882 research outputs found

    A New Electric Field in Asymmetric Magnetic Reconnection

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    We present a theory and numerical evidence for the existence of a previously unexplored in-plane electric field in collisionless asymmetric magnetic reconnection. This electric field, dubbed the "Larmor electric field," is associated with finite Larmor radius effects and is distinct from the known Hall electric field. Potentially, it could be an important indicator for the upcoming Magnetospheric Multiscale (MMS) mission to locate reconnection sites as we expect it to appear on the magnetospheric side, pointing Earthward, at the dayside magnetopause reconnection site.Comment: 5 pages, 3 figures, to be published in Physical Review Letter

    DEEP LEARNING METHODS FOR ANTIBODY STRUCTURE PREDICTION AND DESIGN

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    Antibodies are important immunological proteins, with the capacity to bind and neutralize a broad range of pathogens. The diversity of antibodies is conferred through genetic recombination and mutation, largely focused in a complementarity determining region composed of six loops. This natural diversity and binding capability has made antibodies an increasingly important therapeutic and diagnostic tool. However, despite their biological and medical significance, modeling and design of antibodies remains a challenge. In the first half of this dissertation, I detail the development of a series of tools (DeepH3, DeepAb, and IgFold) to model increasingly complex portions of the antibody variable domain. These methods have progressively advanced the state-of-the-art in antibody modeling, first over traditional homology modeling approaches, then over highly accurate generalist methods for structure prediction. IgFold, the current-generation antibody structure prediction model, is capable of high-throughput antibody structure prediction with accuracy comparable to the best generalist methods, but in a fraction of the time. The speed and accuracy of IgFold should allow structure-based investigation on the scale of immune repertoires and accelerate the rational design of antibody therapeutics. In the second half, I present work on generative language models for protein sequences. The first project describes ProGen2, a suite of language models trained at massive scale. I demonstrate that these models can be used to generate protein sequences resembling those produced by nature and to rank the relative fitness of protein sequences. The second project describes IgLM, a language model designed specifically for antibody design. IgLM can be used to create antibody libraries with favorable therapeutic properties or to generate full-length sequences with a specific species and chain type. Taken together, my work has advanced our understanding of antibody structure through improved modeling, and shown how we might more effectively leverage natural antibody sequence data to achieve design of novel therapeutic molecules

    Estudio no destructivo del interior de piezas de valor histórico mediante gammagrafías

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    La tecnología de Tomografía de Hormigón Armado desarrollada por THASA ha sido aplicada al estudio de piezas ornamentales y otras de valor histórico con el objeto de examinar el interior de las mismas e investigar, en algunos casos, la existencia, configuración y condición de refuerzos metálicos y en otro caso, la existencia de huecos producidos por termitas en vigas de madera. En este trabajo se discuten detalles metodológicos y resultados alcanzados en los casos de las estatuas ubicadas en el coronamiento del Palacio de Tribunales en la Ciudad Autónoma de Buenos Aires, en dragones colgantes de las torres de la Basílica de Luján y en las vigas del techo de la Capilla Doméstica, construida en 1660 y declarada patrimonio de la humanidad por la UNESCO, ubicada en la manzana jesuítica en la Ciudad de Córdoba. El carácter pionero de la investigación de oquedades en madera realizada en este último caso hizo necesario la construcción de modelos de simulación que resultan de utilidad para otras aplicaciones similares

    Editorial: epilepsy and neurodevelopmental diseases

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    The association between epilepsy and neurodevelopmental diseases is well-recognized and has gained significant attention in the field of neuroscience in recent years. One of the main reasons for this interest is the need for a better understanding of the events that lead to the development and maturation of the CNS. This is a fundamental and necessary basis for potential breakthrough strategies that could guide novel and more effective disease-modifying therapeutic approaches to neurodevelopmental syndromes that are frequently characterized by severe and drug-resistant epilepsy. The perspective of such new therapeutic strategies is very promising. At the state-of-theart, patients afflicted by these rare neurodevelopmental disorders mostly rely on “symptomatic” approaches that mitigate seizures and other major symptoms but do not target the underlying biological causes of the disease. The study of this vast field of research is extremely complex and requires a multidisciplinary approach, from neuropathological to molecular and functional studies since even “simple” triggering events (e.g., a genetic mutation) during critical periods of brain development can lead to widespread effects on brain morphological and functional features

    The potential mechanism of black crust development on the historic buildings in Cairo and Venice

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    The development of black crusts on natural stones of historic buildings is mainly related to the surrounded polluted atmosphere. The blackening of surfaces is caused, in fact, by the accumulation of air pollutants produced by human activity, especially carbon particles originating from the incomplete combustion of fossil fuel. Investigations of the chemical composition of such layers in the monuments can be the basis for planning suitable strategies for the protection and conservation of the built cultural heritage. Cairo (Egypt) and Venice (Italy) are two cities with a large amount of cultural heritage buildings; moreover, they suffer high level of air pollution. Black crust with the hosted stones from different sites in Historic Cairo, as well as samples of different archaeological sites in Venice city, were collected and analyzed by using several techniques: polarizing optical microscopy (OM), scanning electron microscopy coupled with energy-dispersive X-ray spectrometry (SEM-EDS), infrared spectroscopic techniques (FT-IR) and laser ablation inductively coupled mass spectrometry (LA-ICP-MS). The characterization of such samples provided information on the chemical composition of black crusts, the state of conservation of the substrates and the crust-stone interactions. The chemical study highlighted a different pattern of elements within the two cities. Regarding the black crusts of Cairo, results suggest that the air pollution in Cairo is mainly related to vehicular traffic. Indeed, in the city there is high vehicular traffic almost 24 h a day and the direct impact of vehicle emissions is particularly severe. Samples from the Venice show different composition in terms of heavy metals with respect to Cairo that can be explained with the emission from several industries sited in the near industrial center of Porto Marghera and Island of Murano. Moreover, the fuels used for marine transportation, which is abundant into the area, have a slight different fingerprinting in terms of metals with respect to the vehicles

    Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS) procedure for colorectal liver metastasis

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    Since first described, Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS) has garnered boisterous praise and fervent criticism. Its rapid adoption and employment for a variety of indications resulted in high perioperative morbidity and mortality. However recent risk stratification, refinement of technique to reduce the impact of stage I and progression along the learning curve have resulted in improved outcomes. The first randomized trial comparing ALPPS to two stage hepatectomy (TSH) for colorectal liver metastases (CRLM) was recently published demonstrating comparable perioperative morbidity and mortality with improved resectability and survival following ALPPS. In this review, as ALPPS enters the thirteenth year since conception, the current status of this contentious two stage technique is presented and best practices for deployment in the treatment of CRLM is codified

    Study of the effects of salt crystallisation on degradation of limestone rocks

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    Salt crystallization is widely recognized as a cause of deterioration of porous building materials. In particular, the crystallization pressure of salt crystals growing in confined pores is found to be the main cause for damage. The aim of this study is to better understand the degradation of porous rocks induced by salt crystallisation and correlate such processes with the intrinsic characteristics of materials. With this intend, an experimental salt weathering simulation has been carried out on two limestones widely used in the Baroque architecture of eastern Sicily. A systematic approach including petrographic, porosimetric and colorimetric analyses, was used to evaluate the correlation among salt crystallisation, microstructural and chromatic variations of limestone. Results showed a quite different resistance of the two limestones to salt damage, and this was found to be strongly dependent on their pore structure and textural characteristics

    Does the polydimethylsiloxane urethral injection (Macroplastique®) improve sexual function in women, in fertile age, affected by stress urinary incontinence?

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    Background and Objectives: Stress urinary incontinence (SUI) negatively affects women's quality of life, including sexual function. The aim of the current study was to evaluate the effect of polydimethylsiloxane (Macroplastique(R)) on sexual function in women of fertile age affected by SUI. Materials and Methods: Single-center prospective study. Sexually active women of fertile age with symptoms of pure SUI, which were urodynamically proven, were submitted to intraurethral Macroplastique(R) injection. At 6-months follow-up, their sexual function was evaluated with Female Sexual Function Index (FSFI), while the SUI cure rate was objectively assessed through a negative stress test and subjectively by a Patient Global Impression of Improvement (PGI-I) score < 3. The difference of coital incontinence prevalence was assessed between the baseline and the 6-month follow-up. Peri- and postoperative complications of Macroplastique(R) injection were recorded and classified according to the Clavien-Dindo system. Results: Twenty-one women fulfilled inclusion criteria and were submitted to Macroplastique(R) procedure. The concerning sexual function, desire, satisfaction, and overall FSFI score significantly improved. Since other domains were less impaired at the baseline, we could not assess significant improvement for all of them. We observed a complete regression of coital incontinence (0/21, 0%) in comparison with the baseline (5/21, 23.8%; p = 0.04). The objective SUI cure rate was 76% (16/21), while the subjective SUI cure rate was 80.9% (17/21). One woman developed de novo overactive bladder, and two women developed postoperative voiding dysfunction (self-solved in 24 h). Conclusions: The Macroplastique(R) urethral injection was demonstrated to be safe and effective in improving sexual function in sexually active women of fertile age affected by pure SUI, urodinamically proven at 6-months follow-up
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