Conjugated, rod-like viologen oligomers: correlation of oligomer length with conductivity and photoconductivity

An iterative synthesis has been used to produce conjugated, monodisperse, viologen-based aromatic oligomers containing up to 12 aromatic/heterocyclic rings. The methoxy-substituted oligomers were soluble in common organic solvents and could be processed by spin coating. The conductivities of the resulting films (30 to 221 nm thick) increased by more than an order of magnitude as the oligomer length increased from unimer (1, 2.20×10-11 S cm-1) through dimer (2) to trimer (3, 6.87×10-10 S cm-1). The bandgaps of the materials were estimated from the absorption spectra of these thin films. The longest oligomer, 3, exhibited a noticeably narrower bandgap (2.3 eV) than the shorter oligomers (1 and 2 both 2.7 eV). Oligomer 3 also showed photoconductivity under irradiation across a wide range of wavelengths in the visible spectral region. In conjunction with DFT calculations of these systems our results suggest that structurally related viologen-type oligomers may find use in optoelectronic devices

Phase separation and crystallization of La2O3 doped ZnO-B2O3-SiO2 glass

In order to investigate the effect of the La2O3 on the phase separation and crystallization of ZnO-B2O3-SiO2 glass, after the occurence of the phase separation and crystallization of glasses by heat treatment, the microstructure morphology and distribution of elements in different sample areas were characterized by the scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS); the non-isothermal crystallization kinetics of the glass samples was studied by using a differential scanning calorimeter (DSC) and the precipitated crystals of crystallized glass were determined by the X-ray diffraction (XRD). The results suggest that the phase separation and crystallization of 60ZnO-30B2O3-10SiO2 glass occur at glass surface, and the incorporation of small amount (<4 mol%) of La2O3 significantly inhibits the glass phase separation and consequently improves the thermal stability of glass. Doping of La2O3 accelerates the glass crystallization at the elevated temperature (660 °C), making the depth of crystal layer thicker and diffraction intensity in XRD patterns stronger. However, due to the precipitation of several crystals that occur simultaneously when La2O3 doping amount is 4 mol%, crystallization of the 60ZnO-30B2O3-10SiO2 glass is obviously depressed, the crystallization activation energy Ec and the relative crystallinity Xc of the glass reach the maximum and the minimum values, respectively. Although transition from one-dimensional growth of crystals to two-dimensional growth of crystals results from La2O3 addition, the one-dimensional growth of crystals remains dominant in crystallization process. This work can provide some useful information for preparing glass ceramics with nano-crystals precipitated in the glass surface

Menstrual hygiene management in schools: midway progress update on the “MHM in Ten” 2014–2024 global agenda

Progress has been made in recent years to bring attention to the challenges faced by school-aged girls around managing menstruation in educational settings that lack adequate physical environments and social support in low- and middle-income countries. To enable more synergistic and sustained progress on addressing menstruation-related needs while in school, an effort was undertaken in 2014 to map out a vision, priorities, and a ten-year agenda for transforming girls’ experiences, referred to as Menstrual Hygiene Management in Ten (MHM in Ten). The overarching vision is that girls have the information, support, and enabling school environment for managing menstruation with dignity, safety and comfort by 2024. This requires improved research evidence and translation for impactful national level policies. As 2019 marked the midway point, we assessed progress made on the five key priorities, and remaining work to be done, through global outreach to the growing network of academics, non-governmental organizations, advocates, social entrepreneurs, United Nations agencies, donors, and national governments. This paper delineates the key insights to inform and support the growing MHM commitment globally to maximize progress to reach our vision by 2024. Corresponding to the five priorities, we found that (priority 1) the evidence base for MHM in schools has strengthened considerably, (priority 2) global guidelines for MHM in schools have yet to be created, and (priority 3) numerous evidence-based advocacy platforms have emerged to support MHM efforts. We also identified (priority 4) a growing engagement, responsibility, and ownership of MHM in schools among governments globally, and that although MHM is beginning to be integrated into country-level education systems (priority 5), resources are lacking. Overall, progress is being made against identified priorities. We provide recommendations for advancing the MHM in Ten agenda. This includes continued building of the evidence, and expanding the number of countries with national level policies and the requisite funding and capacity to truly transform schools for all students and teachers who menstruate

Menstrual hygiene management in schools: midway progress update on the "MHM in Ten" 2014-2024 global agenda.

Progress has been made in recent years to bring attention to the challenges faced by school-aged girls around managing menstruation in educational settings that lack adequate physical environments and social support in low- and middle-income countries. To enable more synergistic and sustained progress on addressing menstruation-related needs while in school, an effort was undertaken in 2014 to map out a vision, priorities, and a ten-year agenda for transforming girls' experiences, referred to as Menstrual Hygiene Management in Ten (MHM in Ten). The overarching vision is that girls have the information, support, and enabling school environment for managing menstruation with dignity, safety and comfort by 2024. This requires improved research evidence and translation for impactful national level policies. As 2019 marked the midway point, we assessed progress made on the five key priorities, and remaining work to be done, through global outreach to the growing network of academics, non-governmental organizations, advocates, social entrepreneurs, United Nations agencies, donors, and national governments. This paper delineates the key insights to inform and support the growing MHM commitment globally to maximize progress to reach our vision by 2024. Corresponding to the five priorities, we found that (priority 1) the evidence base for MHM in schools has strengthened considerably, (priority 2) global guidelines for MHM in schools have yet to be created, and (priority 3) numerous evidence-based advocacy platforms have emerged to support MHM efforts. We also identified (priority 4) a growing engagement, responsibility, and ownership of MHM in schools among governments globally, and that although MHM is beginning to be integrated into country-level education systems (priority 5), resources are lacking. Overall, progress is being made against identified priorities. We provide recommendations for advancing the MHM in Ten agenda. This includes continued building of the evidence, and expanding the number of countries with national level policies and the requisite funding and capacity to truly transform schools for all students and teachers who menstruate

Formate overflow drives toxic folate trapping in MTHFD1 inhibited cancer cells

Cancer cells fuel their increased need for nucleotide supply by upregulating one-carbon (1C) metabolism, including the enzymes methylenetetrahydrofolate dehydrogenase-cyclohydrolase 1 and 2 (MTHFD1 and MTHFD2). TH9619 is a potent inhibitor of dehydrogenase and cyclohydrolase activities in both MTHFD1 and MTHFD2, and selectively kills cancer cells. Here, we reveal that, in cells, TH9619 targets nuclear MTHFD2 but does not inhibit mitochondrial MTHFD2. Hence, overflow of formate from mitochondria continues in the presence of TH9619. TH9619 inhibits the activity of MTHFD1 occurring downstream of mitochondrial formate release, leading to the accumulation of 10-formyl-tetrahydrofolate, which we term a 'folate trap'. This results in thymidylate depletion and death of MTHFD2-expressing cancer cells. This previously uncharacterized folate trapping mechanism is exacerbated by physiological hypoxanthine levels that block the de novo purine synthesis pathway, and additionally prevent 10-formyl-tetrahydrofolate consumption for purine synthesis. The folate trapping mechanism described here for TH9619 differs from other MTHFD1/2 inhibitors and antifolates. Thus, our findings uncover an approach to attack cancer and reveal a regulatory mechanism in 1C metabolism.In this study, Green, Marttila, Kiweler et al. characterize one-carbon metabolism rewiring in response to a dual MTHFD1 and MTHFD2 inhibitor. This work provides insight into one-carbon fluxes, and reveals a previously uncharacterized vulnerability in cancer cells created by folate trapping

Assessing changes in global fire regimes

PAGES, Past Global Changes, is funded by the Swiss Academy of Sciences and the Chinese Academy of Sciences and supported in kind by the University of Bern, Switzerland. Financial support was provided by the U.S. National Science Foundation award numbers 1916565, EAR-2011439, and EAR-2012123. Additional support was provided by the Utah Department of Natural Resources Watershed Restoration Initiative. SSS was supported by Brigham Young University Graduate Studies. MS was supported by National Science Centre, Poland (grant no. 2018/31/B/ST10/02498 and 2021/41/B/ST10/00060). JCA was supported by the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No 101026211. PF contributed within the framework of the FCT-funded project no. UIDB/04033/2020. SGAF acknowledges support from Trond Mohn Stiftelse (TMS) and University of Bergen for the startup grant ‘TMS2022STG03’. JMP participation in this research was supported by the Forest Research Centre, a research unit funded by Fundação para a Ciência e a Tecnologia I.P. (FCT), Portugal (UIDB/00239/2020). A.-LD acknowledge PAGES, PICS CNRS 06484 project, CNRS-INSU, Région Nouvelle-Aquitaine, University of Bordeaux DRI and INQUA for workshop support.Background The global human footprint has fundamentally altered wildfire regimes, creating serious consequences for human health, biodiversity, and climate. However, it remains difficult to project how long-term interactions among land use, management, and climate change will affect fire behavior, representing a key knowledge gap for sustainable management. We used expert assessment to combine opinions about past and future fire regimes from 99 wildfire researchers. We asked for quantitative and qualitative assessments of the frequency, type, and implications of fire regime change from the beginning of the Holocene through the year 2300. Results Respondents indicated some direct human influence on wildfire since at least ~ 12,000 years BP, though natural climate variability remained the dominant driver of fire regime change until around 5,000 years BP, for most study regions. Responses suggested a ten-fold increase in the frequency of fire regime change during the last 250 years compared with the rest of the Holocene, corresponding first with the intensification and extensification of land use and later with anthropogenic climate change. Looking to the future, fire regimes were predicted to intensify, with increases in frequency, severity, and size in all biomes except grassland ecosystems. Fire regimes showed different climate sensitivities across biomes, but the likelihood of fire regime change increased with higher warming scenarios for all biomes. Biodiversity, carbon storage, and other ecosystem services were predicted to decrease for most biomes under higher emission scenarios. We present recommendations for adaptation and mitigation under emerging fire regimes, while recognizing that management options are constrained under higher emission scenarios. Conclusion The influence of humans on wildfire regimes has increased over the last two centuries. The perspective gained from past fires should be considered in land and fire management strategies, but novel fire behavior is likely given the unprecedented human disruption of plant communities, climate, and other factors. Future fire regimes are likely to degrade key ecosystem services, unless climate change is aggressively mitigated. Expert assessment complements empirical data and modeling, providing a broader perspective of fire science to inform decision making and future research priorities.Peer reviewe

Symptom-based stratification of patients with primary Sjögren's syndrome: multi-dimensional characterisation of international observational cohorts and reanalyses of randomised clinical trials

Background Heterogeneity is a major obstacle to developing effective treatments for patients with primary Sjögren's syndrome. We aimed to develop a robust method for stratification, exploiting heterogeneity in patient-reported symptoms, and to relate these differences to pathobiology and therapeutic response. Methods We did hierarchical cluster analysis using five common symptoms associated with primary Sjögren's syndrome (pain, fatigue, dryness, anxiety, and depression), followed by multinomial logistic regression to identify subgroups in the UK Primary Sjögren's Syndrome Registry (UKPSSR). We assessed clinical and biological differences between these subgroups, including transcriptional differences in peripheral blood. Patients from two independent validation cohorts in Norway and France were used to confirm patient stratification. Data from two phase 3 clinical trials were similarly stratified to assess the differences between subgroups in treatment response to hydroxychloroquine and rituximab. Findings In the UKPSSR cohort (n=608), we identified four subgroups: Low symptom burden (LSB), high symptom burden (HSB), dryness dominant with fatigue (DDF), and pain dominant with fatigue (PDF). Significant differences in peripheral blood lymphocyte counts, anti-SSA and anti-SSB antibody positivity, as well as serum IgG, κ-free light chain, β2-microglobulin, and CXCL13 concentrations were observed between these subgroups, along with differentially expressed transcriptomic modules in peripheral blood. Similar findings were observed in the independent validation cohorts (n=396). Reanalysis of trial data stratifying patients into these subgroups suggested a treatment effect with hydroxychloroquine in the HSB subgroup and with rituximab in the DDF subgroup compared with placebo. Interpretation Stratification on the basis of patient-reported symptoms of patients with primary Sjögren's syndrome revealed distinct pathobiological endotypes with distinct responses to immunomodulatory treatments. Our data have important implications for clinical management, trial design, and therapeutic development. Similar stratification approaches might be useful for patients with other chronic immune-mediated diseases. Funding UK Medical Research Council, British Sjogren's Syndrome Association, French Ministry of Health, Arthritis Research UK, Foundation for Research in Rheumatology

Towards a muon collider

A muon collider would enable the big jump ahead in energy reach that is needed for a fruitful exploration of fundamental interactions. The challenges of producing muon collisions at high luminosity and 10 TeV centre of mass energy are being investigated by the recently-formed International Muon Collider Collaboration. This Review summarises the status and the recent advances on muon colliders design, physics and detector studies. The aim is to provide a global perspective of the field and to outline directions for future work

Towards a Muon Collider

A muon collider would enable the big jump ahead in energy reach that is needed for a fruitful exploration of fundamental interactions. The challenges of producing muon collisions at high luminosity and 10 TeV centre of mass energy are being investigated by the recently-formed International Muon Collider Collaboration. This Review summarises the status and the recent advances on muon colliders design, physics and detector studies. The aim is to provide a global perspective of the field and to outline directions for future work.Comment: 118 pages, 103 figure

Erratum:Towards a muon collider

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