A nontraditional method for reducing thermoelastic stresses of variable thickness rotating discs.

Stresses reductions and/or raising the load-carrying capacity for a mechanical structure are always great dilemmas for researchers. In this article, a novel method is proposed, and its efficiency is examined for achieving these goals on functionally graded rotating nonuniform thickness discs. The originality of this method relies on comprising a geometrically well-defined area, into the whole structure, with certain homogeneous properties including density, thermal expansion coefficient, and elasticity matrix. This area acts as a reducer of the maximum values of various stress components. The solution of the magnetoelastic/magneto-thermoelastic problem is accomplished using the finite element method. The disc is subjected to partial uniform outer pressure, whereas, upon applying thermal loads; the thermal boundary conditions are considered symmetric. The proposed method is found to be beneficial as the obtained results demonstrated the ability to reduce the maximum stresses with different percentages depending on the location, angular width, and properties of the predefined area. This is reflected by an attainable decrease in the maximum compressive tangential stress and the von Mises stress by approximately 20.7% and 12.5%, respectively, under certain conditions.

Computational identification of drug-like marine natural products as potential RNA polymerase inhibitors against Nipah virus.

Nipah virus (NiV) has been an alarming threat to human populations in southern Asia for more than a decade. It is one of the most deadly viruses in the Mononegavirales order. Despite its high mortality rate and virulence, no chemotherapeutic agent or vaccine is publicly available. Hence, this work was conducted to computationally screen marine natural products database for drug-like potential inhibitors for the viral RNA-dependent RNA polymerase (RdRp). The structural model was subjected to molecular dynamics (MD) simulation to obtain the native ensemble of the protein. The CMNPDB dataset of marine natural products was filtered to retain only compounds following Lipinski's five rules. The molecules were energy minimized and docked into different conformers of the RdRp using AutoDock Vina. The best 35 molecules were rescored by GNINA, a deep learning-based docking software. The resulting nine compounds were evaluated for their pharmacokinetic profiles and medicinal chemistry properties. The best five compounds were subjected to MD simulation for 100 ns, followed by binding free energy estimation via Molecular Mechanics/ Generalized Born Surface Area (MM/GBSA) calculations. The results showed remarkable behavior of five hits as inferred by stable binding pose and orientation to block the exit channel of RNA synthesis products in the RdRp cavity. These hits are promising starting materials for in vitro validation and structural modifications to enhance the pharmacokinetic and medicinal chemistry properties for developing antiviral lead compounds.

Somaclonal Variation for Genetic Improvement of Starch Accumulation in Potato (Solanum tuberosum) Tubers.

Starch content is one of the major quality criteria targeted by potato breeding programs. Traditional potato breeding is a laborious duty due to the tetraploid nature and immense heterozygosity of potato genomes. In addition, screening for functional genetic variations in wild relatives is slow and strenuous. Moreover, genetic diversity, which is the raw material for breeding programs, is limited due to vegetative propagation used in the potato industry. Somaclonal variation provides a time-efficient tool to breeders for obtaining genetic variability, which is essential for breeding programs, at a reasonable cost and independent of sophisticated technology. The present investigation aimed to create potato somaclones with an improved potential for starch accumulation. Based on the weight and starch content of tubers, the somaclonal variant Ros 119, among 105 callus-sourced clones, recorded a higher tuberization potential than the parent cv Lady Rosetta in a field experiment. Although this somaclone was similar to the parent in the number of tubers produced, it exhibited tubers with 42 and 61% higher fresh and dry weights, respectively. Additionally, this clone recorded 10 and 75% increases in starch content based on the dry weight and average content per plant, respectively. The enhanced starch accumulation was associated with the upregulation of six starch-synthesis-related genes, namely, the AGPase, GBSS I, SBE I, SBE II, SS II and SS III genes. AGPase affords the glycosyl moieties required for the synthesis of amylose and amylopectin. GBSS is required for amylose elongation, while SBE I, SBE II, SS II and SS III are responsible for amylopectin.

In silico structural elucidation of Nipah virus L protein and targeting RNA-dependent RNA polymerase domain by nucleoside analogs.

The large (L) protein of Mononegavirales is a multi-domain protein that performs transcription and genome replication. One of the important domains in L is the RNA-dependent RNA polymerase (RdRp), a promising target for antiviral drugs. In this work, we employed rigorous computational comparative modeling to predict the structure of L protein of Nipah virus (NiV). The RdRp domain was targeted by a panel of nucleotide analogs, previously reported to inhibit different viral RNA polymerases, using molecular docking. Best binder compounds were subjected to molecular dynamics simulation to validate their binding. Molecular mechanics/generalized-born surface area (MM/GBSA) calculations estimated the binding free energy. The predicted model of NiV L has an excellent quality as judged by physics- and knowledge-based validation tests. Galidesivir, AT-9010 and Norov-29 scored the top nucleotide analogs to bind to the RdRp. Their binding free energies obtained by MM/GBSA (-31.01 ± 3.9 to -38.37 ± 4.8 kcal/mol) ranked Norov-29 as the best potential inhibitor. Purine nucleotide analogs are expected to harbor the scaffold for an effective drug against NiV. Finally, this study is expected to provide a start point for medicinal chemistry and drug discovery campaigns toward identification of effective chemotherapeutic agent(s) against NiV.Communicated by Ramaswamy H. Sarma.

Editor's choice--Angulation of the C-arm during complex endovascular aortic procedures increases radiation exposure to the head.

OBJECTIVES/BACKGROUND: The increased complexity of endovascular aortic repair necessitates longer procedural time and higher radiation exposure to the operator, particularly to exposed body parts. The aims were to measure directly exposure to radiation of the bodies and heads of the operating team during endovascular repair of thoracoabdominal aortic aneurysms (TAAA), and to identify factors that may increase exposure. METHODS: This was a single-centre prospective study. Between October 2013 and July 2014, consecutive elective branched and fenestrated TAAA repairs performed in a hybrid operating room were studied. Electronic dosimeters were used to measure directly radiation exposure to the primary (PO) and assistant (AO) operator in three different areas (under-lead, over-lead, and head). Fluoroscopy and digital subtraction angiography (DSA) acquisition times, C-arm angulation, and PO/AO height were recorded. RESULTS: Seventeen cases were analysed (Crawford II-IV), with a median operating time of 280 minutes (interquartile range 200-330 minutes). Median age was 76 years (range 71-81 years); median body mass index was 28 kg/m(2) (25-32 kg/m(2)). Stent-grafts incorporated branches only, fenestrations only, or a mixture of branches and fenestrations. A total of 21 branches and 38 fenestrations were cannulated and stented. Head dose was significantly higher in the PO compared with the AO (median 54 µSv [range 24-130 µSv] vs. 15 µSv [range 7-43 µSv], respectively; p = .022), as was over-lead body dose (median 80 µSv [range 37-163 µSv] vs. 32 µSv [range 6-48 µSv], respectively; p = .003). Corresponding under-lead doses were similar between operators (median 4 µSv [range 1-17 µSv] vs. 1 µSv [range 1-3 µSv], respectively; p = .222). Primary operator height, DSA acquisition time in left anterior oblique (LAO) position, and degrees of LAO angulation were independent predictors of PO head dose (p < .05). CONCLUSIONS: The head is an unprotected area receiving a significant radiation dose during complex endovascular aortic repair. The deleterious effects of exposure to this area are not fully understood. Vascular interventionalists should be cognisant of head exposure increasing with C-arm angulation, and limit this manoeuvre.

Influence of magnetic field on brain activity during administration of caffeine.

The aim of the present work is to evaluate the effect of caffeine, the world's most popular psychoactive drug, on the electric activity of the rat's brain that exposed to extremely low-frequency magnetic field (ELF-MF), during 15 days. The obtained results showed that administration of caffeine in a group of rats by dose of 10 mg/kg (equivalent to human daily consumption) caused a reduction in the mean power amplitude of electroencephalogram (EEG) trace for almost all frequency bands especially α (8-12 Hz). It was observed that the influence of caffeine was more evident in motor cortex than in visual cortex. While the exposure of another group to ELF-MF of intensity 0.2 mT during the same period caused an enhancement in the mean power amplitude of most EEG frequency bands; this was more observed in the right hemisphere of the brain than that of the left hemisphere. The administration of caffeine while rats were exposed to ELF-MF, led, after 5 days of exposure, to a great increase in the mean power amplitude of α band at all places of recording electrodes. It may be concluded that caffeine administration was more effective in reducing the hazardous of ELF-MF in motor cortex than in visual cortex.

A pilot comparative study of fissurectomy/diltiazem and fissurectomy/botulinum toxin in the treatment of chronic anal fissure.

BACKGROUND: Treatment of chronic anal fissure (CAF) by fissurectomy with botulinum toxin A (BTA) injection results in a healing rate of greater than 90%. BTA injection, however, can cause incontinence and perianal sepsis. The decrease in sphincter pressure following topical treatment with 2% diltiazem cream (DTC) is comparable to that following BTA injection but with potentially fewer complications and at less cost. We report the shortterm results of a pilot study comparing fissurectomy with BTA and fissurectomy followed by DTC for the treatment of CAF. METHODS: The recorded outcomes of CAF following treatment with the two methods were analysed retrospectively. Patients underwent either fissurectomy followed by injection of 40 U BTA into the internal sphincter (group A) or fissurectomy followed by the perianal application of DTC twice daily for 8 weeks (group B). Symptom resolution and treatment side effects at the initial follow-up were compared. RESULTS: Demographics, fissure characteristics and the number of multiparous women between the two groups were comparable. At a median follow-up of 12 weeks (range 8-20 weeks), the two groups had similar rates of complete symptom resolution (group A, 25/28, 89.3%; group B, 19/23, 82.6%; p=0.7739), with minor side effects. CONCLUSIONS: In this small pilot study fissurectomy combined with chemical sphincterotomy resulted in high short-term fissure healing rates. The study also suggested that fissurectomy followed by 8 weeks of topical DTC may be as good as fissurectomy with BTA injection in the treatment of CAF. A prospective study, adequately powered to determine the significance of differences is needed.

Stress lesions of the lower leg and foot.

Technetium 99 methylene diphosphonate scans were performed on 32 patients with suspected stress fractures. Twenty-six patients had abnormal scans, 13 had abnormal X-rays and on these only nine had either fresh periosteal new bone and/or a fracture line. A logical approach of the use of X-ray and radionuclide techniques in patient management is suggested.