We study the possible influences of the Russia-Ukraine War on Russia’s research productivity and international collaboration in science. For this purpose, we introduce and apply two recently... Show moreWe study the possible influences of the Russia-Ukraine War on Russia’s research productivity and international collaboration in science. For this purpose, we introduce and apply two recently developed indicators of relative intensity and balance in international collaboration. To see whether longitudinal trends have changed recently, we combine a long-term perspective based on annual updates since the year 2000 with a short-term perspective based on monthly updates since the beginning of 2022. The clearest change is that the productivity of Russian science, as measured within Web of Science, has dramatically decreased after several years of growth. There is also a clear decline in the degree of international collaboration in fields of research that heavily rely on large multinational infrastructures established through state agreements. In other fields, however, the degree of international collaboration is more stable. The general decline in Russian science seems to be more driven by internal factors than by loss of partnerships abroad. Show less
Aging is a multifaceted and intricate physiological process characterized by a gradual decline in functional capacity, leading to increased susceptibility to diseases and mortality. While... Show moreAging is a multifaceted and intricate physiological process characterized by a gradual decline in functional capacity, leading to increased susceptibility to diseases and mortality. While chronological age serves as a strong risk factor for age-related health conditions, considerable heterogeneity exists in the aging trajectories of individuals, suggesting that biological age may provide a more nuanced understanding of the aging process. However, the concept of biological age lacks a clear operationalization, leading to the development of various biological age predictors without a solid statistical foundation. This paper addresses these limitations by proposing a comprehensive operationalization of biological age, introducing the “AccelerAge” framework for predicting biological age, and introducing previously underutilized evaluation measures for assessing the performance of biological age predictors. The AccelerAge framework, based on Accelerated Failure Time (AFT) models, directly models the effect of candidate predictors of aging on an individual’s survival time, aligning with the prevalent metaphor of aging as a clock. We compare predictors based on the AccelerAge framework to a predictor based on the GrimAge predictor, which is considered one of the best-performing biological age predictors, using simulated data as well as data from the UK Biobank and the Leiden Longevity Study. Our approach seeks to establish a robust statistical foundation for biological age clocks, enabling a more accurate and interpretable assessment of an individual’s aging status. Show less
Observations of low-lying dark states in several photosynthetic complexes challenge our understanding of the mechanisms behind their efficient energy transfer processes. Computational models are... Show moreObservations of low-lying dark states in several photosynthetic complexes challenge our understanding of the mechanisms behind their efficient energy transfer processes. Computational models are necessary for providing novel insights into the nature and function of dark states, especially since these are not directly accessible in spectroscopy experiments. Here, we will focus on signatures of dark-type states in chlorosomes, a light-harvesting complex from green sulfur bacteria well-known for uniting a broad absorption band with very efficient energy transfer. In agreement with experiments, our simulations of two-dimensional electronic spectra capture the ultrafast exciton transfer occurring in 100s of femtoseconds within a single chlorosome cylinder. The sub-100 fs process corresponds to relaxation within the single-excitation manifold in a single chlorosome tube, where all initially created populations in the bright exciton states are quickly transferred to dark-type exciton states. Structural inhomogeneities on the local scale cause a redistribution of the oscillator strength, leading to the emergence of these dark-type exciton states, which dominate ultrafast energy transfer. The presence of the dark-type exciton states suppresses energy loss from an isolated chlorosome via fluorescence quenching, as observed experimentally. Our results further question whether relaxation to dark-exciton states is a leading process or merely competes with transfer to the baseplate within the photosynthetic apparatus of green sulfur bacteria. Show less
Castonguay, L.G.; Atzil‑Slonim, D.; Jong, K. de; Youn, S.J. 2024
Research Integrity (RI) is high on the agenda of both institutions and science policy. The European Union as well as national ministries of science have launched ambitious initiatives to combat... Show moreResearch Integrity (RI) is high on the agenda of both institutions and science policy. The European Union as well as national ministries of science have launched ambitious initiatives to combat misconduct and breaches of research integrity. Often, such initiatives entail attempts to regulate scientifc behavior through guidelines that institutions and academic communities can use to more easily identify and deal with cases of misconduct. Rather than framing misconduct as a result of an information defcit, we instead conceptualize Questionable Research Practices (QRPs) as attempts by researchers to reconcile epistemic and social forms of uncertainty in knowledge production. Drawing on previous literature, we defne epistemic uncertainty as the inherent intellectual unpredictability of scientifc inquiry, while social uncertainty arises from the human-made conditions for scientifc work. Our core argument—developed on the basis of 30 focus group interviews with researchers across diferent felds and European countries—is that breaches of research integrity can be understood as attempts to loosen overly tight coupling between the two forms of uncertainty. Our analytical approach is not meant to relativize or excuse misconduct, but rather to ofer a more fne-grained perspective on what exactly it is that researchers want to accomplish by engaging in it. Based on the analysis, we conclude by proposing some concrete ways in which institutions and academic communities could try to reconcile epistemic and social uncertainties on a more collective level, thereby reducing incentives for researchers to engage in misconduct. Show less
Paus, L.V. de; Yu, A.; Janssen, A.P.A.; Berg, R.J.B.H.N. van den; Heitman, L.H.; Stelt, M. van der 2024
The cannabinoid receptor type 2 (CB2R) is a G protein-coupled receptor with therapeutic potential for the treatment of inflammatory disorders. Fluorescent probes are desirable to study its receptor... Show moreThe cannabinoid receptor type 2 (CB2R) is a G protein-coupled receptor with therapeutic potential for the treatment of inflammatory disorders. Fluorescent probes are desirable to study its receptor localization, expression and occupancy. Previously, we have reported a photoaffinity probe LEI-121 that stabilized the inactive conformation of the CB2R. Here, we report the structure-based design of a novel bifunctional probe that captures the active conformation of the CB2R upon irradiation with light. An alkyne handle was incorporated to visualize the receptor using click-chemistry with fluorophore-azides. These probes may hold promise to study different receptor conformations in relation to their cellular localization and function. Show less
Fluency, comprehensibility, and accentedness are considered importantparameters of interpreting quality but have rarely been studiedsystematically in training programs of interpreting. Therefore,... Show moreFluency, comprehensibility, and accentedness are considered importantparameters of interpreting quality but have rarely been studiedsystematically in training programs of interpreting. Therefore, the presentstudy was set up to investigate the effect of fluency training on speechfluency, comprehensibility, and accentedness of interpreter trainees. Twogroups of interpreter trainees at a university in Iran took part in the study,receiving the same amount of instruction and practice (12 hours over 4weeks). The experimental group (N=30) spent 33% of the time (i.e., 4 of the12 hours in the training program) on dedicated fluency strategy training,encouraging the memorization, repetition, and retelling of audio and videomaterials. The remaining 67% was spent on training general speaking skills.The control group (N=30) were only taught general speaking skills in thetraining program but received no dedicated fluency training. Systematicinterviews were run to assess the interpreter trainees’ speech fluency,comprehensibility and accentedness, which were judged independently bythree expert raters at three moments of testing, i.e., pretest, immediateposttest, and delayed posttest (one month later). The findings revealed thatthe fluency training significantly enhanced the interpreter trainees’ fluency,and to a lesser extent the students’ comprehensibility but had only amarginal effect on accentedness. The pedagogical implication would be thatawareness training on speech fluency Show less
Mulholland, M.; Depuydt, M.A.C.; Jakobsson, G.; Ljungcrantz, I.; Grentzmann, A.; To, F.; ... ; Engelbertsen, D. 2024
The interleukin-1 receptor accessory protein (IL1RAP) is a co-receptor required for signalling through the IL-1, IL-33, and IL-36 receptors. Using a novel anti-IL1RAP-blocking antibody, we... Show moreThe interleukin-1 receptor accessory protein (IL1RAP) is a co-receptor required for signalling through the IL-1, IL-33, and IL-36 receptors. Using a novel anti-IL1RAP-blocking antibody, we investigated the role of IL1RAP in atherosclerosis.Single-cell RNA sequencing data from human atherosclerotic plaques revealed the expression of IL1RAP and several IL1RAP-related cytokines and receptors, including IL1B and IL33. Histological analysis showed the presence of IL1RAP in both the plaque and adventitia, and flow cytometry of murine atherosclerotic aortas revealed IL1RAP expression on plaque leucocytes, including neutrophils and macrophages. High-cholesterol diet fed apolipoprotein E-deficient (Apoe-/-) mice were treated with a novel non-depleting IL1RAP-blocking antibody or isotype control for the last 6 weeks of diet. IL1RAP blockade in mice resulted in a 20% reduction in subvalvular plaque size and limited the accumulation of neutrophils and monocytes/macrophages in plaques and of T cells in adventitia, compared with control mice. Indicative of reduced plaque inflammation, the expression of several genes related to leucocyte recruitment, including Cxcl1 and Cxcl2, was reduced in brachiocephalic arteries of anti-IL1RAP-treated mice, and the expression of these chemokines in human plaques was mainly restricted to CD68+ myeloid cells. Furthermore, in vitro studies demonstrated that IL-1, IL-33, and IL-36 induced CXCL1 release from both macrophages and fibroblasts, which could be mitigated by IL1RAP blockade.Limiting IL1RAP-dependent cytokine signalling pathways in atherosclerotic mice reduces plaque burden and plaque inflammation, potentially by limiting plaque chemokine production. Show less
The clinical translation of polysarcosine (pSar) as polyethylene glycol (PEG) replacement in the development of novel nanomedicines creates a broad demand of polymeric material in high-quality... Show moreThe clinical translation of polysarcosine (pSar) as polyethylene glycol (PEG) replacement in the development of novel nanomedicines creates a broad demand of polymeric material in high-quality making high-purity sarcosine N-carboxyanhydride (Sar-NCA) as monomer for its production inevitable. Within this report, we present the use of triethyloxonium tetrafluoroborate in Sar-NCA synthesis with focus on amino acid and chloride impurities to avoid the sublimation of Sar-NCAs. With a view towards upscaling into kilogram or ton scale, a new methodology of monomer purification is introduced by utilizing the Meerwein's Salt triethyloxonium tetrafluoroborate to remove chloride impurities by covalent binding and converting chloride ions into volatile products within a single step. The novel straightforward technique enables access to monomers with significantly reduced chloride content (<100 ppm) compared to Sar-NCA derived by synthesis or sublimation. The derived monomers enable the controlled-living polymerization in DMF and provide access to pSar polymers with Poisson-like molecular weight distribution within a high range of chain lengths (Xn 25-200). In conclusion, the reported method can be easily applied to Sar-NCA synthesis or purification of commercially available pSar-NCAs and eases access to well-defined hetero-telechelic pSar polymers. Show less
The Late Pleistocene archeological record shows emerging patterns of population turnover frequently associated with technological change between c. 50–40 thousand years ago. In Europe, this is... Show moreThe Late Pleistocene archeological record shows emerging patterns of population turnover frequently associated with technological change between c. 50–40 thousand years ago. In Europe, this is thought to be related to indigenous population admixture and/or the diffusion of developing technologies by Homo sapiens resulting in a widely distributed spatiotemporal patchwork of industries with combinations of Middle and Upper Paleolithic traits. The Late Pleistocene record of Romania forms an anomaly in these scenarios. On the one hand, the country has important Pleistocene archives that preserve direct evidence of early modern humans with Neandertal genetic introgression. On the other hand, Romania shows no evidence of novel technology during the Middle to Upper Paleolithic transition. Here, we review the Late Middle and Early Upper Paleolithic archeological record of Romania supplemented with new radiocarbon ages and excavation data to clarify the validity of this current archeological interpretation. We conclude that while Neandertals and modern humans were in regional contact, raw materials eccentricities and incomplete empirical knowledge of past intergroup cultural transmission have obscured our ability to identify indicative material cultural signals indicating that current methods of understanding hybridized material culture are incomplete. Show less
Hasan-Aslih, S.; Pliskin, R.; Shuman, E.; Zomeren, M. van; Saguy, T.; Halperin, E. 2024
The current research examines joint collective action between advantaged and disadvantaged groups, from the perspective of the latter. We hypothesize that joint action poses a dilemma which lies in... Show moreThe current research examines joint collective action between advantaged and disadvantaged groups, from the perspective of the latter. We hypothesize that joint action poses a dilemma which lies in the tension between perceived instrumentality of joint action (i.e., ability to promote the disadvantaged’s goals) and perceived normalization (i.e., its tendency to blur power relations). We test this idea across three studies in the United States and Israel/Palestine. In Study 1 (n = 361) we manipulated perceptions of joint action from the perspective of a hypothetical character, and in Study 2 (n = 378) we presented participants with an article highlighting the risk and benefit of joint activism. Results showed that perceived instrumentality increases, whereas perceived normalization decreases joint action tendencies. In Study 3 (n = 240), we described a joint action event that taps into some of the themes that induce concerns about normalization. We found that normalization perceptions feed into perceptions of instrumentality, and this occurred mainly among high identifiers, for whom the dilemma is most salient. The implications of these findings for understanding the complexity of joint collective action from the perspective of the disadvantaged are discussed. Show less
Tuberculosis (TB) is still among the deadliest infectious diseases, hence there is a pressing need for more effective TB vaccines. Cationic liposome subunit vaccines are excellent vaccine... Show moreTuberculosis (TB) is still among the deadliest infectious diseases, hence there is a pressing need for more effective TB vaccines. Cationic liposome subunit vaccines are excellent vaccine candidates offering effective protection with a better safety profile than live vaccines. In this study, we aim to explore intrinsic adjuvant properties of cationic liposomes to maximize immune activation while minimizing aspecific cytotoxicity. To achieve this, we developed a rational strategy to select liposomal formulation compositions and assessed their physicochemical and immunological properties in vitro models using human monocyte-derived dendritic cells (MDDCs). A broad selection of commercially available cationic compounds was tested to prepare liposomes containing Ag85B-ESAT6-Rv2034 (AER) fusion protein antigen. 1,2-Dioleoyl-sn‑glycero-3-ethylphosphocholine (EPC)-based liposomes exhibited the most advantageous activation profile in MDDCs as assessed by cell surface activation markers, cellular uptake, antigen-specific T-cell activation, cytokine production, and cellular viability. The addition of cholesterol to 20 mol% improved the performance of the tested formulations compared to those without it; however, when its concentration was doubled there was no further benefit, resulting in reduced cell viability. This study provides new insights into the role of cationic lipids and cholesterol in liposomal subunit vaccines. Show less
The functioning of groups and societies requires that individuals cooperate on public goods such as healthcare and state defense. More often than not, individuals face multiple public goods and... Show moreThe functioning of groups and societies requires that individuals cooperate on public goods such as healthcare and state defense. More often than not, individuals face multiple public goods and must choose on which to cooperate, if at all. Such decisions can be difficult when public goods are attractive on one dimension (e.g., being “efficient” in providing comparatively high returns) and unattractive on another (e.g., creating inequality by providing some group members greater returns than others). We examined how people manage such decision conflicts in five preregistered experiments (N = 900) that confronted participants with two public goods that varied in efficiency and (in)equality of returns. People cooperated more on the comparatively efficient public good and on the equal-return (vs. unequal-return) public good (Experiment 1), yet when the unequal-returns public good was also the most efficient, individuals cooperated comparatively more on this unequal-but-efficient public good when they themselves benefitted the most from inequality (Experiments 2–4). Low beneficiaries largely ignored public goods efficiency and preferentially cooperated on the equal- rather than unequal-returns public good. Expectations (Experiments 2–4), preferences for revising the multiple-public-goods provision problems’ choice architecture (Experiments 3–4), and descriptive norms held by uninvolved arbitrators (Experiment 5) echoed these cooperation patterns, but uninvolved arbitrators deemed it socially appropriate to cooperate more on the equal than the unequal public good regardless of beneficiary position. We discuss implications for theory and policy on cooperation Show less
