A Helping Hand: Design process of a soft anthropomorphic end-effector for the construction industry.

This thesis conducts design-led research to develop a soft anthropomorphic end-effector that is specifically designed for use with a collaborative robot on a construction site. As the construction industry changes to meet the demands of increasing populations and lack of skilled trades workers, new approaches are needed. This research explores the possibilities of a collaborative robot working on a construction site to help workers complete tasks deemed unsafe or detrimental to their health. The study acknowledges the different requirements of human-robot collaboration. However, it focuses on designing a hybrid end-effector that allows a collaborative robot to carry out more than a singular task on a construction site to increase productivity through all construction stages. The research conducts an iterative design process using soft robot techniques to replicate human hand elements, such as muscles and ligaments and currently available sensor technologies to create a hybrid end-effector. This end-effector is tested for grip strength and the ability to use both power and precision grasp functions to pick up a paintbrush, screwdriver, and a screw

A study of cytomegalovirus infection, cognitive ability and immunosenescence in older adults

Cytomegalovirus (CMV) is ubiquitous and the incidence of human infection increases with age. CMV exacerbates immunosenescence and is associated with increased mortality and morbidity in older adults. Cognitive decline in older generations causes great personal and financial burden. Here, examination of the Lothian Birth Cohort (1936) establishes an association between higher CMV IgG tires and a decline in general cognitive ability. This work also further defines the influence of CMV and Epstein-Barr virus (EBV) infection upon immune repertoire. Analysis of the 1000 Elders cohort in Birmingham demonstrates that CMV-and EBV-specific T cell responses remain stable over a period of ten years. However, CMV seronegative older adults display higher EBV viral loads compared to CMV seropositive individuals despite a similar frequency of EBV-specific T cell responses in both groups. In addition, CMV serostatus does not appear to influence the phenotype of EBV-specific T cell responses. Collectively, this study defines an association between high CMV IgG titres and decreased cognitive ability in older adults and demonstrates differential control of EBV by CMV seropositive and negative adults. High EBV viral loads may impact negatively upon the health of older adults; this should be studied further in future work

Social familiarity and spatially variable environments independently determine reproductive fitness in a wild bird

The social interactions that an individual experiences are a key component of its environment and can have important consequences for reproductive success. The dear enemy effect posits that having familiar neighbors at a territory boundary can reduce the need for territory defense and competition and potentially increase cooperation. Although fitness benefits of reproducing among familiar individuals are documented in many species, it remains unclear to what extent these relationships are driven by direct benefits of familiarity itself versus other socioecological covariates of familiarity. We use 58 years of great tit (Parus major) breeding data to disentangle the relationship between neighbor familiarity, partner familiarity, and reproductive success while simultaneously considering individual and spatiotemporal effects. We find that neighbor familiarity was positively associated with reproductive success for females but not males, while an individual's familiarity with their breeding partner was associated with fitness benefits for both sexes. There was strong spatial heterogeneity in all investigated fitness components, but our findings were robust and significant over and above these effects. Our analyses are consistent with direct effects of familiarity on individuals' fitness outcomes. These results suggest that social familiarity can yield direct fitness benefits, potentially driving the maintenance of long-term bonds and evolution of stable social systems

Social phenotype-dependent selection of social environment in wild great and blue tits: an experimental study

There is growing evidence that individuals actively assess the match between their phenotype and their environment when making habitat choice decisions (so-called matching habitat choice). However, to our knowledge, no studies have considered how the social environment may interact with social phenotype in determining habitat choice, despite habitat choice being an inherently social process and growing evidence for individual variation in sociability. We conducted an experiment using wild great and blue tits to understand how birds integrate their social phenotype and social environment when choosing where and how to feed. We used programmable feeders to (i) record social interactions and estimate social phenotype, and (ii) experimentally manipulate the local density experienced by birds of differing social phenotype. By tracking feeder usage, we estimated how social environment and social phenotype predicted feeder choice and feeding behaviour. Both social environment and social phenotype predicted feeder usage, but a bird's decision to remain in a particular social environment did not depend on their social phenotype. By contrast, for feeding behaviour, responses to the social environment depended on social phenotype. Our results provide rare evidence of matching habitat choice and shed light on the dependence of habitat choice on between-individual differences in social phenotype

A 18F radiolabelled Zn(ii) sensing fluorescent probe

A selective fluorescent probe for Zn(ii), AQA-F, has been synthesized. AQA-F exhibits a ratiometric shift in emission of up to 80 nm upon binding Zn(ii) ([AQA-F] = 0.1 mM, [Zn(ii)Cl 2 ] = 0-300 μM). An enhancement of quantum yield from Φ = 4.2% to Φ = 35% is also observed. AQA-F has a binding constant, K d = 15.2 μM with Zn(ii). This probe has been shown to respond to endogenous Zn(ii) levels in vitro in prostate and prostate cancer cell lines. [ 18 F]AQA-F has been synthesized with a radiochemical yield of 8.6% and a radiochemical purity of 97% in 88 minutes. AQA-F shows the potential for a dual modal PET/fluorescence imaging probe for Zn(ii)

Receptor-targeted peptide conjugates based on diphosphines enable preparation of 99mTc and 188Re theranostic agents for prostate cancer

Benchtop 99Mo/ 99mTc and 188W/ 188Re generators enable economical production of molecular theranostic 99mTc and 188Re radiopharmaceuticals, provided that simple, kit-based chemistry exists to radiolabel targeting vectors with these radionuclides. We have previously described a diphosphine platform that efficiently incorporates 99mTc into receptor-targeted peptides. Here, we report its application to label a prostate-specific membrane antigen (PSMA)-targeted peptide with 99mTc and 188Re for diagnostic imaging and systemic radiotherapy of prostate cancer. Methods: Two diphosphine-dipeptide bioconjugates, DP1-PSMAt and DP2-PSMAt, were formulated into kits for radiolabeling with 99mTc and 188Re. The resulting radiotracers were studied in vitro, in prostate cancer cells, and in vivo in mouse xenograft models, to assess similarity of uptake and biodistribution for each 99mTc/ 188Re pair of agents. Results: Both DP1-PSMAt and DP2-PSMAt could be efficiently radiolabeled with 99mTc and 188Re using kit-based methods to furnish the isostructural compounds M-DP1-PSMAt and M-DP2-PSMAt (M = [ 99mTc]Tc, [ 188Re]Re). All 99mTc/ 188Re radiotracers demonstrated specific uptake in PSMA-expressing prostate cancer cells, with negligible uptake in prostate cancer cells that did not express PSMA or in which PSMA uptake was blocked. M-DP1-PSMAt and M-DP2-PSMAt also exhibited high tumor uptake (18-30 percentage injected dose per gram at 2 h after injection), low retention in nontarget organs, fast blood clearance, and excretion predominantly via a renal pathway. Importantly, each pair of 99mTc/ 188Re radiotracers showed near-identical biologic behavior in these experiments. Conclusion: We have prepared and developed novel pairs of isostructural PSMA-targeting 99mTc/ 188Re theranostic agents. These generator-based theranostic agents have potential to provide access to the benefits of PSMA-targeted diagnostic imaging and systemic radiotherapy in health care settings that do not routinely have access to either reactor-produced 177Lu radiopharmaceuticals or PET/CT infrastructure. </p

Manipulation of the unfolded protein response: A pharmacological strategy against coronavirus infection.

Coronavirus infection induces the unfolded protein response (UPR), a cellular signalling pathway composed of three branches, triggered by unfolded proteins in the endoplasmic reticulum (ER) due to high ER load. We have used RNA sequencing and ribosome profiling to investigate holistically the transcriptional and translational response to cellular infection by murine hepatitis virus (MHV), often used as a model for the Betacoronavirus genus to which the recently emerged SARS-CoV-2 also belongs. We found the UPR to be amongst the most significantly up-regulated pathways in response to MHV infection. To confirm and extend these observations, we show experimentally the induction of all three branches of the UPR in both MHV- and SARS-CoV-2-infected cells. Over-expression of the SARS-CoV-2 ORF8 or S proteins alone is itself sufficient to induce the UPR. Remarkably, pharmacological inhibition of the UPR greatly reduced the replication of both MHV and SARS-CoV-2, revealing the importance of this pathway for successful coronavirus replication. This was particularly striking when both IRE1α and ATF6 branches of the UPR were inhibited, reducing SARS-CoV-2 virion release (~1,000-fold). Together, these data highlight the UPR as a promising antiviral target to combat coronavirus infection

Genetic and antigenic characterization of complete genomes of Type 1 Porcine Reproductive and Respiratory Syndrome viruses (PRRSV) isolated in Denmark over a period of 10 years

AbstractPorcine Reproductive and Respiratory Syndrome (PRRS) caused by the PRRS virus (PRRSV) is considered one of the most devastating swine diseases worldwide. PRRS viruses are divided into two major genotypes, Type 1 and Type 2, with pronounced diversity between and within the genotypes. In Denmark more than 50% of the herds are infected with Type 1 and/or Type 2 PRRSV. The main objective of this study was to examine the genetic diversity and drift of Type 1 viruses in a population with limited introduction of new animals and semen. A total of 43 ORF5 and 42 ORF7 nucleotide sequences were obtained from viruses collected from 2003 to February 2013. Phylogenetic analysis of ORF5 nucleotide sequences showed that the Danish isolates formed two major clusters within the subtype 1. The nucleotide identity to the subtype 1 protogenotype Lelystad virus (LV) spanned 84.9–98.8% for ORF5 and 90.7–100% for ORF7. Among the Danish viruses the pairwise nucleotide identities in ORF5 and ORF7 were 81.2–100% and 88.9–100%, respectively. Sequencing of the complete genomes, including the 5′- and 3′-end nucleotides, of 8 Danish PRRSV Type 1 showed that the genome lengths differed from 14,876 to 15,098 nucleotides and the pairwise nucleotide identity among the Danish viruses was 86.5–97.3% and the identity to LV was 88.7–97.9%. The study strongly indicated that there have been at least two independent introductions of Type 1 PRRSV in Denmark and analysis of the full genomes revealed a significant drift in several regions of the virus

Promoting physical activity in vulnerable adults “at risk” of homelessness: A Randomised Controlled Trial Protocol

Introduction: People who are homeless, or at risk of homelessness, have substantially poorer health. Sustained and regular participation in physical activity is beneficial for both mental and physical health. Limited data suggests that levels of physical activity in the homeless and those at risk of homelessness are low, and access to community-based exercise is limited or non-existent for this population. Nonetheless, exercise programs for the homeless could provide a feasible and scalable intervention for providing beneficial effects on physical and mental health in this population. The primary aim of this studyis to evaluate the impact of a group exercise intervention on activity levels in people who are homeless or at risk of homelessness in central London, UK. The secondary aim is to evaluate the impact of the intervention on mental and physical health outcomes. Method and analysis: A 2-arm, individually randomised controlled trial in people who are homeless and those vulnerable and at risk of homelessness in central London, UK. Participants will be recruited through a London-based homeless charity, Single Homeless Project. Following baseline assessments and allocation to intervention (exercise classes) or control (usual care), participants will be followed up at 3, 6, 9 and 12 months. The primary outcomes will be change in objective physical activity. The secondary outcomes will includechange in fitness assessments and mental health parameters. Changes in drug use and alcohol dependency will also be explored. Ethics and dissemination: Ethical approval was obtained through the Anglia Ruskin University Department of Sport and Exercise Sciences Research Ethics Committee. Results of this study will be disseminated through peer-reviewed publications and scientific presentations

Genetic dissection of complete genomes of Type 2 PRRS viruses isolated in Denmark over a period of 15 years

AbstractType 2 Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) was first detected in Europe in 1996 co-incident with the introduction of a live attenuated vaccine. Since then, only limited ORF5 and ORF7 sequences of Type 2 PRRS viruses have been reported throughout Europe. In the present study, the genetic and antigenic diversity of 11 complete genomes and 49 ORF5 and 55 ORF7 nucleotide sequences obtained from 57 viruses in Denmark from 2003 to 2012 were examined. The genetic identity of the 11 complete genomes to the vaccine strain (Ingelvac PRRS MLV) ranged between 93.6 and 99.6% while the 49 ORF5 sequences examined were 94.0–99.8% identical to the vaccine strain. Among the Danish sequences, the pairwise nucleotide identity was 90.9–100% and 93.0–100.0% for ORF5 and ORF7, respectively. Analysis of the genetic region encoding NSP2 revealed high diversity among the Danish viruses with an 86.6–98.9% range in similarity. Furthermore, several of the sequenced viruses harbored deletions in the NSP2 coding region. Phylogenetic analysis in a global Type 2 PRRSV framework classified all Danish isolates to a single cluster (sub-lineage 5.1) which comprised strains closely-related to the Type 2 prototype isolate VR2332