Identification of tubulin drug binding sites and prediction of relative differences in binding affinities to tubulin isotypes using digital signal processing

Microtubules are involved in numerous cellular processes including chromosome segregation during mitosis and, as a result, their constituent protein, tubulin, has become a successful target of several chemotherapeutic drugs. In general, these drugs bind indiscriminately to tubulin within both cancerous and healthy cells, resulting in unwanted side effects. However, differences between beta-tubulin isotypes expressed in a wide range of cell types may aid in the development of anti-tubulin drugs having increased specificity for only certain types of cells. Here, we describe a digital signal processing (DSP) method that is capable of predicting hot spots for the tubulin family of proteins as well as determining relative differences in binding affinities to these hot spots based only on the primary sequence of 10 human tubulin isotypes. Due to the fact that several drug binding sites have already been characterized within beta-tubulin, we are able to correlate hot spots with the binding sites for known chemotherapy drugs. We have also verified the accuracy of this method using the correlation between the binding affinities of characterized drugs and the tubulin isotypes. Additionally, the DSP method enables the rapid estimation of relative differences in binding affinities within the binding sites of tubulin isotypes that are yet to be experimentally determined.     

Human pathogenic streptococcal proteomics and vaccine development

Gram-positive streptococci are non-motile, chain-forming bacteria commonly found in the normal oral and bowel flora of warm-blooded animals. Over the past decade, a proteomic approach combining 2-DE and MS has been used to systematically map the cellular, surface-associated and secreted proteins of human pathogenic streptococcal species. The public availability of complete streptococcal genomic sequences and the amalgamation of proteomic, genomic and bioinformatic technologies have recently facilitated the identification of novel streptococcal vaccine candidate antigens and therapeutic agents. The objective of this review is to examine the constituents of the streptococcal cell wall and secreted proteome, the mechanisms of transport of surface and secreted proteins, and describe the current methodologies employed for the identification of novel surface-displayed proteins and potential vaccine antigens.     

Robust Estimation of GARMA Model Parameters with an Application to Cointegration among Interest Rates of Industrialized Countries

We review the literature on long memory ARFIMA and GARMA models andintroduce a new efficient estimator for GARMA models, which we show to berobust. Next we conduct a Monte Carlo study to demonstate the power of theDickie–Fuller test when the data are generated from a stationary GARMAprocess. We conclude with a brief discussion of cointegration in the contextof GARMA models with an application to international interest rates.     

Probabilistic Belief Contraction

Probabilistic belief contraction has been a much neglected topic in the field of probabilistic reasoning. This is due to the difficulty in establishing a reasonable reversal of the effect of Bayesian conditionalization on a probabilistic distribution. We show that indifferent contraction, a solution proposed by Ramer to this problem through a judicious use of the principle of maximum entropy, is a probabilistic version of a full meet contraction. We then propose variations of indifferent contraction, using both the Shannon entropy measure as well as the Hartley entropy measure, with an aim to avoid excessive loss of beliefs that full meet contraction entails.     

Thermal and structural properties of spray pyrolysed CdS thin film

Using photo acoustic technique, the thermal properties of CdS thin films grown by spray pyrolysis are measured. Thermal diffusivity and conductivity in these films decrease at least two orders compared with bulk. These results are compared with our study on nano CdS and the other available literature. The comparison is good. The dependence of thermal diffusivity on the thickness of the layer or the size of the particles on the glass substrate are analysed from the present measurement and discussed. The dependence of thermal diffusivity on the thickness of the layer on the glass substrate is discussed.     

Toward a more realistic performance evaluation of interconnectionnetworks

lnterconnection network design plays a central role in the design of parallel systems. Most of the previous research has evaluated the performance of interconnection networks in isolation. In this study, we investigate the relationship between application program characteristics and interconnection network performance using an execution driven simulation test bed: the Reconfigurable Architecture Workbench (RAW). We simulate five topological configurations of a k-ary n-cube interconnect and four different network link models for a 4,096 node SIMD machine, and quantify the impact of the network on two application programs. We provide experimental evidence that such “in-context” simulation provides a better view of the impact of network design variables on system performance. We show that recent results, indicating that low-dimensional designs provide better ICN performance, ignore application requirements that may favor high-dimensional designs. Furthermore, applications that would appear to favor low dimensional designs may not, in fact, be significantly impacted by the network's dimensionality. We experimentally test the results of published performance models comparing the use of a synthetic load to that of a load generated by a typical application program     

Phase transition in L-alaninium oxalate by photoacoustics

Phase transition in L-alaninium oxalate is studied by using TG, DTA and photoacoustic spectroscopy. A sharp transition at 378 K by photoacoustics is observed whereas at the same temperature the endothermic energy change observed by TG and DTA is not very sharp. This is discussed in detail with reference to the other known data for the organic crystals.     

High‐performance electromagnetic interference shielding material based on an effective mixing protocol

A facile and economic method is developed for the fabrication of new lightweight materials with high electromagnetic interference (EMI) shielding performance, good mechanical properties and low electrical percolation threshold through melt mixing. Electrical properties, DC conductivity, EMI shielding performance and mechanical properties of poly(trimethylene terephthalate) (PTT)/multiwalled carbon nanotube (MWCNT) nanocomposites with varying filler loading of MWCNTs were investigated. High‐resolution transmission electron microscopy was used to determine the distribution of MWCNTs in the PTT matrix. The newly developed nanocomposites show excellent dielectric and EMI shielding properties. Theoretical electrical percolation threshold was achieved at 0.21 wt% loading of MWCNTs, due to the high aspect ratio and the three‐dimensional network formation of MWCNTs. Experimental DC conductivity values were compared with those of theoretical models such as the Voet, Bueche and Scarisbrick models, which showed good agreement. The PTT/3% MWCNT composite showed an EMI shielding value of ～38 dB (99.99% attenuation) with a sample thickness of 2 mm. Power balance was used to determine the actual contribution of reflection, absorption and transmission loss to the total EMI shielding value. The nanocomposites showed good tensile and impact properties and the composite with 2% MWCNTs exhibited an improvement in tensile strength of as much as 96%. © 2018 Society of Chemical Industry     

Dissolution and Solubility Behavior of Fenofibrate in Sodium Lauryl Sulfate Solutions

The solubility of fenofibrate in pH 6.8 McIlvaine buffers containing varying concentrations of sodium lauryl sulfate was determined. The dissolution behavior of fenofibrate was also examined in the same solutions with rotating disk experiments. It was observed that the enhancement in intrinsic dissolution rate was approximately 500-fold and the enhancement in solubility was approximately 2000-fold in a pH 6.8 buffer containing 2% (w/v) sodium lauryl sulfate compared to that in buffer alone. The micellar solubilization equilibrium coefficient (k*) was estimated from the solubility data and found to be 30884 ± 213 L/mol. The diffusivity for the free solute, 7.15 × 10^{? 6} cm²/s, was calculated using Schroeder's additive molal volume estimates and Hayduk-Laurie correlation. The diffusivity of the drug-loaded micelle, estimated from the experimental solubility and dissolution data and the calculated value for free solute diffusivity, was 0.86 × 10^{? 6} cm²/s. Thus, the much lower enhancement in dissolution of fenofibrate compared to its enhancement in solubility in surfactant solutions appears to be consistent with the contribution to the total transport due to enhanced micellar solubilization as well as a large decrease ( ～ 8-fold) in the diffusivity of the drug-loaded micelle.