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The heterohexameric ATPases associated with diverse cellular activities (AAA)-ATPase Pex1/Pex6 is essential for the formation and maintenance of peroxisomes. Pex1/Pex6, similar to other AAA-ATPases, uses the energy from ATP hydrolysis to mechanically thread substrate proteins through its central pore, thereby unfolding them. In related AAA-ATPase motors, substrates are recruited through binding to the motor's N-terminal domains or N terminally bound cofactors. Here, we use structural and biochemical techniques to characterize the function of the N1 domain in Pex6 from budding yeast, Saccharomyces cerevisiae. We found that although Pex1/ΔN1-Pex6 is an active ATPase in vitro, it does not support Pex1/Pex6 function at the peroxisome in vivo. An X-ray crystal structure of the isolated Pex6 N1 domain shows that the Pex6 N1 domain shares the same fold as the N-terminal domains of PEX1, CDC48, and NSF, despite poor sequence conservation. Integrating this structure with a cryo-EM reconstruction of Pex1/Pex6, AlphaFold2 predictions, and biochemical assays shows that Pex6 N1 mediates binding to both the peroxisomal membrane tether Pex15 and an extended loop from the D2 ATPase domain of Pex1 that influences Pex1/Pex6 heterohexamer stability. Given the direct interactions with both Pex15 and the D2 ATPase domains, the Pex6 N1 domain is poised to coordinate binding of cofactors and substrates with Pex1/Pex6 ATPase activity.

A sequence of dye-sensitized solar cells is proposed, utilizing TiO2@Zn/Al-layered double hydroxide (LDH) as their starting materials, in which Ruthenizer N719 was used as a photon absorber. The anticipated system was turned into sheet-like TiO2@mixed metal oxide (MMO) via post-processing treatment. The crystal quality indicated a relation to power conversion efficiency (PCE); this was combined with a comparable morphology profile. In detail, the optimum DSSC device exhibited average sheet-like thickness and a dye loading amount of 43.11 nm and 4.28 ×10−3 mM/cm−2, respectively. Concurrently, a considerable PCE enhancement of the optimum DSSC device (TiO2@MMO-550°) was attained compared to pristine MMO (0.91%), which could be due to boosted electron transfer efficiency. Of the fabricated devices, DSSC fabricated at 550° exhibited the highest PCE (1.91%), with a 35.6% enhancement compared to that obtained at 450°, as a result of its increased open-circuit voltage (3.29 mA/cm2) and short-circuit current (0.81 V). The proposed work delivers an enhanced efficiency as compared to similar geometries.

Background Conducting doctoral research is a challenging endeavour, a challenge which as the growing literature on the subject has shown, the COVD-19 pandemic has made even more so. For some doctoral researchers, however, the pandemic has also been accompanied by political unrest and military conflict, putting them and their networks at risk and making their research especially difficult to sustain. Methods We have used a collaborative auto-ethnography, and we, a group of seven doctoral researchers based in Ethiopia, Rwanda, Sudan and UK have written our experiences. Results Drawing upon the results of a collaborative auto-ethnography (CAE), this article records and discusses the experiences of a group of doctoral researchers who with the support of their organisation, the Social Science for Severe Stigmatised Skin Diseases (5S) Foundation, have been attempting to cope with both the pandemic and internal instability and strife. After firstly setting the context, the article explains why for the purposes of this paper CAE was adopted as our method, and then documents and discusses the experiences of seven doctoral researchers based in Ethiopia, Sudan, Rwanda, and the UK, doing so in terms of four different themes: New Ways of Working and Its Impact, Change and Delay, Mental Health and Well-Being Impact, and Qualities and Capacities. Conclusion What these experiences tell us is that this group of doctoral researchers have found themselves in extremely challenging situations, which have placed exceptionally high demands on them and their support networks, and this has had an impact on their health and well-being although also been the catalyst for some more positive development. Given their lived experiences, the article finishes with a series of recommendations for future research projects of this kind.

Abstract Background Event-based surveillance (EBS) is an essential component of Early Warning Alert and Response (EWAR) as per the International Health Regulations (IHR), 2005. EBS was established in Sudan in 2016 as a complementary system for Indicator-based surveillance (IBS). This review will provide an overview of the current EBS structure, functions and performance in Sudan and identify the gaps and ways forward. Methods The review followed the WHO/EMRO guidelines and tools. Structured discussions, observation and review of records and guidelines were done at national and state levels. Community volunteers were interviewed through phone calls. Directors of Health Emergency and Epidemic Control, surveillance officers and focal persons for EBS at the state level were also interviewed. SPSS software was used to perform descriptive statistical analysis for quantitative data, while qualitative data was analysed manually using thematic analysis, paying particular attention to the health system level allowing for an exploration of how and why experiences differ across levels. Written and verbal consents were obtained from all participants as appropriate. Results Sudan has a functioning EBS; however, there is an underestimation of its contribution and importance at the national and states levels. The link between the national level and states is ad hoc or is driven by the need for reports. While community event-based surveillance (CEBS) is functioning, EBS from health facilities and from non-health sectors is not currently active. The integration of EBS into overall surveillance was not addressed, and the pathway from detection to action is not clear. The use of electronic databases and platforms is generally limited. Factors that would improve performance include training, presence of a trained focal person at state level, and regular follow-up from the national level. Factors such as staff turnover, income in relation to expenses and not having a high academic qualification (Diploma or MSc) were noticed as inhibiting factors. Conclusion The review recommended revisiting the surveillance structure at national and state levels to put EBS as an essential component and to update guidelines and standard operation procedures SOPs to foster the integration between EBS components and the overall surveillance system. The need for strengthening the link with states, capacity building and re-addressing the training modalities was highlighted.

Biological age, distinct from an individual’s chronological age, has been studied extensively through predictive aging clocks. However, these clocks have limited accuracy in short time-scales. Here we trained deep learning models on fundus images from the EyePACS dataset to predict individuals’ chronological age. Our retinal aging clocking, ‘eyeAge’, predicted chronological age more accurately than other aging clocks (mean absolute error of 2.86 and 3.30 years on quality-filtered data from EyePACS and UK Biobank, respectively). Additionally, eyeAge was independent of blood marker-based measures of biological age, maintaining an all-cause mortality hazard ratio of 1.026 even when adjusted for phenotypic age. The individual-specific nature of eyeAge was reinforced via multiple GWAS hits in the UK Biobank cohort. The top GWAS locus was further validated via knockdown of the fly homolog, Alk, which slowed age-related decline in vision in flies. This study demonstrates the potential utility of a retinal aging clock for studying aging and age-related diseases and quantitatively measuring aging on very short time-scales, opening avenues for quick and actionable evaluation of gero-protective therapeutics.

Current aptamer discovery approaches are unable to probe the complete space of possible sequences. Here, the authors use machine learning to facilitate the development of DNA aptamers with improved binding affinities, and truncate them without significantly compromising binding affinity.

In this manuscript, a series of dye-sensitized solar cells (DSSCs) were fabricated as a function of post-processing temperature based on mesoporous CuO@Zn(Al)O-mixed metal oxides (MMO) in conjunction with dye N719 as the main light absorber; the proposed CuO@Zn(Al)O geometry was, in turn, attained using Zn/Al-layered double hydroxide (LDH) as a precursor via combination of co-precipitation and hydrothermal techniques. In particular, the dye loading amount onto the deposited mesoporous materials was anticipated via regression equation-based UV-Vis technique analysis, which evidently demonstrated a robust correlation along with the fabricated DSSCs power conversion efficiency. In detail, of the DSSCs assembled, CuO@MMO-550 exhibited short-circuit current (JSC) and open-circuit voltage (VOC) of 3.42 (mA/cm2) and 0.67 (V) which result in significant fill factor and power conversion efficiency of 0.55% and 1.24%, respectively. This could mainly be due to the relatively high surface area of 51.27 (m2/g) which in turn validates considerable dye loading amount of 0.246 (mM/cm−2).

Summary: We demonstrate early progress toward constructing a high-throughput, single-molecule protein sequencing technology utilizing barcoded DNA aptamers (binders) to recognize terminal amino acids of peptides (targets) tethered on a next-generation sequencing chip. DNA binders deposit unique, amino acid-identifying barcodes on the chip. The end goal is that, over multiple binding cycles, a sequential chain of DNA barcodes will identify the amino acid sequence of a peptide. Toward this, we demonstrate successful target identification with two sets of target-binder pairs: DNA-DNA and Peptide-Protein. For DNA-DNA binding, we show assembly and sequencing of DNA barcodes over six consecutive binding cycles. Intriguingly, our computational simulation predicts that a small set of semi-selective DNA binders offers significant coverage of the human proteome. Toward this end, we introduce a binder discovery pipeline that ultimately could merge with the chip assay into a technology called ProtSeq, for future high-throughput, single-molecule protein sequencing.

Structural variants (SVs) in human genomes contribute diversity and diseases. Here, the authors use a multi-platform strategy to generate haplotype-resolved SVs for three human parent–child trios.

This paper focuses on the design and development of a reconfigurable three-degree-of-freedom articulated robot for conducting pick-and-place tasks. To implement the system, an Android platform for the manual control of an articulated robot using wireless Bluetooth technology was developed. This application allows the user to manually reconfigure the robot following the requirements of the integrated system via a user-friendly display. The articulated robot comprises four motors, three of which are used for positioning and orientation and finally used to carry out the pick-and-place task. An Arduino Un R3 board is used to control the movement of the links via a pulse width modulation method. We introduce a set of conveniently composed kinematic and dynamic mathematical models for positioning the robot’s arms and, in our results and discussion section, calculate and report the torque required to move each joint.

Abstract Objective: The objective of the study was to determine the current prevalence of Helicobacter pylori infection among Dyspepsia patients and correlate this with Endoscopic findings. Methodology: A retrospective, descriptive facility-based study conducted from June to December 2017 to estimate the prevalence of Helicobacter pylori among dyspepsia patients from Majmaah, Sudair, Zulfi and Shaqra areas of Riyadh region, Saudi Arabia. Four years data from January 2012 to December 2016 were reviewd by a checklist and analyzed by SPSS. Results: Out of 1398 dyspepsia patients, 485 (34.7%) were positive, and 913 (65.3%) were negative for H-Pylori infection. Majority of patients (81.7%) had gastritis, out of which, 39.9% of gastritis patients were H-pylori positive. The frequency of H-pylori infection was significantly higher among patients with gastritis (p < 0.001). There was no statistically significant difference in the frequency of H-pylori infection among patients with erosion, ulcer, polyp and cancer (p > 0.05). Conclusion: The prevalence of H.Pylori was low as compared to other governorates in the kingdom and regional countries. Gastritis was dominating finding on upper gastrointestinal (GI) endoscopy. Keywords: Helicobacter pylori, Prevalence, Dyspepsia, Riyadh region

An incomplete ascertainment of genetic variation within the highly polymorphic immunoglobulin heavy chain locus (IGH) has hindered our ability to define genetic factors that influence antibody-mediated processes. Due to locus complexity, standard high-throughput approaches have failed to accurately and comprehensively capture IGH polymorphism. As a result, the locus has only been fully characterized two times, severely limiting our knowledge of human IGH diversity. Here, we combine targeted long-read sequencing with a novel bioinformatics tool, IGenotyper, to fully characterize IGH variation in a haplotype-specific manner. We apply this approach to eight human samples, including a haploid cell line and two mother-father-child trios, and demonstrate the ability to generate high-quality assemblies (>98% complete and >99% accurate), genotypes, and gene annotations, identifying 2 novel structural variants and 15 novel IGH alleles. We show multiplexing allows for scaling of the approach without impacting data quality, and that our genotype call sets are more accurate than short-read (>35% increase in true positives and >97% decrease in false-positives) and array/imputation-based datasets. This framework establishes a desperately needed foundation for leveraging IG genomic data to study population-level variation in antibody-mediated immunity, critical for bettering our understanding of disease risk, and responses to vaccines and therapeutics.

Abstract Background To address the need for more effective genomics training, beginning in 2012 the Icahn School of Medicine at Mount Sinai has offered a unique laboratory-style graduate genomics course, “Practical Analysis of Your Personal Genome” (PAPG), in which students optionally sequence and analyze their own whole genome. We hypothesized that incorporating personal genome sequencing (PGS) into the course pedagogy could improve educational outcomes by increasing student motivation and engagement. Here we extend our initial study of the pilot PAPG cohort with a report on student attitudes towards genome sequencing, decision-making, psychological wellbeing, genomics knowledge and pedagogical engagement across three course years. Methods Students enrolled in the 2013, 2014 and 2015 course years completed questionnaires before (T1) and after (T2) a prerequisite workshop (n = 110) and before (T3) and after (T4) PAPG (n = 66). Results Students’ interest in PGS was high; 56 of 59 eligible students chose to sequence their own genome. Decisional conflict significantly decreased after the prerequisite workshop (T2 vs. T1 p

In the present study, cylindrical ABS P400 polymer parts (diameter 6.5 mm) to be used as die-sinking EDM (electric discharge machining) novel electrodes were fabricated using a fused deposition modeling (FDM) process. To meet the conductivity requirement in EDM, ABS parts were metallized using an innovative method that comprised putting aluminum–charcoal (Al–C) on them followed by their copper electroplating. Real-time EDM of the mild steel workpiece was performed using novel electrodes, and machining performance of the electrodes, measured in terms of dimensional accuracy, i.e., change in diameter (ΔD) and change in depth (ΔH) of the cavity, under varying levels of three EDM factors, i.e., current (I), pulse on time (Ton), and pulse off time (Toff), was investigated. Machining results were analyzed using analysis of variance (ANOVA), perturbation graphs, and 3D surface plots. The optimal setting of the EDM parameters for minimizing ΔD and ΔH was determined using the desirability function approach. The suitability of the novel electrodes for EDM was ascertained by comparing their machining results with those of solid copper (SC) electrodes and electrodes fabricated by FDM and metallized using the electro-deposition method (FDM-EM), already reported in the literature, under similar machining conditions. From the results, it was found that ΔD and ΔH were less when EDM was performed using novel electrodes.

Developments in the design of wind turbines with augmentation are advancing around the globe with the goal of generating electricity close to the user in built-up areas. This is certain to help lessen the power generation load as well as distribution and transmission network costs by reducing the distance between the user and the power source. The main objectives driving the development and advancement of vertical-axis wind turbines are increasing the power coefficient and the torque coefficient by optimizing the upstream wind striking on the rotor blades. Unlike horizontal-axis wind turbines, vertical axis turbines generate not only positive torque but also negative torque during operation. The negative torque generated by the returning blade is a key issue for vertical-axis wind turbines (VAWTs) that is counterproductive. Installation of wind deflectors for flow augmentation helps to reduce the negative torque generated by the returning blades as well as enhance the positive torque by creating a diversion in the upstream wind towards the forwarding blade during operation. This paper reviews various designs, experiments, and CFD simulations of wind deflectors reported to date. Optimization techniques for VAWTs incorporating wind deflectors are discussed in detail. The main focus of the review was on the installation position and orientation of the deflectors and their potential contribution to increasing the power coefficient. Topics for future study are suggested in the conclusion section of the paper.