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During replication, folding of the DNA template into non-B-form secondary structures provides one of the most abundant impediments to the smooth progression of the replisome. The core replisome collaborates with multiple accessory factors to ensure timely and accurate duplication of the genome and epigenome. Here, we discuss the forces that drive non-B structure formation and the evidence that secondary structures are a significant and frequent source of replication stress that must be actively countered. Taking advantage of recent advances in the molecular and structural biology of the yeast and human replisomes, we examine how structures form and how they may be sensed and resolved during replication.

Purpose: Grounded in self-determination theory, this study examined factors of secondary early field experiences that preservice teachers consider significant and how these experiences impact them as educators. Method: Preservice teachers (N = 13) completed two 10-week early field experiences, one at each level—middle school and high school. Data sources included weekly reflections, interviews, emails, and nonparticipant observations. Data were analyzed inductively through constant comparison and deductively to establish meaning through self-determination theory. Results: The cooperating teachers were substantially influential for the preservice teachers, as were establishing connections with concepts learned in methods courses and tending to students’ well-being. The way the early field experiences influenced the preservice teachers as educators was unique to the individual, as negative experiences were channeled positively for some and negatively for others. Conclusion: Early field experiences are quite influential, thus physical education teacher education programs should strongly consider vetting placements or strategically pairing students with placements, particularly at the secondary level, to optimize professional development.

This article provides a brief overview of teacher/coach role conflict and possible implications if inappropriately managed. Following this, the authors provide suggestions on how to prepare pre-ser...

We report on the influence a preferential magnetic vortices motion has on the magnitude of the inverse ac Josephson effect (the appearance of dc current Shapiro steps) and the coherent operation of asymmetrical parallel arrays of YBaCuO Josephson junctions (JJ) irradiated with microwave (MW) radiation in the presence of an applied magnetic field B. The preferential direction of motion of the Josephson vortices is due to the asymmetry-induced ratchet effect and has a dramatic impact: for a particular positive dc bias current I when the flux-flow is robust multiple pronounced Shapiro-steps are observed consistent with a coherent operation of the array. This suggests an efficient emission/detection of MW in related applications. In contrast, when we reverse the direction of I, the flux-flow is reduced and the Shapiro-steps are strongly suppressed due to a highly incoherent operation that suggests an inefficient emission/detection of MW. Remarkably, by changing B slightly, the situation is reversed: Shapiro steps are now suppressed for a positive I, while well pronounced for a reverse current -I. Our results suggest that a preferential vortex-flow has a very significant impact on the coherent MW operation of superconducting devices consisting of either multiple JJs or a single long JJ asymmetrically biased. This is particular relevant in the case of flux-flow oscillators for sub-terahertz integrated-receivers, flux-driven Josephson (travelling-wave) parametric amplifiers, or on-chip superconducting MW generators which usually operate at bias currents in the Shapiro step region., 15 pages, 5 figures that includes a figure in the Supplementary material

Few can argue the marginalized status of physical education in today’s schools, making the advocacy skills of physical educators and preservice teachers (PSTs) increasingly important. This article ...

This study examined two physical educators/coaches’ (one veteran and one induction) perceptions of their two roles. Role socialization theory (Richards, 2015) was used to determine how different roles are socially constructed and contextually bound, how individuals are socialized into their roles, and how socialization affects others’ view of the participants. Triangulation, peer debriefing, member checking, and an audit trial ensured trustworthiness. Data analysis was conducted following Merriam and Tisdell (2016). Analysis revealed three major themes: time conflicts, relationship conflicts, and the value of the role was dependent on the environmental context.Subscribe to TPE

The robust modularity of biological components that are assembled into complex functional systems is central to synthetic biology. Here we apply modular “plug and play” design principles to a microscale solid phase protein display system that enables protein purification and functional assays for biotherapeutics. Specifically, we capture protein molecules from cell lysates on polyacrylamide hydrogel display beads (‘PHD beads’), made in microfluidic droplet generators. These monodisperse PHD beads are decorated with predefined amounts of anchors, methacrylate-PEG-benzylguanine (BG) and methacrylate-PEG-chloroalkane (CA). Anchors form covalent bonds with fusion proteins bearing cognate tag recognition (SNAP and Halo-tags) in specific, orthogonal and stable fashion. Given that these anchors are copolymerised throughout the 3D structure of the beads, proteins are also distributed across the entire bead sphere, allowing attachment of ∼109 protein molecules per bead (Ø 20 μm). This mode of attachment reaches a higher density than possible on widely used surface-modified beads, and additionally mitigates surface effects that often complicate studies with proteins on beads. We showcase a diverse array of protein modules that enable the secondary capture of proteins, either non-covalently (IgG and SUMO-tag) or covalently (SpyCatcher, SpyTag, SnpCatcher and SnpTag). Proteins can be displayed in their monomeric forms, but also reformatted as a multivalent display (using secondary capture modules that create branches) to test the contributions of avidity and multivalency towards protein function. Finally, controlled release of modules by irradiation of light is achieved by incorporating the photocleavable protein PhoCl: irradiation severs the displayed protein from the solid support, so that functional assays can be carried out in solution. As a demonstration of the utility of valency engineering, an antibody drug screen is performed, in which an anti-TRAIL-R1 scFv protein is released into solution as monomers-hexamers, showing a ∼50-fold enhanced potency in the pentavalent format. The ease of protein purification on solid support, quantitative control over presentation and release of proteins and choice of valency make this experimental format a versatile, modular platform for large scale functional analysis of proteins, in bioassays of protein-protein interactions, enzymatic catalysis and bacteriolysis.Table of Contents Graphics

This article (written in April 2013) considers the observations and recommendations made in the Report of the Mid Staffordshire NHS Foundation Trust Public Inquiry as to a duty of candour and, in particular, the recommendation that there should be a statutory duty of candour imposed on healthcare providers, as well as on registered medical practitioners, nurses and other registered professionals, who believe or suspect that patient treatment or care has caused death or serious injury. The article details the Government's initial response to such recommendations, in which it indicated an intention to introduce a statutory duty for health and care providers, and sets out the contractual duty of candour that is currently included in the NHS Standard Contract for 2013/14 (SC35). There is then an analysis of the terms of the contractual duty contrasted with those of the proposed statutory duty; a look at the limitations of the contractual duty; a discussion of some of the issues that may arise in relation to when the relevant duty (either contractual or statutory) will be triggered; a consideration of the apparent novelty of a statutory duty of candour in English law; and a brief discussion in relation to the potential remedies, penalties and offences that may be adopted if such a statutory duty comes into force. In conclusion, on any basis the imposition of the contractual duty of candour and the intention to introduce some form of statutory duty heralds a new era in relation to candour in healthcare.

(2004). Third Party Interventions by the Government. Judicial Review: Vol. 9, No. 2, pp. 130-139.