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Transglutaminases (TGs) catalyze the covalent crosslinking of proteins via isopeptide bonds. The most prominent isoform, TG2, is associated with physiological processes such as extracellular matrix (ECM) stabilization and plays a crucial role in the pathogenesis of e.g. fibrotic diseases, cancer and celiac disease. Therefore, TG2 represents a pharmacological target of increasing relevance. The glycosaminoglycans (GAG) heparin (HE) and heparan sulfate (HS) constitute high-affinity interaction partners of TG2 in the ECM. Chemically modified GAG are promising molecules for pharmacological applications as their composition and chemical functionalization may be used to tackle the function of ECM molecular systems, which has been recently described for hyaluronan (HA) and chondroitin sulfate (CS). Herein, we investigate the recognition of GAG derivatives by TG2 using an enzyme-crosslinking activity assay in combination with in silico molecular modeling and docking techniques. The study reveals that GAG represent potent inhibitors of TG2 crosslinking activity and offers atom-detailed mechanistic insights.

Aims: A nationwide diabetic retinopathy (DR) screening program has been established in Denmark since 2013. We aimed to perform an evaluation of adherence to DR screenings and to examine whether non-adherence was correlated to DR progression. Methods: The population consisted of a register-based cohort, who participated in the screening program from 2013 to 2018. We analyzed age, gender, marital status, DR level (International Clinical DR severity scale, none, mild-, moderate-, severe non-proliferative DR (NPDR) and proliferative DR (PDR)), comorbidities and socioeconomic factors. The attendance pattern of patients was grouped as either timely (no delays > 33%), delayed (delays > 33%) or one-time attendance (unexplained). Results: We included 205,970 patients with 591,136 screenings. Rates of timely, delayed and one-time attendance were 53.0%, 35.5% and 11.5%, respectively. DR level at baseline was associated with delays (mild-, moderate-, severe NPDR and PDR) and one-time attendance (moderate-, severe NPDR and PDR) with relative risk ratios (RRR) of 1.68, 2.27, 3.14, 2.44 and 1.18, 2.07, 1.26, respectively (P < 0.05). Delays at previous screenings were associated with progression to severe NPDR or PDR (hazard ratio (HR) 2.27, 6.25 and 12.84 for 1, 2 and 3+ delays, respectively). Any given delay doubled the risk of progression (HR 2.28). Conclusions: In a national cohort of 205,970 patients, almost half of the patients attended DR screening later than scheduled or dropped out after first screening episode. This was, in particular, true for patients with any levels of DR at baseline. DR progression in patients with delayed attendance, increased with the number of missed appointments.

Introduction: Exposure to perfluoroalkyl substances (PFAS) has been associated with lower bone mineral density (BMD) in animal and human studies, but prospective data from children are limited. Objectives: To determine associations between prenatal and early postnatal PFAS exposure and BMD at age 7 years. Methods: In the Odense Child Cohort, Denmark, pregnant women were recruited in 2010–2012, and their children were invited for subsequent health examinations. At 12 weeks of gestation the pregnant women delivered a serum sample, and at age 18 months serum was obtained from the child to measure perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDA) by LC-MS/MS. At age 7 years DXA scans were performed to measure bone mineral content (BMC) and BMD Z-score. PFAS in pregnancy (n = 924) and/or at age 18 months (n = 511) were regressed against DXA measurements, adjusted for maternal education, child height Z-score, sex (for BMC) and for postnatal exposure, additionally duration of total breastfeeding. We additionally performed structural equation models determining combined effects of pre-and postnatal PFAS exposures. Results: Higher prenatal and early postnatal serum concentrations of all measured PFAS were associated with lower BMC and BMD Z-scores at age 7 years, all estimates were negative although not all significant. For each doubling of prenatal or 18-month exposure to PFDA, BMD Z-scores were lowered by −0.07 (95 % CI −0.10; −0.03) and −0.14 (−0.25; −0.03), respectively after adjustment. Pre- and postnatal PFAS were correlated, but structural equation models suggested that associations with BMD were stronger for 18-month than prenatal PFAS exposure. Discussion: Bone density is established in childhood, and a reduction in BMD during early childhood may have long-term implication for peak bone mass and lifelong bone health. Future studies of the impa

A cluster of research in Affective Computing suggests that it is possible to infer some characteristics of users’ affective states by analyzing their electrophysiological activity in real-time. However, it is not clear how to use the information extracted from electrophysiological signals to create visual representations of the affective states of Virtual Reality (VR) users. Visualization of users’ affective states in VR can lead to biofeedback therapies for mental health care. Understanding how to visualize affective states in VR requires an interdisciplinary approach that integrates psychology, electrophysiology, and audio-visual design. Therefore, this review aims to integrate previous studies from these fields to understand how to develop virtual environments that can automatically create visual representations of users’ affective states. The manuscript addresses this challenge in four sections: First, theories related to emotion and affect are summarized. Second, evidence suggesting that visual and sound cues tend to be associated with affective states are discussed. Third, some of the available methods for assessing affect are described. The fourth and final section contains five practical considerations for the development of virtual reality environments for affect visualization.

Following the IAEA Technical Meeting on 'Advanced Methodologies for the Analysis of Materials in Energy Applications Using Ion Beam Accelerators', this paper reviews the current status of ion beam analysis (IBA) techniques and some aspects of ion-induced radiation damage in materials for the field of materials relevant to fusion. Available facilities, apparatus development, future research options and challenges are presented and discussed. The analysis of beryllium and radioactivity-containing samples from future experiments in JET or ITER represents not only an analytical but also a technical challenge. A comprehensive list of the facilities, their current status, and analytical capabilities comes alongside detailed descriptions of the labs. A discussion of future issues of sample handling and the current status of facilities at JET complete the technical section. To prepare the international IBA community for these challenges, the IAEA technical meeting concludes the necessity for determining new nuclear reaction cross-sections and improving the inter-laboratory comparability by defining international standards and testing these via a round-robin test.

Following the IAEA Technical Meeting on 'Advanced Methodologies for the Analysis of Materials in Energy Applications Using Ion Beam Accelerators', this paper reviews the current status of ion beam analysis (IBA) techniques and some aspects of ion-induced radiation damage in materials for the field of materials relevant to fusion. Available facilities, apparatus development, future research options and challenges are presented and discussed. The analysis of beryllium and radioactivity-containing samples from future experiments in JET or ITER represents not only an analytical but also a technical challenge. A comprehensive list of the facilities, their current status, and analytical capabilities comes alongside detailed descriptions of the labs. A discussion of future issues of sample handling and the current status of facilities at JET complete the technical section. To prepare the international IBA community for these challenges, the IAEA technical meeting concludes the necessity for determining new nuclear reaction cross-sections and improving the inter-laboratory comparability by defining international standards and testing these via a round-robin test., QC 20200701

He-induced nanostructured tungsten (so called W-fuzz) was bombarded with Ar ions under 60 degree and the dynamic erosion behaviour experimentally investigated. By using a highly sensitive quartz-crystal-microbalance technique in a particle catcher configuration the sputtered particles distribution of Wfuzz could be evaluated. In contrast to a at sample, where sputtered particles are emitted primarily in forward direction, we find that W-fuzz samples emit sputtered particles preferably in backward direction (i.e. in the direction of the incident ion beam). After continuous Ar irradiation of a W-fuzz sample the distribution approaches that of a at sample. In addition to experimental data we also show modelling results obtained with a state-of-the-art Monte-Carlo (MC) binary collision approximation (BCA) code TRI3DYN in full 3D. Surface morphology changes as monitored by SEM as well as the dynamic sputtering behaviour can be well reproduced by the full 3D MC-BCA code.

With the coming of age of virtual/augmented reality and interactive media, numerous definitions, frameworks, and models of immersion have emerged across different fields ranging from computer graphics to literary works. Immersion is oftentimes used interchangeably with presence as both concepts are closely related. However, there are noticeable interdisciplinary differences regarding definitions, scope, and constituents that are required to be addressed so that a coherent understanding of the concepts can be achieved. Such consensus is vital for paving the directionality of the future of immersive media experiences (IMEx) and all related matters. The aim of this white paper is to provide a survey of definitions of immersion and presence which leads to a definition of immersive media experience (IMEx). The Quality of Experience (QoE) for immersive media is described by establishing a relationship between the concepts of QoE and IMEx followed by application areas of immersive media experience. Influencing factors on immersive media experience are elaborated as well as the assessment of immersive media experience. Finally, standardization activities related to IMEx are highlighted and the white paper is concluded with an outlook related to future developments.