Short contacts between chains enhancing luminescence quantum yields and carrier mobilities in conjugated copolymers

Abstract: Efficient conjugated polymer optoelectronic devices benefit from concomitantly high luminescence and high charge carrier mobility. This is difficult to achieve, as interchain interactions, which are needed to ensure efficient charge transport, tend also to reduce radiative recombination and lead to solid-state quenching effects. Many studies detail strategies for reducing these interactions to increase luminescence, or modifying chain packing motifs to improve percolation charge transport; however achieving these properties together has proved elusive. Here, we show that properly designed amorphous donor-alt-acceptor conjugated polymers can circumvent this problem; combining a tuneable energy gap, fast radiative recombination rates and luminescence quantum efficiencies >15% with high carrier mobilities exceeding 2.4 cm2/Vs. We use photoluminescence from exciton states pinned to close-crossing points to study the interplay between mobility and luminescence. These materials show promise towards realising advanced optoelectronic devices based on conjugated polymers, including electrically-driven polymer lasers

Exploring Self-Repair in a Coupled Spiking Astrocyte Neural Network

It is now known that astrocytes modulate the activity at the tripartite synapses where indirect signaling via the retrograde messengers, endocannabinoids, leads to a localized self-repairing capability. In this paper, a self-repairing spiking astrocyte neural network (SANN) is proposed to demonstrate a distributed self-repairing capability at the network level. The SANN uses a novel learning rule that combines the spike-timing-dependent plasticity (STDP) and Bienenstock, Cooper, and Munro (BCM) learning rules (hereafter referred to as the BSTDP rule). In this learning rule, the synaptic weight potentiation is not only driven by the temporal difference between the presynaptic and postsynaptic neuron firing times but also by the postsynaptic neuron activity. We will show in this paper that the BSTDP modulates the height of the plasticity window to establish an input-output mapping (in the learning phase) and also maintains this mapping (via self-repair) if synaptic pathways become dysfunctional. It is the functional dependence of postsynaptic neuron firing activity on the height of the plasticity window that underpins how the proposed SANN self-repairs on the fly. The SANN also uses the coupling between the tripartite synapses and γ -GABAergic interneurons. This interaction gives rise to a presynaptic neuron frequency filtering capability that serves to route information, represented as spike trains, to different neurons in the subsequent layers of the SANN. The proposed SANN follows a feedforward architecture with multiple interneuron pathways and astrocytes modulate synaptic activity at the hidden and output neuronal layers. The self-repairing capability will be demonstrated in a robotic obstacle avoidance application, and the simulation results will show that the SANN can maintain learned maneuvers at synaptic fault densities of up to 80% regardless of the fault locations

Immuno-informatics analysis predicts B and T cell consensus epitopes for designing peptide vaccine against SARS-CoV-2 with 99.82% global population coverage.

The current global pandemic due to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has taken a substantial number of lives across the world. Although few vaccines have been rolled-out, a number of vaccine candidates are still under clinical trials at various pharmaceutical companies and laboratories around the world. Considering the intrinsic nature of viruses in mutating and evolving over time, persistent efforts are needed to develop better vaccine candidates. In this study, various immuno-informatics tools and bioinformatics databases were deployed to derive consensus B-cell and T-cell epitope sequences of SARS-CoV-2 spike glycoprotein. This approach has identified four potential epitopes which have the capability to initiate both antibody and cell-mediated immune responses, are non-allergenic and do not trigger autoimmunity. These peptide sequences were also evaluated to show 99.82% of global population coverage based on the genotypic frequencies of HLA binding alleles for both MHC class-I and class-II and are unique for SARS-CoV-2 isolated from human as a host species. Epitope number 2 alone had a global population coverage of 98.2%. Therefore, we further validated binding and interaction of its constituent T-cell epitopes with their corresponding HLA proteins using molecular docking and molecular dynamics simulation experiments, followed by binding free energy calculations with molecular mechanics Poisson-Boltzmann surface area, essential dynamics analysis and free energy landscape analysis. The immuno-informatics pipeline described and the candidate epitopes discovered herein could have significant impact upon efforts to develop globally effective SARS-CoV-2 vaccines

Chasing the ‘Killer’ Phonon Mode for the Rational Design of Low Disorder, High Mobility Molecular Semiconductors

Molecular vibrations play a critical role in the charge transport properties of weakly van der Waals bonded organic semiconductors. To understand which specific phonon modes contribute most strongly to the electron – phonon coupling and ensuing thermal energetic disorder in some of the most widely studied high mobility molecular semiconductors, we have combined state-of-the-art quantum mechanical simulations of the vibrational modes and the ensuing electron phonon coupling constants with experimental measurements of the low-frequency vibrations using inelastic neutron scattering and terahertz time-domain spectroscopy. In this way we have been able to identify the long-axis sliding motion as a ‘killer’ phonon mode, which in some molecules contributes more than 80% to the total thermal disorder. Based on this insight, we propose a way to rationalize mobility trends between different materials and derive important molecular design guidelines for new high mobility molecular semiconductors.Royal Society German Research Foundation European Research Council Engineering and Physical Sciences Research Council ARCHER UK National Supercomputing Service Belgian National Fund for Scientific Research Leverhulme Trust Wiener-Anspach Foundation Belgian Walloon Region GENCI-CINES/IDRI

Decoupling Charge Transport and Electroluminescence in a High Mobility Polymer Semiconductor.

Fluorescence enhancement of a high-mobility polymer semiconductor is achieved via energy transfer to a higher fluorescence quantum yield squaraine dye molecule on 50 ps timescales. In organic light-emitting diodes, an order of magnitude enhancement of the external quantum efficiency is observed without reduction in the charge-carrier mobility resulting in radiances of up to 5 W str(-1) m(-2) at 800 nm.We gratefully acknowledge funding from the Engineering and Physical Sciences Research Council (EPSRC) through a programme grant EP/M005143/1. We would like to thank the Doctoral Training Centre in Plastic Electronics EP/G037515/1. K. B. acknowledges financial support by the Deutsche Forschungsgemeinschaft (BR-4869/1-1). The group at Würzburg would like to acknowledge support from the Deutsche Forschungsgemeinschaft (DFG Research Unit FOR 1809) and from the SolTech Initiative of the Bavarian State Ministry of Science, Research and the Arts. D. H. and K.B. would like to thank Dr. Jiři Novak and Jakub Rozbořil (Central European Institute of Technology, Masaryk University, Czech Republic) and Dr. Tom Arnold (Diamond Light Source, Didcot, UK) for assistance during the synchrotron experiment and Diamond Light Source, Didcot, UK for financial support

Histological phenotypic subtypes predict recurrence risk and response to adjuvant chemotherapy in patients with stage III colorectal cancer

Histological ‘phenotypic subtypes’ that classify patients into four groups (immune, canonical, latent and stromal) have previously been demonstrated to stratify survival in a stage I–III colorectal cancer (CRC) pilot cohort. However, clinical utility has not yet been validated. Therefore, this study assessed prognostic value of these subtypes in additional patient cohorts along with associations with risk of recurrence and response to chemotherapy. Two independent stage I–III CRC patient cohorts (internal and external cohort) were utilised to investigate phenotypic subtypes. The primary endpoint was disease‐free survival (DFS) and the secondary endpoint was recurrence risk (RR). Stage II–III patients, from the SCOT adjuvant chemotherapy trial, were utilised to further validate prognostic value and for exploratory analysis assessing associations with adjuvant chemotherapy. In an 893‐patient internal cohort, phenotypic subtype independently associated with DFS (p = 0.025) and this was attenuated in stage III patients (p = 0.020). Phenotypic subtype also independently associated with RR (p < 0.001) in these patients. In a 146‐patient external cohort, phenotypic subtype independently stratified patients by DFS (p = 0.028), validating their prognostic value. In 1343 SCOT trial patients, the effect of treatment type significantly depended on phenotypic subtype (pinteraction = 0.011). Phenotypic subtype independently associated with DFS in stage III patients receiving FOLFOX (p = 0.028). Furthermore, the immune subtype significantly associated with better response to FOLFOX compared to CAPOX adjuvant chemotherapy in stage III patients (p = 0.013). In conclusion, histological phenotypic subtypes are an effective prognostic classification in patients with stage III CRC that associates with risk of recurrence and response to FOLFOX adjuvant chemotherapy

Immuno-informatics analysis predicts B and T cell consensus epitopes for designing peptide vaccine against SARS-CoV-2 with 99.82% global population coverage.

The current global pandemic due to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has taken a substantial number of lives across the world. Although few vaccines have been rolled-out, a number of vaccine candidates are still under clinical trials at various pharmaceutical companies and laboratories around the world. Considering the intrinsic nature of viruses in mutating and evolving over time, persistent efforts are needed to develop better vaccine candidates. In this study, various immuno-informatics tools and bioinformatics databases were deployed to derive consensus B-cell and T-cell epitope sequences of SARS-CoV-2 spike glycoprotein. This approach has identified four potential epitopes which have the capability to initiate both antibody and cell-mediated immune responses, are non-allergenic and do not trigger autoimmunity. These peptide sequences were also evaluated to show 99.82% of global population coverage based on the genotypic frequencies of HLA binding alleles for both MHC class-I and class-II and are unique for SARS-CoV-2 isolated from human as a host species. Epitope number 2 alone had a global population coverage of 98.2%. Therefore, we further validated binding and interaction of its constituent T-cell epitopes with their corresponding HLA proteins using molecular docking and molecular dynamics simulation experiments, followed by binding free energy calculations with molecular mechanics Poisson-Boltzmann surface area, essential dynamics analysis and free energy landscape analysis. The immuno-informatics pipeline described and the candidate epitopes discovered herein could have significant impact upon efforts to develop globally effective SARS-CoV-2 vaccines

3 versus 6 months of adjuvant oxaliplatin-fluoropyrimidine combination therapy for colorectal cancer (SCOT): an international, randomised, phase 3, non-inferiority trial.

BACKGROUND: 6 months of oxaliplatin-containing chemotherapy is usually given as adjuvant treatment for stage 3 colorectal cancer. We investigated whether 3 months of oxaliplatin-containing chemotherapy would be non-inferior to the usual 6 months of treatment. METHODS: The SCOT study was an international, randomised, phase 3, non-inferiority trial done at 244 centres. Patients aged 18 years or older with high-risk stage II and stage III colorectal cancer underwent central randomisation with minimisation for centre, choice of regimen, sex, disease site, N stage, T stage, and the starting dose of capecitabine. Patients were assigned (1:1) to receive 3 months or 6 months of adjuvant oxaliplatin-containing chemotherapy. The chemotherapy regimens could consist of CAPOX (capecitabine and oxaliplatin) or FOLFOX (bolus and infused fluorouracil with oxaliplatin). The regimen was selected before randomisation in accordance with choices of the patient and treating physician. The primary study endpoint was disease-free survival and the non-inferiority margin was a hazard ratio of 1·13. The primary analysis was done in the intention-to-treat population and safety was assessed in patients who started study treatment. This trial is registered with ISRCTN, number ISRCTN59757862, and follow-up is continuing. FINDINGS: 6088 patients underwent randomisation between March 27, 2008, and Nov 29, 2013. The intended treatment was FOLFOX in 1981 patients and CAPOX in 4107 patients. 3044 patients were assigned to 3 month group and 3044 were assigned to 6 month group. Nine patients in the 3 month group and 14 patients in the 6 month group did not consent for their data to be used, leaving 3035 patients in the 3 month group and 3030 patients in the 6 month group for the intention-to-treat analyses. At the cutoff date for analysis, there had been 1482 disease-free survival events, with 740 in the 3 month group and 742 in the 6 month group. 3 year disease-free survival was 76·7% (95% CI 75·1-78·2) for the 3 month group and 77·1% (75·6-78·6) for the 6 month group, giving a hazard ratio of 1·006 (0·909-1·114, test for non-inferiority p=0·012), significantly below the non-inferiority margin. Peripheral neuropathy of grade 2 or worse was more common in the 6 month group (237 [58%] of 409 patients for the subset with safety data) than in the 3 month group (103 [25%] of 420) and was long-lasting and associated with worse quality of life. 1098 serious adverse events were reported (492 reports in the 3 month group and 606 reports in the 6 month group) and 32 treatment-related deaths occurred (16 in each group). INTERPRETATION: In the whole study population, 3 months of oxaliplatin-containing adjuvant chemotherapy was non-inferior to 6 months of the same therapy for patients with high-risk stage II and stage III colorectal cancer and was associated with reduced toxicity and improved quality of life. Despite the fact the study was underpowered, these data suggest that a shorter duration leads to similar survival outcomes with better quality of life and thus might represent a new standard of care. FUNDING: Medical Research Council, Swedish Cancer Society, NETSCC, and Cancer Research UK