A Spatial Kinetic Model of Crowd Evacuation Dynamics with Infectious Disease Contagion

This paper proposes a kinetic theory approach coupling together the modeling of crowd evacuation from a bounded domain with exit doors and infectious disease contagion. The spatial movement of individuals in the crowd is modeled by a proper description of the interactions with people in the crowd and the environment, including walls and exits. At the same time, interactions among healthy and infectious individuals may generate disease spreading if exposure time is long enough. Immunization of the population and individual awareness to contagion is considered as well. Interactions are modeled by tools of game theory, that let us propose the so-called tables of games that are introduced in the general kinetic equations. The proposed model is qualitatively studied and, through a series of case studies, we explore different scenarios related to crowding and gathering formation within indoor venues under the spread of a respiratory infectious disease, obtaining insights on specific policies to reduce contagion that may be implemented

BCR-ABL residues interacting with ponatinib are critical to preserve the tumorigenic potential of the oncoprotein

Patients with chronic myeloid leukemia in whom tyrosine kinase inhibitors (TKIs) fail often present mutations in the BCR-ABL catalytic domain. We noticed a lack of substitutions involving 4 amino acids (E286, M318, I360, and D381) that form hydrogen bonds with ponatinib. We therefore introduced mutations in each of these residues, either preserving or altering their physicochemical properties. We found that E286, M318, I360, and D381 are dispensable for ABL and BCR-ABL protein stability but are critical for preserving catalytic activity. Indeed, only a "conservative" I360T substitution retained kinase proficiency and transforming potential. Molecular dynamics simulations of BCR-ABLI360T revealed differences in both helix αC dynamics and protein-correlated motions, consistent with a modified ATP-binding pocket. Nevertheless, this mutant remained sensitive to ponatinib, imatinib, and dasatinib. These results suggest that changes in the 4 BCR-ABL residues described here would be selected against by a lack of kinase activity or by maintained responsiveness to TKIs. Notably, amino acids equivalent to those identified in BCR-ABL are conserved in 51% of human tyrosine kinases. Hence, these residues may represent an appealing target for the design of pharmacological compounds that would inhibit additional oncogenic tyrosine kinases while avoiding the emergence of resistance due to point mutations.This work was supported by an investigator grant to P.V. from Associazione Italiana per la Ricerca sul Cancro (AIRC) and by funding from the Biotechnology and Biological Sciences Research Council (BB/I023291/1 and BB/H018409/1 to AP and FF). P.B. is the recipient of an AIRC - Marie Curie fellowship

Gestión colaborativa en la cadena de abastecimiento en Argentina

La búsqueda de mejoras de costo dentro de las empresas se basa en lograr eficiencias dentro del campo de gestión de la propia empresa, muy rara vez estos estudios y acciones se enfocan en integrar acciones entre diferentes empresas. De este modo, dentro de lo que denominamos “cadena de valor” exiten recursos utilizados en forma ineficiente en diferentes grados. La intención de la investigación es analizar en qué grado existe la oportunidad de integrar recursos en diferentes actores de la vida económica, de modo que bajo la visión que los recursos ineficientes se pueden compartir, se detectan oportunidades de mejora, que exceden lo únicamente empresario, ya que abarcan incluso al conjunto de la sociedad. Esta visión es conocida como “Gestión colaborativa de las Cadenas de Abastecimiento” (CSCM, por sus siglas en inglés) y si bien ya está en aplicación en economías más desarrolladas, aún es poco implementada en Argentina como visión estratégica de negocios

Efecto de la variedad y el momento de fertilización sobre la producción y calidad del forraje de verdeos de invierno

En el otoño de 2000 se estableció un ensayo de verdeos de invierno en siembra directa con cuatro cultivares de avena y centeno, aplicando 40 Kg/ha de N en Zadocks 12 (NI), después de un primer pastoreo (N2) y después de un segundo pastoreo (N3). Se utilizó un diseño de bloques al azar y medidas repetidas en el tiempo, con 3 repeticiones y parcelas de 25 m2. Se muestreo mensualmente el suelo por nitratos, densidad aparente y contenido de agua, en intervalos de 0 a 20, 20 a 40, y 40 a 100 cm de profundidad. Se realizaron tres cortes de forraje coincidentes con los meses de mayo, julio y septiembre. En cada uno de ellos se extrajo material de una superficie de 0,5 m2 por parcela a una altura media de corte de 6 cm., seguidos de pastoreo con novillos. Se determinó la producción de materia seca (MS/ha) y se caracterizó la calidad de la misma. En el primer corte, la oferta de MS y proteína bruta (PB)/ha fue mayor en los centenos que en las avenas y también la extracción de N (P < 0,01), sin embargo, la fertilización y la mineralización reabastecieron el nivel de nitratos del perfil diluyendo las diferencias. En ese corte se produjeron los contenidos de MS más bajos, particularmente en centenos. No hubo respuesta a la fertilización en ninguno de los tres cortes en producción de MS/ha (p > 0,371) ni en contenidos de fibra detergente neutro (FDN), fibra detergente ácido (FDA) o carbohidratos solubles no estructurales (CHOS) (P > 0,208). Se detectó un efecto significativo en el contenido de PB del primer corte a favor del tratamiento fertilizado en Zadocks 12 (P > 0,001). Los centenos produjeron más MS/ha que las avenas (4575 vs 3167 ± 88 Kg; P < 0,001). Entre las avenas se destacó el cultivar Millauquén (p < 0,05) Yentre los centenos los cultivares Don Luis y Quehué (P < 0.05). Todos los verdeos registraron niveles de CHOS muy bajos en el primer corte, con valores inferiores para los centenos (3,8 vs 6,5 + 0,26 % para centenos y avenas; P < 0,001). La relación PB/CHOS fue muy alta en ambas especies y mayor en centenos que en las avenas (6,7:1vs4,4:1 ± 0,33; P <0,001). En el segundo corte, la oferta de MS/ ha fue similar entre los materiales evaluados (P = 0,801; 609 kg MS/ha) y las relaciones PB/CHOS más equilibradas que en el corte anterior. En el tercer corte la oferta de MS/contenido de fibras mayor y nivel de CHOS menor (p < 0,01). El conocimiento del nivel de CHOS constituyó un insumo esencial para caracterizar el potencial nutricional del verdeo.Director: Ing. Agr. Anibal Pordoming

A role for SETD2 loss in tumorigenesis through DNA methylation dysregulation

SETD2-dependent H3 Lysine-36 trimethylation (H3K36me3) has been recently linked to the deposition of de-novo DNA methylation. SETD2 is frequently mutated in cancer, however, the functional impact of SETD2 loss and depletion on DNA methylation across cancer types and tumorigenesis is currently unknown. Here, we perform a pan-cancer analysis and show that both SETD2 mutation and reduced expression are associated with DNA methylation dysregulation across 21 out of the 24 cancer types tested. In renal cancer, these DNA methylation changes are associated with altered gene expression of oncogenes, tumour suppressors, and genes involved in neoplasm invasiveness, including TP53, FOXO1, and CDK4. This suggests a new role for SETD2 loss in tumorigenesis and cancer aggressiveness through DNA methylation dysregulation. Moreover, using a robust machine learning methodology, we develop and validate a 3-CpG methylation signature which is sufficient to predict SETD2 mutation status with high accuracy and correlates with patient prognosis

Containment Control in Mobile Networks

(c) 2008 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other users, including reprinting/ republishing this material for advertising or promotional purposes, creating new collective works for resale or redistribution to servers or lists, or reuse of any copyrighted components of this work in other works.Digital Object Identifier: 10.1109/TAC.2008.930098In this paper, the problem of driving a collection of mobile robots to a given target destination is studied. In particular, we are interested in achieving this transfer in an orderly manner so as to ensure that the agents remain in the convex polytope spanned by the leader-agents, while the remaining agents, only employ local interaction rules. To this aim we exploit the theory of partial difference equations and propose hybrid control schemes based on stop-go rules for the leader-agents. Non-Zenoness, liveness and convergence of the resulting system are also analyzed

Prognostic Value of Choline and Betaine Depends on Intestinal Microbiota-Generated Metabolite Trimethylamine-N-Oxide

Aims: Recent metabolomics and animal model studies show trimethylamine-N-oxide (TMAO), an intestinal microbiota-dependent metabolite formed from dietary trimethylamine-containing nutrients such as phosphatidylcholine (PC), choline, and carnitine, is linked to coronary artery disease pathogenesis. Our aim was to examine the prognostic value of systemic choline and betaine levels in stable cardiac patients. Methods and Results: We examined the relationship between fasting plasma choline and betaine levels and risk of major adverse cardiac events (MACE = death, myocardial infraction, stroke) in relation to TMAO over 3 years of follow-up in 3903 sequential stable subjects undergoing elective diagnostic coronary angiography. In our study cohort, median (IQR) TMAO, choline, and betaine levels were 3.7 (2.4–6.2)μM, 9.8 (7.9–12.2)μM, and 41.1 (32.5–52.1)μM, respectively. Modest but statistically significant correlations were noted between TMAO and choline (r = 0.33, P \u3c 0.001) and less between TMAO and betaine (r = 0.09, P \u3c 0.001). Higher plasma choline and betaine levels were associated with a 1.9-fold and 1.4-fold increased risk of MACE, respectively (Quartiles 4 vs. 1; P \u3c 0.01, each). Following adjustments for traditional cardiovascular risk factors and high-sensitivity C-reactive protein, elevated choline [1.34 (1.03–1.74), P \u3c 0.05], and betaine levels [1.33 (1.03–1.73), P \u3c 0.05] each predicted increased MACE risk. Neither choline nor betaine predicted MACE risk when TMAO was added to the adjustment model, and choline and betaine predicted future risk for MACE only when TMAO was elevated. Conclusion: Elevated plasma levels of choline and betaine are each associated with incident MACE risk independent of traditional risk factors. However, high choline and betaine levels are only associated with higher risk of future MACE with concomitant increase in TMAO

WRONG WAY HOME: AN INFANT SOUTHERN ELEPHANT SEAL (MIROUNGA LEONINA) ARRIVAL ON SOUTHEASTERN BRAZILIAN BEACHES

ABSTRACTRecords of southern elephant seals (Mirounga leonina) as vagrants along the SE Brazilian coast date back the late 50’s and have been relatively common over the last decades. These large marine mammals usually call much attention when they arrive on tropical beaches worldwide and are generally treated as ‘occasional visitors’ and ‘vagrants’. This note reports on sightings of a youngelephant seal along SE Brazil in the summer and autumn of 2020. We also reviewed records in both the literature and open sources, totaling eight records of infant southern elephant seals known since the late 70’s along the Brazilian coast. It was noted that the arrival of an infant in February of 2020is coincident with a previous cyclonic activity off the SE and NE Brazilian coast. The connection of such unlikely records of pinnipeds on tropical beaches and extreme weather events associated to ocean currents should be better evaluated in the context of climatic change RESUMOÉ reportada uma ocorrência recente de um infante de elefante-marinho (Mirounga leonina) na costa do estado do Rio de Janeiro com um intervalo aproximado de um mês entre as avistagens do mesmo indivíduo. A comparação das fotografias obtidas em ambos os registros permitiu a comparação e confirmação. Em adição, se discute a presença de infantes na costa brasileira, que totalizam oito casos, mas que não apontam uma sazonalidade marcada, mas uma tendência aos registros serem reportados em junho, seguido por outubro e novembro. Como o presente registro se deu em janeiro, pico do verão, fatores climáticos de larga escala podem estar atuando para deslocar alguns indivíduos muito ao longe das suas colônias.Palavras-chave: Mirounga leonina; Movimentos; Vagante; Atlântico Sul

Disruption of hypoxia-inducible fatty acid binding protein 7 induces beige fat-like differentiation and thermogenesis in breast cancer cells

Background Humans produce heat through non-shivering thermogenesis, a metabolic process that occurs in inducible beige adipocytes expressing uncoupling protein 1 (UCP1). UCP1 dissipates the proton gradient of the mitochondrial inner membrane and converts that energy into heat. It is unclear whether cancer cells can exhibit autonomous thermogenesis. Previously, we found that the knockdown of hypoxia-inducible fatty acid binding protein 7 (FABP7) increased reactive oxygen species (ROS) in breast cancer cells. ROS are known to induce beige adipocyte differentiation. Methods We investigated the association of tumor hypoxia, FABP7, and UCP1 across breast cancer patients using METABRIC and TCGA data sets. Furthermore, using a breast cancer cell line, HCC1806, we tested the effect of FABP7 knockdown on cellular physiology including thermogenesis. Results We found a strong mutual exclusivity of FABP7 and UCP1 expression both in METABRIC and in TCGA, indicating major metabolic phenotypic differences. FABP7 was preferentially distributed in poorly differentiated-, estrogen receptor (ER) negative tumors. In contrast, UCP1 was highly expressed in normal ducts and well-differentiated-, ER positive-, less hypoxic tumors. In the cell line-based experiments, UCP1 and its transcriptional regulators were upregulated upon FABP7 knockdown. UCP1 was induced in about 20% of cancer cells, and the effect was increased further in hypoxia. UCP1 depolarized mitochondrial membranes at the site of expression. UCP1 induction was associated with the increase in proton leak, glycolysis, and maximal respiration, mimicking the typical energy profile of beige adipocytes. Most importantly, UCP1 induction elevated cancer cell temperature associated with increased vulnerability to hypoxia and gamma-irradiation. Conclusions We demonstrated that breast cancer cells can undergo thermogenesis through UCP1 induction. Disrupting FABP7-mediated fatty acid metabolism can unlock UCP1-mediated thermogenesis, potentially making it possible to develop therapies to target thermogenesis. Further study would be warranted to investigate the effect of rise in temperature of cancer cells on patients' outcomes and the relationship to other metabolic pathways

On stability of discretizations of the Helmholtz equation (extended version)

We review the stability properties of several discretizations of the Helmholtz equation at large wavenumbers. For a model problem in a polygon, a complete $k$-explicit stability (including $k$-explicit stability of the continuous problem) and convergence theory for high order finite element methods is developed. In particular, quasi-optimality is shown for a fixed number of degrees of freedom per wavelength if the mesh size $h$ and the approximation order $p$ are selected such that $kh/p$ is sufficiently small and $p = O(\log k)$, and, additionally, appropriate mesh refinement is used near the vertices. We also review the stability properties of two classes of numerical schemes that use piecewise solutions of the homogeneous Helmholtz equation, namely, Least Squares methods and Discontinuous Galerkin (DG) methods. The latter includes the Ultra Weak Variational Formulation