Peptidomimetic inhibitors of the human cytomegalovirus protease

The development of peptidomimetic inhibitors of the human cytomegalovirus (HCMV) protease showing sub-micromolar potency in an enzymatic assay is described. Selective substitution of the amino acid residues of these inhibitors led to the identification of tripeptide inhibitors showing improvements in inhibitor potency of 27-fold relative to inhibitor 39 based upon the natural tetrapeptide sequence. Small side chains at P1 were well tolerated by this enzyme, a fact consistent with previous observations. The S2 binding pocket of HCMV protease was very permissive, tolerating lipophilic and basic residues. The substitutions tried at P3 indicated that a small increase in inhibitor potency could be realized by the substitution of a tert-leucine residue for valine. Substitutions of the N-terminal capping group did not significantly affect inhibitor potency. Pentafluoroethyl ketones, alpha,alpha-difluoro-beta-keto amides, phosphonates and alpha-keto amides were all effective substitutions for the activated carbonyl component and gave inhibitors which were selective for HCMV protease. A slight increase in potency was observed by lengthening the P1' residue of the alpha-keto amide series of inhibitors. This position also tolerated a variety of groups making this a potential site for future modifications which could modulate the physicochemical properties of these molecules.     

System‐based strategies for p53 recovery

The authors have proposed a systems theory‐based novel drug design approach for the p53 pathway. The pathway is taken as a dynamic system represented by ordinary differential equations‐based mathematical model. Using control engineering practices, the system analysis and subsequent controller design is performed for the re‐activation of wild‐type p53. p53 revival is discussed for both modes of operation, i.e. the sustained and oscillatory. To define the problem in control system paradigm, modification in the existing mathematical model is performed to incorporate the effect of Nutlin. Attractor point analysis is carried out to select the suitable domain of attraction. A two‐loop negative feedback control strategy is devised to drag the system trajectories to the attractor point and to regulate cellular concentration of Nutlin, respectively. An integrated framework is constituted to incorporate the pharmacokinetic effects of Nutlin in the cancerous cells. Bifurcation analysis is also performed on the p53 model to see the conditions for p53 oscillation.Inspec keywords: proteins, tumours, cancer, cellular biophysics, molecular biophysics, molecular configurations, biochemistry, differential equations, closed loop systems, bifurcation, biology computingOther keywords: system‐based strategies, p53 recovery, systems theory‐based novel drug design approach, dynamic system, ordinary differential equations‐based mathematical model, control engineering practices, subsequent controller design, wild‐type p53, p53 revival, oscillatory, control system paradigm, mathematical model, Nutlin effect, attractor point analysis, domain‐of‐attraction, two‐loop negative feedback control strategy, cellular concentration, pharmacokinetic effects, cancerous cells, bifurcation analysis, p53 oscillation, anomalous cell     

Creating sentiment lexicon for sentiment analysis in Urdu: The case of a resource‐poor language

The sentiment analysis (SA) applications are becoming popular among the individuals and organizations for gathering and analysing user's sentiments about products, services, policies, and current affairs. Due to the availability of a wide range of English lexical resources, such as part‐of‐speech taggers, parsers, and polarity lexicons, development of sophisticated SA applications for the English language has attracted many researchers. Although there have been efforts for creating polarity lexicons in non‐English languages such as Urdu, they suffer from many deficiencies, such as lack of publically available sentiment lexicons with a proper scoring mechanism of opinion words and modifiers. In this work, we present a word‐level translation scheme for creating a first comprehensive Urdu polarity resource: “Urdu Lexicon” using a merger of existing resources: list of English opinion words, SentiWordNet, English–Urdu bilingual dictionary, and a collection of Urdu modifiers. We assign two polarity scores, positive and negative, to each Urdu opinion word. Moreover, modifiers are collected, classified, and tagged with proper polarity scores. We also perform an extrinsic evaluation in terms of subjectivity detection and sentiment classification, and the evaluation results show that the polarity scores assigned by this technique are more accurate than the baseline methods.     

Phase time delay and Hartman effect in a one-dimensional photonic crystal with four-level atomic defect layer

The Hartman effect is revisited using a Gaussian beam incident on a one-dimensional photonic crystal (1DPC) having a defect layer doped with four-level atoms. It is considered that each atom of the defect layer interacts with three driving fields, whereas a Gaussian beam of width w is used as a probe light to study Hartman effect. The atom–field interaction inside the defect layer exhibits electromagnetically induced transparency (EIT). The 1DPC acts as positive index material (PIM) and negative index material (NIM) corresponding to the normal and anomalous dispersion of the defect layer, respectively, via control of the phase associated with the driving fields and probe detuning. The positive and negative Hartman effects are noticed for PIM and NIM, respectively, via control of the relative phase corresponding to the driving fields and probe detuning. The advantage of using four-level EIT system is that a much smaller absorption of the transmitted beam occurs as compared to three-level EIT system corresponding to the anomalous dispersion, leading to negative Hartman effect.     

Biodiesel feasibility study: An evaluation of material compatibility; performance; emission and engine durability

Biodiesel, derived from the transesterification of vegetable oils or animal fats, is composed of saturated and unsaturated long-chain fatty acid alkyl esters. In spite of having some application problems, recently it is being considered as one of the most promising alternative fuels in internal combustion engine. From scientific literatures, this paper has collected and analyzed the data on both advantages and disadvantages of biodiesel over conventional diesel. Since the aim of this study is to evaluate the biodiesel feasibility in automobiles, the first section is dedicated to materials compatibility in biodiesel as compared to that in diesel. The highest consensus is related to enhanced corrosion of automotive parts due to its compositional differences. In the subsequent sections, data on performance, emission and engine durability have been analyzed and compared. In this case, the highest consensus is found in reducing emissions as well as in increasing moving parts sticking, injector coking and filter plugging. This paper has also summarized the factors of biodiesel in contributing these technical performances.     

Evaluation of CrAlN multilayered coatings deposited by PVD magnetron sputtering

The purpose of this experimental work is to evaluate the mechanical and tribological properties of chromium aluminum nitride (CrAlN) coating deposited on hypereutectic Al–Si-alloy. The microstructural, topographical analysis, and composition of CrAlN-coated substrates were examined by using scanning electron microscopy and energy-dispersive spectroscopy, whereas phase formation was analyzed by X-ray Diffractometer (XRD). Atomic force microscopy (AFM) images were taken from the substrate surface before and after the coating. The scratch adhesion of film-to-substrate was measured by using scratch machine. In an effort to understand the critical point, loads were identified by Scratch track in terms of load vs. depth as a function of scan distance. Moreover, the critical load as the beginning of chipping or spallation of the coating was studied. The tribological properties of CrAlN coating were evaluated by pin on disc tribometer at room temperature. XRD analysis showed that CrAlN successfully deposited with a preferential orientation along the (1?1?1), (2?0?0) and (2?2?0) peaks. The AFM images of coated sample confirmed that the surface roughness was lower(R_a = 14 nm) as compared to uncoated sample (R_a = 46 nm). The hardness of coated hypereutectic Al–Si-alloy was increased about 5.8 times as compared to uncoated sample. The coefficient of friction and wear rate of coated specimen were found to be improved. The coating adhesion strength of 2341 mN was obtained with coating parameters for deposition of DC power (350 W), RF power (200 W), temperature (175 °C), and nitrogen flow rate (5%).     

Effect of Au additions on the structure and properties of (Fe0.5Co0.5)71Nb4Si5B20 bulk metallic glass

The effect of addition of gold (Au) on the structure and mechanical properties of (Fe_0.5Co_0.5)₇₁Nb₄Si₅B₂₀ BMG alloy was studied. Addition of Au formed crystals in the BMG alloy. Gradual increase in the amount of Au added to the BMG alloy resulted in an increase in the amount of crystallinity and hardness of the alloy. Hardness values in excess of 1100 H_V were found in all the alloys with a maximum value of 1245 H_V. The thermal transition temperatures were also found to increase with an increasing amount of Au. Corner cracks were produced in the alloy with 1.5?at.-% Au content showing a low indentation fracture toughness value of 2.98?MPa-m^0.5.     

Two dimensional MoSSe/BSe vdW heterostructures as potential photocatalysts for water splitting with high carrier mobilities

Production of hydrogen fuel from water splitting driven by solar energy is an effective technique to overcome the energy crisis and environmental problems in coming decades. To explore low cost and efficient photocatalysts is highly desired. In this work, we study the electronic, optical and photocatalytic properties of MoSSe/BSe (Model-1 and Model-2) vdW heterostructures by PBE and HSE06 functionals using first-principle calculations. The stabilities of these heterostructures are confirmed through phonon spectra and ab initio molecular dynamic simulations. The Model-1 and Model-2 heterostructures have indirect band gaps of 1.95 and 1.54 eV respectively by HSE06 hybrid functional. Interestingly, the transition from indirect to direct band gap occurs in Model-1 after including spin-orbit coupling effect. Remarkably, the high carrier mobilities are quantitatively explored by means of deformation potential theory. Furthermore, the transition from type-I to type-II band alignment happens at compressive strain in both Model-1 and Model-2, which effectively slows down the recombination of electron-hole pairs. Compared to the isolated monolayers, the MoSSe/BSe (Model-1 and Model-2) heterostructures harvest maximum portion of visible spectrum, revealing the outstanding paybacks of high efficiency utilization of solar spectrum. Most intriguingly, the band edges of MoSSe/BSe vdW heterostructures meet the redox potential requirements for water splitting. Our results will be valuable for easing the investigation and applications of MoSSe/BSe heterostructures for optoelectronics and photocatalytic water splitting.