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.     

江苏德邦化工集团有限公司，江苏连云港 222023

1 简介 印度第一个纯碱厂始建于1932年,位于印度西部古吉拉特邦的Dhrangadhra,装置能力为50t/d。 作为基础无机化工产品,因为整个印度无天然碱矿,全部产品--包括轻灰和重灰只能以合成法生产。     

Evaluation of potential anti‐cancer activity of cationic liposomal nanoformulated Lycopodium clavatum in colon cancer cells

Research dealing with early diagnosis and efficient treatment in colon cancer to improve patient''s survival is still under investigation. Chemotherapeutic agent result in high systemic toxicity due to their non‐specific actions on DNA repair and/or cell replication. Traditional medicine such as Lycopodium clavatum (LC) has been claimed to have therapeutic potentials against cancer. The present study focuses on targeted drug delivery of cationic liposomal nanoformulated LC (CL‐LC) in colon cancer cells (HCT15) and comparing the efficacy with an anti‐colon cancer drug, 7‐ethyl‐10‐hydroxy‐camptothecin (SN38) along with its nanoformulated form (CL‐SN38). The colloidal suspension of LC was made using thin film hydration method. The drugs were characterised using ultraviolet, dynamic light scattering, scanning electron microscopy, energy, dispersive X‐ray spectroscopy. In vitro drug release showed kinetics of 49 and 89% of SN38 and LC, whereas CL‐SN38 and CL‐LC showed 73 and 74% of sustained drug release, respectively. Studies on morphological changes, cell viability, cytotoxicity, apoptosis, cancer‐associated gene expression analysis of Bcl‐2, Bax, p53 by real‐time polymerase chain reaction and western blot analysis of Bad and p53 protein were performed. Nanoformulated LC significantly inhibited growth and increased the apoptosis of colon cancer cells indicating its potential anti‐cancer activity against colon cancer cells.Inspec keywords: cancer, biological organs, cellular biophysics, drug delivery systems, drugs, nanomedicine, genetics, DNA, molecular biophysics, biochemistry, lipid bilayers, toxicology, suspensions, colloids, light scattering, X‐ray chemical analysis, solvation, enzymes, nanostructured materialsOther keywords: energy dispersive X‐ray spectroscopy, in vitro drug release, morphological changes, cell viability, cytotoxicity, apoptosis, cancer‐associated gene expression analysis, Bcl‐2, Bax, real‐time polymerase chain reaction, western blot analysis, Bad protein, p53 protein, scanning electron microscopy, dynamic light scattering, ultraviolet scattering, thin film hydration method, colloidal suspension, nanoformulated form CL‐SN38, 7‐ethyl‐10‐hydroxy‐camptothecin, anticolon cancer drug, colon cancer cells HCT15, cationic liposomal nanoformulated LC, targeted drug delivery, therapeutic potentials, Lycopodium clavatum, traditional medicines, cell replication, DNA repair, nonspecific actions, high systemic toxicity, chemotherapeutic agents, patient survival, colon cancer treatment, colon cancer diagnosis, CL‐LC, potential anticancer activity     

Minimization and identification of conducted emission bearing current in variable speed induction motor drives using PWM inverter

The recent increase in the use of speed control of ac induction motor for variable speed drive using pulse width modulation (PWM) inverter is due to the advent of modern power electronic devices and introduction of microprocessors. There are many advantages of using ac induction motor for speed control applications in process and aerospace industries, but due to fast switching of the modern power electronic devices, the parasitic coupling produces undesirable effects. The undesirable effects include radiated and conducted electromagnetic interference (EMI) which adversely affect nearby computers, electronic/electrical instruments and give rise to the flow of bearing current in the induction motor. Due to the flow of bearing current in the induction motor, electrical discharge machining takes place in the inner race of the bearing which reduces the life of the bearing. In high power converters and inverters, the conducted and radiated emissions become a major concern. In this paper, identification of bearing current due to conducted emission, the measurement of bearing current in a modified induction motor and to minimize the bearing current are discussed. The standard current probe, the standard line impedance stabilization network (LISN)), the electronics interface circuits are used to measure high frequency common mode current, bearing current and to minimize the conducted noise from the system. The LISN will prevent the EMI noise entering the system from the supply source by conductive methods, at the same time prevents the EMI generated if any due to PWM, fast switching in the system, will not be allowed to enter the supply line. For comparing the results with Federal Communications Commission (FCC) and Special Committee on Radio Interference (CISPR) standards, the graphs are plotted with frequency Vs, line voltage in dBμ V, common mode voltage in dBμ V and the bearing current in dBμ A with out and with minimizing circuits.     

Thermal stability of CeO<Subscript>2</Subscript>/ZrO<Subscript>2</Subscript> multilayer thin films prepared by pulsed laser deposition

Multilayers of CeO₂/ZrO₂ thin films were deposited on Si (100) substrates using pulsed laser deposition at an optimized oxygen partial pressure of 3×10⁻² mbar and at room temperature. The CeO₂ layer thickness was 10 nm, while the ZrO₂ layer thickness was varied as 10, 20 and 30 nm. CeO₂ and ZrO₂ layers were deposited alternately to obtain 25 bilayers. High temperature x-ray diffraction (HTXRD) results showed that the multilayer films had cubic ceria and tetragonal ZrO₂. Thermal expansion coefficients were calculated for CeO₂ and t-ZrO₂ and found to increase with the decrease of ZrO₂ layer thickness. The cross sectional transmission electron microscopy (XTEM) of CeO₂/ZrO₂ multilayer also indicated that ceria was found to be in cubic phase while zirconia contained predominantly tetragonal phase along with cubic phase in thermally annealed specimen.     

Palladium‐nanoparticle intercalated vermiculite for selective hydrogenation of α,β‐unsaturated aldehydes

Palladium nanoparticles were generated in the interlamellar region of swelling 2:1 type vermiculite clay using an adsorption excess isotherm. An adsorption excess isotherm was constructed for vermiculite after exchanging the exchangeable Na⁺ ions in the interlamellar region using a binary liquid mixture (ethanol:toluene). Based on adsorption excess isotherm, 1% w/w palladium was intercalated into the interlamellar space of vermiculite. The Pd‐intercalated vermiculite was characterized by X‐ray diffraction, transmission electron microscopy and atomic absorption spectroscopy. The 1% w/w Pd‐intercalated vermiculite was tested for its catalytic activity towards selective hydrogenation reactions involving some α,β‐unsaturated carbonyl compounds using a pulse reactor and its catalytic activity was compared with commercial 1% Pd/C. The intercalated catalyst was found to be very selective towards the desired product of unsaturated alcohols. Copyright © 2007 Society of Chemical Industry     

The iterative contribution and relevance of modelling to UK energy policy

This paper discusses the iterative provision of modelling insights on long-term decarbonisation scenarios for UK energy policy makers. A multi-year model construction process of the UK MARKAL-Macro-hybrid energy-economic model, and four subsequent major policy analyses illustrates the scope of this interaction. The initial set of modelling runs focused on the technical feasibility of long-term 60% carbon dioxide (CO₂) reduction scenarios, the role of key technologies, and the underlying uncertainties. Furthermore subsequent modelling studies were aimed to generate insights on more stringent targets, and on issues and uncertainties that may make targets harder to achieve. Hence, this paper analyses the large number of long-term UK CO₂ reduction scenarios through a clustering approach on target stringency and barriers to implementation. Robust findings and key uncertainties are highlighted, including the critical role of the power sector, trade-offs between resources, sectors, key energy technologies and behavioural responses, and the increasing level and spread of CO₂ marginal prices and GDP impacts. The relevance and use of modelling insights to the UK energy policy process is shown in the continuation of the energy modelling–policy interface. This constitutes both ongoing model development, and nuanced scenario analysis designed to further explore key uncertainties in evolving policy issues.     

Modularization of a Large-Scale Business Application: A Case Study

Large software systems, developed over several years, are the backbone of industries such as banking, retail, transportation, and telecommunications. With multiple bug fixes and feature enhancements, these systems gradually deviate from the intended architecture and deteriorate into unmanageable monoliths. This article presents a case study of a banking application besot with such problems and the modularization approach that the company adopted as a solution. It also highlights benefits unearthed as a result of this reengineering exercise.     

Lattice dynamics of colloidal crystals during photopolymerization of acrylic monomer matrix

The photoinitiated bulk polymerization process, which has been used recently in the manufacture of solid optical diffraction filters, is examined to understand the dynamics of both the crystalline colloidal arrays (CCA) and the host monomer species. Our analysis indicates that volume shrinkage of the monomer, changes in the dielectric properties of the monomer, and inhomogeneities of polymerization reaction rate across the dispersion during the polymerization process, are the major contributors for observed lattice compression and lattice disorder of the CCA of silica spheres in polymerized acrylic/methacrylic ester films. The effect of orientation of photocell with respect to the radiation source on Bragg diffraction of CCA indicated the presence of convective stirring in the thin fluid system during the photopolymerization that deleteriously affects the periodic array structures. To devise reproducible and more efficient optical filters, experimental methods to minimize or eliminate convective instabilities in monomeric dispersions during polymerization are suggested. © 1998 Chapman & Hall