Quantum properties of atomic-sized conductors

Using remarkably simple experimental techniques it is possible to gently break a metallic contact and thus form conducting nanowires. During the last stages of the pulling a neck-shaped wire connects the two electrodes, the diameter of which is reduced to single atom upon further stretching. For some metals it is even possible to form a chain of individual atoms in this fashion. Although the atomic structure of contacts can be quite complicated, as soon as the weakest point is reduced to just a single atom the complexity is removed. The properties of the contact are then dominantly determined by the nature of this atom. This has allowed for quantitative comparison of theory and experiment for many properties, and atomic contacts have proven to form a rich test-bed for concepts from mesoscopic physics. Properties investigated include multiple Andreev reflection, shot noise, conductance quantization, conductance fluctuations, and dynamical Coulomb blockade. In addition, pronounced quantum effects show up in the mechanical properties of the contacts, as seen in the force and cohesion energy of the nanowires. We review this reseach, which has been performed mainly during the past decade, and we discuss the results in the context of related developments.Comment: Review, 120 pages, 98 figures. In view of the file size figures have been compressed. A higher-resolution version can be found at: http://lions1.leidenuniv.nl/wwwhome/ruitenbe/review/QPASC-hr-ps-v2.zip (5.6MB zip PostScript

Depletion of the SR-related protein TbRRM1 leads to cell cycle arrest and apoptosis-like death in Trypanosoma brucei

Arginine-Serine (RS) domain-containing proteins are RNA binding proteins with multiple functions in RNA metabolism. In mammalian cells this group of proteins is also implicated in regulation and coordination of cell cycle and apoptosis. In trypanosomes, an early branching group within the eukaryotic lineage, this group of proteins is represented by 3 members, two of them are SR proteins and have been recently shown to be involved in rRNA processing as well as in pre-mRNA splicing and stability. Here we report our findings on the 3rd member, the SR-related protein TbRRM1. In the present study, we showed that TbRRM1 ablation by RNA-interference in T. brucei procyclic cells leads to cell-cycle block, abnormal cell elongation compatible with the nozzle phenotype and cell death by an apoptosis-like mechanism. Our results expand the role of the trypanosomal RS-domain containing proteins in key cellular processes such as cell cycle and apoptosis-like death, roles also carried out by the mammalian SR proteins, and thus suggesting a conserved function in this phylogenetically conserved protein family.Fil: Levy, Gabriela Vanesa. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); ArgentinaFil: Bañuelos, Carolina Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); ArgentinaFil: Níttolo, Analía Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); ArgentinaFil: Ortiz, Gastón Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Mendiondo, Nicolas. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); ArgentinaFil: Moretti, Georgina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); ArgentinaFil: Tekiel, Valeria Sonia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); ArgentinaFil: Sanchez, Daniel Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); Argentin

Diseño y fabricación de maniquí prototipo antropomórfico para controles de calidad en tratamientos de Braquiterapia Ginecológica HDR 3D

Proyecto Integrador (I.Biom.)--FCEFN-UNC, 2023Fil: Levenzon Levy, Nicolas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; Argentina.Fil: Fortuna, Gastón. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; Argentina.La Braquiterapia 3D HDR (high doce rate) es una técnica de irradiación localizada de alta precisión con mínimos efectos adversos, que mediante el uso de una fuente radioactiva milimétrica permite tratar lesiones en distintas localizaciones con una mayor cantidad de radiación emitida por unidad de tiempo utilizando un sistema de imágenes en tres dimensiones y técnicas de planificación avanzadas. El uso de imágenes para la planificación de tratamientos ha evolucionado de 2D a 3D, incluyendo tomografía computada y resonancia magnética. El Hospital Oncológico de Córdoba, realizó tratamientos de Braquiterapia intracavitaria ginecológica HDR durante seis años consecutivos con fuente de 192Ir y basándose en planificación bidimensional (2D) mediante el uso de películas de rayos X ortogonales. Con el objetivo de avanzar en tecnología y reducir costos, la institución adquirió un nuevo equipo de Braquiterapia para ser utilizado con fuente de 60Co y aplicadores de materiales tales que posibilitaron la adquisición de imágenes por Tomografía Computada y Resonancia Magnética con el fin de introducir un método de planificación tridimensional (3D). Entre los diversos controles que se deben realizar a las partes involucradas, como puede ser la dosis, tiempos de exposición, planificación, etc., en la braquiterapia, el más importante es el que involucra todo el proceso de principio a fin. Para poder llevar a cabo este trabajo se requiere de un maniquí o “phantom” lo más similar posible a un paciente para reproducir las condiciones exactas. En nuestro país no hay desarrollo comercial de maniquí específico para braquiterapia y las empresas que ofrecen dichos dispositivos son extranjeras. En el presente trabajo se desarrolló el proceso de diseño, fabricación y prueba de un maniquí antropomórfico para el control de calidad de principio a fin (End to end, E2E) de un tratamiento completo de braquiterapia ginecológica HDR 3D. Una vez corroborado el buen funcionamiento del dispositivo, con el fin de asegurar una correcta entrega del tratamiento, se realizaron conjuntamente mediciones de QA (quality assurance) sobre la unidad HDR, la fuente radiactiva y su conjunto dosimétrico, el equipo de adquisición de imágenes, el Sistema de Planificación de Tratamientos (TPS), y, por último, sobre el procedimiento en general. Además, se implementó una nueva técnica de prueba dosimétrica mediante placas radio-crómicas EBT3 (nombre de modelo de las placas radiosensibles) que resultaron muy satisfactorias e implica un nuevo avance en control de calidad en lo que respecta al área pública del país. Así mismo permitió realizar una comparación con resultados de mediciones anteriores arrojando resultados muy favorables y de alto impacto para la nueva técnica. La incorporación de este nuevo dispositivo y las pruebas realizadas con él permitieron actualizar el Programa de Garantía de Calidad de la institución, y establecer una base para poder implementarlo en otros servicios de Braquiterapia ginecológica HDR guiada por imágenes 3D del país. Además, cumple la función de capacitación de residentes y el perfeccionamiento de las técnicas de braquiterapia ginecológica intracavitaria.3D HDR (High dose rate) brachytherapy is a technique of localized high precision irradiation with minimal adverse effects, which, by using a millimetric radioactive source, allows treating lesions in different locations with a greater amount of radiation emitted per unit of time using a system of three-dimensional images and advanced planning techniques. The use of images for treatment planning has evolved from 2D to 3D, including computed tomography and magnetic resonance imaging. The Oncological Hospital of Córdoba carried out intracavitary gynecological HDR brachytherapy treatments for six consecutive years with a 192Ir source based on two-dimensional (2D) planning using orthogonal X-ray films. With the aim of advancing technology and reducing costs, the institution acquired a new brachytherapy equipment to be used with a 60Co source and applicators of such materials that enabled the acquisition of images by computed tomography and magnetic resonance imaging in order to introduce a three-dimensional (3D) planning method. Among the various controls that must be carried out on the involved parts, such as dose, exposure times, planning, etc., in brachytherapy, the most important is the one that involves the entire process from start to finish. To carry out this work, a mannequin or "phantom" is required that is as similar as possible to a patient to reproduce the exact conditions. In our country, there is no commercial development of a specific mannequin for brachytherapy, and the companies that offer such devices are foreign. In this work, the process of designing, manufacturing, and testing an anthropomorphic dummy for end-to-end (E2E) quality control of a complete 3D HDR gynecological brachytherapy treatment was developed. Once the proper functioning of the device was corroborated, in order to ensure a correct delivery of the treatment, QA (quality assurance) measurements were jointly performed on the HDR unit, the radioactive source and its dosimetric assembly, the imaging acquisition equipment, the Treatment Planning System (TPS), and finally on the procedure in general. In addition, a new dosimetric test technique was implemented using EBT3 radiochromic plates that were very satisfactory and represent a new advance in quality control in the public area of the country. It also allowed a comparison with previous measurement results, yielding very favorable and high-impact results for the new technique. The incorporation of this new device and the tests carried out with it allowed updating the institution's Quality Assurance Program and establishing a basis for implementing it in other services of 3D image-guided gynecological HDR brachytherapy in the country. Additionally, it serves as training for residents and the improvement of intracavitary gynecological brachytherapy techniques.Fil: Levenzon Levy, Nicolas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; Argentina.Fil: Fortuna, Gastón. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; Argentina

Semaine d'Etude Mathématiques et Entreprises 1 : Modèles de comparaison quantitative de matrices 3D

Air Liquide dispose de jeux de données représentant des champs de quantité de dépôt de particules sur les poumons. Ces données proviennent de mesures 3D (obtenues via SPECT, Single Photon Emission Computer Tomography) du dépôt d'un aérosol contenant des particules radio-labellisées préalablement inhalé par les patients étudiés. Le sujet proposé ici consiste à se demander quelles sont les méthodes permettant de comparer de façon quantitative et systématique les résultats des observations, qui sont donnés sous la forme de matrices 3D correspondant à la quantité de particules estimée dans chaque voxel

Serial daily lactate levels association with 30-day outcome in cardiogenic shock patients treated with VA-ECMO:a post-hoc analysis of the HYPO-ECMO study

Background: Reliable predictors of outcomes in venoarterial extracorporeal membrane oxygenation (VA-ECMO) therapy are limited. While elevated lactate levels over time have been linked to outcomes in cardiogenic shock (CS), their significance in VA-ECMO-treated patients remains inconclusive.Methods: We conducted a post hoc analysis of data from the HYPO-ECMO trial, which compared normothermia to moderate hypothermia in CS patients supported by VA-ECMO. We examined daily lactate levels collected over a week to assess their correlation with 30-day mortality. Results: Among the 318 out of 334 patients (95%) with baseline lactate measurements, 66 had normal levels (&lt; 2.2 mmol/l, 21%). No difference was found in lactate course between moderate hypothermia and normothermia groups. Lactate levels were consistently higher in non-survivors at each time point (p = 0.0002). Baseline hyperlactatemia was associated with an increased risk of death (Hazard Ratio [HR]: 1.85 (1.12–3.05), p = 0.016). When considering all time points, lactate levels during the ICU stay were significantly and gradually associated with a higher risk of death (p &lt; 0.0001). In the overall population, a decrease in lactate levels was not linked to 30-day mortality. However, patients with baseline hyperlactatemia exhibited a more significant decrease in lactate levels from day one to seven (p &lt; 0.0001). In this group, survivors had a significantly greater decrease in lactate levels at day 1 compared to non-survivors (63% (48–77) versus 57% (21–75), p = 0.026). Patients experiencing a secondary increase in lactate (24%) had a worse prognosis (Hazard Ratio: 1.78 (1.21–2.61), p = 0.004), regardless of both baseline lactate levels and the occurrence of severe ischemic adverse events (intestinal and/or limb ischemia). Conclusions: The consistent and significant association between lactate levels, whether assessed at baseline or during ICU treatment, and the risk of mortality underscores the pivotal prognostic relevance of lactate levels in patients with CS undergoing VA-ECMO therapy. The study findings provide some novel insights, regarding the trend profile and the relevance of a second peak during the 7 day period after ECMO start. Trial Registration identifier NCT02754193 registered on 2016–04–12.</p

Three patients with homozygous familial hypercholesterolemia: Genomic sequencing and kindred analysis.

BackgroundHomozygous Familial Hypercholesterolemia (HoFH) is an inherited recessive condition associated with extremely high levels of low-density lipoprotein (LDL) cholesterol in affected individuals. It is usually caused by homozygous or compound heterozygous functional mutations in the LDL receptor (LDLR). A number of mutations causing FH have been reported in literature and such genetic heterogeneity presents great challenges for disease diagnosis.ObjectiveWe aim to determine the likely genetic defects responsible for three cases of pediatric HoFH in two kindreds.MethodsWe applied whole exome sequencing (WES) on the two probands to determine the likely functional variants among candidate FH genes. We additionally applied 10x Genomics (10xG) Linked-Reads whole genome sequencing (WGS) on one of the kindreds to identify potentially deleterious structural variants (SVs) underlying HoFH. A PCR-based screening assay was also established to detect the LDLR structural variant in a cohort of 641 patients with elevated LDL.ResultsIn the Caucasian kindred, the FH homozygosity can be attributed to two compound heterozygous&nbsp;LDLR damaging variants, an exon 12 p.G592E missense mutation and a novel 3kb exon 1 deletion. By analyzing the 10xG phased data, we ascertained that this deletion allele was most likely to have originated from a Russian ancestor. In the Mexican kindred, the strikingly elevated LDL cholesterol level can be attributed to a homozygous frameshift LDLR variant p.E113fs.ConclusionsWhile the application of WES can provide a cost-effective way of identifying the genetic causes of FH, it often lacks sensitivity for detecting structural variants. Our finding of the LDLR exon 1 deletion highlights the broader utility of Linked-Read WGS in detecting SVs in the clinical setting, especially when HoFH patients remain undiagnosed after WES

The Adversarial Implications of Variable-Time Inference

Machine learning (ML) models are known to be vulnerable to a number of attacks that target the integrity of their predictions or the privacy of their training data. To carry out these attacks, a black-box adversary must typically possess the ability to query the model and observe its outputs (e.g., labels). In this work, we demonstrate, for the first time, the ability to enhance such decision-based attacks. To accomplish this, we present an approach that exploits a novel side channel in which the adversary simply measures the execution time of the algorithm used to post-process the predictions of the ML model under attack. The leakage of inference-state elements into algorithmic timing side channels has never been studied before, and we have found that it can contain rich information that facilitates superior timing attacks that significantly outperform attacks based solely on label outputs. In a case study, we investigate leakage from the non-maximum suppression (NMS) algorithm, which plays a crucial role in the operation of object detectors. In our examination of the timing side-channel vulnerabilities associated with this algorithm, we identified the potential to enhance decision-based attacks. We demonstrate attacks against the YOLOv3 detector, leveraging the timing leakage to successfully evade object detection using adversarial examples, and perform dataset inference. Our experiments show that our adversarial examples exhibit superior perturbation quality compared to a decision-based attack. In addition, we present a new threat model in which dataset inference based solely on timing leakage is performed. To address the timing leakage vulnerability inherent in the NMS algorithm, we explore the potential and limitations of implementing constant-time inference passes as a mitigation strategy

EFEITO TOXICOLÓGICO DE QUATRO PRODUTOS QUÍMICOS UTILIZADOS NA PROFILAXIA DE PEIXE ORNAMENTAL AMAZÔNICO

The objective of this study was to determine the acute toxicity of chemotherapeutic drugs used to diseases control in ornamental fish cardinal tetra (Paracheirodon axelrodi). The fish were exposed to four chemicals: formalin, oxytetracycline, copper sulfate and malachite green. Four experiments were performed, distributed in a completely randomized design with seven concentrations of product test (formalin, oxytetracycline, copper sulfate and malachite green), a control and three repetitions. A static system with five fish per recipient containing 2 L of water for 96 hours was used. The estimated lethal concentration 50% (LC initial (I) 50-96h) were 67.94 mg.L-1, 3.83 mg.L-1, 1.65 mg.L-1 and 0.85 mg.L-1 to formalin, oxytetracycline, copper sulfate and malachite green, respectively. Thus the present study considered the formalin low toxicity for the cardinal tetra and the copper sulfate, oxytetracycline and malachite green are moderately toxic.Keywords: ornamental fish; fish diseases; chemotherapeutic; concentration lethal.O objetivo deste estudo foi determinar a toxicidade aguda de fármacos quimioterápicos utilizados para o controle de doenças em peixes cardinais ornamentais (Paracheirodon axelrodi). Os peixes foram expostos a quatro produtos químicos: formalina, oxitetraciclina, sulfato de cobre e verde malaquita. Foram realizados quatro experimentos, distribuídos em delineamento inteiramente aleatorizado com sete concentrações do produto teste (formalina, oxitetraciclina, sulfato de cobre e verde malaquita), um controle e três repetições. Utilizou-se um sistema estático com cinco peixes por recipiente contendo 2 L de água durante 96 horas. Foram estimadas as concentrações letais 50% (LC inicial (I) 50-96h) de 67,94 mg.L-1, 3,83 mg.L-1, 1,65 mg.L-1 e 0,85 mg.L-1 para formalina, oxitetraciclina, sulfato de cobre e verde de malaquita, respectivamente. Assim, no presente estudo a formalina foi considerada de baixa toxicidade para o tetra cardinal e o sulfato de cobre, oxitetraciclina e verde malaquita são moderadamente tóxicos.Palavras-chave: Peixe ornamental, doenças de peixes, quimioterápicos, concentração letal

RUNX1 and FOXP3 interplay regulates expression of breast cancer related genes

Runx1 participation in epithelial mammary cells is still under review. Emerging data indicates that Runx1 could be relevant for breast tumor promotion. However, to date no studies have specifically evaluated the functional contribution of Runx1 to control gene expression in mammary epithelial tumor cells. It has been described that Runx1 activity is defined by protein context interaction. Interestingly, Foxp3 is a breast tumor suppressor gene. Here we show that endogenous Runx1 and Foxp3 physically interact in normal mammary cells and this interaction blocks Runx1 transcriptional activity. Furthermore we demonstrate that Runx1 is able to bind to R-spondin 3 (RSPO3) and Gap Junction protein Alpha 1 (GJA1) promoters. This binding upregulates Rspo3 oncogene expression and downregulates GJA1 tumor suppressor gene expression in a Foxp3-dependent manner. Moreover, reduced Runx1 transcriptional activity decreases tumor cell migration properties. Collectively, these data provide evidence of a new mechanism for breast tumor gene expression regulation, in which Runx1 and Foxp3 physically interact to control mammary epithelial cell gene expression fate. Our work suggests for the first time that Runx1 could be involved in breast tumor progression depending on Foxp3 availability