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Given the demands of modern working life, university studies should support students' life-long learning and agency. This article explores the types of agency learners from an English for Academic Purposes (EAP) course described in interviews. The interviews were conducted in two groups in 2 consecutive years, in two stages: at the end of the EAP course as well as 6 to 7 months later. Through thematic content analysis, three types of agency were identified: instrumental agency, operational agency, and reflective agency. These types usually differed in terms of the contexts in which the learners placed the agency, the positions the learners took, and their descriptions of whether the agency continued or ended. Furthermore, individual learners often described different types of agency within the same interview. This highlights the messiness, fluidity, and dynamic changes in the ways of speaking as the key aspects when learners were authoring their agency. The findings are used to critically evaluate current higher education language teaching practices and discuss what kind of higher education language teaching challenges the students' answers reveal, particularly in regards to compulsory language studies for students of other fields.

Toddlerhood is a period of intensive and rapid socio-emotional development. The effects of different types of childcare settings on child development have been widely studied, but the results have often been contradictory. The aim of this study was to compare social competence and socio-emotional problems in two-year-old children (n = 1104; girls 47.2%) who were either participating in out-of-home, center-based childcare or were cared for at home by their parents in Finland. The results showed that mothers reported more internalizing symptoms in toddlers participating in out-of-home, center-based childcare when compared to children who were cared for at home. No differences regarding externalizing symptoms or social competence were found. Overall, the results suggest that out-of-home, center-based childcare is not associated with major differences in a toddler's socio-emotional development. More research is needed to investigate whether differences in the socio-emotional development of the children participating in different types of childcare develop later in childhood.

How to support young people's agency is a key question of sustainability education. Action competence for sustainability is suggested covering the essential components of youth's readiness to act both individually and collectively, but empirical tests of these associations are scarce. Therefore, this study explores the relationship between action competence and sustainability action among young people. We conducted a national survey of 15 to 29-year-old youths (N = 940) in Finland. Results of structural equation modeling show that self-perceived action competence for sustainability predicts private sphere behavior, but not sustainability action. Further analysis on the components of action competence reveals that high perceived knowledge and low outcome expectations predict low engagement in sustainability action. Knowledge and outcome expectations also affect behavior indirectly via willingness to act. We argue that actions and behaviors have different antecedents, and that the ability to recognize outcome uncertainty affects how young people's sustainability agency is manifested.

Abstract There is a vast literature evaluating the empirical association between stay-at-home policies and crime during the COVID-19 pandemic. However, these academic efforts have primarily focused on the effects within specific cities or regions rather than adopting a cross-national comparative approach. Moreover, this body of literature not only generally lacks causal estimates but also has overlooked possible heterogeneities across different levels of stringency in mobility restrictions. This paper exploits the spatial and temporal variation of government responses to the pandemic in 45 cities across five continents to identify the causal impact of strict lockdown policies on the number of offenses reported to local police. We find that cities that implemented strict lockdowns experienced larger declines in some crime types (robbery, burglary, vehicle theft) but not others (assault, theft, homicide). This decline in crime rates attributed to more stringent policy responses represents only a small proportion of the effects documented in the literature.

India currently has the biggest unelectrified population in the world. Renewable-based microgrids could provide a sustainable solution to providing universal energy access. However, the potential electricity demand in rural areas is unknown and hard to predict. This data is needed to analyse the purchasing power and potential market for microgrids, and to assess their success rate. This study surveyed 73 households in Arunachal Pradesh and Uttar Pradesh in India, to study the energy need in rural communities. The data shows that many unelectrified households are already using electrical appliances powered by small photovoltaic panels or batteries. The consumption is not income-generating but potential productive use cases are widely present. In Uttar Pradesh, small-scale microgrids are already providing homes with enough power for lighting and mobile chargers. An average unelectrified household was found to consume 2.48 kWhe monthly, and to spend ₹ 155 on energy services. Villagers wish for more appliances and more power, and have the required finances to pay for it.

Abstract Background Colorectal cancers (CRCs) in the Lynch syndromes have been assumed to emerge through an accelerated adenoma-carcinoma pathway. In this model adenomas with deficient mismatch repair have an increased probability of acquiring additional cancer driver mutation(s) resulting in more rapid progression to malignancy. If this model was accurate, the success of colonoscopy in preventing CRC would be a function of the intervals between colonoscopies and mean sojourn time of detectable adenomas. Contrary to expectations, colonoscopy did not decrease incidence of CRC in the Lynch syndromes and shorter colonoscopy intervals have not been effective in reducing CRC incidence. The prospective Lynch Syndrome Database (PLSD) was designed to examine these issues in carriers of pathogenic variants of the mis-match repair (path_MMR) genes. Materials and methods We examined the CRC and colorectal adenoma incidences in 3,574 path_MLH1, path_MSH2, path_MSH6 and path_PMS2 carriers subjected to regular colonoscopy with polypectomy, and considered the results based on sojourn times and stochastic probability paradigms. Results Most of the path_MMR carriers in each genetic group had no adenomas. There was no association between incidences of CRC and the presence of adenomas. There was no CRC observed in path_PMS2 carriers. Conclusions Colonoscopy prevented CRC in path_PMS2 carriers but not in the others. Our findings are consistent with colonoscopy surveillance blocking the adenoma-carcinoma pathway by removing identified adenomas which might otherwise become CRCs. However, in the other carriers most CRCs likely arised from dMMR cells in the crypts that have an increased mutation rate with increased stochastic chaotic probabilities for mutations. Therefore, this mechanism, that may be associated with no or only a short sojourn time of MSI tumours as adenomas, could explain the findings in our previous and current reports.

The mixing ratios of highly volatile organic compounds (VOCs) were studied on Utö Island in the Baltic Sea. Measurements of non-methane hydrocarbons (NMHCs) and methanethiol (unexpectedly found during the experiment) were conducted using an in situ thermal desorption–gas chromatography–flame ionization detector/mass spectrometer (TD-GC-FID/MS) from March 2018 until March 2019. The mean mixing ratios of NMHCs (alkanes, alkenes, alkynes, and aromatic hydrocarbons) were at the typical levels for rural/remote sites in Europe, and, as expected, the highest mixing ratios were measured in winter, while in the summertime, the mixing ratios remained close to or below detection limits for most of the studied compounds. Sources of NMHCs during wintertime were studied using positive matrix factorization (PMF) together with wind direction analyses and source area estimates. Shipping was found to be a major local anthropogenic source of NMHCs with a 21 % contribution. It especially contributed to ethene, propene, and ethyne mixing ratios. Other identified sources were petrol fuel (15 %), traffic exhaust (14 %), local solvents (6 %), and long-range-transported background (42 %). Contrary to NMHCs, high mixing ratios of methanethiol were detected in summertime (July mean of 1000 pptv). The mixing ratios followed the variations in seawater temperatures and sea level height and were highest during the daytime. Biogenic phytoplankton or macroalgae emissions were expected to be the main source of methanethiol.

Serum triglyceride concentrations increase in dogs with obesity, which is typically assessed by body condition score (BCS), however little is known about changes that take place in non-obese dogs in overweight condition. Further, the associations of triglyceride levels with other markers of energy homeostasis are poorly characterised in healthy animals. The present study aimed to evaluate associations between both BCS and triglyceride concentrations with other markers of lipid and glucose metabolism in healthy, non-obese dogs, as well as to assess whether these markers change significantly in non-obese dogs with overweight as compared to their lean counterparts. Serum concentrations of cholesterol, free fatty acids, triglycerides, insulin, glucose and fructosamine were measured in 532 healthy, client-owned dogs, assigned either to ‘lean’ (BCS: 3–5) or ‘overweight’ (BCS: 6–7) categories. Generalised linear mixed models were used to assess associations between BCS categories, triglyceride concentrations and other variables, correcting for the effect of breed. Compared with lean dogs, overweight dogs had a greater serum cholesterol concentration (95% CI, 5.3–6.2 mmol/L or 205–237 mg/dL versus 5.1–5.4 mmol/L or 198–210 mg/dL, p = 0.0032), insulin concentration (95% CI, 17.5–22.1 μU/ml versus 16.7–18.0 μU/ml, p = 0.0374) and were older (95% CI, 4.0–5.3 versus 3.4–3.7 years, p = 0.0005). Triglyceride concentrations were positively associated with fructosamine (r2 = 0.31, p = 0.0012), cholesterol (r2 = 0.25, p

Abstract Genetic drift, gene flow, and natural selection commonly influence population genetic diversity. In populations of self‐compatible hermaphrodites, the mating system (e.g., self‐fertilization) further reduces individual heterozygosity. Furthermore, selfing, as a form of inbreeding, significantly impacts genetic drift by reducing effective population size (Ne). This can potentially accelerate genetic drift, particularly in small populations where self‐fertilization is likely during founder events. To investigate the roles of genetic drift and contemporary mating system in populations of the freshwater snail Lymnaea stagnalis, we examined their effective population sizes (Ne) and Tajima's D values, which reflect genetic drift over extended time periods, as well as estimates of within‐population selfing rates and pairwise relatedness reflecting contemporary mating system. We used 4054 SNP markers obtained using restriction site associated DNA (RAD) sequencing from individuals in five snail populations originating from geographically closely located ponds. We found strong population genetic structure and differences in genetic diversity among populations. Covariation between genetic diversity and Ne estimates and Tajima's D values suggested drift being an important determinant of genetic diversity and structure in these populations. However, this effect was independent of the contemporary mating system, as indicated by the similarity of selfing rates and relatedness estimates among populations. Thus, founder events (possibly including historical inbreeding) and/or drift due to small sizes of L. stagnalis populations are likely to explain their genetic structure and limit within‐population genetic diversity.

Objective: Cancer cells must maintain lipid supplies for their proliferation and do so by upregulating lipogenic gene programs. The sterol regulatory element-binding proteins (SREBPs) act as modulators of lipid homeostasis by acting as transcriptional activators of genes required for fatty acid and cholesterol synthesis and uptake. SREBPs have been recognized as chemotherapeutic targets in multiple cancers, however it is not well understood which SREBP target genes are essential for tumorigenesis. In this study, we examined the requirement of SREBP target genes for pancreatic ductal adenocarcinoma (PDAC) tumor growth. Methods: Here we constructed a custom CRISPR knockout library containing known SREBP target genes and performed in vitro 2D culture and in vivo orthotopic xenograft CRISPR screens using a patient-derived PDAC cell line. In vitro, we grew cells in medium supplemented with 10% fetal bovine serum (FBS) or 10% lipoprotein-deficient serum (LPDS) to examine differences in gene essentiality in different lipid environments. In vivo, we injected cells into the pancreata of nude mice and collected tumors after 4 weeks. Results: We identified terpenoid backbone biosynthesis genes as essential for PDAC tumor development. Specifically, we identified the non-sterol isoprenoid product of the mevalonate pathway, geranylgeranyl diphosphate (GGPP), as an essential lipid for tumor growth. Mechanistically, we observed that restricting mevalonate pathway activity using statins and SREBP inhibitors synergistically induced apoptosis and caused disruptions in small G protein prenylation that have pleiotropic effects on cellular signaling pathways. Finally, we demonstrated that geranylgeranyl diphosphate synthase 1 (GGPS1) knockdown significantly reduces tumor burden in an orthotopic xenograft mouse model. Conclusions: These findings indicate that PDAC tumors selectively require GGPP over other lipids such as cholesterol and fatty acids and that this is a targetable vulnerability of pancreatic cancer cells.

The functional properties of proteorhodopsin (PR) have been found to be strongly modulated by oligomeric distributions and lipid membrane mimetics. This study aims to distinguish and explain their effects by investigating how oligomer formation impacts PRs function of proton transport in lipid-based membrane mimetic environments. We find that PR forms stable hexamers and pentamers in both E. coli membranes and synthetic liposomes. Compared with the monomers, the photocycle kinetics of PR oligomers is ∼2 and ∼4.5 times slower for transitions between the K and M and the M and N photointermediates, respectively, indicating that oligomerization significantly slows PRs rate of proton transport in liposomes. In contrast, the apparent pKa of the key proton acceptor residue D97 (pKaD97) of liposome-embedded PR persists at 6.2-6.6, regardless of cross-protomer modulation of D97, suggesting that the liposome environment helps maintain PRs functional activity at neutral pH. By comparison, when extracted directly from E. coli membranes into styrene-maleic acid lipid particles, the pKaD97 of monomer-enriched E50Q PR drastically increases to 8.9, implying that there is a very low active PR population at neutral pH to engage in PRs photocycle. These findings demonstrate that oligomerization impacts PRs photocycle kinetics, while lipid-based membrane mimetics strongly affect PRs active population via different mechanisms.

Abstract Background The dosimetric effect of setup uncertainty and tissue deformations in left-sided whole-breast irradiation with complementary surface-guided radiotherapy (SGRT) and cone-beam computed tomography (CBCT) setup was evaluated. Method Treatment courses of 40.05 Gy prescribed dose in 15 fractions were simulated for 29 patients by calculating the dose on deformed CT images, that were based on daily CBCT images, and deforming and accumulating the dose onto the planning CT image. Variability in clinical target volume (CTV) position and shape was assessed as the 95% Hausdorff distance (HD95) between the planning CTV and deformed CTV structures. DVH metrics were evaluated between the planned and simulated cumulative dose distributions using two treatment techniques: tangential volumetric modulated arc therapy (tVMAT) and conventional 3D-conformal radiotherapy (3D-CRT). Results Based on the HD95 values, the variations in CTV shape and position were enclosed by the 5 mm CTV-PTV margin in 85% of treatment fractions using complementary CBCT and SGRT setup. A residual error of 8.6 mm was observed between the initial SGRT setup and CBCT setup. The median CTV V95% coverage was 98.1% (range 93.1–99.8%) with tVMAT and 98.2% (range 84.5–99.7%) with 3D-CRT techniques with CBCT setup. With the initial SGRT-only setup, the corresponding coverages were 96.3% (range 92.6–99.4%) and 96.6% (range 84.2–99.4%), respectively. However, a considerable bias in vertical residual error between initial SGRT setup and CBCT setup was observed. Clinically relevant changes between the planned and cumulative doses to organs-at-risk (OARs) were not observed. Conclusions The CTV-to-PTV margin should not be reduced below 5 mm even with daily CBCT setup. Both tVMAT and 3D-CRT techniques were robust in terms of dose coverage to the target and OARs. Based on the shifts between setup methods, CBCT setup is recommended as a complementary method with SGRT.

Abstract Circulating metabolites systemically reflect cellular processes and can modulate the tissue microenvironment in complex ways, potentially impacting cancer initiation processes. Genetic background increases cancer risk in individuals with Lynch syndrome; however, not all carriers develop cancer. Various lifestyle factors can influence Lynch syndrome cancer risk, and lifestyle choices actively shape systemic metabolism, with circulating metabolites potentially serving as the mechanical link between lifestyle and cancer risk. This study aims to characterize the circulating metabolome of Lynch syndrome carriers, shedding light on the energy metabolism status in this cancer predisposition syndrome. This study consists of a three-group cross-sectional analysis to compare the circulating metabolome of cancer-free Lynch syndrome carriers, sporadic colorectal cancer (CRC) patients, and healthy non-carrier controls. We detected elevated levels of circulating cholesterol, lipids, and lipoproteins in LS carriers. Furthermore, we unveiled that Lynch syndrome carriers and CRC patients displayed similar alterations compared to healthy non-carriers in circulating amino acid and ketone body profiles. Overall, cancer-free Lynch syndrome carriers showed a unique circulating metabolome landscape. This study provides valuable insights into the systemic metabolic landscape of Lynch syndrome individuals. The findings hint at shared metabolic patterns between cancer-free Lynch syndrome carriers and CRC patients.

The solar forcing prepared for Phase 6 of the Coupled Model Intercomparison Project (CMIP6) has been used extensively in climate model experiments and has been tested in various intercomparison studies. Recently, an International Space Science Institute (ISSI) working group has been established to revisit the solar forcing recommendations, based on the lessons learned from CMIP6, and to assess new datasets that have become available, in order to define a road map for building a revised and extended historical solar forcing dataset for the upcoming Phase 7 of CMIP. This paper identifies the possible improvements required and outlines a strategy to address them in the planned new solar forcing dataset. Proposed major changes include the adoption of the new Total and Spectral Solar Irradiance Sensor (TSIS-1) solar reference spectrum for solar spectral irradiance and an improved description of top-of-the-atmosphere energetic electron fluxes, as well as their reconstruction back to 1850 by means of geomagnetic proxy data. In addition, there is an urgent need to consider the proposed updates in the ozone forcing dataset in order to ensure a self-consistent solar forcing in coupled models without interactive chemistry. Regarding future solar forcing, we propose consideration of stochastic ensemble forcing scenarios, ideally in concert with other natural forcings, in order to allow for realistic projections of natural forcing uncertainties.

A series of environmentally friendly non-isocyanate polyurethanes (NIPUs) was synthesized through a polycondensation reaction of as-synthesized semi-bio-based bis-cyclic carbonate with diamine derivatives. The synthesis of biscyclic carbonate was realized, for the first time, from 1-thioglycerol and polyethylene glycol diacrylate via thiol-ene click and transcarbonation reaction, respectively. The impacts of using different diamine derivatives on the chemical structural, mechanical properties, thermal stability, and surface wettability of the NIPUs were determined. It was found that the NIPU containing fatty acid-based diamine decomposed at a lower temperature than that of other polymers. Besides, it demonstrated a lower Young’s modulus and a higher tensile strain at break, possibly due to its four-branched structure and greater flexibility. Meanwhile, the NIPU prepared with p-xylylenediamine provided the highest decomposition temperature, owing to an aromatic moiety in the polymer’s backbone, which improved its stiffness and thermal stability. Furthermore, it was understood that the NIPU containing diamino-N-methyldipropyl-amine exhibited a higher Young’s modulus and a lower tensile strain at break, as it had a nitrogen atom in its structure and a trigonal pyramidal configuration with the highest density of hydrogen bonds between polymer chains. Most of the developed NIPUs displayed hydrophobic surface properties, offering promising alternatives to isocyanate-based coating materials.

Background Colorectal cancers (CRCs) in the Lynch syndromes have been assumed to emerge through an accelerated adenoma-carcinoma pathway. In this model adenomas with deficient mismatch repair have an increased probability of acquiring additional cancer driver mutation(s) resulting in more rapid progression to malignancy. If this model was accurate, the success of colonoscopy in preventing CRC would be a function of the intervals between colonoscopies and mean sojourn time of detectable adenomas. Contrary to expectations, colonoscopy did not decrease incidence of CRC in the Lynch syndromes and shorter colonoscopy intervals have not been effective in reducing CRC incidence. The prospective Lynch Syndrome Database (PLSD) was designed to examine these issues in carriers of pathogenic variants of the mis-match repair (path_MMR) genes. Materials and methods We examined the CRC and colorectal adenoma incidences in 3,574 path_MLH1, path_MSH2, path_MSH6 and path_PMS2 carriers subjected to regular colonoscopy with polypectomy, and considered the results based on sojourn times and stochastic probability paradigms. Results Most of the path_MMR carriers in each genetic group had no adenomas. There was no association between incidences of CRC and the presence of adenomas. There was no CRC observed in path_PMS2 carriers. Conclusions Colonoscopy prevented CRC in path_PMS2 carriers but not in the others. Our findings are consistent with colonoscopy surveillance blocking the adenoma-carcinoma pathway by removing identified adenomas which might otherwise become CRCs. However, in the other carriers most CRCs likely arised from dMMR cells in the crypts that have an increased mutation rate with increased stochastic chaotic probabilities for mutations. Therefore, this mechanism, that may be associated with no or only a short sojourn time of MSI tumours as adenomas, could explain the findings in our previous and current reports. Keywords: MSI, MLH1, MSH2, MSH6, PMS2, dMMR, Lynch syndromes, Colorectal, cancer, Adenoma, Colonoscopy, Sojourn time, Author(s): Pål Maller[sup.1], Saskia Haupt[sup.2,3], Aysel Ahadova[sup.4,5], Matthias Kloor[sup.4,5], Julian R. Sampson[sup.6], Lone Sunde[sup.7,8,9], Toni Seppälä[sup.10,11,12], John Burn[sup.13], Inge Bernstein[sup.14,15], Gabriel Capella[sup.16], D. Gareth Evans[sup.17], Annika Lindblom[sup.18,19], Ingrid Winship[sup.20,21], Finlay [...]

BackgroundAntitumoral immune response has a crucial role in constraining cancer. However, previous studies on cholangiocarcinoma (CCA), a rare and aggressive cancer, have reported contradictory findings on the prognostic impact of tumor-infiltrating T-lymphocytes. We aimed to clarify the effect of tumor-infiltrating CD3+ and CD8+ lymphocytes and PD-1/PD-L1 expression on CCA prognosis.MethodsCD3+, CD8+, and PD-1+ lymphocyte densities, as well as PD-L1 expression rate were analyzed from stained tissue microarray samples from the tumor center and invasive margin of 47 cholangiocarcinomas. The association of CD3+ and CD8+ based Immune cell score (ICS) and its components with overall survival was evaluated, adjusting for age, sex, TNM stage, radicality of surgery, tumor location, and PD-L1 expression on immune cells.ResultsLow ICS was a strong independent prognostic factor for worse overall survival (Hazard ratio 9.27, 95% confidence interval 2.72-31.64, P

Abstract The past three years (2020–2022) have witnessed the re-emergence of large, long-lived ozone holes over Antarctica. Understanding ozone variability remains of high importance due to the major role Antarctic stratospheric ozone plays in climate variability across the Southern Hemisphere. Climate change has already incited new sources of ozone depletion, and the atmospheric abundance of several chlorofluorocarbons has recently been on the rise. In this work, we take a comprehensive look at the monthly and daily ozone changes at different altitudes and latitudes within the Antarctic ozone hole. Following indications of early-spring recovery, the October middle stratosphere is dominated by continued, significant ozone reduction since 2004, amounting to 26% loss in the core of the ozone hole. We link the declines in mid-spring Antarctic ozone to dynamical changes in mesospheric descent within the polar vortex, highlighting the importance of continued monitoring of the state of the ozone layer.

Abstract The recognition of dominantly inherited micro-satellite instable (MSI) cancers caused by pathogenic variants in one of the four mismatch repair (MMR) genes MSH2, MLH1, MSH6 and PMS2 has modified our understanding of carcinogenesis. Inherited loss of function variants in each of these MMR genes cause four dominantly inherited cancer syndromes with different penetrance and expressivities: the four Lynch syndromes. No person has an “average sex “or a pathogenic variant in an “average Lynch syndrome gene” and results that are not stratified by gene and sex will be valid for no one. Carcinogenesis may be a linear process from increased cellular division to localized cancer to metastasis. In addition, in the Lynch syndromes (LS) we now recognize a dynamic balance between two stochastic processes: MSI producing abnormal cells, and the host’s adaptive immune system’s ability to remove them. The latter may explain why colonoscopy surveillance does not reduce the incidence of colorectal cancer in LS, while it may improve the prognosis. Most early onset colon, endometrial and ovarian cancers in LS are now cured and most cancer related deaths are after subsequent cancers in other organs. Aspirin reduces the incidence of colorectal and other cancers in LS. Immunotherapy increases the host immune system’s capability to destroy MSI cancers. Colonoscopy surveillance, aspirin prevention and immunotherapy represent major steps forward in personalized precision medicine to prevent and cure inherited MSI cancer.