Optimal Design of a Cam Mechanism with Translating Flat-Face Follower using Genetic Algorithm

The optimum design of a cam mechanism is a time consuming task, due to the numerous alternatives considerations. In the present work, the problem of design parameters optimization of a cam mechanism with translating flat - face follower is investigated from a multi - objective point of view. The design parameters, just like the cam base circle radius, the follower face width and the follower offset can be determined considering as the optimization criteria minimization of the cam size, of the input torque and of the contact stress. During the optimization procedure, a number of constraints regarding the pressure angle, the contact stress, etcare taken into account. The optimization approach, based on genetic algorithm, is applied to find the optimal solutions with respect to the a fore - mentioned objective function and to Ensure the kinematic requirements. Finally, the dynamic behavior of the designed cam mechanism is investigated considering the frictional forces

Evaluation of Genetic Variations in Organic Cationic Transporter 3 in Depressed and Nondepressed Subjects

Organic cationic transporter 3 (OCT3, SLS22A3) has only recently emerged as one of the regulators of monoaminergic neurotransmission, which plays a critical role in the pathogenesis of depression and is a potential new antidepressant drug target. OCT3 single-nucleotide polymorphisms (SNPs) have been investigated for their association with psychiatric disorders such as methamphetamine use disorder and obsessive-compulsive disorder in children and adolescents, but not depression. This study was designed to evaluate the allele frequencies of seven OCT3 SNPs in a US Caucasian depressed population and compare these frequencies with a control group of nondepressed subjects. Informed consent and a DNA sample were obtained from 157 subjects and analysis was performed using real-time PCR. Allele and genotype frequencies were compared using a t-test and the Pearson chi-square analysis, respectively. There were no significant differences in OCT3 allele or genotype frequencies between the depressed and non-depressed groups for all seven SNPs evaluated

From High-Level Task Descriptions to Executable Robot Code

For robots to be productive co-workers in the manufacturing industry, it is necessary that their human colleagues can interact with them and instruct them in a simple manner. The goal of our research is to lower the threshold for humans to instruct manipulation tasks, especially sensorcontrolled assembly. In our previous work we have presented tools for high-level task instruction, while in this paper we present how these symbolic descriptions of object manipulation are translated into executable code for our hybrid industrial robot controllers

PCV13 induced IgG responses in serum associate with serotype-specific IgG in the lung

Pneumococcal conjugate vaccine efficacy is lower for non-invasive pneumonia than invasive disease. In this study, participants were vaccinated with PCV13 or HepA (control). Bronchoalveolar lavage samples were taken between 2-6 months and serum at 4- and 7-weeks post vaccination. In the lung, anti-capsular IgG levels were higher in the PCV13 group compared to control for all serotypes, except 3 and 6B. Systemically, IgG levels were elevated in the PCV group at 4-weeks for all serotypes, except 3. IgG in BAL and serum positively correlated for nearly all serotypes. PCV13 shows poor immunogenicity to serotype 3, implying lack of protective efficacy. Clinical trial registration with ISRCTN: 4534043

Full-Length Fibronectin Drives Fibroblast Accumulation at the Surface of Collagen Microtissues during Cell-Induced Tissue Morphogenesis

Generating and maintaining gradients of cell density and extracellular matrix (ECM) components is a prerequisite for the development of functionality of healthy tissue. Therefore, gaining insights into the drivers of spatial organization of cells and the role of ECM during tissue morphogenesis is vital. In a 3D model system of tissue morphogenesis, a fibronectin-FRET sensor recently revealed the existence of two separate fibronectin populations with different conformations in microtissues, i.e. ‘compact and adsorbed to collagen’ versus ‘extended and fibrillar’ fibronectin that does not colocalize with the collagen scaffold. Here we asked how the presence of fibronectin might drive this cell-induced tissue morphogenesis, more specifically the formation of gradients in cell density and ECM composition. Microtissues were engineered in a high-throughput model system containing rectangular microarrays of 12 posts, which constrained fibroblast-populated collagen gels, remodeled by the contractile cells into trampoline-shaped microtissues. Fibronectin’s contribution during the tissue maturation process was assessed using fibronectin-knockout mouse embryonic fibroblasts (Fn-/- MEFs) and floxed equivalents (Fnf/f MEFs), in fibronectin-depleted growth medium with and without exogenously added plasma fibronectin (full-length, or various fragments). In the absence of full-length fibronectin, Fn-/- MEFs remained homogenously distributed throughout the cell-contracted collagen gels. In contrast, in the presence of full-length fibronectin, both cell types produced shell-like tissues with a predominantly cell-free compacted collagen core and a peripheral surface layer rich in cells. Single cell assays then revealed that Fn-/- MEFs applied lower total strain energy on nanopillar arrays coated with either fibronectin or vitronectin when compared to Fnf/f MEFs, but that the presence of exogenously added plasma fibronectin rescued their contractility. While collagen decoration of single fibronectin fibers enhanced the non-persistent migration of both Fnf/f and Fn-/- MEFs, the migration speed was increased for Fn-/- MEFs on plasma fibronectin fibers compared to Fnf/f MEFs. In contrast, the average speed was the same for all cells on collagen-coated Fn fibers. A Fn-FRET sensor revealed that fibronectin on average was more extended on the microtissue surface compared to fibronectin in the core. Gradients of collagen-to-fibronectin ratios and of the fraction of collagen-adsorbed to stretched fibrillar fibronectin conformations might thereby provide critical cell migration cues. This study highlights a dominant role for fibronectin in tissue morphogenesis and the development of tissue heterogeneities

Pneumococcal colonization in healthy adult research participants in the conjugate vaccine era, United Kingdom, 2010-2017.

Pneumococcal colonization is rarely studied in adults, except as part of family surveys. We report the outcomes of colonization screening in healthy adults (non-smokers without major comorbidities or contact with children under five years) who had volunteered to take part in clinical research. Using nasal wash culture, we detected colonization in 6.5% (52/795) of volunteers. Serotype 3 was the commonest serotype (10/52). The majority of the remainder (35/52) were non-vaccine serotypes, but we also identified persistent circulation of serotypes 19A and 19F. Resistance to at least one of six antibiotics tested was found in 8/52 isolates

Respiratory mucosal immune memory to SARS-CoV-2 after infection and vaccination

Respiratory mucosal immunity induced by vaccination is vital for protection from coronavirus infection in animal models. In humans, the capacity of peripheral vaccination to generate sustained immunity in the lung mucosa, and how this is influenced by prior SARS-CoV-2 infection, is unknown. Here we show using bronchoalveolar lavage samples that donors with history of both infection and vaccination have more airway mucosal SARS-CoV-2 antibodies and memory B cells than those only vaccinated. Infection also induces populations of airway spike-specific memory CD4+ and CD8+ T cells that are not expanded by vaccination alone. Airway mucosal T cells induced by infection have a distinct hierarchy of antigen specificity compared to the periphery. Spike-specific T cells persist in the lung mucosa for 7 months after the last immunising event. Thus, peripheral vaccination alone does not appear to induce durable lung mucosal immunity against SARS-CoV-2, supporting an argument for the need for vaccines targeting the airways

Detection of SARS-CoV-2 infection by saliva and nasopharyngeal sampling in frontline healthcare workers: An observational cohort study

Background The SARS-CoV-2 pandemic has caused an unprecedented strain on healthcare systems worldwide, including the United Kingdom National Health Service (NHS). We conducted an observational cohort study of SARS-CoV-2 infection in frontline healthcare workers (HCW) working in an acute NHS Trust during the first wave of the pandemic, to answer emerging questions surrounding SARS-CoV-2 infection, diagnosis, transmission and control. Methods Using self-collected weekly saliva and twice weekly combined oropharyngeal/nasopharyngeal (OP/NP) samples, in addition to self-assessed symptom profiles and isolation behaviours, we retrospectively compared SARS-CoV-2 detection by RT-qPCR of saliva and OP/NP samples. We report the association with contemporaneous symptoms and isolation behaviour. Results Over a 12-week period from 30th March 2020, 40∙0% (n = 34/85, 95% confidence interval 31∙3-51∙8%) HCW had evidence of SARS-CoV-2 infection by surveillance OP/NP swab and/or saliva sample. Symptoms were reported by 47∙1% (n = 40) and self-isolation by 25∙9% (n = 22) participants. Only 44.1% (n = 15/34) participants with SARS-CoV-2 infection reported any symptoms within 14 days of a positive result and only 29∙4% (n = 10/34) reported self-isolation periods. Overall agreement between paired saliva and OP/NP swabs was 93∙4% (n = 211/226 pairs) but rates of positive concordance were low. In paired samples with at least one positive result, 35∙0% (n = 7/20) were positive exclusively by OP/NP swab, 40∙0% (n = 8/20) exclusively by saliva and in only 25∙0% (n = 5/20) were the OP/NP and saliva result both positive. Conclusions HCW are a potential source of SARS-CoV-2 transmission in hospitals and symptom screening will identify the minority of infections. Without routine asymptomatic SARS-CoV-2 screening, it is likely that HCW with SARS-CoV-2 infection would continue to attend work. Saliva, in addition to OP/NP swab testing, facilitated ascertainment of symptomatic and asymptomatic SARS-CoV-2 infections. Combined saliva and OP/NP swab sampling would improve detection of SARS-CoV-2 for surveillance and is recommended for a high sensitivity strategy