Benzobisoxazole cruciforms: a tunable, cross-conjugated platform for the generation of deep blue OLED materials

Four new cross-conjugated small molecules based on a central benzo[1,2-d:4,5-d′]bisoxazole moiety possessing semi-independently tunable HOMO and LUMO levels were synthesized and the properties of these materials were evaluated experimentally and theoretically. The molecules were thermally stable with 5% weight loss occurring well above 350 °C. The cruciforms all exhibited blue emission in solution ranging from 433–450 nm. Host–guest OLEDs fabricated from various concentrations of these materials using the small molecule host 4,4′-bis(9-carbazolyl)-biphenyl (CBP) exhibited deep blue-emission with Commission Internationale de L'Eclairage (CIE) coordinates of (0.15 ≤ x ≤ 0.17, 0.05 ≤ y ≤ 0.11), and maximum luminance efficiencies as high as ∼2 cd A−1. These results demonstrate the potential of benzobisoxazole cruciforms as emitters for developing high-performance deep blue OLEDs.We would like to thank Dr Sarah Cady, Dr Kamel Harrata and Mr Steven Veysey of Iowa State University (ISU) Chemical Instrumentation Facility for compound analysis. We thank Eeshita Manna for technical assistance. We also thank the National Science Foundation (CHE-1413173) for financial support of this work. RK and JS were partially supported by Basic Energy Sciences, Division of Materials Science and Engineering, USDOE. Ames Laboratory is operated by Iowa State University for the US Department of Energy (USDOE) under Contract No. DE-AC 02-07CH11358. Computational resources were provided in part by the MERCURY consortium (http://mercuryconsortium.org/) under NSF grants CHE-0116435, CHE-0521063, CHE-0849677, and CHE-1229354. (CHE-1413173 - National Science Foundation; Basic Energy Sciences, Division of Materials Science and Engineering, USDOE; DE-AC 02-07CH11358 - Iowa State University for the US Department of Energy (USDOE); CHE-0116435 - MERCURY consortium under NSF; CHE-0521063 - MERCURY consortium under NSF; CHE-0849677 - MERCURY consortium under NSF; CHE-1229354 - MERCURY consortium under NSF)http://pubs.rsc.org/en/Content/ArticleLanding/2016/TC/C5TC03622D#!divAbstractPublished versio

Organic−Inorganic Nanocomposites via Directly Grafting Conjugated Polymers onto Quantum Dots

Nanocomposites of poly(3-hexylthiophene)−cadmium selenide (P3HT−CdSe) were synthesized by directly grafting vinyl-terminated P3HT onto [(4-bromophenyl)methyl]dioctylphosphine oxide (DOPO-Br)-functionalized CdSe quantum dot (QD) surfaces via a mild palladium-catalyzed Heck coupling, thereby dispensing with the need for ligand exchange chemistry. The resulting P3HT−CdSe nanocomposites possess a well-defined interface, thus significantly promoting the dispersion of CdSe within the P3HT matrix and facilitating the electronic interaction between these two components. The photophysical properties of nanocomposites were found to differ from the conventional composites in which P3HT and CdSe QDs were physically mixed. Solid-state emission spectra of nanocomposites suggested the charge transfer from P3HT to CdSe QDs, while the energy transfer from 3.5 nm CdSe QD to P3HT was implicated in the P3HT/CdSe composites. A faster decay in lifetime further confirmed the occurrence of charge transfer in P3HT−CdSe nanocomposites

Heteroatom and side chain effects on the optical and photophysical properties: ultrafast and nonlinear spectroscopy of new Naphtho[1,2-b:5,6-b ']difuran donor polymers

The photophysical and electronic properties of four novel conjugated donor polymers were investigated to understand the influence of heteroatoms (based on the first two member chalcogens) in the polymer backbone. The side chains were varied as well to evaluate the effect of polymer solubility on the photophysical properties. The donor–acceptor polymer structure is based on naptho[1,2-b:5,6-b′]difuran as the donor moiety, and either 3,6-di(furan-2-yl)-1,4-diketopyrrolo[3,4-c]pyrrole or 3,6-di(thiophen-2-yl)-1,4-diketopyrrolo[3,4-c]pyrrole as the acceptor moiety. Steady-state absorption studies showed that the polymers with the furan moiety in the backbone displayed a favorable tendency of capturing more solar photons when used in a photovoltaic device. This is observed experimentally by the higher extinction coefficient in the visible and near-infrared regions of these polymers relative to that of their thiophene counterparts. The excitonic lifetimes were monitored using ultrafast dynamics, and the results obtained show that the type of heteroatom π-linker used in the backbone affects the decay dynamics. Furthermore, the side chain also plays a role in determining the fluorescence decay time. Quantum chemical simulations were performed to describe the absorption energies and transition characters. Two-photon absorption cross sections (TPA-δ) were analyzed with the simulations, illustrating the planarity of the backbone in relation to its torsional angles. Because of the planarity in the molecular backbone, the polymer with the furan π-linker showed a higher TPA-δ relative to that of its thiophene counterpart. This suggests that the furan compound will display higher charge transfer (CT) tendencies in comparison to those of their thiophene analogues. The pump–probe transient absorption technique was employed to probe the nonemissive states (including the CT state) of the polymers, and unique activities were captured at 500 and 750 nm for all of the studied compounds. Target and global analyses were performed to understand the dynamics of each peak and deduce the number of components responsible for the transient behavior observed respectively. The results obtained suggest that the furan π-linker component of a donor and acceptor moiety in a conjugated polymer might be a more suitable candidate compared with its more popular chalcogenic counterpart, thiophene, for use as donor materials in bulk heterojunction photovoltaic devices.Support for this investigation is provided by the National Science Foundation (DMR-1709005) Polymers (TGIII) and (DMR 1410088/1640297) Polymers (MJE). (DMR-1709005 - National Science Foundation; DMR 1410088/1640297 - National Science Foundation)Accepted manuscrip

Attenuated Induction of the Unfolded Protein Response in Adult Human Primary Astrocytes in Response to Recurrent Low Glucose

This is the final version. Available on open access from Frontiers Media via the DOI in this record. The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material.AIMS/HYPOTHESIS: Recurrent hypoglycaemia (RH) is a major side-effect of intensive insulin therapy for people with diabetes. Changes in hypoglycaemia sensing by the brain contribute to the development of impaired counterregulatory responses to and awareness of hypoglycaemia. Little is known about the intrinsic changes in human astrocytes in response to acute and recurrent low glucose (RLG) exposure. METHODS: Human primary astrocytes (HPA) were exposed to zero, one, three or four bouts of low glucose (0.1 mmol/l) for three hours per day for four days to mimic RH. On the fourth day, DNA and RNA were collected. Differential gene expression and ontology analyses were performed using DESeq2 and GOseq, respectively. DNA methylation was assessed using the Infinium MethylationEPIC BeadChip platform. RESULTS: 24 differentially expressed genes (DEGs) were detected (after correction for multiple comparisons). One bout of low glucose exposure had the largest effect on gene expression. Pathway analyses revealed that endoplasmic-reticulum (ER) stress-related genes such as HSPA5, XBP1, and MANF, involved in the unfolded protein response (UPR), were all significantly increased following low glucose (LG) exposure, which was diminished following RLG. There was little correlation between differentially methylated positions and changes in gene expression yet the number of bouts of LG exposure produced distinct methylation signatures. CONCLUSIONS/INTERPRETATION: These data suggest that exposure of human astrocytes to transient LG triggers activation of genes involved in the UPR linked to endoplasmic reticulum (ER) stress. Following RLG, the activation of UPR related genes was diminished, suggesting attenuated ER stress. This may be a consequence of a successful metabolic adaptation, as previously reported, that better preserves intracellular energy levels and a reduced necessity for the UPR.Diabetes UKJDRF postdoctoral fellowshipMedical Research Council (MRC)Wellcome TrustBiotechnology & Biological Sciences Research Council (BBSRC)Novo Nordisk UK Research FoundationMary Kinross Charitable TrustEuropean Foundation for the Study of Diabetes/Novo Nordisk Programm

Evaluating the impact of fluorination on the electro-optical properties of cross-conjugated benzobisoxazoles

Published as part of The Journal of Physical Chemistry virtual special issue “William M. Jackson Festschrift”.Six 2,4,6,8-tetrarylbenzo[1,2-d:4,5-d′]bisoxazoles (BBOs) were synthesized: three bearing phenyl substituents at the 2- and 6-positions and three bearing perfluorophenyl groups at those positions. The influence of perfluoro-aryl group substitution on the physical, optical, and electronic properties of 2,4,6,8-tetrarylbenzo[1,2-d:4,5-d′]bisoxazoles (BBO) was evaluated using both experimental and theoretical methods. The density functional theory (DFT) model was found to be well-matched to the experimental optical data, as evidenced by the UV–vis spectra. Both cyclic voltammetry (CV) and ultraviolet photoelectron spectroscopy (UPS) were used to determine the position of the HOMO with varying results. The values obtained by CV were deeper than those obtained via UPS and correlated well with the theoretical calculations. However, the UPS values were more consistent with the expected outcomes for a system with segregated frontier molecular orbitals (FMOs). The UPS results are also supported by the electrostatic potential maps, which indicate that the electron density within the LUMO and HOMO is nearly completely localized along the 2,6- or 4,8-axis, respectively. The summation of the results indicates that strongly electron-withdrawing groups can be used to selectively tune the LUMO level with minor perturbation of the HOMO, something that is challenging to accomplish in typical donor–acceptor systems.We thank Dr. Norman Lee, Stephon Betts, and Dr. Paul Ralifo from the Chemical Instrumentation Facility at Boston University for compound analysis. We also thank Margaret Chern from the Dennis Lab at Boston University for assistance in obtaining fluorescence lifetimes and quantum yields. Next, we thank Volodimyr Duzhko at the Center for Electronic Materials and Devices at the University of Massachusetts-Amherst. We also thank the National Science Foundation (CHE-141373, CHE-1640298, and CHE-1413207) as well a supercomputer allocation by the Extreme Science and Engineering Discovery Environment (XSEDE) for the Comet supercomputer cluster provided by the San Diego Supercomputing Center (DMR-160146) for supporting this work. (CHE-141373 - National Science Foundation; CHE-1640298 - National Science Foundation; CHE-1413207 - National Science Foundation)Accepted manuscrip

The health response to the Rohingya refugee crisis post August 2017: Reflections from two years of health sector coordination in Cox’s Bazar, Bangladesh

On August 25 2017, an unprecedented influx of Rohingya refugees began from Rakhine State in Myanmar into Bangladesh’s district of Cox’s Bazar. The scale and acuteness of this humanitarian crisis was unprecedented and unique globally, requiring strong coordination of a multitude of actors. This paper reflects on the health sector coordination from August 2017 to October 2019, focusing on selected achievements and persisting challenges of the health sector strategic advisory group (HSSAG), and the health sector working groups including epidemiology and case management, sexual and reproductive health, community health, mental health and psychosocial support, and emergency preparedness. In the early days of the response, minimum service standards for primary health care were established, a fundamental initial step which enabled the standardization of services based on critical needs. Similarly, establishing standards for community health outreach was the backbone for capitalizing on this important health workforce. Novel approaches were adopted for infectious disease responses for acute watery diarrhoea and varicella, drawing on inter-sectoral collaborations. Sexual and reproductive health services were prioritized from the initial onset of the crisis and improvements in skilled delivery attendance, gender-based violence services, abortion care and family planning were recorded. Mental health service provision was strengthened through community-based approaches although integration of mental health programmes into primary health care has been limited by availability of specialist psychiatrists. Strong, collaborative and legitimate leadership by the health sector strategic advisory group, drawing on inter-sectoral collaborations and the technical expertise of the different technical working groups, were critical in the response and proved effective, despite the remaining challenges to be addressed. Anticipated reductions in funding as the crisis moves into protracted status threatens the achievements of the health sector in provision of health services to the Rohingya refugees

Functional characterization of the schizophrenia associated gene AS3MT identifies a role in neuronal development

This is the final version. Available from Wiley via the DOI in this record. DATA AVAILABILITY STATEMENT: All raw RNAseq files are available at GSE182157 and generated cell lines available on request.Genome-wide association studies (GWAS) have identified multiple genomic regions associated with schizophrenia, although many variants reside in noncoding regions characterized by high linkage disequilibrium (LD) making the elucidation of molecular mechanisms challenging. A genomic region on chromosome 10q24 has been consistently associated with schizophrenia with risk attributed to the AS3MT gene. Although AS3MT is hypothesized to play a role in neuronal development and differentiation, work to fully understand the function of this gene has been limited. In this study we explored the function of AS3MT using a neuronal cell line (SH-SY5Y). We confirm previous findings of isoform specific expression of AS3MT during SH-SY5Y differentiation toward neuronal fates. Using CRISPR-Cas9 gene editing we generated AS3MT knockout SH-SY5Y cell lines and used RNA-seq to identify significant changes in gene expression in pathways associated with neuronal development, inflammation, extracellular matrix formation, and RNA processing, including dysregulation of other genes strongly implicated in schizophrenia. We did not observe any morphological changes in cell size and neurite length following neuronal differentiation and MAP2 immunocytochemistry. These results provide novel insights into the potential role of AS3MT in brain development and identify pathways through which genetic variation in this region may confer risk for schizophrenia.Academy of Medical SciencesBiotechnology and Biological Sciences Research CouncilMedical Research CouncilMedical Research CouncilWellcome TrustWellcome TrustUniversity of Exete

Novel epigenetic clock for fetal brain development predicts prenatal age for cellular stem cell models and derived neurons

Induced pluripotent stem cells (iPSCs) and their differentiated neurons (iPSC-neurons) are a widely used cellular model in the research of the central nervous system. However, it is unknown how well they capture age-associated processes, particularly given that pluripotent cells are only present during the earliest stages of mammalian development. Epigenetic clocks utilize coordinated age-associated changes in DNA methylation to make predictions that correlate strongly with chronological age. It has been shown that the induction of pluripotency rejuvenates predicted epigenetic age. As existing clocks are not optimized for the study of brain development, we developed the fetal brain clock (FBC), a bespoke epigenetic clock trained in human prenatal brain samples in order to investigate more precisely the epigenetic age of iPSCs and iPSC-neurons. The FBC was tested in two independent validation cohorts across a total of 194 samples, confirming that the FBC outperforms other established epigenetic clocks in fetal brain cohorts. We applied the FBC to DNA methylation data from iPSCs and embryonic stem cells and their derived neuronal precursor cells and neurons, finding that these cell types are epigenetically characterized as having an early fetal age. Furthermore, while differentiation from iPSCs to neurons significantly increases epigenetic age, iPSC-neurons are still predicted as being fetal. Together our findings reiterate the need to better understand the limitations of existing epigenetic clocks for answering biological research questions and highlight a limitation of iPSC-neurons as a cellular model of age-related diseases

Synthesis, characterization and photovoltaic properties of poly(thiophenevinylene-alt-benzobisoxazole)swz

Herein we report the synthesis of two solution processible, conjugated polymers containing the benzobisoxazole moiety. The polymers were characterized using 1 H NMR, UV-Vis and fluorescence spectroscopy. Thermal gravimetric analysis shows that the polymers do not exhibit significant weight loss until approximately 300 1C under nitrogen. Cyclic voltammetry shows that the polymers have reversible reduction waves with estimated LUMO levels at À3.02 and À3.10 eV relative to vacuum and optical bandgaps of 2.04-2.17 eV. Devices based on blends of the copolymers and [6,6]-phenyl C61 butyric acid methyl ester (PCBM) exhibited modest power conversion efficiencies. Theoretical models reveal that there is poor electron delocalization along the polymer backbone, leading to poor performance. However, the energy levels of these polymers indicate that the incorporation of benzobisoxazoles into the polymer backbone is a promising strategy for the synthesis of new materials

Life and times:synthesis, trafficking, and evolution of VSG

Evasion of the acquired immune response in African trypanosomes is principally mediated by antigenic variation, the sequential expression of distinct variant surface glycoproteins (VSGs) at extremely high density on the cell surface. Sequence diversity between VSGs facilitates escape of a subpopulation of trypanosomes from antibody-mediated killing. Significant advances have increased understanding of the mechanisms underpinning synthesis and maintenance of the VSG coat. In this review, we discuss the biosynthesis, trafficking, and turnover of VSG, emphasising those unusual mechanisms that act to maintain coat integrity and to protect against immunological attack. We also highlight new findings that suggest the presence of unique or highly divergent proteins that may offer therapeutic opportunities, as well as considering aspects of VSG biology that remain to be fully explored