Yes / Execution of lineage-specific differentiation programs requires tight coordination between many regulators including Ten-eleven translocation (TET) family enzymes, catalyzing 5-methylcytosine oxidation in DNA. Here, by using Keratin 14–Cre–driven ablation of Tet genes in skin epithelial cells, we demonstrate that ablation of Tet2/Tet3 results in marked alterations of hair shape and length followed by hair loss. We show that, through DNA demethylation, Tet2/Tet3 control chromatin accessibility and Dlx3 binding and promoter activity of the Krt25 and Krt28 genes regulating hair shape, as well as regulate interactions between the Krt28 gene promoter and distal enhancer. Moreover, Tet2/Tet3 also control three-dimensional chromatin topology in Keratin type I/II gene loci via DNA methylation–independent mechanisms. These data demonstrate the essential roles for Tet2/3 in establishment of lineage-specific gene expression program and control of Dlx3/Krt25/Krt28 axis in hair follicle epithelial cells and implicate modulation of DNA methylation as a novel approach for hair growth control. / This work was supported by the National Institutes of Health grant 5R01 AR075776 (V.A.B. and A.A.S.) and grant 5R01 AR071727 (V.A.B. and A.A.S.) and the National Science Foundation of China (G.-L.X.). / Research Development Fund Publication Prize Award winner, Dec 2022.

Yes / Carbon monoxide (CO) is both a substance hazardous to health and a side product of a number of industrial processes, such as methanol steam reforming and large-scale oxidation reactions. The separation of CO from nitrogen (N2) in industrial processes is considered to be difficult because of the similarities of their electronic structures, sizes, and physicochemical properties (e.g., boiling points). Carbon monoxide is also a major poison in fuel cells because of its adsorption onto the active sites of the catalysts. It is therefore of the utmost economic importance to discover new materials that enable effective CO capture and release under mild conditions. However, methods to specifically absorb and easily release CO in the presence of contaminants, such as water, nitrogen, carbon dioxide, and oxygen, at ambient temperature are not available. Here, we report the simple and versatile fabrication of a new class of hybrid materials that allows capture and release of carbon monoxide under mild conditions. We found that carborane-containing metal complexes encapsulated in networks made of poly(dimethylsiloxane) react with CO, even when immersed in water, leading to dramatic color and infrared signature changes. Furthermore, we found that the CO can be easily released from the materials by simply dipping the networks into an organic solvent for less than 1 min, at ambient temperature and pressure, which not only offers a straightforward recycling method, but also a new method for the “on-demand” release of carbon monoxide. We illustrated the utilization of the on-demand release of CO from the networks by carrying out a carbonylation reaction on an electron-deficient metal complex that led to the formation of the CO-adduct, with concomitant recycling of the gel. We anticipate that our sponge-like materials and scalable methodology will open up new avenues for the storage, transport, and controlled release of CO, the silent killer and a major industrial poison. / The Royal Society, The Romanian Ministry of Education and Research, The University of Bradford, European Regional Development Fund of the European Union / Research Development Fund Publication Prize Award winner.

Yes / Cocrystals consist of two molecules bonded together in a single crystal lattice giving rise to wide applications including improving solubility of poorly soluble pharmaceuticals. Cocrystallization reaction occurs in the oily phase of liquid–liquid phase separation (LLPS) after it is mixed with coformers. Indomethacin–saccharin cocrystal formation was monitored in situ, and the kinetics of crystallization were determined. The crystallization rates show that the process can be proposed to prevent unwanted oily phase formation during LLPS. / Research Development Fund Publication Prize Award winner, Sep 2022.

Yes / Beneficial effects have been observed following the transplant of lipoaspirates containing adipose-derived stem cells into chronic wounds caused by oncologic radiotherapy. It is not yet certain whether adipose-derived stem cells are resistant to radiation exposure. Therefore, the aims of this study were to isolate stromal vascular fraction from human breast tissue exposed to radiotherapy and determine the presence of adipose-derived stem cells. Stromal vascular fraction from irradiated donor tissue was compared to commercially sourced pre-adipocytes. Immunocytochemistry was used to determine the presence of adipose-derived stem cell markers. Conditioned media from stromal vascular fraction isolated from irradiated donors was used as a treatment in a scratch wound assay of dermal fibroblasts also isolated from irradiated donors and compared to pre-adipocyte conditioned media and serum free control. This is the first report of human stromal vascular fraction being cultured from previously irradiated breast tissue. Stromal vascular fraction conditioned media from irradiated donors had a similar effect in increasing the migration of dermal fibroblasts from irradiated skin to pre-adipocyte conditioned media from healthy donors. Therefore, the ability of adipose-derived stem cells in the stromal vascular fraction to stimulate dermal fibroblasts in wound healing appears to be preserved following radiotherapy. This study demonstrates that stromal vascular fraction from irradiated patients is viable, functional and may have potential for regenerative medicine techniques following radiotherapy. / This research was funded by a Bradford City FC Supporters Fellowship for L.V.T. administered through the Plastic Surgery and Burns Research Unit, University of Bradford. / Research Development Fund Publication Prize Award winner, Mar 2023.

Yes / Care after the death of a child and support of their bereaved family is an important element of the services offered by children’s hospices in the United Kingdom. The study aims to explore the emotional challenges of those delivering care to families of children in hospice cool rooms. An internet-based questionnaire was sent to all practitioners to explore their perspectives of providing care to bereaved families whilst the child’s body was in the hospice, as well as caring for a child’s body after death. In total, 94.9% (n=56) of staff responded. Two key themes were identified that represent the emotional challenges perceived by staff: the impact of deterioration of a child’s body; and witnessing the acute grief of families. Practitioners seek to provide care that recognises the importance of family and demonstrates family-centred care, as well as supporting families to deal with the changes that occur after death. Organisations can support practitioners to deliver care in cool rooms by providing training and education on anticipating and managing the pathophysiological changes that occur after death as well as training in grief and loss, and how to support a bereaved family. / Research Development Fund Publication Prize Award winner, May 2021.

Yes / The number of benzodiazepines appearing as new psychoactive substances (NPS) is continually increasing. Information about the pharmacological parameters of these compounds is required to fully understand their potential effects and harms. One parameter that has yet to be described is the blood-to-plasma ratio. Knowledge of the pharmacodynamics of designer benzodiazepines is also important, and the use of quantitative structure–activity relationship (QSAR) modelling provides a fast and inexpensive method of predicting binding affinity to the GABAA receptor. Methods: In this work, the blood-to-plasma ratios for six designer benzodiazepines (deschloroetizolam, diclazepam, etizolam, meclonazepam, phenazepam, and pyrazolam) were determined. A previously developed QSAR model was used to predict the binding affinity of nine designer benzodiazepines that have recently appeared. Results: Blood-to-plasma values ranged from 0.57 for phenazepam to 1.18 to pyrazolam. Four designer benzodiazepines appearing since 2017 (fluclotizolam, difludiazepam, flualprazolam, and clobromazolam) had predicted binding affinities to the GABAA receptor that were greater than previously predicted binding affinities for other designer benzodiazepines. Conclusions: This work highlights the diverse nature of the designer benzodiazepines and adds to our understanding of their pharmacology. The greater predicted binding affinities are a potential indication of the increasing potency of designer benzodiazepines appearing on the illicit drugs market. / Engineering and Physical Sciences Research Council. / Research Development Fund Publication Prize Award winner, Feb 2022.

Yes / Anticholinergic medicines are associated with adverse outcomes for older people. However, little is known about their use in frailty. The objectives were to (1) investigate the prevalence of anticholinergic prescribing for older patients, and (2) examine anticholinergic burden according to frailty status. Methods: Cross-sectional analysis of Welsh primary care data from the Secure Anonymised Information Linkage (SAIL) databank including patients aged ≥65 at their first GP consultation between 1st January and 31st December 2018. Frailty was identified using the electronic Frailty Index (eFI) and anticholinergic burden using the Anticholinergic Cognitive Burden (ACB) scale. Descriptive analysis and logistic regression were conducted to 1) describe the type and frequency of anticholinergics prescribed; 2) to estimate the association between frailty and cumulative ACB score (ACB-Sum). Results: In this study of 529,095 patients, 47.4% of patients receiving any prescription medications were prescribed at least one anticholinergic medicine. Adjusted regression analysis showed that patients with increasing frailty had higher odds of having an ACB-Sum of >3 compared to patients who were fit (mild frailty, adj OR 1.062 (95%CI 1.061–1.064), moderate frailty, adj OR 1.134 (95%CI 1.131–1.136), severe frailty, adj OR 1.208 (95%CI 1.203–1.213)). Conclusions: Anticholinergic prescribing was high in this older population. Older people with advancing frailty are exposed to the highest anticholinergic burden despite being the most vulnerable to the associated adverse effects. Older people with advancing frailty should be considered for medicines review to prevent overaccumulation of anticholinergic medications given the risks of functional and cognitive decline that frailty presents. / NIHR / Research Development Fund Publication Prize Award winner, May 2023.

This report includes my translation of the short story “Tread on a Snake” (Hebi o Fumu) by Kawakami Hiromi, which is presented here as a significant contribution to modern Japanese literature in translation. The story received the prestigious Akutagawa Prize in 1996, although support for it was not unanimous as seen in my translation of the judges’ comments offered here as well. Following the translation of the story itself is an essay that discusses my personal experiences translating the story. I discuss elements that may be unique to the experience of translating Kawakami’s works, but also many that are applicable more broadly to issues of translation that go beyond her works and even Japanese literature as well. Challenges included maintaining the author’s tone and voice, the appropriate use of notes to provide cultural background, and the deliberate use of non-translated terms in a translation. / text

The images of Japanese women in the Japanese contemporary literature (1935-1975) — Short-stories crowned with the Akutagawa Prize Japanese women carry with them the myth to be Japanese. But is it a reality? How were their lives before the Second World War, after it and during the economic growth until 1975? Were they unhappy submitted to this myth? I try to present the contemporary history of Japanese women through a research on the short-stories crowned with the Akutagawa Prize from 1935 to 1975. These short-stories are autobiographic, journalistic or documentary, and they are a true reflection of their time. Also, the female characters give witness of Japanese women’s lives in each period through literature, that is the most active, direct, touching and understandable form for the reader. Thus, I intend to contribute to a larger understanding of the Japanese society and culture. The first chapter is devoted to the period of war between 1935 and 1945. And the second chapter is about the period of rapid economic upturn, starting with the ruins and famine of the post-war years from 1945 to 1955. Indeed, the post-war years end in 1955 in Japan. Then, the third chapter is about the dazzling economic growth between 1955 and 1970. And finally in the fourth chapter, during the period going from 1970 to 1975, most Japanese people think they are now out of misery, being part of the middle class and happy about the situation. In total, I examine 57 short-stories : 18 in the first chapter, 10 in the second chapter, 21 in the third chapter, and 8 in the fourth chapter. Also, there are 112 female characters to analyse in all : 41 in the fist chapter, 18 in the second chapter, 33 in the third chapter and 20 in the fourth chapter. Through the evolution and changes along this period of time, the lives of our heroines change too. First, they are kept under the strict respect of social rules. And during the war, they suffer from poverty and misery. Then, the time comes for the share of tasks between women and men. From then on, women take mostly care of their homes. Besides, let us note that the importance of the education of girls is continuously stressed, even if the main aim is to make them “good wives and good mothers”. Finally, Japanese women’s morale stays intact during the period chosen for our research. A significant change seems to happen thereafter. / Images de femmes dans la littérature japonaise contemporaine (1935-1975) — cas des nouvelles couronnées par le prix Akutagawa Les Japonaises portent en elles le mythe de la Japonaise. Mais est-ce une réalité ? Quelle était leur vie pendant la période de l’avant-guerre, de l’après-guerre et de la croissance économique jusqu’en 1975 ? Étaient-elles malheureuses en étant soumises à ce mythe ? Nous avons tenté de transcrire l’histoire contemporaine des Japonaises à travers une recherche sur les nouvelles couronnées par le prix Akutagawa entre 1935 et 1975. Les œuvres sont autobiographiques, journalistiques ou documentaires, ancrées dans chaque époque et leurs personnages féminins témoignent des vies des Japonaises de leur temps sous forme littéraire, c’est-à-dire la forme la plus active, la plus directe, la plus touchante et la plus compréhensive pour le lecteur. Ainsi contribuons-nous à la compréhension de la société et de la culture japonaises. Le premier chapitre est consacré à la période de la guerre entre 1935 et 1945. Le deuxième chapitre concerne l’époque de la remontée économique rapide, partant des ruines et de la famine de l’après-guerre entre 1945 et 1955. En effet, 1955 marque la fin de l’après-guerre au Japon. Le troisième chapitre porte sur l’époque de la croissance économique fleurissante entre 1955 et 1970. Et le dernier et quatrième chapitre parcourt la période entre 1970 et 1975. C’est la période où quasiment tous les Japonais se croient sortis de la misère, ils se considèrent appartenir à la classe moyenne et ils s’en réjouissent. Quant au nombre de nouvelles, nous analysons en tout cinquante-sept nouvelles : dix-huit œuvres dans le premier chapitre, dix dans le deuxième, vingt-et-une dans le troisième et huit dans le quatrième. Et nous comptons au total cent-douze personnages féminins à étudier, soit quarante-et-un dans le premier chapitre, dix-huit dans le deuxième, trente-trois dans le troisième et vingt dans le quatrième. À travers l'évolution et les bouleversements dans le temps, les vies de nos héroïnes se modifient. D’abord, elles vivent dans la stricte obéissance de la règle sociale. Ensuite, elles tombent dans la pauvreté et la misère à cause de la guerre. Et puis arrive le temps du partage des tâches entre les hommes et les femmes et ces dernières se retirent presque complètement dans leur foyer. Néanmoins, l’éducation des filles est renforcée régulièrement, même si la raison principale est d'en faire de « bonnes épouses et bonnes mères ». Nous remarquons que la morale des Japonaises ne se transforme pas pendant la période concernée par notre recherche. Un changement significatif semble intervenir par la suite.

Dominant market theories analyze markets as ahistorical entities without the need for professional groups that manage crucial functions within them. This thesis, in contrast, approaches markets as historical systems that develop over time and that can be constituted in many different ways because of different historical trajectories. Different professional groups managing market routines, further, are seen as a crucial part of markets. Two concepts are introduced: “market architecture”, the specific way a market is constituted at a given time; and “market technocrats”, the seemingly disinterested third party functionaries that manage routines in markets and advocate changes in market architecture. The thesis argues that market technocrats exist because of uncertainty and lack of trust between market actors, and that they are an important part of how market architectures develop over time. It presents an analytical framework for understanding market technocrats and how they interact with and develop markets. Four different aspects of market technocrats are explored: the process of establishing market technocrats in market routines; the capture of the authority of market technocrats by other market actors; the expansionistic behavior of market technocrats; and the way changes in economic theory, as an important part of how economists with technocratic authority advocate market change, can help to explain changes in markets. These aspects are explored through four empirical papers: The Market Technocracy of Import Substitution: The Role of Asymmetric Information and The Swedish Seed Association 1880–1935; Limits of Market Technocracy: Swedish Fertilizer Research and the Crisis of Objectivity 1945–1960; Central Banks, and the Pursuit of Influence, Prestige, and Legitimacy: The Creation of the Nobel Memorial Prize; and From Market Engineering to Institutional Engineering: Reform Economics in Sweden 1950–2000. The results of the papers form the basis of a hypothetical narrative of how the role of market technocrats has changed during the 20th century. This provides a roadmap for further research in the development of markets and the role of market technocrats.