Adecuación del software •Dosaviña• al método LWA (Leaf Wall Area) para la determinación del volumen de aplicación en viña

One of the most controversial aspects in the application of pesticides in vineyards, is determining the optimal treatment volume, given the large number of factors involved. To help farmers in this issue, there are tools such as Dosaviña software, which takes into account all the factors affecting this decision and calculates the application volume according to the vegetation to be treated. The main objective of this project is to change the current calculation method of this program, which is based on the volume of vegetation or Tree Row Volume (TRV), by another one based on the surface of vegetation or Leaf Wall Area (LWA), given the current European trends. This requires the study of a data set of field trials conducted over the past 20 years (1995-2015), complemented with new field trials conducted with the same objective. Finally, we succeeded in establishing a reliable calculation method of the application volume based on LWA, for most vegetation traits. Basically it involves multiplying the LWA index by a factor of 0.3, thus obtaining optimal broth volume for vegetation. It was also concluded that the application volume could be calculated considering only the height of the vegetation.Un dels aspectes més controvertits en l'aplicació de fitosanitaris en vinya, és la determinació del volum òptim de tractament, donat l'elevat nombre de factors que hi intervenen. Per ajudar a l'agricultor existeixen eines com el programari Dosaviña que té en compte tots els factors que afecten aquesta decisió i calcula un volum d'aplicació d'acord amb la vegetació a tractar. L'objectiu principal d'aquest projecte és canviar el mètode de càlcul actual del programa, basat en el volum de vegetació o Tree Row Volume (TRV), per un basat en la superfície de vegetació o Leaf Wall Area (LWA), donada l'actual tendència europea. Per a això es van analitzar una sèrie de dades d'assaigs de camp realitzats en els últims 20 anys (1995-2015) i es van realitzar uns assajos de camp amb l'objectiu d'establir un mètode de càlcul fiable basat el LWA. Finalment es va aconseguir establir un mètode de càlcul fiable, per a la majoria de vegetacions, del volum d'aplicació basat en el LWA, que consisteix en multiplicar aquest índex per un coeficient de 0.3, obtenint així el volum de brou òptim per a la vegetació. També es va arribar a la conclusió que es podria calcular el volum d'aplicació considerant només l'alçada de la vegetació.Resumen Uno de los aspectos más controvertidos en la aplicación de fitosanitarios en viña, es la determinación del volumen óptimo de tratamiento, dado el elevado número de factores que intervienen. Para ayudar al agricultor existen herramientas como el software Dosaviña que tiene en cuenta todos los factores que afectan a esta decisión y calcula un volumen de aplicación acorde a la vegetación a tratar. El objetivo principal de este proyecto es cambiar el método de cálculo actual del programa, basado en el volumen de vegetación o Tree Row Volume (TRV), por uno basado en la superficie de vegetación o Leaf Wall Area (LWA), dada la actual tendencia europea. Para ello se analizaron una serie de datos de ensayos de campo realizados en los últimos 20 años (1995-2015) y se realizaron unos ensayos de campo con el objetivo de establecer un método de cálculo fiable basado el LWA. Finalmente se consiguió establecer un método de cálculo fiable, para la mayoría de vegetaciones, del volumen de aplicación basado en el LWA, que consiste en multiplicar este índice por un coeficiente de 0.3, obteniendo así el volumen de caldo óptimo para la vegetación. También se llegó a la conclusión de que se podría calcular el volumen de aplicación considerando solo la altura de la vegetación

Studies on the Interaction of Isocyanides with Imines: Reaction Scope and Mechanistic Variations

The interaction of imines with isocyanides has been studied. The main product results from a sequential process involving the attack of two units of isocyanide, under Lewis acid catalysis, upon the carbon-nitrogen double bond of the imine to form the 4-membered ring system. The scope of the reaction regarding the imine and isocyanide ranges has been determined, and also some mechanistic variations and structural features have been described

Heterocycle-Based Multicomponent Reactions in Drug Discovery: From Hit Finding to Rational Design

In the context of the structural complexity necessary for a molecule to selectively display a therapeutical action and the requirements for suitable pharmacokinetics, a robust synthetic approach is essential. Typically, thousands of relatively similar compounds should be prepared along the drug discovery process. In this respect, heterocycle‐based multicomponent reactions offer advantages over traditional stepwise sequences in terms of synthetic economy, as well as the fast access to chemsets to study the structure activity relationships, the fine tuning of properties, and the preparation of larger amounts for preclinical phases. In this account, we briefly summarize the scientific methodology backing the research line followed by the group. We comment on the main results, clustered according to the targets and, finally, in the conclusion section, we offer a general appraisal of the situation and some perspectives regarding future directions in academic and private research

New trimethoprim-like molecules: bacteriological evaluation and insights into their action

This work reports a detailed characterization of the antimicrobial profile of two trimethoprim-like molecules (compounds 1a and 1b) identified in previous studies. Both molecules displayed remarkable antimicrobial activity, particularly when combined with sulfamethoxazole. In disk difusion assays on Petri dish, compounds 1a and 1b showed synergistic effects with colistin. Specifically, in combinations with low concentrations of colistin very large increases in the activities of compounds 1a and 1b were determined, as demonstrated by alterations in the kinetics of bacterial growth despite only slight changes in the fractional inhibitory concentration index. The effect of colistin may be to increase the rate of antibiotic entry while reducing efflux pump activity. Compounds 1a and 1b were susceptible to extrusion by efflux pumps, whereas the inhibitor phenylalanine arginyl ß-naphthylamide (PAßN) exerted effects similar to those of colistin. The interactions between the target enzyme (dihydrofolate reductase), the coenzyme nicotinamide adenine dinucleotide phosphate (NADPH), and the studied molecules were explored using enzymology tools and computational chemistry. A model based on docking results is reported

Bridging the gap between researchers and patients: The role of the Institutional Review Boards in the informed consent process

Background: The Institutional-Review-Boards (IRB) frequently give unfavorable opinions to evaluated studies due to deficiencies in informed consent forms (ICFs), which delays the ethical approval of the study and increases waste in research. Objective: To analyze the extent to which IRB in our center gives unfavorable opinions due to documents deficiencies and to evaluate types of objection. Material and methods: Retrospective observational study of decisions during the first review by the IRB in our center (2012-2015). We carried out a systematic review of minutes when decisions on approval of studies are collected. If not approval, we analyzed appealed objections. Results: 1858 clinical studies were evaluated by the IRB. 1558 required informed consent for participating (83.9%, CI95%:82.1-85.5), 987 were not approved during the first review due to deficiencies in ICFs (63.3%, CI95%:60.9-65.7). The main causes of objections for non-approval were unreadability (11.7%, CI95%:10.6-12.9), inadequate information given about access to personal data rights (9.2%, CI95%:8.1-10.2), biological samples management (7.8%, IC95%:6.9-8.8), and expected benefits (7.6%, IC95%:6.7-8.6). Conclusions: Deficiencies in ICFs are an important reason for non-approval of protocols evaluated by an IRB. There are three fundamental weaknesses on which the IRB plays a key role: 1) improving readability; 2) adapting them to regulations concerning data protection and biological materials management; 3) avoiding misleading information towards enrollment

A Bivalent Activatable Fluorescent Probe for Screening and Intravital Imaging of Chemotherapy‐Induced Cancer Cell Death

The detection and quantification of apoptotic cells is a key process in cancer research, particularly during the screening of anticancer therapeutics and in mechanistic studies using preclinical models. Intravital optical imaging enables high-resolution visualisation of cellular events in live organisms; however, there are few fluorescent probes that can reliably provide functional readouts in situ without interference from tissue autofluorescence. Here we report the design and optimisation of the fluorogenic probe Apotracker Red for real-time detection of cancer cell death. The strong fluorogenic behaviour, high selectivity, and excellent stability of Apotracker Red make it a reliable optical reporter for the characterisation of the effects of anticancer drugs in cells in vitro and for direct imaging of chemotherapy-induced apoptosis in vivo in mouse models of breast cancer

A multicomponent reaction platform towards multimodal near-infrared BODIPY dyes for STED and fluorescence lifetime imaging

We report a platform combining multicomponent reaction synthesis and automated cell-based screening to develop biocompatible NIR-BODIPY fluorophores. From a library of over 60 fluorophores, we optimised compound NIRBD-62c as a multimodal probe with suitable properties for STED super-resolution and fluorescence lifetime imaging. Furthermore, we employed NIRBD-62c for imaging trafficking inside cells and to examine how pharmacological inhibitors can alter the vesicular traffic between intracellular compartments and the plasma membrane

Enzyme enhancement therapy through non-competitive pharmacological chaperones

Pharmacological chaperones, Chemical chaperones , Enzyme e n- hancement therapy, GM1, Gangliosidosis, Morqui B, Lysosomal Storage Disease, Lysosomal Storage DisordersMost Pharmacological chaperones (PC’s) described until now are substrate analogues which bind to the active site of the target protein. C ons e- quently, such PC’s also inhibit the target protein at higher concentrations thus rendering a narrow therapeutic window and have poor drug-like properties. Through our proprietary technology platform SEE-Tx™, we identify a new generation of non-substrate competitive pharmacological chaperones which p o- tentially offer a much broader therapeutic window. What’s more, such co m- pounds are not substrate analogues, thus presenting much better drug-like pro p- erties, particularly for indications with CNS involvement. Here we present our methodology to identify non-competitive pharmacological chaperones applied to the enzyme beta-galactosidase, whose deficiency is related with GM1 Gangliosidosis and Morquio B.Postprint (published version