Structural models in the assessment of protein druggability based on HTS data

Insights on the potential of target proteins to bind small molecules with high affinity can be derived from the knowledge of their three-dimensional structural details especially of their binding pockets. The present study uses high-throughput screening (HTS) results on various targets, to obtain mathematical predictive models in which a minimal set of structural parameters significantly contributing to the hit rates or the affinity of the protein binding pockets for small molecular entities, is identified. An emphasis is given to focus on target variation aspect of the data by consideration of commonly tested compounds against the HTS targets. We identify ‘four-parameter’ models with R ², , SEE, and LOO q ² values of 0.70, 0.60, 0.27 and 0.50, respectively, or better. We demonstrate through cross-validation exercises that our regression models apply well on varied data sets. Thus we can use these models to estimate hit rates for HTS campaigns and thereby assign priority to drug targets before they undergo such resource intense experimental screening and follow-up.

Crystal growth and comparison of vibrational and thermal properties of semi-organic nonlinear optical materials

Single crystals of urea thiourea mercuric sulphate (UTHS) and urea thiourea mercuric chloride (UTHC), semi-organic nonlinear optical materials, were grown by low-temperature solution growth technique by slow evaporation method using water as the solvent. Good quality single crystals were grown within three weeks. The nonlinear nature of the crystals was confirmed by SHG test. The UV-Vis spectrum showed the transmitting ability of the crystals in the entire visible region. FTIR spectrum was recorded and vibrational assignments were made. The degree of dopant inclusion was ascertained by AAS. The TGA-DTA studies showed the thermal properties of the crystals.     

TL and EPR studies of CaSO4:Dy phosphor to investigate its efficacy in measurement of food irradiation dose at sub-ambient temperatures

The effects of sub-ambient temperatures of irradiation and dose response of CaSO₄:Dy phosphor was investigated. The irradiation dose in the range 0.5–7.0 kGy was chosen to meet the requirement of commercial food irradiation at low temperature. Commercially available phosphor showed no significant change in glow curve structure with low temperature of irradiation. In order to enhance the sensitivity of the low temperature glow peak (142 °C), the phosphor was subjected to different post-preparation thermal treatments at 700–900 °C. The change in glows and improvement in dose response characteristics were explained by Electron Paramagnetic Resonance (EPR) spectroscopy. At sub-ambient temperature of irradiation, the behavior of thermally treated CaSO₄:Dy phosphor with increasing dose revealed improved linear response of the low temperature glow peak and could be an efficient dosimetry system for the food commodities irradiated at low temperatures.     

An insight into the schizophrenic self‐assembly of thermo and proton sensitive graphene oxide grafted block copolymer

In order to study the self‐assembly of block copolymer grafted from graphene oxide (GO) by the fluorescence of GO, poly(ε‐caprolactone) (PCL)‐block‐poly(dimethyl aminoethyl methacrylate) (PDMAEMA) is grafted from its surface using consecutive ring opening (ROP) and atom transfer radical polymerization (ATRP). GO‐g‐(PCL₁₃‐b‐PDMAEMA₁₁₇) (GPCLD) at pH 9.2 exhibits cloud point (T_c) at 32 °C. At pH 9.2 HRTEM images indicate schizophrenic morphology from vesicle at 26 °C to annular ring at 30 °C followed by giant size aggregation at 38 °C. But the reference block copolymer (PCL₁₄‐b‐PDMAEMA₁₂₆, PCLD), synthesized using benzyl alcohol as ROP initiator, exhibits only core–shell morphology whose size increases with rising temperature at pH 9.2. GPCLD solution exhibits good photoluminescence (PL) property arising from GO at pH 9.2 and PL‐intensity increases abruptly during phase transition. Both T_c and size of GPCLD assembly can be reversibly tuned by CO₂ and N₂ gas purging. ¹H NMR spectra exhibit a gradual shift of resonance peaks of the protons on CO₂ bubbling. Thus at pH 9.2 and at 38 °C the GPCLD acts as a good CO₂ sensor. Additionally, the GPCLD vesicle can load hydrophobic guest molecules which can be released by triggering with CO₂. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 3878–3887     

Track geometry defect rectification based on track deterioration modelling and derailment risk assessment

Analysing track geometry defects is critical for safe and effective railway transportation. Rectifying the appropriate number, types and combinations of geo-defects can effectively reduce the probability of derailments. In this paper, we propose an analytical framework to assist geo-defect rectification decision making. Our major contributions lie in formulating and integrating the following three data-driven models: (1) A track deterioration model to capture the degradation process of different types of geo-defects; (2) A survival model to assess the dynamic derailment risk as a function of track defect and traffic conditions; (3) An optimization model to plan track rectification activities with two different objectives: a cost-based formulation (CF) and a risk-based formulation (RF). We apply these approaches to solve the optimal rectification planning problem for a real-world railway application. We show that the proposed formulations are efficient as well as effective, as compared with existing strategies currently in practice.     

‘One-pot’ organocatalyzed enantioselective synthesis of highly functionalized 3,4,5,6-tetrasubstituted dihydropyrans by sequential Knoevenagel condensation/Michael addition and hemiacetalization

An organocatalytic ‘one-pot’ synthesis of highly functionalized 3,4,5,6-tetrasubstituted dihydropyrans has been developed. Excellent enantio- and diastereo selectivity with good yields are some of the salient features of this methodology. This reaction takes advantage of proline based catalysts and follows stepwise sequential transformations including Knoevenagel condensation–Michael addition–hemiacetalization towards the synthesis of complex dihydropyranol framework.     

Study of size-dependent glass transition and Kauzmann temperature of titanium dioxide nanoparticles

In this article, we have studied the size effect on glass transition and Kauzmann temperature of spherical TiO₂ nanoparticles using Arrhenius relation and Lindemann’s criteria under their dynamic limit. The melting point of nanoparticles decreases with decrease in size of the nanoparticles. The glass transition temperature and Kauzmann temperature are analyzed through the size effect on the melting temperature. The glass transition and Kauzmann temperatures decrease with the decrease in size of TiO₂ nanoparticles.