Asymmetrically Difunctionalized 1,1′-Ferrocenyl Metalloligands and Their Transition Metal Complexes

FcBipy: Novel redox-active bipyridine ligands based on 1,1′ difunctionalized ferrocenyl backbone, in conjunction with their metal complexes, are reported. The influence of the implemented functional groups on both the iron-centred redox potential and the N,N′-coordinated nickel complexes were confirmed for the reductive elimination reaction of an aryl ether induced by oxidation of the corresponding methoxides

Deconstructing sarcomeric structure-function relations in titin-BioID knock-in mice

Proximity proteomics has greatly advanced the analysis of native protein complexes and subcellular structures in culture, but has not been amenable to study development and disease in vivo. Here, we have generated a knock-in mouse with the biotin ligase (BioID) inserted at titin's Z-disc region to identify protein networks that connect the sarcomere to signal transduction and metabolism. Our census of the sarcomeric proteome from neonatal to adult heart and quadriceps reveals how perinatal signaling, protein homeostasis and the shift to adult energy metabolism shape the properties of striated muscle cells. Mapping biotinylation sites to sarcomere structures refines our understanding of myofilament dynamics and supports the hypothesis that myosin filaments penetrate Z-discs to dampen contraction. Extending this proof of concept study to BioID fusion proteins generated with Crispr/CAS9 in animal models recapitulating human pathology will facilitate the future analysis of molecular machines and signaling hubs in physiological, pharmacological, and disease context

Multiwavelength Monitoring of the BL Lacertae Object PKS 2155-304 in May 1994. II. The IUE Campaign

PKS 2155-304, the brightest BL Lac object in the ultraviolet sky, was monitored with the IUE satellite at ~1 hour time-resolution for ten nearly uninterrupted days in May 1994. The campaign, which was coordinated with EUVE, ROSAT, and ASCA monitoring, along with optical and radio observations from the ground, yielded the largest set of spectra and the richest short time scale variability information ever gathered for a blazar at UV wavelengths. The source flared dramatically during the first day, with an increase by a factor ~2.2 in an hour and a half. In subsequent days, the flux maintained a nearly constant level for ~5 days, then flared with ~35% amplitude for two days. The same variability was seen in both short- and long-wavelength IUE light curves, with zero formal lag (~<2 hr), except during the rapid initial flare, when the variations were not resolved. Spectral index variations were small and not clearly correlated with flux. The flux variability observed in the present monitoring is so rapid that for the first time, based on the UV emission alone, the traditional Delta L/Delta t limit indicating relativistic beaming is exceeded. The most rapid variations, under the likely assumption of synchrotron radiation, lead to a lower limit of 1 G on the magnetic field strength in the UV emitting region. These results are compared with earlier intensive monitoring of PKS 2155-304 with IUE in November 1991, when the UV flux variations had completely different characteristics.Comment: 45 pages, Latex, 11 PostScript figures, to appear in The Astrophysical Journa

Corrigendum : Different Strokes for Different Folks: The BodyMind Approach as a Learning Tool for Patients With Medically Unexplained Symptoms to Self-Manage

© 2019 Payne and Brooks. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.In the original article, there was an error regarding the cost of medically unexplained symptoms (MUS). A correction has been made to the Abstract: “Medically unexplained symptoms (MUS) are common in both primary and secondary health care. It is gradually being acknowledged that there needs to be a variety of interventions for patients with MUS tomeet the needs of different groups of patients with such chronic long-termsymptoms. The proposed intervention described herewith is called The BodyMind Approach (TBMA) and promotes learning for self-management through establishing a dynamic and continuous process of emotional self-regulation. The problem is the mismatch between the patient’s mind-set and profile and current interventions. This theoretical article, based on practice-based evidence, takes forward the idea that different approaches (other than cognitive behavioral therapy) are required for people with MUS. The mind-set and characteristics of patients with MUS are reflected upon to shape the rationale and design of this novel approach. Improving services for this population in primary care is crucial to prevent the iterative spiraling downward of frequent general practitioner (GP) visits, hospital appointments, and accident and emergency attendance (A&E), all of which are common for these patients. The approach derives from embodied psychotherapy (authentic movement in dance movement psychotherapy) and adult models of learning for self-management. It has been developed from research and practice-based evidence. In this article the problem of MUS in primary care is introduced and the importance of the reluctance of patients to accept a psychological/mental health referral in the first instance is drawn out. A description of the theoretical underpinnings and philosophy of the proposed alternative to current interventions is then presented related to the design, delivery, facilitation, and educational content of the program. The unique intervention is also described to give the reader a flavor.” Additionally, a correction has been made to the Introduction, paragraph one: “Medically unexplained symptoms (MUS) are a thorny issue in primary care. Despite the differing nomenclature, the recent DSM-5 terms it as somatic symptom disorder (SSD) but is yet to achieve general usage. Many general practitioners (GPs) appear to reliably recognize MUS without the need for standardized assessments (Rasmussen et al., 2008). This population present with many, various and nebulous physical and psychological ailments (Rosendal et al., 2005) and constitute more than 25% of all new hospital and GP appointments (Fink et al., 1999; Reid et al., 2001). In England MUS has been estimated to cost £3 billion in 2008–2009 rising to £18 billion if loss of productivity, benefits and quality of life are accounted for Bermingham et al. (2010).” The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.Peer reviewedFinal Published versio

Automation of Space Inventory Management

This viewgraph presentation describes the utilization of automated space-based inventory management through handheld RFID readers and BioNet Middleware. The contents include: 1) Space-Based INventory Management; 2) Real-Time RFID Location and Tracking; 3) Surface Acoustic Wave (SAW) RFID; and 4) BioNet Middleware

RWE in Europe Paper II: The use of Real World Evidence in the disease context

Real World Evidence (RWE), the use of data not collected via traditional randomised controlled trials (RCT) for decision-making, is becoming more interesting to market-access and reimbursement decision-makers, despite potential methodological issues around its use. This paper, the second in a series looking at the use of Real World Evidence (RWE) in Europe, analyses the opinions of a number of key experts in pricing and reimbursement from a selection of countries across Europe. Discussion centred on the use of RWE in licensing, commissioning, clinical decision-making and patient and outcome related decision-making in the context of three different treatment areas – chronic disease, oncology and rare diseases. Results of discussion sessions with ‘RWE experts’ indicated that the associated benefits of RWE are becoming more relevant but there is a need for a well-organised, high quality system for data generation, interpretation and use. It is likely that different treatment areas will have differing RWE requirements and differing levels of utility. In the rare disease arena, RWE may have a role in licensing based decisions, but this is unlikely for chronic disease or oncology. In order to enhance the role of RWE, and to ensure it meets its full potential in all treatment areas, a multi-stakeholder approach at the EU level is required, with collaboration between national and supranational organisations and all stakeholders including patient organisations, manufacturers and reimbursement agencies