86 research outputs found

    Surface-roughness improvement in ultrasonically assisted turning

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    Ultrasonically assisted machining is a hybrid technique based on superimposition of ultrasonic vibration on a movement of a cutting tool. Such vibration with relatively small amplitude - below 20 microns - changes dramatically the response of a machined material to a cutting process. As a result, a significant - in excess of 80% in turning of aerospace superalloys - reduction of average cutting forces is observed together with improvement of surface roughness. The paper presents results of analysis of the effect of ultrasonically assisted turning (UAT) on surface roughness (using a broad range of parameters) for a broad range of metals and alloys - from copper, aluminium and stainless steel to Ni- And Ti-based alloys. The effect of machining parameters for both conventional turning and UAT was investigated to provide an optimum range for each material and its relation to surface roughness

    Computational investigation of mechanistic insights of Aβ42 interactions against extracellular domain of nAChRα7 in Alzheimer's disease

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    Aim: Amyloid beta (Aβ) 1-42, which is a basic constituent of amyloid plaques, binds with extracellular transmembrane receptor nicotine acetylcholine receptor α7 (nAChRα7) in Alzheimer’s disease. Materials and Methods: In the current study, a computational approach was employed to explore the active binding sites of nAChRα7 through Aβ 1–42 interactions and their involvement in the activation of downstream signalling pathways. Sequential and structural analyses were performed on the extracellular part of nAChRα7 to identify its core active binding site. Results: Results showed that a conserved residual pattern and well superimposed structures were observed in all nAChRs proteins. Molecular docking servers were used to predict the common interactive residues in nAChRα7 and Aβ1–42 proteins. The docking profile results showed some common interactive residues such as Glu22, Ala42 and Trp171 may consider as the active key player in the activation of downstream signalling pathways. Moreover, the signal communication and receiving efficacy of best-docked complexes was checked through DynOmic online server. Furthermore, the results from molecular dynamic simulation experiment showed the stability of nAChRα7. The generated root mean square deviations and fluctuations (RMSD/F), solvent accessible surface area (SASA) and radius of gyration (Rg) graphs of nAChRα7 also showed its backbone stability and compactness, respectively. Conclusion: Taken together, our predicted results intimated the structural insight on the molecular interactions of beta amyloid protein involved in the activation of nAChRα7 receptor. In future, a better understanding of nAChRα7 and their interconnected proteins signalling cascade may be consider as target to cure Alzheimer’s disease.This was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2017R1D1A1B03034948).Scopu

    Effect of radiotherapy on local recurrence, distant metastasis and overall survival in 1200 extremity soft tissue sarcoma patients: retrospective analysis using IPTW-adjusted models

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    Background and purposeNeoadjuvant (NRTX) and adjuvant radiotherapy (ARTX) reduce local recurrence (LR) risk in extremity soft tissue sarcoma (eSTS), yet their impact on distant metastasis (DM) and overall survival (OS) is less well defined. This study aimed at analysing the influence of NRTX/ARTX on all three endpoints using a retrospective, multicentre eSTS cohort.Materials and methods1200 patients (mean age: 60.7 ± 16.8 years; 44.4 % females) were retrospectively included, treated with limb sparing surgery and curative intent for localised, high grade (G2/3) eSTS. 194 (16.2 %), 790 (65.8 %), and 216 (18.0 %) patients had received NRTX, ARTX and no RTX, respectively. For the resulting three groups (no RTX vs. NRTX, no RTX vs. ARTX, NRTX vs. ARTX) Fine&Gray models for LR and DM, and Cox-regression models for OS were calculated, with IPTW-modelling adjusting for imbalances between groups.ResultsIn the IPTW-adjusted analysis, NRTX was associated with lower LR-risk in comparison to no RTX (SHR [subhazard ratio]: 0.236; p = 0.003), whilst no impact on DM-risk (p = 0.576) or OS (p = 1.000) was found. IPTW-weighted analysis for no RTX vs. ARTX revealed a significant positive association between ARTX and lower LR-risk (SHR: 0.479, p = 0.003), but again no impact on DM-risk (p = 0.363) or OS (p = 0.534). IPTW-weighted model for NRTX vs. ARTX showed significantly lower LR-risk for NRTX (SHR for ARTX: 3.433; p = 0.003) but no difference regarding DM-risk (p = 1.000) or OS (p = 0.639).ConclusionNRTX and ARTX are associated with lower LR-risk, but do not seem to affect DM-risk or OS. NRTX may be favoured over ARTX as our results indicate better local control rates.Orthopaedics, Trauma Surgery and Rehabilitatio

    Structural dynamics as a contributor to error-prone replication by an RNA-dependent RNA polymerase

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    RNA viruses encoding high- or low-fidelity RNA-dependent RNA polymerases (RdRp) are attenuated. The ability to predict residues of the RdRp required for faithful incorporation of nucleotides represents an essential step in any pipeline intended to exploit perturbed fidelity as the basis for rational design of vaccine candidates. We used x-ray crystallography, molecular dynamics simulations,NMRspectroscopy, and pre-steady-state kinetics to compare a mutator (H273R) RdRp from poliovirus to the wild-type (WT) enzyme. We show that the nucleotide-binding site toggles between the nucleotide binding-occluded and nucleotide binding-competent states. The conformational dynamics between these states were enhanced by binding to primed template RNA. For the WT, the occluded conformation was favored; for H273R, the competent conformation was favored. The resonance for Met-187 in our NMR spectra reported on the ability of the enzyme to check the correctness of the bound nucleotide. Kinetic experiments were consistent with the conformational dynamics contributing to the established pre-incorporation conformational change and fidelity checkpoint. For H273R, residues comprising the active site spent more time in the catalytically competent conformation and were more positively correlated than the WT. We propose that by linking the equilibrium between the binding-occluded and binding-competent conformations of the nucleotide-binding pocket and other active-site dynamics to the correctness of the bound nucleotide, faithful nucleotide incorporation is achieved. These studies underscore the need to apply multiple biophysical and biochemical approaches to the elucidation of the physical basis for polymerase fidelity

    The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

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    INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

    Automatic Voltage Generation Control for Two Area Power System Based on Particle Swarm Optimization

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    This article presentes a PID controller for two area power system equipped with both automatic generation control and automatic voltage regulator loops. The research has been done to control two area power systems with PSO optimized self-tuning PID controller. The comparison between different controllers and the suggested PSO based controller illustrates that the proposed controller can generate the best dynamic response for a step load change. For this purpose, MATLAB-Simulink software is used. The obtained results are promising

    Removal of azo dye acid orange 7 using aerobic membrane bioreactor

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    A laboratory scale aerobic membrane bioreactor (MBR) using a submerged microfiltration (MF); hollow-fiber membrane was used for treating wastewater polluted with azo dye acid orange 7 (AO7). Initial dye concentrations studied were from 50 to 400 mg/l with a COD ranging from 95 to 550 mg O2/l and hydraulic retention times (HRT) 4, 6, 8 and 24 h. Results showed that the biological process was responsible for almost 60–80% of COD removal and almost all the removal of AO7 color. Membrane microfiltration merely balanced the unstable biological treatment of COD and demonstrated almost no contribution to AO7 color removal. Trans-membrane pressure (TMP) increased with time, and with the increase of dye concentration reaching a maximum of 4.175 psi. Scanning electron microscope (SEM) images of the membrane’s filament were taken and compared with a SEM image of a virgin membrane; clear deformation in membrane’s pore structure could be noticed as well as scale formation on the outer surface of filaments, foulants were determined using the energy dispersive X-ray analysis (EDX)
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