Virtual Pharmacophore Screening Identifies Small-Molecule Inhibitors of the Rev1-CT/RIR Protein–Protein Interaction

Translesion synthesis (TLS) has emerged as a mechanism through which several forms of cancer develop acquired resistance to first-line genotoxic chemotherapies by allowing replication to continue in the presence of damaged DNA. Small molecules that inhibit TLS hold promise as a novel class of anticancer agents that can serve to enhance the efficacy of these front-line therapies. We previously used a structure-based rational design approach to identify the phenazopyridine scaffold as an inhibitor of TLS that functions by disrupting the protein–protein interaction (PPI) between the C-terminal domain of the TLS DNA polymerase Rev1 (Rev1-CT) and the Rev1 interacting regions (RIR) of other TLS DNA polymerases. To continue the identification of small molecules that disrupt the Rev1-CT/RIR PPI, we generated a pharmacophore model based on the phenazopyridine scaffold and used it in a structure-based virtual screen. In vitro analysis of promising hits identified several new chemotypes with the ability to disrupt this key TLS PPI. In addition, several of these compounds were found to enhance the efficacy of cisplatin in cultured cells, highlighting their anti-TLS potential.     

Sick building syndrome—A case study in a multistory centrally air-conditioned building in the Delhi City

Recently, airtight envelope system has become popular in the design of office buildings to reduce heating and cooling loads. Maintaining allowable indoor air quality (IAQ) for such airtight buildings totally depends on mechanical ventilation systems. Subsequently, poor operation of the ventilation system in such office buildings causes ineffective removal of polluted indoor air, and displays a sign of “sick building syndrome” (SBS). User's perception is an important parameter for evaluating IAQ. A questionnaire study was carried out to investigate the prevalence of the SBS at a multistory centrally air-conditioned Airport Authority of India (AAI) building in the New Delhi city. Quantification of the perceptions of the users regarding IAQ was done by converting their responses to a SBS score. The quantified answers were then subjected to statistical analysis. Qualitative analysis of the questionnaire was carried out to evaluate relationships between SBS score and carbon dioxide (CO₂) and other parameters related to building and work environment. Quantitative analysis of IAQ was also conducted by monitoring indoor concentrations of four pollutants, namely, nitrogen dioxide (NO₂), sulphur dioxide (SO₂), suspended particulate matter (SPM) and carbon monoxide (CO). Concentrations of pollutants were complying with IAQ standards as given by ASHRAE and WHO. The SBS was higher on the third floor as compared to other floors and the control tower. The main symptoms prevailing were headache (51%), lethargy (50%), and dryness in body mucous (33%). The third floor and the control tower were affected by infiltration, mainly from entrance doors. A direct relation between the average SBS score and CO₂ concentration was found, i.e., the average SBS score increased with CO₂ concentration and vice versa, clearly signifying the usefulness of SBS score in IAQ.     

One step synthesis and characterization of copper doped sulfated titania and its enhanced photocatalytic activity in visible light by degradation of methyl orange

This paper reports on the synthesis of copper doped sulfated titania nano-crystalline powders with varying(2.0%–10.0%, by mass) by single step sol gel method. The synthesized photo catalyst has been characterized by employing various techniques like X-ray Diffraction(XRD), Ultraviolet–Visible Diffuse Reflection Spectroscopy(UV–Vis DRS), X-ray Photoelectron Spectroscopy(XPS), Scanning Electron Microscopy(SEM), Energy Dispersive Spectrometry(EDS), Fourier Transform Infrared Spectroscopic Studies(FT-IR), and Transmission Electron Microscopy(TEM). From the XRD and TEM results, all the samples were reported in anatase phase with reduction in particle size in the range of 7 to 12 nm. SEM indicated the change in morphology of the particles. The presence of copper in titania lattice was evidenced by XPS. From UV–Vis DRS and FT-IR studies indicated that prominent absorption shift is observed towards visible region(red shift), the entry of Cu2+into Ti O2 lattice as a substitutional dopant and SO42-ions were covalently bonded with Ti4 +on the surface of the copper doped titania respectively.The photocatalytic activity studies were investigated by considering methyl orange(MO) as dye pollutant in the presence of the visible light. The effect of various parameters like effect of dosage of the catalyst, dopant concentration, p H of the solution, and concentration of the dye was studied in detail.     

Chicken Tallow,a Renewable Source for the Production of Biosurfactant by Yarrowia lipolytica MTCC9520, and its Application in Silver Nanoparticle Synthesis

The present study is focused on the production of a biosurfactant using Yarrowia lipolytica MTCC 9520 by employing inexpensive lipid waste, chicken tallow from slaughterhouses. Plackett–Burman and Box–Behnken Design analyses were adopted for preliminary screening of medium variables and further optimization. The maximal yield of 4.4 g L⁻¹ of the biosurfactant was obtained from the optimized medium. The highest emulsification activity was found to be 55%, and the surface tension decreased to 37 mN m⁻¹ at the end of 96 h. The critical micelle concentration of the biosurfactant was calculated as 1.2%. The produced biosurfactant was characterized as cationic lipoprotein in type, and the proteins present in the biosurfactant were observed to have molecular weights between 75 and 100 kDa. The fatty acids composition of the biosurfactant was detected by gas chromatography–mass spectrometry (GC–MS) analysis. Fourier transform infra red (FTIR) and nuclear magnetic resonance (NMR) analysis confirmed the lipoprotein nature of the extracted biosurfactant. Thermogravimetric (TG) and differential scanning calorimetry (DSC) analysis revealed the thermostable nature of the extracted biosurfactant. Surface plasmon resonance vibration peak at 421 nm was observed for the surfactant-stabilized silver nanoparticles (AgNP) through UV–Vis spectrophotometry. The average particle size of the synthesized AgNP was calculated as 7.2 ± 0.4 nm from transmission electron microscopy (TEM) analysis. Energy dispersive x-ray (EDX) spectroscopy exhibited the presence of silver in the synthesized nanoparticles. The zeta potential value of the synthesized AgNP was measured as −22.2 mV, and the polydispersity index was found as 2.3 through dynamic light scattering (DLS) analysis.     

A Secure Key Predistribution Scheme for WSN Using Elliptic Curve Cryptography

Security in wireless sensor networks (WSNs) is an upcoming research field which is quite different from traditional network security mechanisms. Many applications are dependent on the secure operation of a WSN, and have serious effects if the network is disrupted. Therefore, it is necessary to protect communication between sensor nodes. Key management plays an essential role in achieving security in WSNs. To achieve security, various key predistribution schemes have been proposed in the literature. A secure key management technique in WSN is a real challenging task. In this paper, a novel approach to the above problem by making use of elliptic curve cryptography (ECC) is presented. In the proposed scheme, a seed key, which is a distinct point in an elliptic curve, is assigned to each sensor node prior to its deployment. The private key ring for each sensor node is generated using the point doubling mathematical operation over the seed key. When two nodes share a common private key, then a link is established between these two nodes. By suitably choosing the value of the prime field and key ring size, the probability of two nodes sharing the same private key could be increased. The performance is evaluated in terms of connectivity and resilience against node capture. The results show that the performance is better for the proposed scheme with ECC compared to the other basic schemes.     

A hybrid neural network–genetic algorithm approach for permutation flow shop scheduling

The objective of this paper is to find a sequence of jobs for the permutation flow shop to minimise the makespan. The shop consists of 10 machines. A feed-forward back-propagation artificial neural network (ANN) is used to solve the problem. The network is trained with the optimal sequences for five-, six- and seven-job problems. This trained network is then used to solve a problem with a greater number of jobs. The sequence obtained using the neural network is used to generate the initial population for the genetic algorithm (GA) using the random insertion perturbation scheme (RIPS). The makespan of the sequence obtained by this approach (ANN-GA-RIPS) is compared with that obtained using GA starting with a random population (ANN-GA). It was found that the ANN-GA-RIPS approach performs better than ANN-GA starting with a random population. The results obtained are compared with those obtained using the Nawaz, Enscore and Ham (NEH) heuristic and upper bounds of Taillard's benchmark problems. ANN-GA-RIPS performs better than the NEH heuristic and the results are found to be within 5% of the upper bounds.     

Ultimate strength of submarine pressure hulls with failure governed by inelastic buckling

The analysis of submarine pressure hull assumes great importance among structural engineers due to the complexity involved in the collapse mechanism of stiffened shell structures. In most of the cases, the failure of stiffened shell structures occurs due to elastic buckling. But for some combinations of shell-stiffener geometry and material characteristics, the structure can fail by inelastic buckling, for which the methods of analysis are meagre. In this paper, the analysis of submarine pressure hull structure in which the failure gets governed by inelastic buckling is demonstrated. Three different approaches have been employed to investigate the ultimate strength of the ring stiffened submarine pressure hull structure with inelastic buckling modes of failure. The methods used are ‘Johnson–Ostenfeld inelastic correction’, ‘imperfection method’ and ‘finite element approach’. A typical submarine shell structure has been analysed for the inelastic buckling failure using these three approaches and the results are discussed.