Clínica Dental S.L., gestión y análisis económico-financiero de una clínica odontológica

[ES] Para poder realizar el plan de empresa, se llevará a cabo un análisis de su viabilidad tanto económica como técnica del proyecto y se describirán todas las operaciones necesarias para la puesta en funcionamiento de la empresa. Por otro lado se definirá la misión, visión, valor, objetivos del negocio y se realizará un estudio detallado del organigrama y un análisis del puesto de trabajo, junto con un plan de marketing detallado y su plan de operaciones. Para finalizar se desarrollarán algunas conclusiones, sintetizando los puntos más importantes de cada capítulo del plan de empresa.Ballester Borrell, IJ. (2016). CLÍNICA DENTAL S.L. GESTIÓN Y ANÁLISIS ECONÓMICO-FINANCIERO DE UNA CLÍNICA ODONTOLÓGICA. http://hdl.handle.net/10251/74754.Archivo delegad

LEY DE CONTRATACIÓN PÚBLICA Y LEY DE CONTRATOS DEL SECTOR PÚBLICO EN LOS ÁMBITOS DE DEFENSA Y SEGURIDAD. PROCEDIMIENTOS DE CONTRATACIÓN EN EL ÁMBITO DEL MINISTERIO DE DEFENSA

La contratación pública es una herramienta de primer orden en el funcionamiento diario de las Administraciones Públicas. Tanto en inversiones, como en equipamiento y servicios, así como el principal benefactor de todo ello, que es el ciudadano. La contratación pública debe ser una prestación objetiva y neutral que deber servir a los fines de la Administración Pública. La motivación de realizar un trabajo que profundice de una manera más concreta en el marco normativo referido a la Defensa y Seguridad, es una vinculación personal estrecha con mandos de Intendencia del Cuartel General Terrestre de Alta Disponibilidad de Valencia, que me han guiado a lo largo del estudio. Por todo ello, ahondaremos en la Ley de Contratos del Sector Público en los ámbitos de la Defensa y la Seguridad, que tiene un cariz más particular respecto al de un ámbito generalista que es la Lay de Contratos del Sector Público. Posteriormente, uno de los objetivos de este trabajo consiste en identificar los diferentes principios rectores de la contratación pública tanto a nivel nacional como internacional en el ámbito de la defensa y en realizar una recapitulación de los diferentes procedimientos de contratación y así como sus respectivos umbrales establecidos en Territorio Nacional para la realización de obras, la adquisición de bienes y la contratación de servicios por parte de los Órganos de Contratación del Ministerio de Defensa; convirtiéndose el mencionado resumen, en referencia para la comparación, objeto primordial de este estudio, de la normativa en materia de contratación empleada en el desarrollo de op (Conceptos, 2021) (García Calvo, 2018)eraciones dependientes del Ministerio de Defensa y por diferentes organismos internacionales tales como la Organización de las Naciones Unidas (ONU), la Organización del Tratado del Atlántico Norte (OTAN) y la Unión Europea (UE). También se estudiarán los procedimientos de contratación empleados por el Foreign Military Sales (FMS), basados en las leyes de los Estados Unidos de América y la Agencia de Adquisiciones y Mantenimiento de la OTAN (NSPA).<br /

Molecular basis of the selective binding of MDMA enantiomers to the Alpha4Beta2 nicotinic receptor subtype: synthesis, pharmacological evaluation and mechanistic studies

The α4β2 nicotinic acetylcholine receptor (nAChR) is a molecular target of 3,4-methylenedioxymethamphetamine (MDMA), a synthetic drug also known as ecstasy, and it modulates the MDMA-mediated reinforcing properties. However, the enantioselective preference of the α4β2 nAChR subtype still remains unknown. Since the two enantiomers exhibit different pharmacological profiles and stereoselective metabolism, the aim of this study is to assess a possible difference in the interaction of the MDMA enantiomers with this nAChR subtype. To this end, we report a novel simple, yet highly efficient enantioselective synthesis of the MDMA enantiomers, in which the key step is the diastereoselective reduction of imides derived from optically pure tert-butylsulfinamide. The enantioselective binding to the receptor is examined using [3H]epibatidine in a radioligand assay. Even though the two enantiomers induced a concentration-dependent binding displacement, (S)-MDMA has an inhibition constant 13-fold higher than (R)-MDMA, which shows a Hill's coefficient not significantly different from unity, implying a competitive interaction. Furthermore, when NGF-differentiated PC12 cells were pretreated with the compounds, a significant increase in binding of [3H]epibatidine was found for (R)-MDMA, indicating up-regulation of heteromeric nAChR in the cell surface. Finally, docking and molecular dynamics studies have been used to identify the binding mode of the two enantiomers, which provides a structural basis to justify the differences in affinity from the differential interactions played by the substituents at the stereogenic center of MDMA. The results provide a basis to explore the distinct psychostimulant profiles of the MDMA enantiomers mediated by the α4β2 nAChR subtype

The Biodiversity of the Mediterranean Sea: Estimates, Patterns, and Threats

The Mediterranean Sea is a marine biodiversity hot spot. Here we combined an extensive literature analysis with expert opinions to update publicly available estimates of major taxa in this marine ecosystem and to revise and update several species lists. We also assessed overall spatial and temporal patterns of species diversity and identified major changes and threats. Our results listed approximately 17,000 marine species occurring in the Mediterranean Sea. However, our estimates of marine diversity are still incomplete as yet—undescribed species will be added in the future. Diversity for microbes is substantially underestimated, and the deep-sea areas and portions of the southern and eastern region are still poorly known. In addition, the invasion of alien species is a crucial factor that will continue to change the biodiversity of the Mediterranean, mainly in its eastern basin that can spread rapidly northwards and westwards due to the warming of the Mediterranean Sea. Spatial patterns showed a general decrease in biodiversity from northwestern to southeastern regions following a gradient of production, with some exceptions and caution due to gaps in our knowledge of the biota along the southern and eastern rims. Biodiversity was also generally higher in coastal areas and continental shelves, and decreases with depth. Temporal trends indicated that overexploitation and habitat loss have been the main human drivers of historical changes in biodiversity. At present, habitat loss and degradation, followed by fishing impacts, pollution, climate change, eutrophication, and the establishment of alien species are the most important threats and affect the greatest number of taxonomic groups. All these impacts are expected to grow in importance in the future, especially climate change and habitat degradation. The spatial identification of hot spots highlighted the ecological importance of most of the western Mediterranean shelves (and in particular, the Strait of Gibraltar and the adjacent Alboran Sea), western African coast, the Adriatic, and the Aegean Sea, which show high concentrations of endangered, threatened, or vulnerable species. The Levantine Basin, severely impacted by the invasion of species, is endangered as well

Immune activation and psychoneurogenic stress modulate corticosterone-releasing effects of lymphokines and ACTH

Possible modulatory effects of psychoneurogenic stress and endotoxin-induced immune activation on the in vitro corticosterone-releasing effects of lymphokine-containing supernatants (LCS) and adrenocorticotropic hormone (ACTH) were studied in rats. We have found that activation of the immune system by endotoxin increases the in vitro sensitivity of the adrenocortical cells to LCS and ACTH. In addition, we found that psychoneurogenic stress not only produced an increase of in vitro adrenal sensitivity to ACTH, but it also enhanced the release of corticosterone after perfusion of LCS. A synergistic interaction between ACTH and LCS was observed in all experimental groups of animals studied. An increased adrenal sensitivity to LCS and ACTH after stress or immune activation might have a functional significance, since the adrenal cortex is a major site in the response of the organism to alterations in the homeostatic balance. On the other hand, the temporal pattern of in vitro corticosterone release after LCS was different in all groups under study compared with that observed after ACTH challenge. LCS elicited a more rapid corticosterone response that lasted for a shorter time than after giving ACTH. These latter results suggest that different mechanisms may underlie the effects of LCS and ACTH on adrenal corticosteroidogenesis. In conclusion, the present findings further reinforce the existence of possible physiologically relevant interactions between the immune system and the pituitary-adrenal axis.Peer Reviewe

PPNA and PPNB lithic industries at Kharaysin (Jordan)

The recent archaeological fieldwork at the large Pre-Pottery Neolithic site of Kharaysin (Zarqa Valley, North Jordan) has revealed one PPNA and three PPNB architectural phases. Phase 1 is dated to the end of the 10th and the beginning of the 9th millennia cal. BC, corresponding to the PPNA occupation of the site, with oval sunken dwellings with mud and lime plastered floors. Phase 2, attributed to the late Early PPNB, is dated in the second half of the 9th millennium cal. BC. At that time architectural structures consisted of contiguous houses sharing intermediate walls, rectangular rooms with rounded corners, plastered floors and walls, and central round fireplaces. In Phase 3, corresponding to the Middle PPNB and dated to the beginning of the 8th millennium cal. BC, rectangular houses were arranged parallel to one another, with internal divisions, plastered floors and burials inside the houses. Phase 4, dated at the end of the 8th millennium cal. BC, during the Late PPNB, has been detected in a test sounding in the upper part of the site. In this paper, we present the preliminary results of the techno-typological analysis of the abundant chipped industry recovered at the site. In this sense, the long and almost unique (for the Southern Levant) occupational sequence at Kharaysin allows full characterization of stone tool production and use during the PPNA to PPNB transition, thus providing interesting insights into the evolution of lithic production during this still poorly understood period in the region. In addition, the results shed light on the chronology of the dissemination of bidirectional blade technology to the Southern Levant.Peer reviewe

Cognate RNA-Binding Modes by the Alternative-Splicing Regulator MBNL1 Inferred from Molecular Dynamics

The muscleblind-like protein family (MBNL) plays a prominent role in the regulation of alternative splicing. Consequently, the loss of MBNL function resulting from sequestration by RNA hairpins triggers the development of a neuromuscular disease called myotonic dystrophy (DM). Despite the sequence and structural similarities between the four zinc-finger domains that form MBNL1, recent studies have revealed that the four binding domains have differentiated splicing activity. The dynamic behaviors of MBNL1 ZnFs were simulated using conventional molecular dynamics (cMD) and steered molecular dynamics (sMD) simulations of a structural model of MBNL1 protein to provide insights into the binding selectivity of the four zinc-finger (ZnF) domains toward the GpC steps in YGCY RNA sequence. In accordance with previous studies, our results suggest that both global and local residue fluctuations on each domain have great impacts on triggering alternative splicing, indicating that local motions in RNA-binding domains could modulate their affinity and specificity. In addition, all four ZnF domains provide a distinct RNA-binding environment in terms of structural sampling and mobility that may be involved in the differentiated MBNL1 splicing events reported in the literature

Production and Use of Nahal Hemar Knives in the Southern Levant during the PPNB. New Evidence from Kharaysin (Jordan)

This article presents the results of the techno-typological and use-wear analyses and contextualization of the Nahal Hemar knives from PPNB Kharaysin. The assemblage is the third largest of this enigmatic and rare tool type in the southern Levant and presents several interesting peculiarities. Almost all the knives were found in two concentrations very close to a funerary area, to which they seem to be related. Some of the knives are the longest ones found to date in the Near East and, interestingly, some could be retted. Use-wear analysis concludes that Nahal Hemar knives from Kharaysin were basically used for cutting soft animal tissue and, less frequently, scraping bones (human bodies?). The results suggest the two concentrations of knives were caches of artefacts of particular signifcance, possibly ritual and associated with the mortuary practices that took place next to where they were found. Thus, would establish, for the first time after Nahal Hemar Cave, a connection between Nahal Hemar knives and the mortuary practices of PPNB communities in the southern Levant.This study has been supported by the Ministerio de Ciencia e Innovación/Fondo Europeo de Desarrollo Regional (PGC2018-096634-B-I00, PID2019-105767GB-I00 and RYC2016-21108 projects), the Fundación PALARQ, the Spanish National Research Council (PIAR program) and the Generalitat de Catalunya (SGR-2017-995)

El Laboratorio de Tecnología prehistórica en la IMF: misión, infraestructuras, servicios CT y colecciones

Desde que en 1990 se retomó la investigación arqueológica en la Institución Milá y Fontanals (IMF) con la incorporación de la Dra. Assumpció Vila, las líneas de investigación vinculadas a la gestión de los recursos minerales y producción del instrumental lítico y sus dinámicas de uso han sido un elemento distintivo de su actividad investigadora. Ello llevó a la creación del Laboratorio de Tecnología prehistórica, cuya denominación constituía una declaración de principios y un homenaje a S.A. Semenov, autor de la obra de referencia Tecnología prehistórica (1957). Desde su inicio, el laboratorio pretendía desarrollar herramientas para afrontar las problemáticas económicas y sociales vinculadas al estudio de la tecnología prehistórica, por lo que proponía un método de estudio para afrontar la fenomenología asociada a la gestión de los recursos minerales en su totalidad, desde las fuentes de aprovisionamiento de las materias primas hasta el abandono de sus evidencias de explotación y consumo en los que hoy reconocemos como yacimientos arqueológicos. En este marco, las colecciones de referencia y la experimentación han sido dos pilares fundamentales de las líneas de investigación del grupo `Arqueología de las Dinámicas sociales¿ (ASD), por lo que hubo que implementar distintas colecciones, en distinto grado de desarrollo. Estas conciernen a una litoteca de rocas silíceas, a técnicas de desbastado para la manufactura de instrumental lítico y al desarrollo de huellas de uso a partir de distintas acciones llevadas a cabo con estos útiles. Su singularidad radica en que las muestras de las colecciones sobrepasan el ámbito estrictamente taxonómico, recogiendo evidencias de distintas acciones técnicas vinculadas al estudio de la tecnología prehistórica. Además de las colecciones, nuestro instituto dispone de otras infraestructuras vinculadas al estudio de la tecnología prehistórica. Más allá de los laboratorios para la limpieza, preparación y conservación de distintos tipos de muestras destacamos: 1. la sala de microscopía, cuyos equipos cubren una amplia gama de técnicas, incluyendo la observación microscópica mediante luz reflejada y transmitida, así como el análisis de superficies mediante métodos 3D, basados en microscopía estereoscópica y confocal. 2. Los equipos de escaneo 3D, con dispositivos que constituyen soluciones de alta gama para la generación de modelos 3D de objetos y superficies, con gran capacidad de captura y tratamiento de datos y una elevada resolución, que permiten su uso en aplicaciones relacionadas con la metrología arqueológica. Todas estas infraestructuras y equipos forman parte de los Servicios científico-técnicos de la IMF que, más allá de la prestación de servicios a instituciones y equipos de investigación, generan una atracción notable. A modo de ejemplo, el grupo ASD tiene ahora 5 MSCA-IF vinculados, más otros 6 investigadores postdoctorales (1 RyC, 2 JdC y 3 contratados por otras instituciones). Sin embargo, este hecho contrasta con la casi nula disponibilidad de personal técnico capaz de gestionar el conjunto de estas infraestructuras, limitada a un Titulado superior (contrato temporal PTA) y un Ayudante de Investigación OPI, pendiente de incorporación y vinculado a los Servicios CT de Arqueología de la IMF

Characterization of a Large Outbreak by CTX-M-1-Producing Klebsiella pneumoniae and Mechanisms Leading to In Vivo Carbapenem Resistance Development

All extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae isolates from patients admitted to and adult intensive care unit were prospectively documented from 2002 to 2005, when a large outbreak (51 patients affected) of multiresistant ESBL-producing Klebsiella pneumoniae infection was detected. The involvement of a single K. pneumoniae clone was demonstrated by pulsed-field gel electrophoresis. In addition to the ESBL-mediated resistance, the epidemic strain uniformly showed cross-resistance to ciprofloxacin, gentamicin, tobramycin, trimethoprim-sulfamethoxazole, and tetracycline, whereas resistance to the β-lactam-β-lactamase inhibitor combinations was variable. The ESBL involved was CTX-M-1, as demonstrated by isoelectric focusing, PCR amplification, and sequencing. CTX-M-1 as well as the aminoglycoside resistance determinants were encoded in a 50-kb plasmid that could be transferred to Escherichia coli only by transformation. In two of the infected patients, carbapenem resistance development (MICs of 8 to 12, 16, and >32 μg/ml for imipenem, meropenem, and ertapenem, respectively) was documented, both in clinical samples and in intestinal colonization studies. The analysis of the outer membrane proteins of the carbapenem-susceptible and -resistant isolates revealed that the former expressed only one of the two major porins, OmpK36, whereas the latter did not express either of them. In one of the cases, the lack of expression of OmpK36 was demonstrated to be mediated by the interruption of the coding sequence by the insertion sequence IS26. This is the first report of a large outbreak of CTX-M-1-producing Enterobacteriaceae and, curiously, the first documented description in the literature of CTX-M-1 in K. pneumoniae, despite the fact that this enzyme has been found in multiple species. Furthermore, we document and characterize for the first time carbapenem resistance development in CTX-M-1-producing Enterobacteriaceae