71446 research outputs found
Sort by
Imagining the Future: Memory, Simulation and Beliefs
No full textHow do people form beliefs about novel risks, with which they have little or no experience? Motivated by survey data on beliefs about Covid we collected in 2020, we build a model based on the psychology of selective memory. When a person thinks about an event, different experiences compete for retrieval, and retrieved experiences are used to simulate the event based on how similar they are to it. The model predicts that different experiences interfere with each other in recall and that non domain-specific experiences can bias beliefs based on their similarity to the assessed event. We test these predictions using data from our Covid survey and from a primed-recall experiment about cyberattack risk. In line with our theory of similarity-based retrieval and simulation, experiences and their measured similarity to the cued event help account for experience effects, priming effects, and the interaction of the two in shaping beliefs.Author's Origina
Medieval and Early Modern European, African and Asian ivories seen through the Data Lens
No full textIvories of different natures are one of the oldest materials of artistic expression, and they have been used widely through space and time. The purpose of this article is twofold: on the one hand, to offer a data driven analysis of Medieval and Early Modern ivories in Europe, Africa and Asia (ca. 1000 to 1600); on the other hand, to offer a critical perspective on the proposed query method itself. Nine museums with 2123 objects have been chosen for this analysis, based on the availability of a query endpoint. The proposed method has clear advantages and disadvantages. To the advantages belong the possibility of researching through several museum holdings at the same time (once the dataset is modelled), to query museum object data on view and on deposit all together, to be potentially able to provide insights into a given category from a very broad perspective, but also to search for unusual objects. To the disadvantages belong the fact that data is changeable, and that the selection of the museums is driven by the availability of a query structure. Therefore, the choice of the museums is also problematic, if one wants to address an international comparison. Furthermore, each museum offered data only in specific fields, which adds complexity to an overall query.Version of Recor
Discovery of a broad-spectrum, fluorinated macrobicyclic antibiotic through chemical synthesis
No full textWe report the discovery through chemical synthesis of BT-33, a fluorinated macrobicyclic oxepanoprolinamide antibiotic. BT-33 potently inhibits the growth of multidrug-resistant clinical isolates of Gram-positive and Gram-negative bacteria and has an extended half-life in vivo relative to its predecessors cresomycin and iboxamycin. We report structure-activity relationships within the macrobicyclic substructure, which reveal structural features that are essential to the enhanced potency of BT-33 as well as its increased metabolic stability. We determine the structure of BT-33 in complex with the bacterial ribosome by X-ray crystallography, analysis of which suggests that the newly introduced fluorine atom makes an additional Van der Waals contact with nucleobase G2505. Finally, we show that the C7-methyl group of BT-33 rigidifies the macrocyclic ring in a conformation that is highly preorganized for ribosomal binding by using variable-temperature 1H-NMR experiments, density-functional theory calculations, and vibrational circular dichroism spectroscopy to compare macrobicyclic homologs of BT-33 and a C7-desmethyl analog.Chemistry and Chemical BiologyAccepted Manuscrip
Export-led Growth
No full textGrowth Lab Working Paper Series No. 231In this paper, I argue that a focus on exports, both at the intensive margin (where existing products increase their volume), but especially at the extensive margin (where new products start being exported), can help countries figure out what policies to adopt in order to achieve sustained growth. I present five stylized facts about growth and its trends in the decades that followed the Washington Consensus.Version of Recor
Efferocytosis drives a tryptophan metabolism pathway in macrophages to promote tissue resolution
No full textIt will be great for us to have such a waiver statement as below:
While all authors subscribe to NIH Open Policy, Harvard Medical School (HMS) does not demand that a non-HMS lead author of a manuscript on which an HMS co-author appears must pay the fee for the journal's own open access program.Author's Origina
Finding Underlying Morphology Trends and Significant Genes across Mental Illnesses using Dimensionality Reduction
No full textMental health diagnoses can be difficult to make due to the high comorbidity and
overlapping symptoms across different diseases. It has been suggested that rather than
focusing on a standard checklist, diagnoses be based on a hierarchy that can align to one
or more disorders, some tiers of which can be identified by neuroimaging. The ENIGMA
consortium has collated a group of standardized MRI case-control studies and provided
this data in the ENIGMA toolbox, a Python package. In this study, we used this package
to retrieve effect sizes from seven mental disorders and analyzed them using two
dimensionality reduction methods: principal component analysis (PCA) and uniform
manifold approximation and projection (UMAP) to uncover the latent dimensions
underlying the cortical thickness commonalities. We compared PCA results with and
without prior z-score normalization, as well as 2D with 3D UMAP results. We then
correlated the first component of a PCA and a UMAP reduction with the Allen Human
Brain Atlas (AHBA) to identify relevant genes, which we annotated to determine their
biological contexts. We have found that z-scored PCA had stronger correlation across
disorders. We also found that 2D and 3D UMAP are equivalently suitable for finding
latent dimensions. We also determined that genes that correspond with these first
components are differentially expressed in the brain, reproductive organs, hormone
glands, fibroblasts, lymphocytes, liver, heart, pancreas, whole blood, and muscular
skeletal system. In addition, analysis of overrepresented GO gene sets has shown that
surviving genes are expressed in neurological contexts, particularly synapse signaling
A Place for Dead Things
No full textA Place For Dead Things is a crime drama with hints of noir that blurs the lines between good and bad people and works to show the more realistic grey area that lives between the two concepts. It follows a veteran struggling to avoid violence and a young woman embroiled in gang life. It poses the question of what people are willing to do for those they love. The story is stationed in the oft forgotten valley of California where deserts, agriculture, and oil fields reign supreme. A seemingly small act of violence cascades into a nationwide nefarious plot
Sublime Frequencies: Metaphysics of Resonance in Arvo Pärt, Cecilia Vicuña, and M.R. Bawa Muhaiyaddeen
No full textThrough an inter-disciplinary and comparative study of the acoustic phenomenon of resonance—i.e., the synchronous vibration between two or more sounds—this dissertation thinks through a socially-engaged “sonic metaphysics” and phenomenology of sound in the field of religious studies, in three case studies of contemporary aesthetic and mystical works: Eastern Orthodox Estonian composer Arvo Pärt’s (1935-present) selected works from his early tintinnabuli period of composition; Mestizo Indigenous Chilean poet and artist Cecilia Vicuña’s (1948-present) selected Précario and Quipu works; and transnational Sri Lankan Sufi Shaikh M.R. Bawa Muhaiyaddeen’s (?-1986) The Resonance of Allah: Resplendent Explanations Arising from the Nūr, Allāh’s Wisdom of Grace. Critically, the study discovers how these three contemporary forms and dimensions of sonic religiosity act formally (through their content, form, and reception) to open up within and beyond established discourses of mysticism, animism, and aesthetics, to speak in new and socially-engaged ways about actual human and environmental relations and transformations.
Each case study traces clear, detailed connections between metaphysical ideas about resonance and the impact of resonance on concerns such as self-realization and healing, social and environmental justice, humanitarian aid, medical care, and inter-religious tolerance, while examining the capacity of resonance to express continuities between metaphysics and the phenomenology of lived religious experience; to convey meaning across religious, political, and aesthetic categories of belonging; and to expand our capacity for listening and ethical action. Each case study likewise contributes both theoretical and ethnographic insights into how resonance, and sound more generally, convey roles as prayer, as presence, and as mode(s) of attunement that enact the creation of the cosmos and dialogue with the divine. The dissertation also uncovers the psychoacoustics of the listener’s embodied relationship with sound and presence and the capacity of resonance to elucidate commonalities in intersubjective experience (relational ontologies). The study contributes methodologically to the study of religion by situating resonance as a vital concept of contemporary interdisciplinary and comparative inquiry and positioning the listening subject and their experience at the center of the unfurling of sound within complex multi-religious and secular global spaces. More broadly, the study addresses how developing an account of the metaphysics of resonance in religion helps us to hear differently, with and for each other
SKI complex loss renders 9p21.3-deleted or MSI-H cancers dependent on PELO
No full textCancer genome alterations often lead to vulnerabilities that can be used to selectively target cancer cells. Various inhibitors of such synthetic lethal targets are FDA-approved or in clinical trials, highlighting the potential of this approach.1–3 Here, we analyzed large-scale CRISPR knockout screening data and identified a new synthetic lethal target, pelota mRNA surveillance and ribosome rescue factor (PELO), for two independent molecular subtypes of cancer: biallelic deletion of chromosomal region 9p21.3 (9p21.3-/-) or microsatellite instability-high (MSI-H). In 9p21.3-/- cancers, PELO dependency emerges from biallelic deletion of the 9p21.3 gene focadhesin (FOCAD), a stabilizer of the superkiller complex (SKIc). In MSI-H cancers, PELO is required due to MSI-H-associated mutations in tetratricopeptide repeat domain 37 (TTC37), a critical component of the SKIc. We show that both cancer subtypes converge to destabilize the SKIc, which extracts mRNA from stalled ribosomes. In SKIc-deficient cells, PELO depletion induces the unfolded protein response (UPR), a stress response to accumulated misfolded or unfolded nascent polypeptides. Together, our findings nominate PELO as a promising therapeutic target for a large patient population with cancers characterized as MSI-H with deleterious TTC37 mutations or with biallelic 9p21.3 deletions involving FOCAD.Author's Origina
Identification of more than 40 gravitationally magnified stars in a galaxy at redshift 0.725
No full textStrong gravitational magnifications enable to detect faint background sources, resolve their internal structures, and even identify individual stars in distant galaxies. Highly magnified individual stars allow various appli- cations, including studies of stellar populations in dis- tant galaxies and constraining dark matter structures in the lensing plane. However, these applications have been hampered by the small number of individual stars observed, as typically one or a few stars are identified from each distant galaxy. Here, we report the discovery of more than 40 microlensed stars in a single galaxy be- hind Abell 370 at redshift of 0.725 when the Universe was half of its current age (dubbed “the Dragon arc”), using James Webb Space Telescope (JWST) observations with the time-domain technique. These events are found near the expected lensing critical curves, suggesting that these are magnified stars that appear as transients from intr- acluster stellar microlenses. Through multi-wavelength photometry, we constrain stellar types and find that many of them are consistent with red giants/supergiants magnified by factors of hundreds. This finding reveals an unprecedented high occurrence of microlensing events in the Dragon arc, and proves that JWST’s time-domain observations open up the possibility of conducting statistical studies of high-redshift stars.Other Research UnitProo