Copper isotopes (δ65Cu) in hydrothermal fluids have the potential to provide information on ore-forming processes occurring below the seafloor, but Cu isotope data from high-temperature fluids are scarce. Here, we examine the extent to which coexisting sulfide minerals in a hydrothermal chimney can preserve fluid Cu isotope ratios using a fluid-solid pair of a black smoker (333°C) from the Roman Ruins vent area (PACMANUS) in the Manus Basin. Two ca. 3 cm long transects through the chalcopyrite-rich chimney wall show an increase in δ65Cu from 0.48 to 2.28‰ from the interior to the exterior, coupled with limited variation in sulfide δ34S (1.52–4.72‰). The Cu isotopic composition of chalcopyrite from the innermost wall closely resembles the δ65Cu value of the paired hydrothermal fluid, indicating that chalcopyrite in the inner ∼5 mm of the chimney records the Cu isotope ratio of the venting fluid. Beyond this, an increase in sulfide δ65Cu toward the exterior correlates with an increase in the relative abundance of secondary Cu sulfides. The appearance of bornite coincides with the presence of small barite crystals, suggesting this represents a redox gradient between reduced hydrothermal fluids and oxidized seawater admixing inwards. Elevated δ65Cu in this zone can be explained by the precipitation of secondary Cu sulfides from 65Cu-enriched fluids formed during oxidative chalcopyrite dissolution. Our findings indicate that interactions with oxidizing seawater shift chalcopyrite δ65Cu values over small spatial scales, and that caution must be applied if chimney sulfides are used to reconstruct δ65Cu values of high-temperature hydrothermal fluids.
View lessFlyovers have featured in critical urban planning scholarship in the Global South as fetishized symbols of modernity, often fragmenting urban environments, fracturing space, exacerbating inequalities, and embodying “worlding”’ aspirations of city planners. Acknowledging the role of such infrastructure as technologies of (dis)connection in increasingly enclaved cities, I seek to situate the flyover, its material form, and attendant gaps, characterized by raised ribbons of “smooth” flows, leftover spaces, and proliferation of informal practices, as important sites of encounters. As such, I take “borderland urbanism” as an impetus to think flyover geographies anew by locating the flyover as a particular place in the city that is transient, contested, and constantly re-made. Through ethnographic vignettes and interviews, I sketch out everyday urban experiences over and under a flyover in Karachi, Pakistan. I illustrate how the flyover as a spatial and temporal leap is perceived and experienced by a range of differently mobile urban dwellers, paying particular attention to how walking bodies inhabit an infrastructural landscape that heavily privileges cars and motorcycles. Furthermore, I trace how life in the interstices under the flyover is assembled through social collaboration, resisting eviction, and a politics of visibility.
View lessAdverse effects of psychological stress on physical and mental health, especially in older age, are well documented. How perceived stress relates to the epigenetic clock measure, DNA methylation age acceleration (DNAmAA), is less well understood and existing studies reported inconsistent results. DNAmAA was estimated from five epigenetic clocks (7-CpG, Horvath's, Hannum's, PhenoAge and GrimAge DNAmAA). Cohen's Perceived Stress Scale (PSS) was used as marker of psychological stress. We analyzed data from 1,100 Berlin Aging Study II (BASE-II) participants assessed as part of the GendAge study (mean age = 75.6 years, SD = 3.8 years, 52.1% women). In a first step, we replicated well-established associations of perceived stress with morbidity, frailty, and symptoms of depression in the BASE-II cohort studied here. In a second step, we did not find any statistically significant association of perceived stress with any of the five epigenetic clocks in multiple linear regression analyses that adjusted for covariates. Although the body of literature suggests an association between higher DNAmAA and stress or trauma during early childhood, the current study found no evidence for an association of perception of stress with DNAmAA in older people. We discuss possible reasons for the lack of associations and highlight directions for future research.
View lessClinical translation from bench to bedside often remains challenging even despite promising preclinical evidence. Among many drivers like biological complexity or poorly understood disease pathology, preclinical evidence often lacks desired robustness. Reasons include low sample sizes, selective reporting, publication bias, and consequently inflated effect sizes. In this context, there is growing consensus that confirmatory multicenter studies -by weeding out false positives- represent an important step in strengthening and generating preclinical evidence before moving on to clinical research. However, there is little guidance on what such a preclinical confirmatory study entails and when it should be conducted in the research trajectory. To close this gap, we organized a workshop to bring together statisticians, clinicians, preclinical scientists, and meta-researcher to discuss and develop recommendations that are solutionoriented and feasible for practitioners. Herein, we summarize and review current approaches and outline strategies that provide decision-critical guidance on when to start and subsequently how to plan a confirmatory study. We define a set of minimum criteria and strategies to strengthen validity before engaging in a confirmatory preclinical trial, including sample size considerations that take the inherent uncertainty of initial (exploratory) studies into account. Beyond this specific guidance, we highlight knowledge gaps that require further research and discuss the role of confirmatory studies in translational biomedical research. In conclusion, this workshop report highlights the need for close interaction and open and honest debate between statisticians, preclinical scientists, meta-researchers (that conduct research on research), and clinicians already at an early stage of a given preclinical research trajectory.
View lessBackground: Migraine frequency increases after the cessation of successful preventive treatment with CGRP(-receptor) monoclonal antibodies (mAbs). In this study, we aimed to evaluate the course of migraine after treatment resumption.
Methods: Patients with migraine, who started treatment with the same CGRP(-R) mAb after a three-month drug holiday were included in this analysis. We collected headache data at four prospective visits: 1) during the four weeks before the initial mAb treatment (baseline); 2) during the four weeks before the last mAb injection; 3) in weeks 13-16 of the drug holiday; 4) in weeks 9-12 after treatment restart. Outcomes were the changes in monthly migraine days (MMD), monthly headache days (MHD), monthly days with acute medication use (AMD) and Headache Impact Test-6 (HIT-6) scores across the observation period.
Results: This study included 39 patients (erenumab n = 16; galcanezumab/ fremanezumab n = 23). MMD decreased from 12.3 +/- 6.3 at the end of the drug holiday to 7.8 +/- 5.5 three months after treatment restart (p = 0.001). The improvement after treatment resumption was similar to the response in the initial treatment period (baseline: 12.3 +/- 6.3 MMD vs. 7.5 +/- 5.2 MMD before treatment interruption). MHD and AMD showed a significant improvement after treatment restart. HIT-6 scores decreased, indicating a diminished impact of headache on everyday life.
Conclusions: Reinitiation of treatment with CGRP(-R) mAbs after a drug holiday leads to a significant reduction of migraine frequency and medication use as well as improvement in quality of life.
View lessBackground: Art therapy is a form of complementary therapy to treat a wide variety of health problems. Existing studies examining the effects of art therapy differ substantially regarding content and setting of the intervention, as well as their included populations, outcomes, and methodology. The aim of this review is to evaluate the overall effectiveness of active visual art therapy, used across different treatment indications and settings, on various patient outcomes.
Methods: We will include randomised controlled studies with an active art therapy intervention, defined as any form of creative expression involving a medium (such as paint etc.) to be actively applied or shaped by the patient in an artistic or expressive form, compared to any type of control. Any treatment indication and patient group will be included. A systematic literature search of the Cochrane Library, EMBASE (via Ovid), MEDLINE (via Ovid), CINAHL, ERIC, APA PsycArticles, APA Psyclnfo, and PSYNDEX (all via EBSCOHost), ClinicalTrials.gov and the WHO's International Clinical Trials Registry Platform (ICTRP) will be conducted. Psychological, cognitive, somatic and economic outcomes will be used. Based on the number, quality and outcome heterogeneity of the selected studies, a meta-analysis might be conducted, or the data synthesis will be performed narratively only. Heterogeneity will be assessed by calculating the p-value for the chi' test and the I-2 statistic. Subgroup analyses and meta-regressions are planned.
Discussion: This systematic review will provide a concise overview of current knowledge of the effectiveness of art therapy. Results have the potential to (1) inform existing treatment guidelines and clinical practice decisions, (2) provide insights to the therapy's mechanism of change, and (3) generate hypothesis that can serve as a starting point for future randomised controlled studies.
View lessBackground: People with depression often present with concurrent cognitive impairment. Computerized cognitive training (CCT) is a safe and efficacious strategy to maintain or enhance cognitive performance in a range of clinical populations. However, its efficacy in people with depression and how it varies across populations and design factors are currently unclear.
Methods: We searched MEDLINE, EMBASE, and PsycINFO from inception to 13 July 2021 for randomised controlled trials examining the efficacy of CCT vs any control condition on cognitive, mood, psychiatric symptoms, psychosocial, and daily functioning in adults with depression. Eligible samples include studies specifically targeting people with major depressive disorder as well as those with other diagnoses where at least 50% of the sample meets the clinical criteria for depression, with the exception of major psychiatric disorders or dementia. The primary outcome is change in the overall cognitive performance. Multivariate analyses will be used to examine the effect sizes on each outcome category as well as possible effect modifiers and correlations between categories. The risk of bias will be assessed using the Cochrane risk of bias tool version 2.
Discussion: To the best of our knowledge, this will be the first systematic review and meta-analysis of narrowly defined CCT across clinical populations with depression. We aim to investigate not only whether CCT is efficacious for cognition, but also how such effects vary across design factors, what other clinically relevant outcomes might respond to CCT, and the extent to which they differ across populations.
View lessThis work analyses the symbols and utopian thought in the book of Ibn Bājja as well as his philosophy about the purpose of the human being to reach perfection and the essence of life. Through reading closely his work Tadbīr al-mutawaḥḥid and with some other sources about the work, I formulated some questions which I will then answer in this essay. From Ibn Bājja’s, what are the ways to achieve perfection ? How do solitary people achieve a utopian life? What is the meaning of al-mutawaḥḥid (solitary)? Tadbīr al-mutawaḥḥid was used for analysis to answer these questions. By reading this book, I can directly understand Ibn Bajja's philosophy on utopia and the idea of solitude from the corrupt society and upgrading the soul with virtuous morals. Also there are secondary sources, between articles and books that analyse Ibn Bājja’s book, as well as discuss the idea of isolation from society. In order to be able at the end of this work to conclude whether the Ibn Bājja’s work leads a utopian life or not, it was necessary to define the concept of utopianism. There are some general sources that give a brief overview of what Utopia is, as well as compar it with the utopianism of Ibn Bājja in his book Tadbīr al-mutawaḥḥid. It'll be interesting at the start of this essay to introduc the author of the book Tadbīr al-mutawaḥḥid. This summary introductory of the aspects and circumstances of his life may be of some help in understanding the idea of his book, especially the idea of isolation and loneliness.
View lessHaving a tool to monitor the microbial abundances rapidly and to utilize the data to predict the reactor performance would facilitate the operation of an anaerobic membrane bioreactor (AnMBR). This study aims to achieve the aforementioned scenario by developing a linear regression model that incorporates a time-lagging mode. The model uses low nucleic acid (LNA) cell numbers and the ratio of high nucleic acid (HNA) to LNA cells as an input data set. First, the model was trained using data sets obtained from a 35 L pilot-scale AnMBR. The model was able to predict the chemical oxygen demand (COD) removal efficiency and methane production 3.5 days in advance. Subsequent validation of the model using flow cytometry (FCM)-derived data (at time t – 3.5 days) obtained from another biologically independent reactor did not exhibit any substantial difference between predicted and actual measurements of reactor performance at time t. Further cell sorting, 16S rRNA gene sequencing, and correlation analysis partly attributed this accurate prediction to HNA genera (e.g., Anaerovibrio and unclassified Bacteroidales) and LNA genera (e.g., Achromobacter, Ochrobactrum, and unclassified Anaerolineae). In summary, our findings suggest that HNA and LNA cell routine enumeration, along with the trained model, can derive a fast approach to predict the AnMBR performance.
View lessIn this article, we study the quantum field theoretic generalization of the Caldeira-Leggett model in general curved space-time considering interactions between two scalar fields in a classical gravitational background. The thermalization phenomena is then studied from the obtained de Sitter solution using quantum quench from one scalar field model obtained from path integrated effective action. We consider an instantaneous quench in the time-dependent mass protocol of the field of our interest. We find that the dynamics of the field post-quench can be described in terms of the state of the generalized Calabrese-Cardy (gCC) form and computed the different types of two-point correlation functions in this context. We explicitly found the conserved charges of algebra that represents the gCC state after a quench in de Sitter space and found it to be significantly different from the flat space-time results. We extend our study for the different two-point correlation functions not only considering the pre-quench state as the ground state, but also a squeezed state. We found that irrespective of the pre-quench state, the post quench state can be written in terms of the gCC state showing that the subsystem of our interest thermalizes in de Sitter space. Furthermore, we provide a general expression for the two-point correlators and explicitly show the thermalization process by considering a thermal Generalized Gibbs ensemble (GGE). Finally, from the equal time momentum dependent counterpart of the obtained results for the two-point correlators, we have studied the hidden features of the power spectra and studied its consequences for different choices of the quantum initial conditions.
View lessWhile nighttime curfews are less severe restrictions compared to around-the-clock curfews in mitigating the spread of Covid-19, they are nevertheless highly controversial, with the scarce literature on their effectiveness providing mixed evidence. We study the effectiveness of the nighttime curfew in Hamburg, Germany’s second largest city, in mitigating the spread of Covid-19. This curfew forbid people from leaving their home between 9 p.m. and 5 a.m. for non-essential businesses. Applying both difference-in-differences and synthetic control group methods, we find that the curfew was effective in reducing the number of Covid-19 cases. As it is unclear whether and how the virus will mutate in the next time, policy-makers might have to resort to non-pharmaceutical interventions again. Nighttime curfews should be kept in the toolbox of policy-makers to fight Covid-19.
View lessFibroblast growth factor 2 (FGF2) exits cells by direct translocation across the plasma membrane, a type I pathway of unconventional protein secretion. This process is initiated by phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2)-dependent formation of highly dynamic FGF2 oligomers at the inner plasma membrane leaflet, inducing the formation of lipidic membrane pores. Cell surface heparan sulfate chains linked to glypican-1 (GPC1) capture FGF2 at the outer plasma membrane leaflet, completing FGF2 membrane translocation into the extracellular space. While the basic steps of this pathway are well understood, the molecular mechanism by which FGF2 oligomerizes on membrane surfaces remains unclear. In the current study, we demonstrate the initial step of this process to depend on C95-C95 disulfide-bridge-mediated FGF2 dimerization on membrane surfaces, producing the building blocks for higher FGF2 oligomers that drive the formation of membrane pores. We find FGF2 with a C95A substitution to be defective in oligomerization, pore formation, and membrane translocation. Consistently, we demonstrate a C95A variant of FGF2 to be characterized by a severe secretion phenotype. By contrast, while also important for efficient FGF2 secretion from cells, a second cysteine residue on the molecular surface of FGF2 (C77) is not involved in FGF2 oligomerization. Rather, we find C77 to be part of the interaction interface through which FGF2 binds to the α1 subunit of the Na,K-ATPase, the landing platform for FGF2 at the inner plasma membrane leaflet. Using cross-linking mass spectrometry, atomistic molecular dynamics simulations combined with a machine learning analysis and cryo-electron tomography, we propose a mechanism by which disulfide-bridged FGF2 dimers bind with high avidity to PI(4,5)P2 on membrane surfaces. We further propose a tight coupling between FGF2 secretion and the formation of ternary signaling complexes on cell surfaces, hypothesizing that C95-C95-bridged FGF2 dimers are functioning as the molecular units triggering autocrine and paracrine FGF2 signaling.
View lessBackground: During the COVID-19 pandemic, governments worldwide issued lockdown and social-distancing measures, which triggers psychological distress and may increase the occurrence of domestic violence (DV). We examined the role of the LGBT+ status in the relationship between risk factors of DV and its occurrence during the pandemic. Methods: In this cross-sectional study (n = 5,148), an online self-report questionnaire was administered to a non-probabilistic sample of participants living in Belgium, Germany, and Portugal between March and June 2020. Participants were sampled through national media, social media, and snowballing procedures. Results: LGBT+ persons reported significantly higher levels of perceived stress, more acute stress symptoms, and more illegal drug use during the first weeks of the lockdown compared to non-LGBT+ persons. DV in LGBT+ persons was not more prevalent than in the non-LGBT under COVID-19 lockdown measures. No significant evidence was found indicating that identifying as LGBT+ itself increases the risk of DV exposure. Conclusion: LGBT+ persons were more at risk of DV compared to non-LGBT+ persons prior to but not during COVID-19 lockdown measures. The increased risk for DV can be linked to socio-demographic characteristics, levels of stress, and illegal drug use which are more prevalent in LGBT+ persons than in non-LGBT+ persons.
View lessR&D capacity is claimed to be a stimulant for open innovation. We argue that after a specific level of R&D investment, firms diminish their external innovation collaboration due to the risk of knowledge imitation and unwanted spillovers, which generates a concave relationship between the two variables. This concave relationship can be flattened if an appropriation strategy is applied. Using 3815 firm observations from the German Mannheim Innovation Panel (MIP) in 2013 and 2017, our regression results support our hypotheses. Theoretically, our study suggests that the absorptive capacity literature should consider the potential negative impact of internal R&D capacity on openness. Similarly, economists should approach knowledge spillovers as a manageable issue if an appropriation strategy is present. Specifically, appropriation stimulates openness by playing a double role in protecting internal knowledge against imitation while also sending a quality signal for external partners to collaborate. This effect is driven by the presence of an appropriation strategy regardless of its form or strength.
View lessTo confront the climate crisis requires fundamental system change in order to break the convention of relentless economic exploitation of nature. In this Special Issue we extend understanding of the opportunities for an organizing perspective on sustainability in order that organization studies might contribute more effectively to the challenges of organizing sustainably. This organizing perspective is particularly sensitive to (1) a variety of forms and practices of sustainable organizing in different societal spheres and on different levels, (2) the social institutions, logics and value systems in which these forms and practices are embedded, (3) the power and politics of promoting (or blocking) sustainable organization, and (4) the ways in which work, voice, participation, and inclusion are organized and contribute to developing societal capabilities. These features formed the basis of our original call for papers and we review selected literature on sustainability, including the contribution of organization studies and the articles in this Special Issue, through this organizing perspective. In so doing we identify four key themes of a future research agenda that builds from the foundations of existing research and addresses key current limitations in both theory and practice: sustainability requires social justice; connecting local and global scale shifts; democratizing governance; and acting collectively. We conclude with some implications for our own scholarship in organization studies if we are to meet the twin challenges of the need for new theorizing in combination with devising practically relevant support for change.
View lessThe NASA MODIS MOD10A1 snow albedo product has enabled numerous glaciological applications. The temporal consistency of MODIS albedo is critical to obtaining reliable results from this 22-year time series. The orbit of Terra began to drift toward earlier acquisition times after the final inclination adjustment maneuver to maintain its nominal orbit by NASA on 27 February 2020, which may introduce biases that compromise the accuracy of quantitative time series analysis as the drift continues. Here, we evaluate the impact of Terra's orbital drift by comparing the differences between the Terra MODIS albedo and albedo products derived from Aqua MODIS, harmonized Landsat and Sentinel 2, Sentinel 3, and PROMICE (Programme for Monitoring of the Greenland Ice Sheet) ground measurements over the Greenland ice sheet. Our results suggest that the influence of orbital drift on albedo is small (+0.01 in 2020), but potentially biased for time series analysis. Our analysis also finds that the drift effect that causes earlier image acquisition time may lead to more apparently cloudy pixels and thus effectively reduce the Terra MODIS temporal resolution over Greenland.
View lessHfO2-based thin films hold huge promise for integrated devices as they show full compatibility with semiconductor technologies and robust ferroelectric properties at nanometer scale. While their polarization switching behavior has been widely investigated, their electromechanical response received much less attention so far. Here, we demonstrate that piezoelectricity in Hf0.5Zr0.5O2 ferroelectric capacitors is not an invariable property but, in fact, can be intrinsically changed by electrical field cycling. Hf0.5Zr0.5O2 capacitors subjected to ac cycling undergo a continuous transition from a positive effective piezoelectric coefficient d33 in the pristine state to a fully inverted negative d33 state, while, in parallel, the polarization monotonically increases. Not only can the sign of d33 be uniformly inverted in the whole capacitor volume, but also, with proper ac training, the net effective piezoresponse can be nullified while the polarization is kept fully switchable. Moreover, the local piezoresponse force microscopy signal also gradually goes through the zero value upon ac cycling. Density functional theory calculations suggest that the observed behavior is a result of a structural transformation from a weakly-developed polar orthorhombic phase towards a well-developed polar orthorhombic phase. The calculations also suggest the possible occurrence of a non-piezoelectric ferroelectric Hf0.5Zr0.5O2. Our experimental findings create an unprecedented potential for tuning the electromechanical functionality of ferroelectric HfO2-based devices.
View lessWetland restoration has received increasing attention to compensate for the continuing loss of natural wetlands and revive biodiversity and associated ecological functions. The development of methods for assessing the effectiveness of restoration measures is important for wetland management. However, most studies assessing restoration success in freshwater ecosystems are based on taxonomic biodiversity; trait-based approaches remain limited, particularly in wetland ecosystems. Here, we assess the effectiveness of wetland restoration in the Sanjiang Plain, Northeast China, based on the trait composition and functional diversity of aquatic insect assemblages. We found that functional richness in restored wetlands was significantly higher than impacted wetlands but lower than natural wetlands. Compared to natural wetlands, functional beta diversity of impacted wetlands was higher. In terms of dissimilarity between wetland types, trait composition of aquatic insects in restored wetlands showed a higher similarity to natural wetlands compared to those in impacted wetlands. Trait compositions of aquatic insect assemblages in restored wetlands were more similar to impacted wetlands in May but showed a greater similarity to natural wetlands in October. Our study shows that restoration measures have facilitated the partial recovery of functional diversity and trait composition of aquatic insect assemblages in the Sanjiang Plain wetlands. Our study confirms the potential of using trait-based approach to assess the effectiveness of wetland restoration. Given that assessments based on taxonomic and trait data can provide complementary information, we recommend incorporating both taxonomic and functional metrics and considering seasonal dynamics of wetlands in post-restoration monitoring and assessment in wetlands.
View lessPolycomb Repressive Complexes (PRCs) control gene expression through the incorporation of H2Aub and H3K27me3. In recent years, there is increasing evidence of the complexity of PRCs’ interaction networks and the interplay of these interactors with PRCs in epigenome reshaping, which is fundamental to understand gene regulatory mechanisms. Here, we identified UBIQUITIN SPECIFIC PROTEASE 5 (UBP5) as a chromatin player able to counteract the deposition of the two PRCs’ epigenetic hallmarks in Arabidopsis thaliana. We demonstrated that UBP5 is a plant developmental regulator based on functional analyses of ubp5-CRISPR Cas9 mutant plants. UBP5 promotes H2A monoubiquitination erasure, leading to transcriptional de-repression. Furthermore, preferential association of UBP5 at PRC2 recruiting motifs and local H3K27me3 gaining in ubp5 mutant plants suggest the existence of functional interplays between UBP5 and PRC2 in regulating epigenome dynamics. In summary, acting as an antagonist of the pivotal epigenetic repressive marks H2Aub and H3K27me3, UBP5 provides novel insights to disentangle the complex regulation of PRCs’ activities.
View lessAdaptive decision-making is governed by at least two types of memory processes. On the one hand, learned predictions through integrating multiple experiences, and on the other hand, one-shot episodic memories. These two processes interact, and predictions – particularly prediction errors – influence how episodic memories are encoded. However, studies using computational models disagree on the exact shape of this relationship, with some findings showing an effect of signed prediction errors and others showing an effect of unsigned prediction errors on episodic memory. We argue that the choice-confirmation bias, which reflects stronger learning from choice-confirming compared to disconfirming outcomes, could explain these seemingly diverging results. Our perspective implies that the influence of prediction errors on episodic encoding critically depends on whether people can freely choose between options (i.e., instrumental learning tasks) or not (Pavlovian learning tasks). The choice-confirmation bias on memory encoding might have evolved to prioritize memory representations that optimize reward-guided decision-making. We conclude by discussing open issues and implications for future studies.
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