Selective CO₂ capture in metal-organic frameworks with azine-functionalized pores generated by mechanosynthesis

Two new three-dimensional porous Zn(II)-based metal-organic frameworks, containing azine-functionalized pores, have been readily and quickly isolated via mechanosynthesis, by using a nonlinear dicarboxylate and linear N-donor ligands. The use of nonfunctionalized and methyl-functionalized N-donor ligands has led to the formation of frameworks with different topologies and metal-ligand connectivities and therefore different pore sizes and accessible volumes. Despite this, both metal-organic frameworks (MOFs) possess comparable BET surface areas and CO₂ uptakes at 273 and 298 K at 1 bar. The network with narrow and interconnected pores in three dimensions shows greater affinity for CO compared to the network with one-dimensional and relatively large pores-attributable to the more effective interactions with the azine groups

Genetical genomics: spotlight on QTL hotspots

No abstract available

Investigating hyper-vigilance for social threat of lonely children

The hypothesis that lonely children show hypervigilance for social threat was examined in a series of three studies that employed different methods including advanced eye-tracking technology. Hypervigilance for social threat was operationalized as hostility to ambiguously motivated social exclusion in a variation of the hostile attribution paradigm (Study 1), scores on the Children’s Rejection-Sensitivity Questionnaire (Study 2), and visual attention to socially rejecting stimuli (Study 3). The participants were 185 children (11 years-7 months to 12 years-6 months), 248 children (9 years-4 months to 11 years-8 months) and 140 children (8 years-10 months to 12 years-10 months) in the three studies, respectively. Regression analyses showed that, with depressive symptoms covaried, there were quadratic relations between loneliness and these different measures of hypervigilance to social threat. As hypothesized, only children in the upper range of loneliness demonstrated elevated hostility to ambiguously motivated social exclusion, higher scores on the rejection sensitivity questionnaire, and disengagement difficulties when viewing socially rejecting stimuli. We found that very lonely children are hypersensitive to social threat

Roles for Treg expansion and HMGB1 signaling through the TLR1-2-6 axis in determining the magnitude of the antigen-specific immune response to MVA85A

© 2013 Matsumiya et al. This 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 creditedA better understanding of the relationships between vaccine, immunogenicity and protection from disease would greatly facilitate vaccine development. Modified vaccinia virus Ankara expressing antigen 85A (MVA85A) is a novel tuberculosis vaccine candidate designed to enhance responses induced by BCG. Antigen-specific interferon-γ (IFN-γ) production is greatly enhanced by MVA85A, however the variability between healthy individuals is extensive. In this study we have sought to characterize the early changes in gene expression in humans following vaccination with MVA85A and relate these to long-term immunogenicity. Two days post-vaccination, MVA85A induces a strong interferon and inflammatory response. Separating volunteers into high and low responders on the basis of T cell responses to 85A peptides measured during the trial, an expansion of circulating CD4+ CD25+ Foxp3+ cells is seen in low but not high responders. Additionally, high levels of Toll-like Receptor (TLR) 1 on day of vaccination are associated with an increased response to antigen 85A. In a classification model, combined expression levels of TLR1, TICAM2 and CD14 on day of vaccination and CTLA4 and IL2Rα two days post-vaccination can classify high and low responders with over 80% accuracy. Furthermore, administering MVA85A in mice with anti-TLR2 antibodies may abrogate high responses, and neutralising antibodies to TLRs 1, 2 or 6 or HMGB1 decrease CXCL2 production during in vitro stimulation with MVA85A. HMGB1 is released into the supernatant following atimulation with MVA85A and we propose this signal may be the trigger activating the TLR pathway. This study suggests an important role for an endogenous ligand in innate sensing of MVA and demonstrates the importance of pattern recognition receptors and regulatory T cell responses in determining the magnitude of the antigen specific immune response to vaccination with MVA85A in humans.This work was funded by the Wellcome Trust. MM has a Wellcome Trust PhD studentship and HM is a Wellcome Trust Senior Fello

Evaluation of the current knowledge limitations in breast cancer research: a gap analysis

BACKGROUND A gap analysis was conducted to determine which areas of breast cancer research, if targeted by researchers and funding bodies, could produce the greatest impact on patients. METHODS Fifty-six Breast Cancer Campaign grant holders and prominent UK breast cancer researchers participated in a gap analysis of current breast cancer research. Before, during and following the meeting, groups in seven key research areas participated in cycles of presentation, literature review and discussion. Summary papers were prepared by each group and collated into this position paper highlighting the research gaps, with recommendations for action. RESULTS Gaps were identified in all seven themes. General barriers to progress were lack of financial and practical resources, and poor collaboration between disciplines. Critical gaps in each theme included: (1) genetics (knowledge of genetic changes, their effects and interactions); (2) initiation of breast cancer (how developmental signalling pathways cause ductal elongation and branching at the cellular level and influence stem cell dynamics, and how their disruption initiates tumour formation); (3) progression of breast cancer (deciphering the intracellular and extracellular regulators of early progression, tumour growth, angiogenesis and metastasis); (4) therapies and targets (understanding who develops advanced disease); (5) disease markers (incorporating intelligent trial design into all studies to ensure new treatments are tested in patient groups stratified using biomarkers); (6) prevention (strategies to prevent oestrogen-receptor negative tumours and the long-term effects of chemoprevention for oestrogen-receptor positive tumours); (7) psychosocial aspects of cancer (the use of appropriate psychosocial interventions, and the personal impact of all stages of the disease among patients from a range of ethnic and demographic backgrounds). CONCLUSION Through recommendations to address these gaps with future research, the long-term benefits to patients will include: better estimation of risk in families with breast cancer and strategies to reduce risk; better prediction of drug response and patient prognosis; improved tailoring of treatments to patient subgroups and development of new therapeutic approaches; earlier initiation of treatment; more effective use of resources for screening populations; and an enhanced experience for people with or at risk of breast cancer and their families. The challenge to funding bodies and researchers in all disciplines is to focus on these gaps and to drive advances in knowledge into improvements in patient care

Contemporary Asian Artistic Expressions and Tourism – An Introduction

This introductory chapter presents and critically discusses the various themes underpinning this book. Firstly, it provides an examination of the notion of ‘contemporary art’, including an overview of the existing definitions and debates in the current literature. Secondly, this chapter discusses the nexus between tourism and contemporary art by providing an overview of the past studies conducted on cultural and heritage tourism. In this section, the various themes underpinning the different parts of the literature on art tourism (e.g. identity, authenticity, commoditisation and capitalism) are considered. Thirdly, a discussion on the relationship between tourism and Asian contemporary art is presented, which also includes a part problematising and questioning terms like ‘Asia’ and ‘Asian art’. Finally, an overview of the different chapters that constitute the backbone of this collection is offered alongside the four themes around which the book is structured

Immune-Complex Mimics as a Molecular Platform for Adjuvant-Free Vaccine Delivery

Protein-based vaccine development faces the difficult challenge of finding robust yet non-toxic adjuvants suitable for humans. Here, using a molecular engineering approach, we have developed a molecular platform for generating self-adjuvanting immunogens that do not depend on exogenous adjuvants for induction of immune responses. These are based on the concept of Immune Complex Mimics (ICM), structures that are formed between an oligomeric antigen and a monoclonal antibody (mAb) to that antigen. In this way, the roles of antigens and antibodies within the structure of immune complexes are reversed, so that a single monoclonal antibody, rather than polyclonal sera or expensive mAb cocktails can be used. We tested this approach in the context of Mycobacterium tuberculosis (MTB) infection by linking the highly immunogenic and potentially protective Ag85B with the oligomeric Acr (alpha crystallin, HspX) antigen. When combined with an anti-Acr monoclonal antibody, the fusion protein formed ICM which bound to C1q component of the complement system and were readily taken up by antigen-presenting cells in vitro. ICM induced a strong Th1/Th2 mixed type antibody response, which was comparable to cholera toxin adjuvanted antigen, but only moderate levels of T cell proliferation and IFN-γ secretion. Unfortunately, the systemic administration of ICM did not confer statistically significant protection against intranasal MTB challenge, although a small BCG-boosting effect was observed. We conclude that ICM are capable of inducing strong humoral responses to incorporated antigens and may be a suitable vaccination approach for pathogens other than MTB, where antibody-based immunity may play a more protective role

Design and Rationale of the Fontan Udenafil Exercise Longitudinal (FUEL) Trial

The Fontan operation creates a circulation characterized by elevated central venous pressure and low cardiac output. Over time, these characteristics result in a predictable and persistent decline in exercise performance that is associated with an increase in morbidity and mortality. A medical therapy that targets the abnormalities of the Fontan circulation might, therefore, be associated with improved outcomes. Udenafil, a phosphodiesterase type 5 inhibitor, has undergone phase I/II testing in adolescents who have had the Fontan operation and has been shown to be safe and well tolerated in the short-term. However, there are no data regarding the long-term efficacy of udenafil in this population. The Fontan Udenafil Exercise Longitudinal (FUEL) Trial is a randomized, double blind, placebo controlled phase III clinical trial being conducted by the Pediatric Heart Network in collaboration with Mezzion Pharma Co., Ltd. This trial is designed to test the hypothesis that treatment with udenafil will lead to an improvement in exercise capacity in adolescents who have undergone the Fontan operation. A safety extension trial, the FUEL Open-Label Extension Trial (FUEL OLE), offers the opportunity for all FUEL subjects to obtain open-label udenafil for an additional 12 months following completion of FUEL, and evaluates the long-term safety and tolerability of this medication. This manuscript describes the rationale and study design for FUEL and FUEL OLE. Together, these trials provide an opportunity to better understand the role of medical management in the care of those who have undergone the Fontan operation

Challenges of rapid migration to fully virtual education in the age of the Corona virus pandemic: experiences from across the world

The social disruption caused by the sudden eruption of the Corona Virus pandemic has shaken the whole world, influencing all levels of education immensely. Notwithstanding there was a lack of preparedness for this global public health emergency which continues to affect all aspects of work and life. The problem is, naturally, multifaceted, fast evolving and complex, affecting everyone, threatening our well-being, the global economy, the environment and all societal and cultural norms and our everyday activities. In a recent UNESCO report it is noted that nearly a billion and a quarter (which is 67,7 % of the total number) of learners have been affected by the Corona Virus pandemic worldwide. The education sector at all levels has been one of the hardest hit sectors particularly as the academic/school year was in full swing. The impact of the pandemic is widespread, representing a health hazard worldwide. Being such, it profoundly affects society as a whole, and its members that are, in particular, i) individuals (the learners, their parents, educators, support staff), ii) schools, training organisations, pedagogical institutions and education systems, iii) quickly transformed policies, methods and pedagogies to serve the newly appeared needs of the latter. Lengthy developments of such scale usually take years of consultation, strategic planning and implementation. In addition to raising awareness across the population of the dangers of the virus transmission and instigating total lockdown, it has been necessary to develop mechanisms for continuing the delivery of education as well as demanding mechanisms for assuring the quality of the educational experience and educational results. There is often scepticism about securing quality standards in such a fast moving situation. Often in the recent past, the perception was that courses and degrees leading to an award are inferior if the course modules (and sometimes its assessment components) were wholly online. Over the last three decades most Higher Education institutions developed both considerable infrastructure and knowhow enabling distance mode delivery schools (Primary and Secondary) had hardly any necessary infrastructure nor adequate knowhow for enabling virtual education. In addition, community education and various training providers were mainly delivered face-to-face and that had to either stop altogether or rapidly convert materials, exercises and tests for online delivery and testing. A high degree of flexibility and commitment was demanded of all involved and particularly from the educators, who undertook to produce new educational materials in order to provide online support to pupils and students. Apart from the delivery mode of education, which is serving for certificated programmes, it is essential to ensure that learners’ needs are thoroughly and continuously addressed and are efficiently supported throughout the Coronavirus or any other future lockdown. The latter can be originated by various causes and reasons that vary in nature, such as natural or socioeconomical. Readiness, thus, in addition to preparedness, is the primary key question and solution when it comes to quality education for any lockdown. In most countries, the compulsory primary and secondary education sectors have been facing a more difficult challenge than that faced by Higher Education. The poor or in many cases non-existent technological infrastructure and low technological expertise of the teachers, instructors and parents, make the delivery of virtual education difficult or even impossible. The latter, coupled with phenomena such as social exclusion and digital divide where thousands of households do not have adequate access to broadband Internet, Wi-Fi infrastructure and personal computers hamper the promising and strenuous virtual solutions. The shockwaves of the sudden demands on all sectors of society and on individuals required rapid decisions and actions. We will not attempt to answer the question “Why was the world unprepared for the onslaught of the Coronavirus pandemic” but need to ascertain the level of preparedness and readiness particularly of the education sector, to effect the required rapid transition. We aimed to identify the challenges, and problems faced by the educators and their institutions. Through first-hand experiences we also identify best practices and solutions reached. Thus we constructed a questionnaire to gather our own responses but also experiences from colleagues and members of our environment, family, friends, and colleagues. This paper reports the first-hand experiences and knowledge of 33 co-authors from 27 institutions and from 13 different countries from Europe, Asia, and Africa. The communication technologies and development platforms used are identified; the challenges faced as well as solutions and best practices are reported. The findings are consolidated into the four areas explored i.e. Development Platforms, Communications Technologies, Challenges/Problems and Solutions/Best Practices. The conclusion summarises the findings into emerging themes and similarities. Reflections on the lasting impact of the effect of Coronavirus on education, limitations of study, and indications of future work complete the paper