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A linac consisting of six rf cavities has been constructed as an energy booster of the RIKEN heavy-ion linac. Various heavy ion beams have been accelerated to 5.8 MeV/u with intensities of more than 1 pμA (particle microampere) in the continuous-wave mode. The booster cavities are based on a quarter-wavelength resonator of a coaxial structure. The first two cavities are frequency-variable in a range from 36 to 76.4 MHz, whereas the last four are operated at a fixed frequency of 75.5 MHz. The design study started in 1997 and the booster was commissioned in 2001. The total voltage gain of the booster ever achieved is 11 MV, which is 70% of the designed value of 16 MV. The high-intensity beams from the booster have been successfully applied to a systematic study on the synthesis of superheavy elements. The beam energy from the ring cyclotron has also been increased, owing to the additional velocity gain provided by the booster. [ABSTRACT FROM AUTHOR]

La proximité a fait l’objet, au cours des dernières années, de plus en plus d’intérêt du point de vue de ses effets potentiels sur l’innovation, ainsi que sur le développement et la structuration de l’espace économique. De nombreux travaux ont souligné l’importance de la proximité géographique comme source de l’innovation et du développement de régions compétitives. Ces travaux font le lien entre la réalisation d’activités innovantes et la colocalisationdes acteurs sur un même territoire. Cette littérature, regroupée sous le terme générique de clusteradmetquel’ancrage territorial des membres d’un réseau d’innovation a un impact sur leur capacité à apprendre et à innover collectivement.Doit-on en conclure que la simple concentration d’acteurs (entreprises, preneurs de décision, université) doublée de la proximité physique serait suffisante pour jeter les bases de l’innovation au sein du territoire?De nombreux auteurs estiment que les effets potentiels de la proximité géographique ne peuvent se concrétiser qu’en la présence au sein du territoire d’une proximité organisée fournie par un cadre institutionnel adéquat.La présente études’interroge sur le rôle de la proximité dans le processus de transfert de connaissances et le potentiel d’innovation des entreprises en s’appuyant sur des données issues d’une enquête directe auprès de 42 entreprises installées dans la région de Fès.Trois conclusionsprincipales se dégagent de cette étude, attestant de l’exigence d’une forme alternative d’organisation du processus d’innovation, moins sensible à la proximité spatiale des acteurs. Tout d’abord, La proximité spatiale n’a pas été suffisante pour que les entreprises de la région développent leur capacité d’innovation. Pourtant, l’accès aux réseaux d’information et les interactions personnelles sont des facteurs clés lorsqu’une entreprise entend développer des innovations.L’étude révèle ensuite, que les facteurs clés de l’innovation relèvent de la qualité des ressources retrouvées à l’échelle locale. Autrement dit, si le fait de cohabiter avec d’autres entreprises importe peu, la qualité de la main-d’œuvre locale, des relations interpersonnelles et la facilité de communiquer influent sur la capacité d’innover d’une entreprise. Enfin, les aspects social, cognitif et communicationnel du territoire sont considérés vitaux par des entrepreneurs pour expliquer l’innovation prenant place au sein d’entreprises de leur secteur d’activités .

Objective: To develop a more thorough understanding of the risk factors for loneliness in persons with a physical impairment, using a population-based sample of persons with spinal cord injury (SCI), based on regression modeling and a recursive partitioning approach., Design: Cross-sectional, observational cohort., Setting: Community, Switzerland., Participants: Community-dwelling persons with spinal cord injury (N=1283) 16 years or older., Interventions: Not applicable., Main Outcome Measures: Loneliness was assessed using a modified version of the UCLA Three-Item Loneliness Scale., Results: Those with the most disadvantaged socioeconomic characteristics in terms of education, income, subjective social position, employment status, and financial hardship demonstrated the highest risk for loneliness. Of the sociodemographic characteristics, only age had an association with loneliness, whereby persons aged 31-45 had the highest propensity for experiencing loneliness. We also saw that those with higher lesion levels and less functional independence were associated with higher levels of loneliness. In conditional inference tree analysis subjective social position, financial hardship, and functional independence had the highest discriminative power, with nationality and living arrangement having a less important role., Conclusions: Our findings highlight the vulnerability of persons with SCI with unfavorable socioeconomic status to loneliness. Furthermore, our findings show that persons who are more constrained because of functional limitations may face restrictions to social participation and therefore be at a higher risk of loneliness. This population-based evidence contributes to the better targeting of services aimed at alleviating loneliness for persons with a lower socioeconomic position and those with more functional limitations in everyday life., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The experience of loneliness can have drastic consequences for health and quality of life. Given that loneliness is highly prevalent in persons with physical disabilities and that loneliness more profoundly affects persons of low socioeconomic status, more evidence is required in order to understand the mechanisms determining loneliness in this population. The objective of this study is therefore to investigate the potential pathways through which socioeconomic status influences loneliness in persons with spinal cord injury., Methods: Mediation analysis utilising structural equation models and bias corrected and accelerated confidence intervals were used in order to test the mediation effects of health status, functioning, participation, social support and self-efficacy on the association between socioeconomic status and loneliness in persons with spinal cord injury. A latent construct was created for socioeconomic status with the indicators education, household income, financial hardship, subjective social status and engagement in paid work., Results: This study found evidence to support the mediating role of psychosocial resources and of secondary health conditions in the association between socioeconomic status and loneliness. The study demonstrated robust associations between socioeconomic status and all potential mediators, whereby higher socioeconomic status was associated with better health, participation and psychosocial resources, however, not all potential mediators were associated with loneliness. The serial mediation model explained the interplay between socioeconomic status, mediators on different levels, and loneliness. For example, emotional support and self-efficacy were both positively associated with fewer restrictions to participation (0.08 (CI: 0.05, 0.12); 0.29 (CI: 0.24, 0.36) respectively), and fewer restrictions to participation were found to be a result of improved functional independence and fewer secondary health conditions (0.23 (CI: 0.15, 0.39); - 0.29 (CI: - 0.36, - 0.20) respectively)., Conclusions: Our findings highlight the vulnerability of persons with low socioeconomic status to loneliness in persons with spinal cord injury and identified potential mediating factors, such as health, functioning, participation and psychosocial resources, in the association between socioeconomic status and loneliness. This population-based evidence suggests potential targets of interventions on the pathway to loneliness, through which socioeconomic status influences loneliness. The complexity of the model shows the need for comprehensive interprofessional rehabilitation to identify and support people with lower socioeconomic status and concomitant risk factors for loneliness., (© 2021. The Author(s).)

Background: Social relationships are powerful determinants of health and inequalities in social relationships across socioeconomic status (SES) groups may contribute to social inequalities in health. This study investigates inequalities in social relationships in an international sample of persons with spinal cord injury and explores whether social gradients in relationships are moderated by the countries' socioeconomic development (SED)., Methods: Data from 12,330 participants of the International SCI Community Survey (InSCI) performed in 22 countries were used. We regressed social relationships (belongingness, relationship satisfaction, social interactions) on individual SES (education, income, employment, financial hardship, subjective status) and countries' SED (Human Development Index) using multi-level models (main effects). To test potential moderation of the SED, interaction terms between individual SES and countries' SED were entered into multi-level models., Results: Paid work, absence of financial hardship and higher subjective status were related to higher belongingness (OR, 95% CI: 1.50, 1.34-1.67; 1.76, 1.53-2.03; 1.16, 1.12-1.19, respectively), higher relationship satisfaction (OR, 95% CI: 1.28, 1.15-1.42; 1.97, 1.72-2.27; 1.20, 1.17-1.24, respectively) and fewer problems with social interactions (Coeff, 95% CI: 0.96, 0.82-1.10; 1.93, 1.74-2.12; 0.26, 0.22-0.29, respectively), whereas associations with education and income were less consistent. Main effects for countries' SED showed that persons from lower SED countries reported somewhat higher relationship satisfaction (OR, 95% CI: 0.97, 0.94-0.99) and less problems with social interactions (Coeff, 95% CI: -0.04, -0.09- -0.003). Results from moderation analysis revealed that having paid work was more important for relationships in lower SED countries, while education and subjective status were more important for relationships in higher SED countries (interaction terms p<0.05)., Conclusion: Social relationships in persons with spinal cord injury are patterned according to individual SES and the countries' SED and larger socioeconomic structures partly moderate associations between individual SES and social relationships., Competing Interests: The authors have declared that no competing interests exist.

Objective: To analyze and compare how performance of the health system are linked to the self-reported quality of life (QOL) of people with spinal cord injury (SCI) in 22 countries participating in the International Spinal Cord (InSCI) community survey., Design: Cross-sectional survey., Setting: Twenty-two countries representing all 6 World Health Organization regions, community setting., Participants: Persons (N=12,591) with traumatic or nontraumatic SCI aged ≥18 years., Interventions: Not applicable., Main Outcomes: Self-reported satisfaction on several indicators that include: health, ability to perform daily activities, oneself, personal relationships, and living conditions. A total score of QOL was calculated using these 5 definitions., Results: The most important indicators for self-reported QOL of persons with SCI were social attitudes and access to health care services, followed by nursing care, access to public spaces, the provision of vocational rehabilitation, transportation, medication, and assistive devices. In general, persons with SCI living in higher-income countries reported a higher QOL than people in lower-income countries, with some exceptions. The top performing country was The Netherlands with an estimated median QOL of 66% (on a 0%-100% scale)., Conclusions: The living situation of people with SCI is highly influenced by the performance of the health system. Measuring and comparing health systems give accountability to a country's citizens, but it also helps to determine areas for improvement., (Copyright © 2020 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Persons experiencing disabilities often face difficulties to establish and maintain intimate partnerships and the decision whether to live alone or with others is often not their own to make. This study investigates whether individual and country-level characteristics predict the partnership status and the living situation of persons with spinal cord injury (SCI) from 22 countries. We used data from 12,591 participants of the International SCI Community Survey (InSCI) and regressed partnership status and living situation on individual (sociodemographic and injury characteristics) and country-level characteristics (Human Development Index, HDI) using multilevel models. Females, younger persons, those with lower income, without paid work, more severe injuries, and longer time since injury were more often single. Males, older persons, those with higher income, paid work, less severe injuries, and those from countries with higher HDI more often lived alone. This study provides initial evidence for the claim that the partnership status and the living situation of people with SCI are influenced by sociodemographic and socioeconomic factors and are not merely a matter of choice, in particular for those with severe injuries.

Pre-existing anti-adenovirus (Ad) neutralizing antibodies (AdNAbs) are a major barrier in clinical gene therapy using Ad vectors and oncolytic Ads; however, it has not been fully elucidated which Ad capsid protein-specific antibodies are involved in AdNAb-mediated inhibition of Ad infection in vivo. In this study, mice possessing antibodies specific for each Ad capsid protein were prepared by intramuscular electroporation of each Ad capsid protein-expressing plasmid. Ad vector-mediated hepatic transduction was efficiently inhibited by more than 100-fold in mice immunized with a fiber protein-expressing plasmid or a penton base-expressing plasmid. An Ad vector pre-coated with FX before administration mediated more than 100-fold lower transduction efficiencies in the liver of warfarinized mice immunized with a fiber protein-expressing plasmid or a penton base-expressing plasmid, compared with those in the liver of warfarinized non-immunized mice. These data suggest that anti-fiber protein and anti-penton base antibodies bind to an Ad vector even though FX has already bound to the hexon, and inhibit Ad vector-mediated transduction. This study provides important clues for the development of a novel Ad vector that can circumvent inhibition with AdNAbs.

The sensitive detection of thiols including glutathione and cysteine is desirable owing to their roles as indispensable biomolecules in maintaining intracellular biological redox homeostasis. Herein, we report the design and synthesis of SEluc-1 (sulfinate ester luciferin), a chemoselective probe exhibiting a ratiometric and turn-on response towards thiols selectively in fluorescence and bioluminescence, respectively. The probe, which was designed based on the "caged" luciferin strategy, displays excellent selectivity, high signal/noise ratio (>240 in the case of bioluminescence), and a biologically relevant limit of detection (LOD, 80 nm for cysteine), which are all desirable traits for a sensitive bioluminescent sensor. SEluc-1 was further applied to fluorescence imaging of thiol activity in living human cervical cancer HeLa cell cultures, and was successfully able to detect fluctuations in thiol concentrations induced by oxidative stress in a bioluminescent assay utilizing African green monkey fibroblast COS-7 cells and human breast adenocarcinoma MCF-7 cells., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Few current vaccines can establish antigen (Ag)-specific immune responses in both mucosal and systemic compartments. Therefore, development of vaccines providing defense against diverse infectious agents in both compartments is of high priority in global health. Intramuscular vaccination of an adenovirus vector (Adv) has been shown to induce Ag-specific cytotoxic T lymphocytes (CTLs) in both systemic and gut-mucosal compartments. We previously found that type I interferon (IFN) signaling is required for induction of gut-mucosal, but not systemic, CTLs following vaccination; however, the molecular mechanism involving type I IFN signaling remains unknown. Here, we found that T helper 17 (Th17)-polarizing cytokine expression was down-regulated in the inguinal lymph nodes (iLNs) of Ifnar2 -/- mice, resulting in the reduction of Ag-specific Th17 cells in the iLNs and gut mucosa of the mice. We also found that prior transfer of Th17 cells reversed the decrease in the number of Ag-specific gut-mucosal CTLs in Ifnar2 -/- mice following Adv vaccination. Additionally, prior transfer of Th17 cells into wild-type mice enhanced the induction of Ag-specific CTLs in the gut mucosa, but not in systemic compartments, suggesting a gut mucosa-specific mechanism where Th17 cells regulate the magnitude of vaccine-elicited Ag-specific CTL responses. These data suggest that Th17 cells translate systemic type I IFN signaling into a gut-mucosal CTL response following vaccination, which could promote the development of promising Adv vaccines capable of establishing both systemic and gut-mucosal protective immunity.

Background: Regulatory problems such as excessive crying, sleeping-and feeding difficulties in infancy are some of the earliest precursors of later mental health difficulties emerging throughout the lifespan. In the present study, the inter-rater reliability and acceptance of a structured computer-assisted diagnostic interview for regulatory problems (Baby-DIPS) was investigated., Methods: Using a community sample, 132 mothers of infants aged between 3 and 18 months (mean age = 10 months) were interviewed with the Baby-DIPS regarding current and former (combined = lifetime) regulatory problems. Severity of the symptoms was also rated. The interviews were conducted face-to-face at a psychology department at the university (51.5 %), the mother's home (23.5 %), or via telephone (25.0 %). Inter-rater reliability was assessed with Cohen's kappa (k). A sample of 48 mothers and their interviewers filled in acceptance questionnaires after the interview., Results: Good to excellent inter-rater reliability on the levels of current and lifetime regulatory problems (k = 0.77-0.98) were found. High inter-rater agreement was also found for ratings of severity (ICC = 0.86-0.97). Participants and interviewers' overall acceptance ratings of the computer-assisted interview were favourable. Acceptance scores did not differ between interviews that revealed one or more clinically relevant regulatory problem(s) compared to those that revealed no regulatory problems., Conclusions: The Baby-DIPS was found to be a reliable instrument for the assessment of current and lifetime problems in crying and sleeping behaviours. The computer-assisted version of the Baby-DIPS was well accepted by interviewers and mothers. The Baby-DIPS appears to be well-suited for research and clinical use to identify infant regulatory problems.

Adenovirus vectors (Adv) elicit innate immune responses via several pattern-recognition receptors. Although it has been suggested that various Adv-induced mechanisms play important roles in the induction of innate immunity in vitro, the impacts of these mechanisms in vivo remain unclear. Viral nucleic acids elicit innate immune responses through the recognition of cytosolic nucleic acid sensors and transduce intracellular signals to TANK-binding kinase (TBK) 1. In this study, to determine the impacts of viral nucleic acids on innate immune responses in vivo, we administered transgene-expressing Adv to Tbk1-deficient mice. The systemic Adv administration failed to induce type I interferons (type I IFNs) in the spleen, but not the liver, of Tbk1-deficient mice, resulting in the increase of transgene-expressing cells in the spleen, but not the liver. Moreover, Adv failed to induce type I IFNs in the bone-marrow-derived dendritic cells, but not the mouse embryonic fibroblasts, from Tbk1-deficient mice in vitro. These results support the idea that Adv elicit innate immunity in immune cells and non-immune cells in a TBK1-dependent and TBK1-independent manner, respectively., (© The Japanese Society for Immunology. 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Few of the vaccines in current use can induce antigen- (Ag-) specific immunity in both mucosal and systemic compartments. Hence, the development of vaccines that realize both mucosal and systemic protection against various pathogens is a high priority in global health. Recently, it has been reported that intramuscular (i.m.) vaccination of an adenovirus vector (Adv) can induce Ag-specific cytotoxic T lymphocytes (CTLs) in both systemic and gut mucosal compartments. We previously revealed that type I IFN signaling is required for the induction of gut mucosal CTLs, not systemic CTLs. However, the molecular mechanism via type I IFN signaling is largely unknown. Here, we report that type I IFN signaling following i.m. Adv vaccination is required for the expression of type I IFN in the inguinal lymph nodes (iLNs), which are the draining lymph nodes of the administration site. We also showed that the type I IFN signaling is indispensable for the early activation of CTLs in iLNs. These data suggested that type I IFN signaling has an important role in the translation of systemic innate immune response into mucosal adaptive immunity by amplifying the innate immune signaling and activating CTLs in the iLN.