Jig-less end-effector system for automating exhausting composite fuselage assembly tasks

Collections: Brunel Composite CentreIn this study, the jig-less end-effector system developed to assemble components of a full-scale multifunctional integrated composite thermoplastic lower fuselage section is tested and validated. To offset the environmental impact of higher volume of air transport, the aviation industry wants to design lighter and more environmentally friendly aircraft. To achieve this, there is a need to exploit novel materials and technologies. Advanced thermoplastic composites provide an excellent material option thanks to their weldability, low density, low overall production cost, improved fracture toughness and recyclability. However, to fully appreciate their capabilities and benefits, new manufacturing approaches and techniques are needed. Hence, projects such as TCTool, "innovative tooling, end-effector development and industrialisation for welding of thermoplastic components", aim to develop innovative tooling and end-effector systems for the assembly of a multifunctional thermoplastic fuselage. This study presents the development, operation, and testing of the jig-less end-effector system used in the TCTool project for picking, placing, and temporary welding and fixing fuselage's clips and stringers.This study has received funding from the Clean Sky 2 Joint Undertaking under the European Union's Horizon 2020 research and innovation program under grant agreement No. 865131 for TCTool Project, and has been partially funded by the projet “5R – Cervera Network in robotic technologies for intelligent manufacturing”, contract number CER-20211007, under “Centros Tecnológicos de Excelencia Cervera” (founded by “The Centre for the Development of Industrial Technology (CDTI)”). The authors would like to thank TWI Ltd. for conducting the tensile tests and optical microscopy. TCTool project partners: GKN-Fokker Aerospace, TWI Ltd., Andalusian Foundation for Aerospace Development – Advanced Center for Aerospace Technologies, Brunel University London, London South Bank University, Acroflight Ltd

Large introns in relation to alternative splicing and gene evolution: a case study of Drosophila bruno-3

Background: Alternative splicing (AS) of maturing mRNA can generate structurally and functionally distinct transcripts from the same gene. Recent bioinformatic analyses of available genome databases inferred a positive correlation between intron length and AS. To study the interplay between intron length and AS empirically and in more detail, we analyzed the diversity of alternatively spliced transcripts (ASTs) in the Drosophila RNA-binding Bruno-3 (Bru-3) gene. This gene was known to encode thirteen exons separated by introns of diverse sizes, ranging from 71 to 41,973 nucleotides in D. melanogaster. Although Bru-3's structure is expected to be conducive to AS, only two ASTs of this gene were previously described. Results: Cloning of RT-PCR products of the entire ORF from four species representing three diverged Drosophila lineages provided an evolutionary perspective, high sensitivity, and long-range contiguity of splice choices currently unattainable by high-throughput methods. Consequently, we identified three new exons, a new exon fragment and thirty-three previously unknown ASTs of Bru-3. All exon-skipping events in the gene were mapped to the exons surrounded by introns of at least 800 nucleotides, whereas exons split by introns of less than 250 nucleotides were always spliced contiguously in mRNA. Cases of exon loss and creation during Bru-3 evolution in Drosophila were also localized within large introns. Notably, we identified a true de novo exon gain: exon 8 was created along the lineage of the obscura group from intronic sequence between cryptic splice sites conserved among all Drosophila species surveyed. Exon 8 was included in mature mRNA by the species representing all the major branches of the obscura group. To our knowledge, the origin of exon 8 is the first documented case of exonization of intronic sequence outside vertebrates. Conclusion: We found that large introns can promote AS via exon-skipping and exon turnover during evolution likely due to frequent errors in their removal from maturing mRNA. Large introns could be a reservoir of genetic diversity, because they have a greater number of mutable sites than short introns. Taken together, gene structure can constrain and/or promote gene evolution

No increased bleeding events in patients with relapsed chronic lymphocytic leukemia and indolent non-Hodgkin lymphoma treated with idelalisib

The advent of novel B-cell receptor pathway targeting agents like ibrutinib dramatically changed management of B-cell malignancies. However, with concomitant anticoagulation (AC) and antiplatelet (AP) therapy, ibrutinib is associated with increased bleeding. This post hoc analysis aimed to determine the role of AC/AP therapy in patients with idelalisib-treated B-cell malignancies and to establish if it contributes to increased bleeding events. Data from two idelalisib trials (rituximab ± idelalisib in chronic lymphocytic leukemia [CLL] and idelalisib monotherapy in indolent non-Hodgkin lymphoma [iNHL]) were analyzed. Antithrombotic therapy was common (36%–63%), with comparable bleeding incidence across treatment groups (14%–19%; p = 0.56). Bleeding events of grade ≥3 occurred in 0.9% and 3.2% of the idelalisib-treated CLL and iNHL cohorts, respectively. Our findings demonstrate no increase in bleeding events with simultaneous AC/AP treatment and idelalisib use. Hemorrhagic risk is prevalent in these patients and an important consideration when evaluating available treatment options

Mitochondrial impairment increases FL-PINK1 levels by calcium-dependent gene expression.

Mutations of the PTEN-induced kinase 1 (PINK1) gene are a cause of autosomal recessive Parkinson's disease (PD). This gene encodes a mitochondrial serine/threonine kinase, which is partly localized to mitochondria, and has been shown to play a role in protecting neuronal cells from oxidative stress and cell death, perhaps related to its role in mitochondrial dynamics and mitophagy. In this study, we report that increased mitochondrial PINK1 levels observed in human neuroblastoma SH-SY5Y cells after carbonyl cyanide m-chlorophelyhydrazone (CCCP) treatment were due to de novo protein synthesis, and not just increased stabilization of full length PINK1 (FL-PINK1). PINK1 mRNA levels were significantly increased by 4-fold after 24h. FL-PINK1 protein levels at this time point were significantly higher than vehicle-treated, or cells treated with CCCP for 3h, despite mitochondrial content being decreased by 29%. We have also shown that CCCP dissipated the mitochondrial membrane potential (Δψm) and induced entry of extracellular calcium through L/N-type calcium channels. The calcium chelating agent BAPTA-AM impaired the CCCP-induced PINK1 mRNA and protein expression. Furthermore, CCCP treatment activated the transcription factor c-Fos in a calcium-dependent manner. These data indicate that PINK1 expression is significantly increased upon CCCP-induced mitophagy in a calcium-dependent manner. This increase in expression continues after peak Parkin mitochondrial translocation, suggesting a role for PINK1 in mitophagy that is downstream of ubiquitination of mitochondrial substrates. This sensitivity to intracellular calcium levels supports the hypothesis that PINK1 may also play a role in cellular calcium homeostasis and neuroprotection

Labor force participation in later life: Evidence from a cross-sectional study in Thailand

<p>Abstract</p> <p>Background</p> <p>The labor force participation rate is an important indicator of the state of the labor market and a major input into the economy's potential for creating goods and services. The objectives of this paper are to examine the prevalence of labor force participation among older people in Thailand and to investigate the factors affecting this participation.</p> <p>Methods</p> <p>The data for this study were drawn from the '2007 Survey of Older Persons' in Thailand. Bivariate analysis was used to identify the factors associated with labor force participation. The variables were further examined using multivariate analysis in order to identify the significant predictors of the likelihood of older people participating in the labor force, after controlling for other variables.</p> <p>Results</p> <p>Overall, 30,427 elderly people aged 60 or above were interviewed. More than a third (35%) of all respondents had participated in the labor force during the seven days preceding the survey. Respondents who were female (OR = 0.56), those who were older (OR = 0.47 for 70-79 and 0.21 for 80+ years), those who were widowed/divorced (OR = 0.85), those who were living with their children (OR = 0.69), those whose family income was relatively low, and those who worked in government sectors (OR = 0.33) were less likely to participate in the labor force than were their counterparts. On the other hand, those who lived in urban areas (OR = 1.2), those who had a low level of education (OR, secondary level 1.8, primary 2.4, and no schooling 2.5), those who were the head of the household (OR = 1.9), and those who were in debt (OR = 2.3) were more likely be involved in the labor force than their comparison groups. Furthermore, respondents who experienced greater difficulty in daily living, those who suffered from more chronic diseases, and those who assessed their health as poor were less likely to participate in the labor force than their counterparts.</p> <p>Conclusion</p> <p>Labor force participation in their advanced years is not uncommon among the Thai elderly. The results suggest that improving the health status of the elderly is necessary in order to encourage their employment. By doing so, the country can fulfill the labor shortage and further improve the economic condition of the nation. The results of this study also suggest that for policies encouraging employment among older persons to succeed, special focus on the rural elderly is necessary.</p

Growth factor-enriched autologous plasma improves wound healing after surgical debridement in odontogenic necrotizing fasciitis: a case report

<p>Abstract</p> <p>Background</p> <p>Odontogenic necrotizing fasciitis of the neck is a fulminant infection of odontogenic origin that quickly spreads along the fascial planes and results in necrosis of the affected tissues. It is usually polymicrobial, occurs frequently in immunocompromised patients, and has a high mortality rate.</p> <p>Case presentation</p> <p>A 69-year old Mexican male had a pain in the maxillar right-canine region and a swelling of the submental and submandibular regions. Our examination revealed local pain, tachycardia, hyperthermia (39°C), and the swelling of bilateral submental and submandibular regions, which also were erythematous, hyperthermic, crepitant, and with a positive Godet sign. Mobility and third-degree caries were seen in the right mandibular canine. Bacteriological cultures isolated <it>streptococcus pyogenes </it>and <it>staphylococcus aureus</it>. The histopathological diagnosis was odontogenic necrotizing fasciitis of the submental and submandibular regions. The initial treatment was surgical debridement and the administration of antibiotics. After cultures were negative, the surgical wound was treated with a growth factor-enriched autologous plasma eight times every third day until complete healing occurred.</p> <p>Conclusions</p> <p>The treatment with a growth factor-enriched autologous plasma caused a rapid healing of an extensive surgical wound in a patient with odontogenic necrotizing fasciitis. The benefits were rapid tissue regeneration, an aesthetic and a functional scar, and the avoidance of further surgery and possible complications.</p

Gene Expression Disruptions of Organism versus Organ in Drosophila Species Hybrids

Hybrid dysfunctions, such as sterility, may result in part from disruptions in the regulation of gene expression. Studies of hybrids within the Drosophila simulans clade have reported genes expressed above or below the expression observed in their parent species, and such misexpression is associated with male sterility in multigenerational backcross hybrids. However, these studies often examined whole bodies rather than testes or had limited replication using less-sensitive but global techniques. Here, we use a new RNA isolation technique to re-examine hybrid gene expression disruptions in both testes and whole bodies from single Drosophila males by real-time quantitative RT-PCR. We find two early-spermatogenesis transcripts are underexpressed in hybrid whole-bodies but not in assays of testes alone, while two late-spermatogenesis transcripts seem to be underexpressed in both whole-bodies and testes alone. Although the number of transcripts surveyed is limited, these results provide some support for a previous hypothesis that the spermatogenesis pathway in these sterile hybrids may be disrupted sometime after the expression of the early meiotic arrest genes

Future therapeutic targets in rheumatoid arthritis?

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by persistent joint inflammation. Without adequate treatment, patients with RA will develop joint deformity and progressive functional impairment. With the implementation of treat-to-target strategies and availability of biologic therapies, the outcomes for patients with RA have significantly improved. However, the unmet need in the treatment of RA remains high as some patients do not respond sufficiently to the currently available agents, remission is not always achieved and refractory disease is not uncommon. With better understanding of the pathophysiology of RA, new therapeutic approaches are emerging. Apart from more selective Janus kinase inhibition, there is a great interest in the granulocyte macrophage-colony stimulating factor pathway, Bruton's tyrosine kinase pathway, phosphoinositide-3-kinase pathway, neural stimulation and dendritic cell-based therapeutics. In this review, we will discuss the therapeutic potential of these novel approaches

Extended follow-up and impact of high-risk prognostic factors from the phase 3 RESONATE(TM) study in patients with previously treated CLL/SLL.

In the phase 3 RESONATE(TM) study, ibrutinib demonstrated superior progression-free survival (PFS), overall survival (OS), and overall response rate (ORR) compared with ofatumumab in relapsed/refractory CLL patients with high-risk prognostic factors. We report updated results from RESONATE in these traditionally chemotherapy resistant high-risk genomic subgroups at a median follow-up of 19 months. Mutations were detected by Foundation One Heme Panel. Baseline mutations in the ibrutinib arm included TP53 (51%), SF3B1 (31%), NOTCH1 (28%), ATM (19%), and BIRC3 (14%). Median PFS was not reached, with 74% of patients randomized to ibrutinib alive and progression-free at 24 months. The improved efficacy of ibrutinib vs. ofatumumab continues in all prognostic subgroups including del17p and del11q. No significant difference within the ibrutinib arm was observed for PFS across most genomic subtypes, although a subset carrying both TP53 mutation and del17p had reduced PFS compared to patients with neither abnormality. Reduced PFS or OS was not evident in patients with only del17p. PFS was significantly better for ibrutinib-treated patients in second-line vs. later lines of therapy. The robust clinical activity of ibrutinib continues to show ongoing efficacy and acceptable safety consistent with prior reports, independent of various known high-risk mutations