Optimization of low aspect ratio, iron dominated dipole magnets

A study of the optimization of iron dominated dipole magnets with pole face widths comparable or less than the gap size, i.e., low aspect ratio (AR), is conducted using both theoretical and computational approaches. This regime of magnet design is particularly relevant in the context of laser plasma accelerators (LPA) due to unique beam parameters and geometric constraints, namely large energy spreads and the requirement for large apertures to accommodate drive laser passage. The breakdown of commonly employed approximations and rules of thumb in typical AR1 magnet design is examined. A library of generalized, optimized pole face geometries is provided to expedite optimization of future magnets. Finally, this methodology is used to design an electromagnetic chicane which has been fabricated, validated, and is currently in use in an x-ray free electron laser driven LPA experiment at LBNL

A study of the reporting of patient and public involvement and engagement (PPIE) in orthodontic research

Introduction: Patient and public involvement and engagement (PPIE) in research is an essential component of high-quality research. Patients and the public can identify which research topics are most relevant to them, contribute to study design, and interpretation and dissemination of findings. While inclusion of PPIE is widely adopted in medical research, awareness within the dental research community is more limited. Aim: To examine patient and public involvement and engagement in orthodontic research activity. Design: Identification and appraisal of use of PPIE in orthodontic research reporting and funding applications using a systematic approach. Methods: Three sources of information were examined: (1) research articles published between September 2018 and September 2019 in four major orthodontic journals. Articles were examined for reported PPIE; (2) common funding bodies for orthodontic research were assessed to establish whether PPIE was mandated (National Institute for Health Research, Medical Research Council, Wellcome Trust, Chief Scientist Office (Scotland), Health and Care Research Wales, British Orthodontic Society Foundation, Royal College of Surgeons and CLEFT); and (3) publication guidance for authors in these journals was examined to identify whether reporting of PPIE was included. Results: Of the 363 research articles, 2 (0.6%) mention patient/public involvement. None of the 363 research articles mention patient/public engagement. Of nine funding bodies, 2 (22%) request evidence of patient/public involvement as a condition of receiving funding with one (11%) expecting evidence of public engagement to be provided as a condition of receiving funding. None of the four major orthodontic journals include patient/public involvement and/or engagement in their guidance for authors. Conclusion: There is currently: (1) a notable lack of reporting of PPIE in orthodontic research; (2) variability in the requirements of funding bodies for researchers to include PPIE in funding applications and throughout the research process; and (3) no stipulation in journals’ instructions for authors

A human MAP kinase interactome.

Mitogen-activated protein kinase (MAPK) pathways form the backbone of signal transduction in the mammalian cell. Here we applied a systematic experimental and computational approach to map 2,269 interactions between human MAPK-related proteins and other cellular machinery and to assemble these data into functional modules. Multiple lines of evidence including conservation with yeast supported a core network of 641 interactions. Using small interfering RNA knockdowns, we observed that approximately one-third of MAPK-interacting proteins modulated MAPK-mediated signaling. We uncovered the Na-H exchanger NHE1 as a potential MAPK scaffold, found links between HSP90 chaperones and MAPK pathways and identified MUC12 as the human analog to the yeast signaling mucin Msb2. This study makes available a large resource of MAPK interactions and clone libraries, and it illustrates a methodology for probing signaling networks based on functional refinement of experimentally derived protein-interaction maps

A bovine lymphosarcoma cell line infected with theileria annulata exhibits an irreversible reconfiguration of host cell gene expression

Theileria annulata, an intracellular parasite of bovine lymphoid cells, induces substantial phenotypic alterations to its host cell including continuous proliferation, cytoskeletal changes and resistance to apoptosis. While parasite induced modulation of host cell signal transduction pathways and NFκB activation are established, there remains considerable speculation on the complexities of the parasite directed control mechanisms that govern these radical changes to the host cell. Our objectives in this study were to provide a comprehensive analysis of the global changes to host cell gene expression with emphasis on those that result from direct intervention by the parasite. By using comparative microarray analysis of an uninfected bovine cell line and its Theileria infected counterpart, in conjunction with use of the specific parasitacidal agent, buparvaquone, we have identified a large number of host cell gene expression changes that result from parasite infection. Our results indicate that the viable parasite can irreversibly modify the transformed phenotype of a bovine cell line. Fifty percent of genes with altered expression failed to show a reversible response to parasite death, a possible contributing factor to initiation of host cell apoptosis. The genes that did show an early predicted response to loss of parasite viability highlighted a sub-group of genes that are likely to be under direct control by parasite infection. Network and pathway analysis demonstrated that this sub-group is significantly enriched for genes involved in regulation of chromatin modification and gene expression. The results provide evidence that the Theileria parasite has the regulatory capacity to generate widespread change to host cell gene expression in a complex and largely irreversible manner

Polycation-π Interactions Are a Driving Force for Molecular Recognition by an Intrinsically Disordered Oncoprotein Family

Molecular recognition by intrinsically disordered proteins (IDPs) commonly involves specific localized contacts and target-induced disorder to order transitions. However, some IDPs remain disordered in the bound state, a phenomenon coined "fuzziness", often characterized by IDP polyvalency, sequence-insensitivity and a dynamic ensemble of disordered bound-state conformations. Besides the above general features, specific biophysical models for fuzzy interactions are mostly lacking. The transcriptional activation domain of the Ewing's Sarcoma oncoprotein family (EAD) is an IDP that exhibits many features of fuzziness, with multiple EAD aromatic side chains driving molecular recognition. Considering the prevalent role of cation-π interactions at various protein-protein interfaces, we hypothesized that EAD-target binding involves polycation- π contacts between a disordered EAD and basic residues on the target. Herein we evaluated the polycation-π hypothesis via functional and theoretical interrogation of EAD variants. The experimental effects of a range of EAD sequence variations, including aromatic number, aromatic density and charge perturbations, all support the cation-π model. Moreover, the activity trends observed are well captured by a coarse-grained EAD chain model and a corresponding analytical model based on interaction between EAD aromatics and surface cations of a generic globular target. EAD-target binding, in the context of pathological Ewing's Sarcoma oncoproteins, is thus seen to be driven by a balance between EAD conformational entropy and favorable EAD-target cation-π contacts. Such a highly versatile mode of molecular recognition offers a general conceptual framework for promiscuous target recognition by polyvalent IDPs. © 2013 Song et al

Adaptive Evolution of the Myo6 Gene in Old World Fruit Bats (Family: Pteropodidae)

PMCID: PMC3631194This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Distinguishing Asthma Phenotypes Using Machine Learning Approaches.

Asthma is not a single disease, but an umbrella term for a number of distinct diseases, each of which are caused by a distinct underlying pathophysiological mechanism. These discrete disease entities are often labelled as asthma endotypes. The discovery of different asthma subtypes has moved from subjective approaches in which putative phenotypes are assigned by experts to data-driven ones which incorporate machine learning. This review focuses on the methodological developments of one such machine learning technique-latent class analysis-and how it has contributed to distinguishing asthma and wheezing subtypes in childhood. It also gives a clinical perspective, presenting the findings of studies from the past 5 years that used this approach. The identification of true asthma endotypes may be a crucial step towards understanding their distinct pathophysiological mechanisms, which could ultimately lead to more precise prevention strategies, identification of novel therapeutic targets and the development of effective personalized therapies

Uncovering treatment burden as a key concept for stroke care: a systematic review of qualitative research

<b>Background</b> Patients with chronic disease may experience complicated management plans requiring significant personal investment. This has been termed ‘treatment burden’ and has been associated with unfavourable outcomes. The aim of this systematic review is to examine the qualitative literature on treatment burden in stroke from the patient perspective.<p></p> <b>Methods and findings</b> The search strategy centred on: stroke, treatment burden, patient experience, and qualitative methods. We searched: Scopus, CINAHL, Embase, Medline, and PsycINFO. We tracked references, footnotes, and citations. Restrictions included: English language, date of publication January 2000 until February 2013. Two reviewers independently carried out the following: paper screening, data extraction, and data analysis. Data were analysed using framework synthesis, as informed by Normalization Process Theory. Sixty-nine papers were included. Treatment burden includes: (1) making sense of stroke management and planning care, (2) interacting with others, (3) enacting management strategies, and (4) reflecting on management. Health care is fragmented, with poor communication between patient and health care providers. Patients report inadequate information provision. Inpatient care is unsatisfactory, with a perceived lack of empathy from professionals and a shortage of stimulating activities on the ward. Discharge services are poorly coordinated, and accessing health and social care in the community is difficult. The study has potential limitations because it was restricted to studies published in English only and data from low-income countries were scarce.<p></p> <b>Conclusions</b> Stroke management is extremely demanding for patients, and treatment burden is influenced by micro and macro organisation of health services. Knowledge deficits mean patients are ill equipped to organise their care and develop coping strategies, making adherence less likely. There is a need to transform the approach to care provision so that services are configured to prioritise patient needs rather than those of health care systems

A review on boiling heat transfer enhancement with nanofluids

There has been increasing interest of late in nanofluid boiling and its use in heat transfer enhancement. This article covers recent advances in the last decade by researchers in both pool boiling and convective boiling applications, with nanofluids as the working fluid. The available data in the literature is reviewed in terms of enhancements, and degradations in the nucleate boiling heat transfer and critical heat flux. Conflicting data have been presented in the literature on the effect that nanofluids have on the boiling heat-transfer coefficient; however, almost all researchers have noted an enhancement in the critical heat flux during nanofluid boiling. Several researchers have observed nanoparticle deposition at the heater surface, which they have related back to the critical heat flux enhancement

Accelerated and Improved Quantification of Lymphocytic Choriomeningitis Virus (LCMV) Titers by Flow Cytometry

Lymphocytic choriomeningitis virus (LCMV), a natural murine pathogen, is a member of the Arenavirus family, may cause atypical meningitis in humans, and has been utilized extensively as a model pathogen for the study of virus-induced disease and immune responses. Historically, viral titers have been quantified by a standard plaque assay, but for non-cytopathic viruses including LCMV this requires lengthy incubation, so results cannot be obtained rapidly. Additionally, due to specific technical constraints of the plaque assay including the visual detection format, it has an element of subjectivity along with limited sensitivity. In this study, we describe the development of a FACS-based assay that utilizes detection of LCMV nucleoprotein (NP) expression in infected cells to determine viral titers, and that exhibits several advantages over the standard plaque assay. We show that the LCMV-NP FACS assay is an objective and reproducible detection method that requires smaller sample volumes, exhibits a ∼20-fold increase in sensitivity to and produces results three times faster than the plaque assay. Importantly, when applied to models of acute and chronic LCMV infection, the LCMV-NP FACS assay revealed the presence of infectious virus in samples that were determined to be negative by plaque assay. Therefore, this technique represents an accelerated, enhanced and objective alternative method for detection of infectious LCMV that is amenable to adaptation for other viral infections as well as high throughput diagnostic platforms