High operational and environmental stability of high-mobility conjugated polymer field-effect transistors through the use of molecular additives.

Due to their low-temperature processing properties and inherent mechanical flexibility, conjugated polymer field-effect transistors (FETs) are promising candidates for enabling flexible electronic circuits and displays. Much progress has been made on materials performance; however, there remain significant concerns about operational and environmental stability, particularly in the context of applications that require a very high level of threshold voltage stability, such as active-matrix addressing of organic light-emitting diode displays. Here, we investigate the physical mechanisms behind operational and environmental degradation of high-mobility, p-type polymer FETs and demonstrate an effective route to improve device stability. We show that water incorporated in nanometre-sized voids within the polymer microstructure is the key factor in charge trapping and device degradation. By inserting molecular additives that displace water from these voids, it is possible to increase the stability as well as uniformity to a high level sufficient for demanding industrial applications.We gratefully acknowledge financial support from Innovate UK (PORSCHED project) and the Engineering and Physical Sciences Research Council though a Programme Grant (EP/M005141/1). I.N. acknowledges studentship support from FlexEnable Ltd. K.B. gratefully acknowledges financial support from the Deutsche Forschungsgemeinschaft (BR 4869/1-1). B.R., M.K.R., and J.L.B. thank the financial support from King Abdullah University of Science and Technology (KAUST), the KAUST Competitive Research Grant program, and the Office of Naval Research Global (Award N62909-15-1-2003 );This is the author accepted manuscript. The final version is available from Nature Publishing Group via https://doi.org/10.1038/nmat478

The Role of Side Chains and Hydration on Mixed Charge Transport in <i>n</i> ‐Type Polymer Films

Introducing ethylene glycol (EG) side chains to a conjugated polymer backbone is a well‐established synthetic strategy for designing organic mixed ion‐electron conductors (OMIECs). However, the impact that film swelling has on mixed conduction properties has yet to be scoped, particularly for electron‐transporting (n‐type) OMIECs. Here, the authors investigate the effect of the length of branched EG chains on mixed charge transport of n‐type OMIECs based on a naphthalene‐1,4,5,8‐tetracarboxylic‐diimide‐bithiophene backbone. Atomic force microscopy (AFM), grazing‐incidence wide‐angle X‐ray scattering (GIWAXS), and scanning tunneling microscopy (STM) are used to establish the similarities between the common‐backbone films in dry conditions. Electrochemical quartz crystal microbalance with dissipation monitoring (EQCM‐D) and in situ GIWAXS measurements reveal stark changes in film swelling properties and microstructure during electrochemical doping, depending on the side chain length. It is found that even in the loss of the crystallite content upon contact with the aqueous electrolyte, the films can effectively transport charges and that it is rather the high water content that harms the electronic interconnectivity within the OMIEC films. These results highlight the importance of controlling water uptake in the films to impede charge transport in n‐type electrochemical devices

Polaron spin dynamics in high-mobility polymeric semiconductors

Polymeric semiconductors exhibit exceptionally long spin lifetimes, and recently observed micrometre spin diffusion lengths in conjugated polymers demonstrate the potential for organic spintronics devices. Weak spin–orbit and hyperfine interactions lie at the origin of their long spin lifetimes, but the coupling mechanism of a spin to its environment remains elusive. Here, we present a systematic study of polaron spin lifetimes in field-effect transistors with high-mobility conjugated polymers as an active layer. We demonstrate how spin relaxation is governed by the charges’ hopping motion at low temperatures, whereas an Elliott–Yafet-like relaxation due to a transient localization of the carrier wavefunctions is responsible for spin relaxation at high temperatures. In this regime, charge, spin and structural dynamics are intimately related and depend sensitively on the local conformation of polymer backbones and the crystalline packing of the polymer chains.* ERC Synergy grant SC2 (no. 610115) * Alexander von Humboldt Foundation * Transregional Collaborative Research Center (SFB/TRR) 173 SPIN+X * Winton Programme for the Physics of Sustainability * Engineering and Physical Sciences Research Council (EPSRC) * Excellence Initiative by the Graduate School Materials Science in Mainz (GSC 266) * European Commission/Région Wallonne (FEDER–BIORGEL project), the Consortium des Équipements de Calcul Intensif (CÉCI), funded by the Fonds National de la Recherche Scientifique (FRS-FNRS) under grant no. 2.5020.11 * Tier-1 supercomputer of the Fédération Wallonie-Bruxelles, infrastructure funded by the Walloon Region under grant agreement n111754

Durabilité de la culture cotonnière selon l'utilisation des insecticides : cas du Togo de 1991-2010

Dans la perception des profanes, le coton est encore associé à la culture consommant le plus d'insecticides néfastes pour la santé et l'environnement. Une telle mauvaise image n'est plus méritée selon une étude internationale, mais les pays producteurs ont peu analysé et informé sur l'évolution de l'utilisation d'insecticides. Cette communication comble la lacune dans le cas du Togo. L'étude est basée sur la reconstitution des séries de données des surfaces emblavées et d'insecticides distribués aux producteurs de coton du Togo, de 1990 à 2010. Les données sur les insecticides concernent les volumes distribués ainsi que leurs compositions en matières actives, permettant ainsi de déduire la consommation de matières actives par hectare. Par ailleurs, les charges toxicologiques vis-à-vis de divers éléments de la faune ont été calculées à partir des indices d'écotoxicité établis par la FAO pour chaque matière active. La consommation de matières actives insecticides au Togo a chuté régulièrement jusqu'à un litre/hectare, du même niveau que l'Australie qui recourt par ailleurs aux variétés génétiquement modifiées. La charge toxicologique, pesant sur l'homme mais aussi sur divers éléments de la faune comme les abeilles ou les daphnés des cours d'eau, a diminué quoique de manière moins régulière. Cette évolution est la conséquence d'une protection limitée depuis trois décennies à moins de six traitements et de l'adoption de nouvelles générations de molécules insecticides. Au Togo, l'utilisation des insecticides dans la culture cotonnière a évolué dans une direction plus compatible avec le souci de la santé humaine et de la préservation de l'environnement, mais cette évolution est extrapolable à tous les pays cotonniers de l'Afrique francophone. Il convient de poursuivre l'évolution engagée dans les décisions relatives aux insecticides à commander, en s'inspirant des indicateurs utilisés dans cette étude. (Résumé d'auteur

REV1 restrains DNA polymerase ζ to ensure frame fidelity during translesion synthesis of UV photoproducts in vivo

Exposure to ultraviolet light induces a number of forms of damage in DNA, of which (6–4) photoproducts present the most formidable challenge to DNA replication. No single DNA polymerase has been shown to bypass these lesions efficiently in vitro suggesting that the coordinate use of a number of different enzymes is required in vivo. To further understand the mechanisms and control of lesion bypass in vivo, we have devised a plasmid-based system to study the replication of site-specific T–T(6–4) photoproducts in chicken DT40 cells. We show that DNA polymerase ζ is absolutely required for translesion synthesis (TLS) of this lesion, while loss of DNA polymerase η has no detectable effect. We also show that either the polymerase-binding domain of REV1 or ubiquitinated PCNA is required for the recruitment of Polζ as the catalytic TLS polymerase. Finally, we demonstrate a previously unappreciated role for REV1 in ensuring bypass synthesis remains in frame with the template. Our data therefore suggest that REV1 not only helps to coordinate the delivery of DNA polymerase ζ to a stalled primer terminus but also restrains its activity to ensure that nucleotides are incorporated in register with the template strand

A phase I trial of antibody directed enzyme prodrug therapy (ADEPT) in patients with advanced colorectal carcinoma or other CEA producing tumours

Antibody-directed enzyme prodrug therapy is a targeted therapy in which a prodrug is activated selectively at the tumour site by an enzyme, which has been targeted to the tumour by an antibody (antibody-enzyme conjugate). Previous clinical trials have shown evidence of tumour response, however, the activated drug had a long half-life, which resulted in dose-limiting myelosuppression. Also, the targeting system, although giving high tumour to blood ratios of antibody-enzyme conjugate (10 000 : 1) required administration of a clearing antibody in addition to the antibody-enzyme conjugate. The purpose of this current study therefore was to attempt tumour targeting of the antibody-enzyme conjugate without the clearing antibody, and to investigate a new prodrug (bis-iodo phenol mustard, ZD2767P) whose activated form is highly potent and has a short half-life. Twenty-seven patients were treated with antibody-directed enzyme prodrug therapy using A5CP antibody-enzyme conjugate and ZD2767P prodrug, in a dose-escalating phase I trial. The maximum tolerated dose of ZD2767P was reached at 15.5 mg m−2×three administrations with a serum carboxypeptidase G2 level of 0.05 U ml−1. Myelosuppression limited dose escalation. Other toxicities were mild. Patients' quality of life was not adversely affected during the trial as assessed by the measures used. There were no clinical or radiological responses seen in the study, but three patients had stable disease at day 56. Human anti-mouse antibody and human anti-carboxypeptidase G2 antibody were produced in response to the antibody enzyme conjugate (A5CP). The antibody-enzyme conjugate localisation data (carboxypeptidase G2 enzyme levels by HPLC on tumour and normal tissue samples, and gamma camera analysis of I-131 radiolabelled conjugate) are consistent with inadequate tumour localisation (median tumour: normal tissue ratios of antibody-enzyme conjugate of less than 1). A clearance system is therefore desirable with this antibody-enzyme conjugate or a more efficient targeting system is required. ZD2767P was shown to clear rapidly from the circulation and activated drug was not measurable in the blood. ZD2767P has potential for use in future antibody-directed enzyme prodrug therapy systems

Effect of CGRP and sumatriptan on the BOLD response in visual cortex

To test the hypothesis that calcitonin gene-related peptide (CGRP) modulates brain activity, we investigated the effect of intravenous CGRP on brain activity in response to a visual stimulus. In addition, we examined if possible alteration in brain activity was reversed by the anti-migraine drug sumatriptan. Eighteen healthy volunteers were randomly allocated to receive CGRP infusion (1.5 μg/min for 20 min) or placebo. In vivo activity in the visual cortex was recorded before, during and after infusion and after 6 mg subcutaneous sumatriptan by functional magnetic resonance imaging (3 T). 77% of the participants reported headache after CGRP. We found no changes in brain activity after CGRP (P = 0.12) or after placebo (P = 0.41). Sumatriptan did not affect brain activity after CGRP (P = 0.71) or after placebo (P = 0.98). Systemic CGRP or sumatriptan has no direct effects on the BOLD activity in visual cortex. This suggests that in healthy volunteers both CGRP and sumatriptan may exert their actions outside of the blood–brain barrier

The need for multidisciplinarity in specialist training to optimize future patient care

Harmonious interactions between radiation, medical, interventional and surgical oncologists, as well as other members of multidisciplinary teams, are essential for the optimization of patient care in oncology. This multidisciplinary approach is particularly important in the current landscape, in which standard-of-care approaches to cancer treatment are evolving towards highly targeted treatments, precise image guidance and personalized cancer therapy. Herein, we highlight the importance of multidisciplinarity and interdisciplinarity at all levels of clinical oncology training. Potential deficits in the current career development pathways and suggested strategies to broaden clinical training and research are presented, with specific emphasis on the merits of trainee involvement in functional multidisciplinary teams. Finally, the importance of training in multidisciplinary research is discussed, with the expectation that this awareness will yield the most fertile ground for future discoveries. Our key message is for cancer professionals to fulfil their duty in ensuring that trainees appreciate the importance of multidisciplinary research and practice

Corporate Governance for Sustainability

The current model of corporate governance needs reform. There is mounting evidence that the practices of shareholder primacy drive company directors and executives to adopt the same short time horizon as financial markets. Pressure to meet the demands of the financial markets drives stock buybacks, excessive dividends and a failure to invest in productive capabilities. The result is a ‘tragedy of the horizon’, with corporations and their shareholders failing to consider environmental, social or even their own, long-term, economic sustainability. With less than a decade left to address the threat of climate change, and with consensus emerging that businesses need to be held accountable for their contribution, it is time to act and reform corporate governance in the EU. The statement puts forward specific recommendations to clarify the obligations of company boards and directors and make corporate governance practice significantly more sustainable and focused on the long term