The Cream of the Crop of the Medicinal Chemistry Section of Molecules 2019

The MDPI journal Molecules is organized into 25 sections that cover many different areas of the broad field of chemistry. Among them, the Medicinal Chemistry section is one of the most classical. The overarching aim of this section is the publication of original re-search and review articles that increase our knowledge on how the chemical structure of molecules can be advantageously modulated to enhance their physicochemical and pharmacokinetic properties and/or their interaction with particular biological targets of therapeutic or diagnostic interest. With Medicinal Chemistry being multidisciplinary in essence, the contents of the articles published in this section partly overlap with those of other sections namely, organic, natural products, bioorganic, and computational theo-retical chemistry or chemical biology, which contributes to the integration and coherence among the different areas of the journal. Driven by a very active board of Academic Editors and imaginative section Managing Editors, new actions are continuously undertaken to attract, visualize, and promote high quality articles and reviews, with the final goal of disseminating in open access medicinal chemistry of excellence. On this line, we are initiating a series of Editorials to highlight the most influential articles, overall or considering specific topics, published in the Medicinal Chemistry section of Molecules in a particular year. We will start with the articles published in 2019, now that all of them have had an exposure to readers of at least one year

Aplicación de visión artificial basada en Siemens Industrial Edge

El principal objetivo de este TFG ha sido el estudio de las aplicaciones que la computación perimetral (Edge Computing) tiene en el ámbito industrial. En el desarrollo se ha implementado una aplicación de visión artificial basada en los servicios ofrecidos por Azure Custom Vision y el motor de ejecución de aplicaciones industriales perimetrales (Edge) de Siemens, Industrial Edge. El hecho de elegir para nuestra aplicación de Industrial Edge un ejemplo con Visión Artificial viene motivado por el hecho de que las aplicaciones de visión artificial son fundamentales en multitud de procesos industriales hoy en día, desde la detección de anomalías, el guiado de AGVs o el empaquetado con robots. En el presente trabajo se han aplicado los últimos avances en visión artificial en combinación con las tecnologías de contenedores y computación perimetral (Edge Computing) de Siemens Industrial Edge. De esta manera se ha intentado resolver, de un modo lo más eficiente posible, tareas de reconocimiento y posicionado de materiales para robots con visión artificial en entornos industriales.The main objective of this TFG has been the study of the applications that perimeter computing (Edge Computing) has in the industrial field, for which an artificial vision application has been implemented based on the services offered by Azure Custom Vision and the running industrial edge applications from Siemens, Industrial Edge. The fact of choosing an example with Machine Vision for our Industrial Edge application is motivated by the fact that machine vision applications are essential in many industrial processes today, like anomaly detection, AGV guidance or the picking-pack with robots. In the present work, the latest advances in artificial vision have been applied in combination with container technologies and edge computing (Edge Computing) from Siemens Industrial Edge. In this way it has been possible to solve, in the most efficient way possible, tasks of recognition and positioning of materials for robots with artificial vision in industrial environments.Grado en Ingeniería Electrónica de Comunicacione

Acetylcholinesterase: A versatile template to coin potent modulators of multiple therapeutic targets

The enzyme acetylcholinesterase (AChE) hydrolyzes the neurotransmitter acetylcholine (ACh) at cholinergic synapses of the peripheral and central nervous system. Thus, it is a prime therapeutic target for diseases that occur with a cholinergic deficit, prominently Alzheimer’s disease (AD). Working at a rate near the diffusion limit, it is considered one of nature’s most efficient enzymes. This is particularly meritorious considering that its catalytic site is buried at the bottom of a 20-Å-deep cavity, which is preceded by a bottleneck with a diameter shorter than that of the trimethylammonium group of ACh, which has to transit through it. Not only the particular architecture and amino acid composition of its active site gorge enable AChE to largely overcome this potential drawback, but it also offers plenty of possibilities for the design of novel inhibitor drug candidates.In this Account, we summarize our different approaches to colonize the vast territory of the AChE gorge in the pursuit of increased occupancy and hence of inhibitors with increased affinity. We pioneered the use of molecular hybridization to design inhibitors with extended binding at the CAS, reaching affinities among the highest reported so far. Further application of molecular hybridization to grow CAS extended binders by attaching a PAS-binding moiety through suitable linkers led to multisite inhibitors that span the whole length of the gorge, reaching the PAS and even interacting with midgorge residues. We show that multisite AChE inhibitors can also be successfully designed the other way around, by starting with an optimized PAS binder and then colonizing the gorge and CAS. Molecular hybridization from a multicomponent reaction-derived PAS binder afforded a single-digit picomolar multisite AChE inhibitor with more than 1.5 million-fold increased potency relative to the initial hit. This illustrates the powerful alliance between molecular hybridization and gorge occupancy for designing potent AChE inhibitors.Beyond AChE, we show that the stereoelectronic requirements imposed by the AChE gorge for multisite binding have a templating effect that leads to compounds that are active in other key biological targets in AD and other neurological and non-neurological diseases, such as BACE-1 and the aggregation of amyloidogenic proteins (β-amyloid, tau, α-synuclein, prion protein, transthyretin, and human islet amyloid polypeptide). The use of known pharmacophores for other targets as the PAS-binding motif enables the rational design of multitarget agents with multisite binding within AChE and activity against a variety of targets or pathological events, such as oxidative stress and the neuroinflammation-modulating enzyme soluble epoxide hydrolase, among others.We hope that our results can contribute to the development of drug candidates that can modify the course of neurodegeneration and may inspire future works that exploit the power of molecular hybridization in other proteins featuring large cavities

Development of hybrid compounds to tackle Alzheimer’s disease

Podeu consultar el llibre complet a: http://hdl.handle.net/2445/128014Alzheimer’s disease (AD) is the main neurodegenerative disorder worldwide. Its pathogenesis involves a network where various mechanisms are interconnected. This complex pathological network makes it extremely challenging to find an efficacious treatment. Herein, we give an overview on the design of the so-called multi-target-directed ligands, i.e. compounds that concurrently hit several key pathogenic factors within the network, as a realistic option to tackle AD, with a particular emphasis on some structural classes of multitarget hybrids recently developed in our group

Individual Subjective Preferences for the Relationship between SPL and Different Cinema Shot Sizes

The main motivation for this study was to find Individual Subjective Preferences (ISP) for the relationship between SPL and different cinema shot sizes. By means of the psychophysical method of Adjustment (MA) [1], the preferred SPL for four of the most frequently used shot sizes, i.e., wide shot, long shot, medium shot, and close-up, was subjectively quantified. Also using the Constant Stimulus Method [1], the preferred difference of SPL for different combinations of the above-mentioned shot sizes was studied. The results of this study could be used to develop sound mixing criteria for audiovisual productions

Recent advances in pharmaceutical sciences VII

The E-book series Recent Advances in Pharmaceutical Sciences reports research contributions from different areas of the multidisciplinary field of Pharmaceutical Sciences. This seventh volume consists of nine chapters, mainly dealing with the fields of botany, physiology, food science, biochemistry & molecular biology, plant physiology, microbiology, parasitology, pharmacology, and medicinal chemistry

Absolute Threshold of Coherence Position Perception between Auditory and Visual Sources for Dialogs

Under certain conditions, auditory and visual information are integrated into a single unified perception, even when they originate from different locations in space. The main motivation for this study was to find the absolute perception threshold of position coherence between sound and image, when moving the image across the screen, and when panning the sound. In this manner, it is possible to subjectively quantify, by means of the constant stimulus psychophysical method [1], the maximum difference of position between sound and image considered coherent by a viewer of audiovisual productions. This paper discusses the accuracy necessary to match the position of the sound and its image on the screen. The results of this study could be used to develop sound mixing criteria for audiovisual production

Epidemiological Survey of Ascosphaera apis in Small-Scale Migratory Apis mellifera iberiensis Colonies

Honey bee hives are moved yearly mainly for pollination, but also to take advantage of consecutive flowering events to get as many harvests of honey as possible and/or to find favorable sites for food sources and summer temperatures. Such movements may lead to pathogen spill-over with consequences on the honey bee health and finally on population decline. Ascosphaera apis is the causative agent of the chalkbrood disease, a pathology affecting honey bee larvae that significantly harms population growth and colony productivity. In this study, we detected the presence of A. apis in adult worker honey bees by PCR-amplification of the intergenic transcribed spacer (ITS1) of the ribosomal gene (rDNA). We first optimized the DNA extraction by testing different protocols in individual and pooled (colony level) adult honey bee samples. Subsequently, the presence of the fungus A. apis was assessed in both stationary and migratory colonies (subjected to small scale regional level movements) to determine the effect of migratory practices on the dispersal of this pathogen. Results confirmed a higher prevalence of A. apis in migratory apiaries when compared to stationary ones, indicating that migratory colonies are more likely to develop chalkbrood disease. Given these results, we suggest that beekeepers should be aware of the risks of pathogens spreading while moving beehives, even within a reduced geographic range

Exploring how us popular culture changes first year students' identities and how it fosters their motivations to enroll in the english teacher training program at UNAB, Casona

Tesis (Profesor de Inglés para la Enseñanza Básica y Media)Este estudio social fue conducido para poder comprender los roles que juega la cultura popular estadounidense en las motivaciones que los estudiantes tienen al matricularse en la Carrera de pedagogía en inglés en la UNAB, campus Casona y el impacto que esta tiene en las identidades de los alumnos. El área de este estudio no ha sido explorada previamente en el contexto chileno; sin embargo, los resultados proporcionados por la investigación pueden facilitar la comprensión por parte del campo pedagógico con respecto al fenómeno causado por la cultura popular estadounidense. Las preguntas de jerarquización fueron aplicadas para así poder reducir el número de estudiantes que se someterían a la siguiente etapa -entrevista semi estructurada. Para esta etapa, dos de treinta y cuatro estudiantes de primer año de la carrera Pedagogía en Inglés en UNAB, Casona fueron seleccionados. A pesar de que aquellos estudiantes pudieron haber tenido más de una razón para estudiar dicha carrera, fue posible apreciar como la cultura popular estadounidense cambió las identidades y motivaciones que los alumnos tenían al momento de decidir estudiar Pedagogía en Inglés en la Universidad Andrés Bello, campus Casona.This social study was conducted in order to comprehend what roles US Popular Culture plays in the motivations that students have to enroll in the English Teacher Training Program (ETTP) at UNAB, Casona, and its impact on students’ identities. This research area has not been explored before in the Chilean context; however, the results provided by this study might help the English pedagogical field understand the phenomenon caused by US Popular Culture. Ranking questions were applied in order to reduce the number of students who would undergo the next stage - semi-structured interview. The main participants of this qualitative study were two students out of thirty four from first year of the ETTP at UNAB, Casona. Even though, first year students might have had several reasons to study in the ETTP, it was possible to see how US Popular Culture changed the participants’ identities and motivations before and when making a decision to study English pedagogy at UNAB, Casona

Recent advances in pharmaceutical sciences IV

Reproducció del llibre publicat a: http://www.trnres.com/ebookcontents.php?id=234Like in the three previous editions, this E-book compiles a series of contributions in the multidisciplinary research arena of Pharmaceutical Sciences. The E-book has been organized in 12 chapters, whose main topics belong to the fields of pharmacology, physical chemistry, plant physiology, microbiology, physiology, preventive medicine and public health, food science, botany, clinical pharmacy and pharmacotherapy, organic chemistry, biochemistry and molecular biology, and parasitology..