533 research outputs found
Denying humanness to victims: How gang members justify violent behavior
The high prevalence of violent offending amongst gang-involved youth has been established in the literature. Yet the underlying psychological mechanisms that enable youth to engage in such acts of violence remain unclear. 189 young people were recruited from areas in London, UK, known for their gang activity. We found that gang members, in comparison to non-gang youth, described the groups they belong to as having recognized leaders, specific rules and codes, initiation rituals, and special clothing. Gang members were also more likely than non-gang youth to engage in violent behavior and endorse moral disengagement strategies (i.e., moral justification, euphemistic language, advantageous comparison, displacement of responsibility, attribution of blame, and dehumanization). Finally, we found that dehumanizing victims partially mediated the relationship between gang membership and violent behavior. These findings highlight the effects of groups at the individual level and an underlying psychological mechanism that explains, in part, how gang members engage in violence
Mapping cortical activations underlying covert and overt language production using high-density diffuse optical tomography
Gold standard neuroimaging modalities such as functional magnetic resonance imaging (fMRI), positron emission tomography (PET), and more recently electrocorticography (ECoG) have provided profound insights regarding the neural mechanisms underlying the processing of language, but they are limited in applications involving naturalistic language production especially in developing brains, during face-to-face dialogues, or as a brain-computer interface. High-density diffuse optical tomography (HD-DOT) provides high-fidelity mapping of human brain function with comparable spatial resolution to that of fMRI but in a silent and open scanning environment similar to real-life social scenarios. Therefore, HD-DOT has potential to be used in naturalistic settings where other neuroimaging modalities are limited. While HD-DOT has been previously validated against fMRI for mapping the neural correlates underlying language comprehension and covert (i.e., silent ) language production, HD-DOT has not yet been established for mapping the cortical responses to overt (i.e., out loud ) language production. In this study, we assessed the brain regions supporting a simple hierarchy of language tasks: silent reading of single words, covert production of verbs, and overt production of verbs in normal hearing right-handed native English speakers (n = 33). First, we found that HD-DOT brain mapping is resilient to movement associated with overt speaking. Second, we observed that HD-DOT is sensitive to key activations and deactivations in brain function underlying the perception and naturalistic production of language. Specifically, statistically significant results were observed that show recruitment of regions in occipital, temporal, motor, and prefrontal cortices across all three tasks after performing stringent cluster-extent based thresholding. Our findings lay the foundation for future HD-DOT studies of imaging naturalistic language comprehension and production during real-life social interactions and for broader applications such as presurgical language assessment and brain-machine interfaces
Shifting perspectives on coastal impacts and adaptation
The Intergovernmental Panel on Climate Change reports reflect evolving attitudes in adapting to
sea-level rise by taking a systems approach and recognizing that multiple responses exist to achieve a
less hazardous coast.info:eu-repo/semantics/publishedVersio
Modelling the cascade of biomarker changes in progranulinârelated frontotemporal dementia
AbstractBackgroundProgranulin related frontotemporal dementia (FTDâGRN) is a fast progressive disorder, in which pathophysiological changes precede overt clinical symptoms in only a short time period. Modelling the cascade of multimodal biomarker changes aids in understanding the etiology of this disease, enables monitoring of individual mutation carriers, and would give input for diseaseâmodifying treatments. In this crossâsectional study, we estimated the temporal cascade of biomarker changes for FTDâGRN, in a dataâdriven way.MethodWe included 56 presymptomatic and 35 symptomatic GRN mutation carriers, and 35 healthy nonâcarriers. Of the symptomatic subjects, 17 had behavioural variant FTD (bvFTD), 16 presented as nonâfluent variant primary progressive aphasia (nfvPPA). The selected biomarkers for establishing the cascade of changes were neurofilament light chain, regional grey matter volumes, fractional anisotropy of white matter tracts, and cognitive domains. We used a dataâdriven analysis called discriminative eventâbased modelling (Venkatraghavan, NeuroImage, 2019) with a novel modification to its Gaussian Mixture Model (GMM) called Siamese GMM, to estimate the cascade of biomarker changes for FTDâGRN. Using crossâvalidation, we estimated disease severities of individual mutation carriers in the test set based on their progression along the biomarker cascade established on the training set.ResultNeurofilament light chain and white matter tracts were the earliest biomarkers to become abnormal in FTDâGRN mutation carriers. Attention and executive functioning were also affected early on in the disease process. Based on the estimated individual disease severities, presymptomatic mutation carriers could be distinguished from symptomatic mutation carriers with a sensitivity of 95% and specificity of 100% in the crossâvalidation experiment. There was a high correlation (r=0.94, p<0.001) between estimated disease severity and years since symptom onset in nfvPPA, but not in bvFTD (r=0.33, p=0.46).ConclusionIn this study, we unravelled the temporal cascade of multimodal biomarker changes for FTDâGRN. Our results suggest that axonal degeneration is one of the first disease events in FTDâGRN, which calls for designing disease modifying treatments that strengthens the axons. We also demonstrated a good delineation between symptomatic and presymptomatic carriers using the estimated disease severities, which suggest that our model could enable monitoring of individual mutation carriers
A modular approach toward producing nanotherapeutics targeting the innate immune system.
Immunotherapies controlling the adaptive immune system are firmly established, but regulating the innate immune system remains much less explored. The intrinsic interactions between nanoparticles and phagocytic myeloid cells make these materials especially suited for engaging the innate immune system. However, developing nanotherapeutics is an elaborate process. Here, we demonstrate a modular approach that facilitates efficiently incorporating a broad variety of drugs in a nanobiologic platform. Using a microfluidic formulation strategy, we produced apolipoprotein A1-based nanobiologics with favorable innate immune system-engaging properties as evaluated by in vivo screening. Subsequently, rapamycin and three small-molecule inhibitors were derivatized with lipophilic promoieties, ensuring their seamless incorporation and efficient retention in nanobiologics. A short regimen of intravenously administered rapamycin-loaded nanobiologics (mTORi-NBs) significantly prolonged allograft survival in a heart transplantation mouse model. Last, we studied mTORi-NB biodistribution in nonhuman primates by PET/MR imaging and evaluated its safety, paving the way for clinical translation.This work was supported by NIH grants R01 CA220234, R01 HL144072, P01 HL131478, and NWO/ZonMW Vici 91818622 (to W.J.M.M.); R01 HL143814 and P01HL131478 (to Z.A.F.); R01 AI139623 (to J.O.); and P30 CA008748 (to T.R.). M.M.T.v.L. was supported by the American Heart Association (grant 19PRE34380423). M.G.N. was supported by a Spinoza grant from the Netherlands Organization for Scientific Research and an ERC Advanced Grant (no. 833247); L.A.B.J. was supported by a Competitiveness Operational Programme grant of the Romanian Ministry of European Funds (P_37_762, MySMIS 103587).S
ADRA1A-Gα<sub>q</sub> signalling potentiates adipocyte thermogenesis through CKB and TNAP
Noradrenaline (NA) regulates cold-stimulated adipocyte thermogenesis(1). Aside from cAMP signalling downstream of ÎČ-adrenergic receptor activation, how NA promotes thermogenic output is still not fully understood. Here, we show that coordinated α(1)-adrenergic receptor (AR) and ÎČ(3)-AR signalling induces the expression of thermogenic genes of the futile creatine cycle(2,3), and that early B cell factors, oestrogen-related receptors and PGC1α are required for this response in vivo. NA triggers physical and functional coupling between the α(1)-AR subtype (ADRA1A) and Gα(q) to promote adipocyte thermogenesis in a manner that is dependent on the effector proteins of the futile creatine cycle, creatine kinase B and tissue-non-specific alkaline phosphatase. Combined Gα(q) and Gα(s) signalling selectively in adipocytes promotes a continual rise in whole-body energy expenditure, and creatine kinase B is required for this effect. Thus, the ADRA1AâGα(q)âfutile creatine cycle axis is a key regulator of facultative and adaptive thermogenesis
Developing Transdisciplinary Approaches to Sustainability Challenges: The Need to Model Socio-Environmental Systems in the Longue Durée
Human beings are an active component of every terrestrial ecosystem on Earth. Although our local impact on the evolution of these ecosystems has been undeniable and extensively documented, it remains unclear precisely how our activities are altering them, in part because ecosystems are dynamic systems structured by complex, non-linear feedback processes and cascading effects. We argue that it is only by studying humanâenvironment interactions over timescales that greatly exceed the lifespan of any individual human (i.e., the deep past or longue durĂ©e), we can hope to fully understand such processes and their implications. In this article, we identify some of the key challenges faced in integrating long-term datasets with those of other areas of sustainability science, and suggest some useful ways forward. Specifically, we (a) highlight the potential of the historical sciences for sustainability science, (b) stress the need to integrate theoretical frameworks wherein humans are seen as inherently entangled with the environment, and (c) propose formal computational modelling as the ideal platform to overcome the challenges of transdisciplinary work across large, and multiple, geographical and temporal scales. Our goal is to provide a manifesto for an integrated scientific approach to the study of socio-ecological systems over the long term
Investigating the Effect of Conflicting Goals and Transparency on Trust and Collaboration in Multi-Team Systems
In Air Traffic Management (ATM) multiple teams have to collaborate to achieve efficient and safe operation. Multiple-team operations rely on
communication and information sharing between the team members. In this field, multi-team systems (MTSs) are the most common form of organization. The interface between the organizations involved (e.g. air traffic control, cockpit crews, airports) is of central importance. Apart from a common goal, different stakeholders may pursue individual goals governed by their own company culture or policies. Therefore, simply sharing all available information may not be enough to ensure safe and efficient operation. As part of the project ITC (Inter-Team Collaboration), an experimental study with 48 teams of three (n=144) has just started to investigate the impact that conflicting goals have on communication and collaboration. Additionally, it examines whether and how transparency in roles, processes, and goals can affect performance, communication, and trust in multi-team systems. In the synthetic task environment (STE) ConCenT (Control Center Task Environment), teams of three have to collaborate to detect system failures in time, determine their causes, and decide on a solution in order to ensure successful production processes. Measurements of performance, perceived trust, communication, and gaze data will be analyzed to examine and compare different coordination and communication patterns on a group level. Results of the study will identify factors that may facilitate or hinder collaborative work processes in an MTS, thus enabling the validation of an approach to improve collaboration through transparency and mutual trust
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