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As electric bikes continue to grow in popularity, it is important to ensure that they are equipped with well-designed components. One such component is the rear swing arm (RSA). This study deals with the design and structural analysis of an RSA used for electric bikes. This RSA is composed of two swing arms (one on each side of the bikes), a yoke, a suspension block, and bolts or screws. First, an analytical approach was developed to calculate the initial values for the width and shape of the swing arm. Next, experimental data were used to analyze the response of the RSA and determine the final profile for the swing arms and yoke structure. Finally, the finite element approach was implemented to assess the stress, displacement, and fatigue responses of the RSA when subjected to realistic excitations and conditions. The initial results depicted the following characteristics for the RSA: C-channel profile, 43 mm height, and 2 mm wall thickness. These results implied that the maximum shear force would occur in a region representing approximately 15.5% of the total length of the RSA. Further analysis and calculations showed that this region would decrease to approximately 2.85% of the total length of the RSA. For the final design, the mechanical performance of the RSA was observed to remain acceptable despite the relatively high Von Mises stress values around these singularities. This study assumed the use of 7075 T651 aluminum alloy as the primary material for the RSA.

Background: Drone transport regulations in Europe require a crash-protected container (CPC) to be used for the carriage of dangerous goods. With increasing interest in the use of drones for medical logistics, the motivation behind this research was to investigate whether the existing approved medical carriers could also pass as CPCs. To date, there has been little practical experimentation on or theoretical research into the crash protection performance of medical containers. Methods: Addressing this gap, this paper reports findings from a series of drop test experiments to investigate the crashworthiness of a standard medical carrier bag used by the National Health Service (NHS) in the UK. Th drop tests were performed from heights of up to 122 m using standard medical carriers containing bags of dyed saline to examine the robustness of the carrier and whether it could contain any leakages, a key requirement for transporting dangerous goods. Results: The tests found that the medical carrier failed on some drops, with the zipped lid being identified as the main weakness. Conclusions: A new understanding of the carrier’s terminal velocity, impact acceleration, and failure mechanisms were gained and subsequent strengthening and waterproofing remedial measures recommended. New insights and practical recommendations are provided relating to performing formal drop tests and how to conduct these using a drone.

Abstract The preservative effects of low temperature on biological materials have been long recognised, and cryopreservation is now widely used in biomedicine, including in organ transplantation, regenerative medicine and drug discovery. The lack of organs for transplantation constitutes a major medical challenge, stemming largely from the inability to preserve donated organs until a suitable recipient is found. Here, we review the latest cryopreservation methods and applications. We describe the main challenges—scaling up to large volumes and complex tissues, preventing ice formation and mitigating cryoprotectant toxicity—discuss advantages and disadvantages of current methods and outline prospects for the future of the field.

The larvae of Drosophila melanogaster is a model organism widely used to study the muscular and nervous systems. Drosophila larvae are surrounded by a waxy cuticle that prevents permeation by most substances. Here we develop a method to remove this layer, rendering the larvae permeable to small molecules without causing death, allowing the larvae to develop to adulthood and reproduce. Permeability was assessed using fluorescein diacetate dye uptake, and mortality upon exposure to toxic levels of ethylene glycol (EG) and Dimethyl sulfoxide (DMSO). Potential uses for this method include drug delivery, toxicity assays, cryopreservation, staining, and fixation.

Abstract Background Cellular senescence, a permanent state of replicative arrest in otherwise proliferating cells, is a hallmark of aging and has been linked to aging-related diseases. Many genes play a role in cellular senescence, yet a comprehensive understanding of its pathways is still lacking. Results We develop CellAge ( http://genomics.senescence.info/cells ), a manually curated database of 279 human genes driving cellular senescence, and perform various integrative analyses. Genes inducing cellular senescence tend to be overexpressed with age in human tissues and are significantly overrepresented in anti-longevity and tumor-suppressor genes, while genes inhibiting cellular senescence overlap with pro-longevity and oncogenes. Furthermore, cellular senescence genes are strongly conserved in mammals but not in invertebrates. We also build cellular senescence protein-protein interaction and co-expression networks. Clusters in the networks are enriched for cell cycle and immunological processes. Network topological parameters also reveal novel potential cellular senescence regulators. Using siRNAs, we observe that all 26 candidates tested induce at least one marker of senescence with 13 genes (C9orf40, CDC25A, CDCA4, CKAP2, GTF3C4, HAUS4, IMMT, MCM7, MTHFD2, MYBL2, NEK2, NIPA2, and TCEB3) decreasing cell number, activating p16/p21, and undergoing morphological changes that resemble cellular senescence. Conclusions Overall, our work provides a benchmark resource for researchers to study cellular senescence, and our systems biology analyses reveal new insights and gene regulators of cellular senescence.

Abstract The presence of civilian witnesses and victims in court is central to the effective operation of the criminal justice system. However, there is evidence of significant non-attendance which can result in ineffective and cracked trials. To address this, West Midlands Police Witness Care Unit and the Behavioural Insights Team designed an intervention using behavioural insight principles consisting of (1) a new conversation guide for Witness Care Officers (WCOs); (2) a redesigned ‘Warning Letter’ confirming details of the proceedings; and (3) a new reminder call and SMS. The impact of the new approach was evaluated through a randomised controlled trial in which 36 WCOs were randomly assigned to either “business as usual” (control) or treatment. The evaluation used an intention-to-treat design with implementation guided and encouraged at several points. Subgroup analysis was undertaken to explore whether differential effects were seen for domestic violence cases or between those that were victims and witnesses. Results indicated that the treatment approach was directionally positive in all cases, but that the increase in attendance was not statistically significant. This is in line with findings of other similar research in this area.

While interplay between BRCA1 and AURKA-RHAMM-TPX2-TUBG1 regulates mammary epithelial polarization, common genetic variation in HMMR (gene product RHAMM) may be associated with risk of breast cancer in BRCA1 mutation carriers. Following on these observations, we further assessed the link between the AURKA-HMMR-TPX2-TUBG1 functional module and risk of breast cancer in BRCA1 or BRCA2 mutation carriers. Forty-one single nucleotide polymorphisms (SNPs) were genotyped in 15,252 BRCA1 and 8,211 BRCA2 mutation carriers and subsequently analyzed using a retrospective likelihood approach. The association of HMMR rs299290 with breast cancer risk in BRCA1 mutation carriers was confirmed: per-allele hazard ratio (HR) = 1.10, 95% confidence interval (CI) 1.04-1.15, p = 1.9 x 10(-4) (false discovery rate (FDR)-adjusted p = 0.043). Variation in CSTF1, located next to AURKA, was also found to be associated with breast cancer risk in BRCA2 mutation carriers: rs2426618 per-allele HR = 1.10, 95% CI 1.03-1.16, p = 0.005 (FDR-adjusted p = 0.045). Assessment of pairwise interactions provided suggestions (FDR-adjusted pinteraction values > 0.05) for deviations from the multiplicative model for rs299290 and CSTF1 rs6064391, and rs299290 and TUBG1 rs11649877 in both BRCA1 and BRCA2 mutation carriers. Following these suggestions, the expression of HMMR and AURKA or TUBG1 in sporadic breast tumors was found to potentially interact, influencing patients' survival. Together, the results of this study support the hypothesis of a causative link between altered function of AURKA-HMMR-TPX2-TUBG1 and breast carcinogenesis in BRCA1/2 mutation carriers.

BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7 × 10(-8), HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4 × 10(-8), HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4 × 10(-8), HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific association. The 17q21.31 locus was also associated with ovarian cancer risk in 8,211 BRCA2 carriers (P = 2×10(-4)). These loci may lead to an improved understanding of the etiology of breast and ovarian tumors in BRCA1 carriers. Based on the joint distribution of the known BRCA1 breast cancer risk-modifying loci, we estimated that the breast cancer lifetime risks for the 5% of BRCA1 carriers at lowest risk are 28%-50% compared to 81%-100% for the 5% at highest risk. Similarly, based on the known ovarian cancer risk-modifying loci, the 5% of BRCA1 carriers at lowest risk have an estimated lifetime risk of developing ovarian cancer of 28% or lower, whereas the 5% at highest risk will have a risk of 63% or higher. Such differences in risk may have important implications for risk prediction and clinical management for BRCA1 carriers.

It had become commonplace in the 1890s to think of cultures and literatures entering periods of decline. English Decadence, the conventional narrative goes, was a product of Francophilia. Yet in the 1880s young authors were uncovering alternative models of literary decline and stylistic artifice. In their study of playwrights such as John Ford and Philip Massinger, Arthur Symons and Havelock Ellis began to interrogate the dominant historiographical narratives of the late-Victorian period. The example of the Elizabethans offered a model of literature that strained style to its limits in an attempt to express the extremes of sensation, an example that would be invaluable for Decadent writers as they negotiated the moral orthodoxy of Victorian England, challenging the moral frameworks that sustained the myth of "decadence" in literature, and forging the autonomous aestheticism that would underpin the Decadent Movement. [138 words] [ABSTRACT FROM AUTHOR]