, the results are compared to results from geometrical models, Monte Carlo, and reservoir simulation.These methods were applied to estimate interwell connectivity for three non-communicating stratigraphic intervals in Monument Butte oil field, Utah. The results suggest that the percolation method can estimate the probability of interwell connectivity reliably for thin intervals for any values of p_sand, well spacing, and reservoir length. The geometrical model also performs well, but can only be applied in fields where the well spacing is less than one-half of the sandbody size.The proposed method requires that the reservoir interval for evaluation be sufficiently thin so that 2D percolation results can be applied. For thick intervals or heterogeneous sandbody distributions, the percolation method developed here is not suitable because it assumes thin layers. Future percolation research will be needed to adapt this new method to 3D cases.     

A Moving Grid Framework for Geometric Deformable Models

Geometric deformable models based on the level set method have become very popular in the last decade. To overcome an inherent limitation in accuracy while maintaining computational efficiency, adaptive grid techniques using local grid refinement have been developed for use with these models. This strategy, however, requires a very complex data structure, yields large numbers of contour points, and is inconsistent with the implementation of topology-preserving geometric deformable models (TGDMs). In this paper, we investigate the use of an alternative adaptive grid technique called the moving grid method with geometric deformable models. In addition to the development of a consistent moving grid geometric deformable model framework, our main contributions include the introduction of a new grid nondegeneracy constraint, the design of a new grid adaptation criterion, and the development of novel numerical methods and an efficient implementation scheme. The overall method is simpler to implement than using grid refinement, requiring no large, complex, hierarchical data structures. It also offers an extra benefit of automatically reducing the number of contour vertices in the final results. After presenting the algorithm, we demonstrate its performance using both simulated and real images. This work was supported in part by NSF/ERC Grant CISST#9731748 and by NIH/NINDS Grant R01NS37747.