Oxford nanopore sequencing enables rapid discovery of single-domain antibodies from phage display libraries.

Antibody (Ab) repertoire sequencing using high-throughput massively parallel technologies has contributed substantially to the understanding of Ab responses following infection, vaccination and autoimmunity. Because individual B-cell receptors are recombined and diversified somatically, genomic comparisons are limited, and distinguishing rare variants from sequencing errors is a major challenge. Oxford Nanopore Technologies' MinION is a highly portable and cost-effective third-generation sequencing instrument, but has not been used for Ab repertoire sequencing due to its high error rate (approximately 1/10 bases). Here, we applied nanopore sequencing to single-domain Ab (sdAb) repertoires and phage-displayed sdAb libraries. We show that despite low overall data fidelity, sdAb sequences could be reconstructed above a frequency threshold (∼100 copies); however, distinguishing clonal sdAb variants was not always possible. The data quality was sufficient to enable rapid identification of antigen-specific sdAb sequences enriched during panning of phage display libraries, obviating the need for screening single clones

Epidermal Growth Factor Ameliorates Autosomal Recessive Polycystic Kidney Disease in Mice

AbstractC57BL/6J mice homozygous for the cpk gene exhibit an autosomal recessive (AR) form of polycystic kidney disease (PKD), similar to human ARPKD, with massive collecting duct cysts. These cysts are lined by epithelia with an immature phenotype. Since renal expression of epidermal growth factor (EGF) is also significantly decreased in affected mice, we hypothesized that renal EGF is necessary for normal developmental maturation of the collecting duct. To determine if the lack of EGF may be a decisive factor in the initiation and/or growth of collecting duct cysts, we administered exogenous EGF (1 μg/g body wt subcutaneously) daily for Postnatal Days 3-9 (a critical period for collecting duct maturation) to C57BL/6J-cpk mice. EGF but not sham or albumin treatment retarded the development of PKD, reduced the degree of renal failure associated with the disease, and prolonged the survival of cystic mice. Sulfated glycoprotein-2 gene expression, a marker of immaturity in collecting duct cells, was reduced in cystic kidney by EGF treatment. This finding indicates that EGF treatment was associated with an increase in the maturation of the collecting duct epithelial cells. These findings support the view that decreased EGF may play a significant role in promoting the enlargement of collecting duct cysts in a hereditary model of ARPKD and that PKD involves defective and/or arrested collecting duct cell maturation

Comprehensive behavioral testing in the R6/2 mouse model of Huntington's disease shows no benefit from CoQ10 or minocycline

Previous studies of the effects of coenzyme Q10 and minocycline on mouse models of Huntington’s disease have produced conflicting results regarding their efficacy in behavioral tests. Using our recently published best practices for husbandry and testing for mouse models of Huntington’s disease, we report that neither coenzyme Q10 nor minocycline had significant beneficial effects on measures of motor function, general health (open field, rotarod, grip strength, rearing-climbing, body weight and survival) in the R6/2 mouse model. The higher doses of minocycline, on the contrary, reduced survival. We were thus unable to confirm the previously reported benefits for these two drugs, and we discuss potential reasons for these discrepancies, such as the effects of husbandry and nutrition

Collaboration between Science and Religious Education teachers in Scottish Secondary schools

The article reports on quantitative research that examines: (1) the current practice in collaboration; and (2) potential for collaboration between Science and Religious Education teachers in a large sample of Scottish secondary schools. The authors adopt and adapt three models (conflict; concordat and consonance) to interrogate the relationship between science and religion (and the perceived relation between these two subjects in schools) (Astley and Francis 2010). The findings indicate that there is evidence of limited collaboration and, in a few cases, a dismissive attitude towards collaboration (conflict and concordat and very weak consonance). There is, however, evidence of a genuine aspiration for greater collaboration among many teachers (moving towards a more robust consonance model). The article concludes by discussing a number of key factors that must be realised for this greater collaboration to be enacted

Where do graduates Develop their Enterprise Skills? The Value of the Contribution of Higher Education Institutions’ Context

This study investigates the value of the contribution of HEIs’ context in developing graduates enterprise skills. HEIs are under pressure to develop more enterprising graduates, particularly with the increasing numbers of graduates seeking employment and the growing dissatisfaction of employers. This study explores where graduates develop enterprise skills through investigating the impact of HE and employment contexts on their development. The paper draws on a qualitative study in the social constructionist paradigm within the pharmacy context, where interviews were conducted with pharmacy academics and employers. Results show that ability to demonstrate skills in one context does not necessarily mean ability to demonstrate them in another since the development and demonstration of enterprise skills is impacted by the contexts in which they are developed and demonstrated. The study adds value by highlighting the significant role of both HE and employment contexts in developing enterprise skills, while emphasising that these skills become more transferable through exposure to more contexts

Structural relaxation in a system of dumbbell molecules

The interaction-site-density-fluctuation correlators, the dipole-relaxation functions, and the mean-squared displacements of a system of symmetric dumbbells of fused hard spheres are calculated for two representative elongations of the molecules within the mode-coupling theory for the evolution of glassy dynamics. For large elongations, universal relaxation laws for states near the glass transition are valid for parameters and time intervals similar to the ones found for the hard-sphere system. Rotation-translation coupling leads to an enlarged crossover interval for the mean-squared displacement of the constituent atoms between the end of the von Schweidler regime and the beginning of the diffusion process. For small elongations, the superposition principle for the reorientational $\alpha$-process is violated for parameters and time intervals of interest for data analysis, and there is a strong breaking of the coupling of the $\alpha$-relaxation scale for the diffusion process with that for representative density fluctuations and for dipole reorientations.Comment: 15 pages, 14 figures, Phys. Rev. E in pres

Industrial work placement in higher education: a study of civil engineering student engagement

For civil engineering undergraduates, the opportunity to spend a period of time in formal industrial work placement provides an invaluable learning experience. This paper reviews student engagement with short-term industrial placement and provides analysis of questionnaires (n=174) returned by undergraduates studying civil engineering at four Higher Education Institutes (HEI’s) in the West of Scotland. The data captures industrial placement statistics, employability skill-sets and presents brief testimonies from students. Whilst the journey to becoming a professional civil engineer is undoubtedly enhanced by short-term placement clear opportunities exist for HEI’s to affect and change existing pedagogical discourse. Commentary is likely to resonate beyond civil engineering and serve as a timely reminder of the need to re-invigorate academia / industry curriculum partnerships

Evaluating the impact of career management skills module and internship programme within a university business school

This study evaluates the impact of an intervention on business school graduates’ employability comprising of a curriculum-based career management skills (CMS) module and an industrial placement year. The study uses data from the destinations of leavers of higher education survey to examine the employability of different groups within the cohort (no intervention, CMS module only and CMS module plus structured work experience). It finds that structured work experience has clear, positive effects on the ability of graduates to secure employment in ‘graduate level’ jobs within six months of graduation. Furthermore, participation in the CMS module also has a clear, positive effect upon the ability of participants to secure employment

COIVF-9 %Ob 6Y-- N EAR-N ET-SHAPE FABRICATION BY FORCED-FLOW, THERMAL-G RAD1 ENT CVI*

Forced-flow, thermal gradient chemical vapor infiltration (FCVI) has been developed for the rapid densification of ceramic matrix composites. For preforms of >3 mm thickness FCVl can produce a near-net-shape part in less than one day as opposed to isothermal, isobaric CVI which requires several weeks to densify such a component. Efforts at ORNL and elsewhere have resulted in capability to produce prototypical thick-walled heat exchanger tubes and turbine disk blanks. This paper will review recent modeling and experimental efforts related to the FCVl of cylindrical forms

Big Area Additive Manufacturing of High Performance Bonded NdFeB Magnets

Additive manufacturing allows for the production of complex parts with minimum material waste, offering an effective technique for fabricating permanent magnets which frequently involve critical rare earth elements. In this report, we demonstrate a novel method - Big Area Additive Manufacturing (BAAM) - to fabricate isotropic near-net-shape NdFeB bonded magnets with magnetic and mechanical properties comparable or better than those of traditional injection molded magnets. The starting polymer magnet composite pellets consist of 65 vol% isotropic NdFeB powder and 35 vol% polyamide (Nylon-12). The density of the final BAAM magnet product reached 4.8 g/cm3, and the room temperature magnetic properties are: intrinsic coercivity Hci = 688.4 kA/m, remanence Br = 0.51 T, and energy product (BH)max = 43.49 kJ/m3 (5.47 MGOe). In addition, tensile tests performed on four dogbone shaped specimens yielded an average ultimate tensile strength of 6.60 MPa and an average failure strain of 4.18%. Scanning electron microscopy images of the fracture surfaces indicate that the failure is primarily related to the debonding of the magnetic particles from the polymer binder. The present method significantly simplifies manufacturing of near-net-shape bonded magnets, enables efficient use of rare earth elements thus contributing towards enriching the supply of critical materials