Self-assembled nanoparticles as multifunctional drugs for anti-microbial therapies

crosscheck: This document is CrossCheck deposited related_data: Supplementary Information copyright_licence: The Royal Society of Chemistry has an exclusive publication licence for this journal copyright_licence: The accepted version of this article will be made freely available after a 12 month embargo period history: Received 15 January 2014; Accepted 22 May 2014; Accepted Manuscript published 22 May 2014; Advance Article published 4 June 2014; Version of Record published 19 June 201

A Simple Biomimetic Receptor Selectively Recognizing the GlcNAc2 Disaccharide in Water

AbstractGlcNAc2 is the core disaccharide fragment present in N‐glycans exposed on the surface of enveloped viruses of high health concern, such as coronaviruses. Because N‐glycans are directly involved in the docking of viruses to host cells, recognition of GlcNAc2 by a biomimetic receptor may be a convenient alternative to the use of lectins to interfere with viral entry and infection. Herein, we describe a simple biomimetic receptor recognizing the methyl‐β‐glycoside of GlcNAc2 in water with an unprecedented affinity of 160 μM, exceeding that of more structurally complex receptors reported in the literature. The tweezers‐shaped acyclic structure exhibits marked selectivity among structurally related disaccharides, and complete discrimination between mono‐ and disaccharides. Molecular modelling calculations supported by NOE data provided a three‐dimensional description of the binding mode, shedding light on the origin of the affinities and selectivities exhibited by the receptor

Descuento de flujos de fondos, inflación, tipo de cambio y COVID-19: un modelo aplicado en el mercado argentino

The current health crisis translates into a black swan that impacted all economies. Unlike other crises whose impact was general, this one affected certain business segments. Particularly those with markets focused on transportation, leisure and discretionary consumption, with intensive use of the human factor for operations and significant financial leverage applied to significant capital stocks. Along these lines, company valuation models, more than ever, must be based on value fundamentals and macroeconomic risks. Argentina, as an emerging market, adds to the difficulty of the important inflationary process. The work proposes a valuation model where the own risks and value foundations are incorporated in the projected flows and the systemic risks are contained in the rates. The model proposes the valuation in two currencies, legal tender and US dollars, within the framework of theories of parity of interest rates and purchasing power. The firm's value will be a function of real revenue growth and the return to pre-pandemic operating margin levels, variables analyzed with the Monte Carlo simulation method. The operation of the model is illustrated by the valuation of listed companies in the local market as of June 12, 2020, exposing an destruction of intrinsic value measured in dollars of 38%.La actual crisis sanitaria se traduce en un cisne negro que impactó en todas las economías. A diferencia de otras crisis cuyo impacto fue general, esta afectó determinados segmentos de negocios. En particular aquellos con mercados enfocados al transporte, ocio y consumo discrecional, con uso intensivo de factor humano para operaciones y significativo apalancamiento financiero aplicado a significativos stocks de capital. En esa línea los modelos de valuación de empresa, más que nunca, deben apoyarse en los fundamentos de valor y los riesgos macroeconómicos. Argentina, como mercado emergente, suma la dificultad del importante proceso inflacionario. El trabajo propone un modelo de valuación donde los riesgos propios y fundamentos de valor son incorporados en los flujos proyectados y los riesgos sistémicos son contenidos en las tasas. El modelo plantea la valuación en dos monedas, curso legal y dólares EE.UU., en el marco de las teorías de paridad de tipos de interés y poder adquisitivo. El valor de la firma será función del crecimiento real de los ingresos y la vuelta a niveles de márgenes operativos prepandemia, variables analizadas con método de simulación Monte Carlo. El funcionamiento del modelo se ilustra mediante la valuación de las empresas cotizantes en el mercado local al 12 de junio del 2020, exponiendo una destrucción de valor intrínseco medido en dólares del 38%

DESCUENTO DE FLUJO DE FONDOS Y VALUACIÓN EN DOS MONEDAS CON MATEMÁTICAS BORROSAS

El modelo descuento de flujos de fondos debe incorporar, en sistemas económicos emergentes, un marco conceptual para el tratamiento de la inflación y valuación en dos monedas. El punto de partida son las teorías de paridad en los tipos de interés, poder de compra y efecto Fisher, añadiendo lógica borrosa para proyectar variables inciertas: tasas de interés, inflación, tipo de cambio y cantidades, siendo uno de sus principales aportes. El trabajo se estructura de la siguiente manera: son desarrolladas las teorías de paridad y las ecuaciones del modelo en el marco de la lógica borrosa. Su funcionamiento es ilustrado con un caso de una empresa radicada en una economía emergente e inflacionaria como Argentina utilizando planillas de cálculo. Finalmente, los resultados obtenidos demostraron la consistencia de las teorías de la paridad, incorporando lógica borrosa para el tratamiento de la incertidumbre, en el marco de un modelo integral de descuento de flujos de fondos en dos monedas

POS0250 SIGNIFICANT DAMAGE OCCURS EARLY IN THE COURSE OF EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS AND IS MAINLY DUE TO DISEASE-RELATED SEQUELAE

Background:Following the introduction of effective immunosuppressive treatments, ANCA-associated vasculitides (AAV) have become chronic diseases with a remitting-relapsing course. Therefore, preventing chronic damage accrual during follow-up is critical, as relapses, treatment-related side effects, and comorbidities may significantly affect the long-term outcomes of AAV patients. At present, no study specifically evaluated the burden of damage in patients with eosinophilic granulomatosis with polyangiitis (EGPA).Objectives:To describe short-term (6 months) and long-term (5 years) damage accrual in patients with newly diagnosed EGPA.Methods:Patients diagnosed with EGPA, according to ACR criteria and/or Chapel Hill definitions and regularly followed-up in our vasculitis center for ≥5 years were included. Damage accrual was assessed with the Vasculitis Damage Index (VDI). Short-term and long-term damage accrual was defined by VDI at 6 months and at 5 years, respectively, and categorized as related to vasculitis or its treatment.Results:VDI data at 6 months were available for 45 EGPA patients: 24 (53.3%) female, mean age at diagnosis 51.6±13.0 years. ANCA were positive in 17 patients (37.8%), with MPO being the only detected enzyme immunoassay (EIA)-specificity. At 6 months mean VDI was 2.8±1.3; 25/45 (55.6%) and 6/45 patients (13.3%) presented ≥3 and ≥5 items, respectively, whilst only 1 patient (2.2%) showed no items of damage. VDI data at 5 years were available for 32/45 EGPA patients (71.1%): 16 (50%) female, mean age at diagnosis 51.5±13.1 years. MPO-ANCA were positive in 13 patients (40.6%). At 5 years mean VDI was 3.5±1.3, with 26/32 (81.3%) and 7/32 patients (21.9%) presenting ≥3 and ≥5 items, respectively; notably, no patients presented a VDI=0 at 5 years.The most frequent disease-related VDI items at 6 months and at 5 years were asthma, chronic sinusitis, peripheral neuropathy, cardiomyopathy, pulmonary function tests abnormalities and nasal blockage (Figure 1). Osteoporotic fractures, diabetes and systemic hypertension were the most commonly reported treatment-related items at 6 months and at 5 years (Figure 1). Damage accrual progressively rose during the 5-year follow-up (P=0.023), mainly due to disease-related items rather than treatment-related items both at 6 months (disease related VDI 2.6±1.2, treatment-related VDI 0.3±0.6) and at 5 years (disease related VDI 2.9±1.2, treatment-related VDI 0.6±0,7). No significant difference in terms of damage accrual was observed between ANCA-positive and ANCA-negative patients (P >0.5).Conclusion:In our cohort of EGPA patients damage accrual occurs early, with more than half of the patients displaying ≥3 VDI items already at 6 months. Poor control of previous disease activity, particularly ENT and respiratory manifestations, contributes to progressive damage accrual more than treatment side effects.Figure 1.Disease-related and treatment-related VDI items at 6 months and at 5 years in patients with EGPA.Disclosure of Interests:None declare

PANEV: an R package for a pathway-based network visualization

BACKGROUND: During the last decade, with the aim to solve the challenge of post-genomic and transcriptomic data mining, a plethora of tools have been developed to create, edit and analyze metabolic pathways. In particular, when a complex phenomenon is considered, the creation of a network of multiple interconnected pathways of interest could be useful to investigate the underlying biology and ultimately identify functional candidate genes affecting the trait under investigation. RESULTS: PANEV (PAthway NEtwork Visualizer) is an R package set for gene/pathway-based network visualization. Based on information available on KEGG, it visualizes genes within a network of multiple levels (from 1 to n) of interconnected upstream and downstream pathways. The network graph visualization helps to interpret functional profiles of a cluster of genes. CONCLUSIONS: The suite has no species constraints and it is ready to analyze genomic or transcriptomic outcomes. Users need to supply the list of candidate genes, specify the target pathway(s) and the number of interconnected downstream and upstream pathways (levels) required for the investigation. The package is available at https://github.com/vpalombo/PANEV

Análisis del impacto de heurísticas en la toma de decisiones en condiciones de incertidumbre en PyMEs

Las decisiones y la incertidumbre son parte de la vida. Dentro de las teorías clásicas de la elección y los métodos cuantitativos, se encuentran los árboles de decisión. Éstos emplean el teorema de Bayes y el criterio del valor esperado, proponiendo la mejor alternativa. Sin embargo, el individuo ilimitadamente racional que suponen los clásicos no describe fielmente la realidad. Se ha probado que sus decisiones se encuentran afectadas por heurísticas y sesgos, los cuales están incorporados en los nuevos modelos conductuales. Este escenario no sólo se visualiza en individuos, sino también en organizaciones. La problemática se acrecienta en las PyMEs, producto de su particular caracterización. Así, el objetivo de este artículo es presentar las heurísticas más observadas en las decisiones de empresarios PyME de la región de Bahía Blanca. La metodología empleada fue el panel de expertos. Se les presentó a docentes investigadores de dos universidades locales y a referentes de instituciones relacionadas con PyMEs nueve heurísticas, para que definieran el nivel de presencia de cada una. Se concluyó que lasDecisions and uncertainty are part of life. Within the classical theories of choice and quantitative methods, we could find decision trees. They use Bayes theorem and the expected value criterion proposing the best alternative. However, the unlimited rational individual defined by the classics does not truly describe reality. It has been proven that their decisions are influenced by heuristics and biases, which are now added to the new behaviour models. This structure is not only observed in individuals but in organizations as well. And it is increased in SMEs as a result of their peculiar characteristics. For this reason, the objective of this article is to present the most commonly observed heuristics in the decisions made by SMEs business managers in the region of Bahía Blanca. The methodology employed a panel of experts. Nine heuristics were submitted to researcher professors of two local universities as well as to representatives of institutions related to SMEs in order for them to define the level of occurrence of each one. It was concluded that the most observed ones were: Availability, Representativeness, and Overconfidence.Fil: Manzanal, Melisa Noemí. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Ciencias de la Administración; ArgentinaFil: Milanesi, Gastón S.. Universidad Nacional del Sur. Departamento de Ciencias de la Administración; ArgentinaFil: Vigier, Hernan Pedro. Provincia de Buenos Aires. Dirección General de Cultura y Educación. Universidad Provincial del Sudoeste; ArgentinaFil: Toscana, Lidia. Universidad Nacional del Sur. Departamento de Ciencias de la Administración; Argentin