Importance of receptor flexibility in binding of cyclam compounds to the chemokine receptor CXCR4

We have elucidated the binding sites of four moncyclam and one bicyclam antagonist AMD3100, in the human chemokine receptor CXCR4. Using the predicted structural models of CXCR4, we have further predicted the binding sites of these cyclam compounds. We used the computational method LITiCon to map the differences in receptor structure stabilized by the mono and bicyclam compounds. Accounting for the receptor flexibility lead to a single binding mode for the cyclam compounds, that has not been possible previously using a single receptor structural model and fixed receptor docking algorithms. There are several notable differences in the receptor conformations stabilized by monocyclam antagonist compared to a bicylam antagonist. The loading of the Cu(2+) ions in the cyclam compounds, shrinks the size of the cyclam rings and the residue D262(6.58) plays an important role in bonding to the copper ion in the monocylam compounds while residue E288(7.39) is important for the bicyclam compound.     

Insulator-based dielectrophoretic single particle and single cancer cell trapping

Trapping of individual cells at specific locations in a microfluidic lab-on-a-chip platform is essential for single cell studies, especially those requiring individual stimulation followed by downstream analysis. To this aim, we have designed microdevices based on direct current (DC) insulator-based dielectrophoresis (iDEP) acting as individual single cell traps. We present both the design of a negative iDEP trap and a positive iDEP trap using insulating posts integrated at microchannel intersections. We obtained electric field distributions via numerical simulations adapted to the intersection and trap geometry with which we predict single particle pathlines. With polystyrene particles of 10?μm diameter, we demonstrated an effective design for a single particle trap in the case of negative dielectrophoresis. The onset trapping voltage shows an inverse relation to the buffer conductivity, thus indicating the influence of electrokinetic effects on the trapping behavior. Additionally, we demonstrated the proof-of-principle of single MCF-7 breast cancer cell trapping in a positive iDEP trap. Our single particle trapping experiments were further in very good agreement with numerical simulations. To ensure that no significant damage occurred to the cells during the experiment, we further optimized medium conditions to ensure viability of the cells for at least 1?h, more than sufficient for microfluidic trapping experiments. Our results thus indicated the successful design of DC iDEP traps, which can easily be integrated into a variety of microchip operations for single cell analysis.     

Tunable solvatochromic response of newly synthesized antioxidative naphthalimide derivatives: intramolecular charge transfer associated with hydrogen bonding effect

The solvatochromic behavior of two newly synthesized naphthalimide derivatives (I and II) which have potential antioxidative activities in anticarcinogenic drug development treatment, has been monitored in protic and aprotic solvents of different polarity applying steady-state and time-resolved fluorescence techniques. The compounds exhibit unique photophysical response in different solvent environments. The spectral trends do not appear to originate only from changes in the solvent polarity but also indicate that hydrogen bonding interactions and intramolecular charge transfer (ICT) influence the energy of electronic excitation of the compounds. Incorporation of an amino group at C(4) position of the naphthalimide ring in II makes it behave differently from I in terms of spectral characterization and fluorescence efficacy of the systems. The nonradiative relaxation process of the compounds is governed by medium polarity. The ground state geometry, lowest energy transition, and the UV-vis absorption energy of the compounds were studied using density functional theory (DFT) and time-dependent density functional theory (TDDFT) at the B3LYP/6-31G* level, which showed that the calculated outcomes were in good agreement with experimental data.     

Switchable Optical Probes for Simultaneous Targeting of Multiple Anions

Traditional optical probes primarily work on the concept of one‐to‐one recognition strategy. Therefore, simultaneous detection of multiple anions is difficult using this kind of sensory systems. Similarly, designing of multi‐responsive array‐based materials is synthetically challenging as well as difficult to optimize. Thus, researchers across the globe became interested in developing single molecular probes, capable of detecting multiple anions (or anionic biomolecules) by simultaneously activating optically distinguishable output channels. Here, the modes of interaction largely depend on the structural features of the binding sites (cleft size, number of available coordination sites etc.), characteristics of the anions (ionic radius, hydration enthalpy, basicity, coordination number, pk_a of corresponding acids etc.) and the microenvironment around the probe molecules (micropolarity, viscosity, dielectric constant etc.) in the host matrix. In this review, we are mostly focusing on the structure‐activity relationships of such multiple anions sensing optical probes and their stimuli‐responsive properties.     

Studies on the Effects of Salt and Surfactant in Wet Phase Separation of Polysulfone

This study investigates the effect of additives in the nonsolvent water in terms of cloud point during the phase inversion of Polysulfone (PS) in dimethyl formamide (DMF). The exponential pattern is observed with PS concentration (0.2 to 0.6% (w/w)). It needs a low amount of water to get the cloud point at low temperature. The cloud point varied with the nature of water matrix and depended on the amount of salt, as well as the PS amount. The presence of salts (sodium chloride and sodium sulfate) lowers the cloud point of the solution. The network distribution of the particles at the cloud point is disturbed in the presence of salt. The requirement is more for Sodium lauryl sulfate (SLS) added water to reach the cloud point in the low range of PS solution up to 0.3% PS (w/w). The morphological and distribution pattern of PS particles are very different compared to PS particles produced from pure water. XRD study of PS particles produced from the mixed water system reflects relatively more amorphous character with respect to PS particles from pure water. The presence of both surfactant and salts in water systems also influences the cloud point in synergistic manner.     

Defect studies in small CdTe clusters

We study Cd vacancy formation in prototype stoichiometric and non-stoichiometric CdTe clusters with and without passivation. For certain clusters like Cd₁₃Te₁₆, vacancy leads to severe distortion of the geometry due to propagation of defect. Annealing of the vacancy out of the cluster is observed in all unpassivated clusters. Passivated clusters retain their initial geometry and vacancy induced structural distortions are not seen in these clusters since the defect gets localized. Vacancy also induces intragap states. However, it was observed that the passivation of the dangling bonds created by the vacancy removes the intragap states. In an attempt to have CdTe clusters with extrinsic carriers, we substituted a Cd atom by its adjacent atoms Pd/Ag/In/Sn in these CdTe clusters. Substitutional doping of Cd by metal atoms increases the stability of unpassivated clusters. For certain clusters, metal atom doping leads to a half-metallic character. Pd/Ag-doped clusters are p-type semiconductors whereas In-doped clusters are n-type semiconductors. Sn doping in these clusters does not result in n-type semiconductors.     

Estimation of the offspring mean in a controlled branching process with a random control function

Controlled branching processes (CBP) with a random control function provide a useful way to model generation sizes in population dynamics studies, where control on the growth of the population size is necessary at each generation. An important special case of this process is the well known branching process with immigration. Motivated by the work of Wei and Winnicki [C.Z. Wei, J. Winnicki, Estimation of the mean in the branching process with immigration, Ann. Statist. 18 (1990) 1757–1773], we develop a weighted conditional least squares estimator of the offspring mean of the CBP and derive the asymptotic limit distribution of the estimator when the process is subcritical, critical and supercritical. Moreover, we show the strong consistency of this estimator in all the cases. The results obtained here extend those of Wei and Winnicki [C.Z. Wei, J. Winnicki, Estimation of the mean in the branching process with immigration, Ann. Statist. 18 (1990) 1757–1773] for branching processes with immigration and provide a unified limit theory of estimation.     

AnO(m + n log n) Algorithm for the Maximum-Clique Problem in Circular-Arc Graphs

We present an algorithm to compute, inO(m + n log n) time, a maximum clique in circular-arc graphs (withnvertices andmedges) provided a circular-arc model of the graph is given. If the circular-arc endpoints are given in sorted order, the time complexity isO(m). The algorithm operates on the geometric structure of the circular arcs, radially sweeping their endpoints; it uses a very simple data structure consisting of doubly linked lists. Previously, the best time bound for this problem wasO(m log log n + n log n), using an algorithm that solved an independent subproblem for each of thencircular arcs. By using the radial-sweep technique, we need not solve each of these subproblems independently; thus we eliminate the log log nfactor from the running time of earlier algorithms. For vertex-weighted circular-arc graphs, it is possible to use our approach to obtain anO(m log log n + n log n) algorithm for finding a maximum-weight clique—which matches the best known algorithm.     

Synthesis and electrochemical studies of phenylazo substituted tetraaza macrocyclic complexes of Ni(II)

Synthesis and characterization of some phenyl azo substituted tetraaza macrocyclic complexes of Ni(II) are reported. Electrochemical behaviour of these macrocyclic complexes has been examined using polarographic, voltammetric and spectroscopic techniques. These studies show that both the ligand and the metal are electrochemically active. The electrochemical behaviour of the azo function has been shown to occur through a single four-electron process. When a nitro group is also present, the nitro function of the azo moiety is reduced in a six-electron cathodic wave.     

Synthesis and properties of MoSi2 based engineering ceramics

Molybdenum disilicide is a high temperature structural ceramic with many attractive properties for engineering applications. Foremost amongst these is its stability in corrosive atmospheres up to about 1600°C. However, there are a few undesirable properties that need to be addressed before it can become a viable material in high temperature applications. Since MoSi₂ forms thermodynamically stable composites with both metals and ceramics, many reinforcing materials are incorporated into the matrix to improve the fracture toughness and creep properties. The low temperature oxidation can be controlled by making high density (> 95% of theoretical density) compacts. This article summarizes the important attempts that are made in improving the properties of molybdenum disilicide-based ceramics by the reinforcement with other materials.