The Fluorenyl Cation

The fluorenyl cation is a textbook example for a 4π antiaromatic cation. However, contrasting results have been published on how the annelated benzene rings compensate the destabilizing effect of the 4π antiaromatic five-membered ring in its core. Whereas previous attempts to synthesize this cation in superacidic media resulted in undefined polymeric material only, we herein report that it can be generated and isolated in amorphous water ice at temperatures below 30 K by photolysis of diazofluorene. Under these conditions, the fluorenylidene is protonated by water to give the fluorenyl cation, which could be characterized spectroscopically. Its absorption in the visible-light range matches that previously obtained by ultrafast absorption spectroscopy, and furthermore, its IR spectrum could be recorded. The IR bands in amorphous ice very nicely match predictions from DFT and DFT/MM calculations, suggesting the absence of strong interactions between the cation and surrounding water molecules

Multifuncionalidad y Sistemas Agroalimentarios locales: prioridades de investigación e innovación en medio ambiente, territorio y desarrollo rural en el sector español del aceite de oliva

Los sistemas agroalimentarios locales (SIAL) de aceite de oliva en España son un buen ejemplo del comportamiento multifuncional y de su contribución potencial a la gobernanza territorial. Se detectan cambios significativos en la geografía del olivar español, derivados, por una parte, de la expansión de nuevas superficies de olivar en regadío de cultivo intensivo y superintensivo y, por otra, de la creciente marginalización a la que se ve abocado el olivar español de media y alta pendiente. Por otra parte, el olivar español produce un fuerte grado de externalidades ambientales negativas, como la erosión o la contaminación difusa de suelos y acuíferos. El principal objetivo del trabajo es detectar las relaciones que se establecen entre la definición de los principales problemas que atañen a los SIAL de aceite de oliva en España y las prioridades de investigación e innovación en materia de territorio y medio ambiente, desde una óptica multidisciplinar que integre enfoques procedentes de las Ciencias Sociales y de las Ciencias Agronómicas y Ambientales. El marco teórico procede de las teorías sobre la multifuncionalidad de los espacios rurales y sobre los SIAL. La metodología utiliza información cualitativa y cuantitativa procedente de dos fuentes primarias: i) un grupo de discusión integrado en un panel presencial de expertos sobre innovación en olivicultura, sostenibilidad y aprovechamiento de residuos; ii) un análisis Delphi dirigido a un conjunto amplio de expertos sobre medio ambiente, territorio y desarrollo rural sostenible en el sector oleícola. En cuanto al análisis de resultados, el grupo de discusión ha tenido como misión categorizar las grandes tipologías de olivicultura en España y sintetizar sus respectivos problemas ambientales y territoriales. Estos resultados sirven como marco de referencia del análisis Delphi, que tiene un doble objetivo: por una parte, el análisis de los principales problemas ambientales y territoriales de los SIAL oleícolas en España; por otra, el estudio de las prioridades en materia de programas y de grupos de líneas de investigación sobre la materia, así como las relaciones entre dichas líneas de investigación y los problemas a los que se enfrentan los SIAL oleícolas.prioridades de investigación e innovación, medio ambiente y territorio, análisis Delphi., Agribusiness, Agricultural and Food Policy, Community/Rural/Urban Development, Food Consumption/Nutrition/Food Safety, Labor and Human Capital,

CHK1 expression in gastric cancer is modulated by p53 and RB1/E2F1: Implications in chemo/radiotherapy response

Radiation has a limited but relevant role in the adjuvant therapy of gastric cancer (GC) patients. Since Chk1 plays a critical function in cellular response to genotoxic agents, we aimed to analyze the role of Chk1 in GC as a biomarker for radiotherapy resistance. We analyzed Chk1 expression in AGS and MKN45 human GC cell lines by RT-QPCR and WB and in a small cohort of human patient’s samples. We demonstrated that Chk1 overexpression specifically increases resistance to radiation in GC cells. Accordingly, abrogation of Chk1 activity with UCN-01 and its expression with shChk1 increased sensitivity to bleomycin and radiation. Furthermore, when we assessed Chk1 expression in human samples, we found a correlation between nuclear Chk1 accumulation and a decrease in progression free survival. Moreover, using a luciferase assay we found that Chk1’s expression is controlled by p53 and RB/E2F1 at the transcriptional level. Additionally, we present preliminary data suggesting a posttranscriptional regulation mechanism, involving miR-195 and miR-503, which are inversely correlated with expression of Chk1 in radioresistant cells. In conclusion, Chk1/microRNA axis is involved in resistance to radiation in GC, and suggests Chk1 as a potential tool for optimal stratification of patients susceptible to receive adjuvant radiotherapy after surgeryThis work was supported by Instituto de Salud Carlos III–Fondo de Investigación Sanitaria (PS09/1988 to ISP; PI11-00949, pI014-1495 and Feder Funds to RP); Comunidad Autónoma de Madrid-Universidad Autónoma de Madrid (CCG10-UAM/BIO-5871 to ISP); Fundación Leticia Castillejo Castillo and Ministerio de Ciencia e Innovación (SAF2012-30862 to RSP), Spain

Studying the accretion geometry of EXO 2030+375 at luminosities close to the propeller regime

The Be X-ray binary EXO 2030+375 was in an extended low luminosity state during most of 2016. We observed this state with NuSTAR and Swift, supported by INTEGRAL observations as well as optical spectroscopy with the NOT. We present a comprehensive spectral and timing analysis of these data here to study the accretion geometry and investigate a possible onset of the propeller effect. The H-alpha data show that the circumstellar disk of the Be-star is still present. We measure equivalent widths similar to values found during more active phases in the past, indicating that the low-luminosity state is not simply triggered by a smaller Be disk. The NuSTAR data, taken at a 3-78 keV luminosity of ~6.8e35 erg/s (for a distance of 7.1 kpc), are well described by standard accreting pulsar models, such as an absorbed power-law with a high-energy cutoff. We find that pulsations are still clearly visible at these luminosities, indicating that accretion is continuing despite the very low mass transfer rate. In phase-resolved spectroscopy we find a peculiar variation of the photon index from ~1.5 to ~2.5 over only about 3% of the rotational period. This variation is similar to that observed with XMM-Newton at much higher luminosities. It may be connected to the accretion column passing through our line of sight. With Swift/XRT we observe luminosities as low as 1e34 erg/s during which the data quality did not allow us to search for pulsations, but the spectrum is much softer and well described by either a blackbody or soft power-law continuum. This softer spectrum might be due to the fact that accretion has been stopped by the propeller effect and we only observe the neutron star surface cooling.Comment: 11 pages, 6 figures, accepted for publication in A&A (v2 including language edits

Enfermedad de Hirschsprung, a propósito de un caso

Introduction: Hirschsprung's disease (HD) is within theclinical context one of Pediatric diseases that lowerIncidencehas, representing barely 2.7% of all of them, according todata from the American College of Pediatrics (ACP). However, its pathophysiologyand clinical behavior governed by the age of the patient are the main variablesthat complicate the diagnosis and give errors of up to 35%(ACP). The mortality of patients can amount up to 65% whenthe EH is complicated with a picture of Necrotizingenterocolitis, in a patient who has notbeen theeliminationof meconium within the first 12 hours of life must suspecteh, always takinginto account the patient's age and recallingthat preterm the same delay can be considered normal, while in the case oflarger aged patients the incidence of thedisease is lower, however the diagnostic probability should not be disregarded. Sepsis in abdominal origin andnecrotising enterocolitis are two of the major complicationsof which the physician should be prevented, even when, asreported in the present case, even patients who are opposedto the main factors of risk described in literature, such asage, can develop a HD box and a latent risk of complicationlikethe rest of patients that if shared these risk factors. Objective: To describe a case of Hirschsprung's disease. Material and methods: a descriptive, retrospective studyabout Hirschsprung's disease clinical case presenta-tion. Results: Describes a case of Hirschsprung's disease inpediatric patient with complications and resolution satisfactory quirurgica. Conclusions: The proper implementation of the clinicalmethod allows an accurate diagnosis and timely treatmentof Hirschsprung's disease.Introducción: La Enfermedad deHirschsprung (EH) es dentro del contexto clínico-quirúrgico una de las patologías pediátricas que menor incidencia posee, representando a penas el 2,7% de todas ellas según datos del Colegio Americano de Pediatría (ACP). Sin embargo, su fisiopatología y su comportamiento clínico regido por la edad del paciente son las principales variables que complican el diagnóstico y dan errores de hasta un 35% (ACP). La mortalidad de los pacientes puede ascender hasta un 65% cuando la EHse complica con un cuadro de enterocolitis necrotizante, en un paciente que no se ha conseguido la eliminación de meconio dentro de las 12 primeras horas de vida deberá sospecharse de EH, siempre tomando en cuenta la edad del pacientey recordando que en pretérminos el retraso del mismopuede considerarse normal, mientras que en el caso de pacientes más grandes de edadla incidencia de la patología es menor, sin embargo la probabilidad diagnóstica no debe de ser menospreciada. La sepsis de origen abdominal y enterocolitis necrotizante son dos de las grandes complicaciones de las cuales el médico debe estar prevenido, más aún, cuando, como se relata en el presente caso clínico, incluso pacientes que se contraponen a los principales factores de riesgo descritos por la literatura, como la edad, pueden desarrollar un cuadro de EH y tener un riesgo latente de complicación al igual que el resto de pacientes que si comparten dichos factores de riesgos. Objetivo: Describir un caso clínico de Enfermedad de Hirschsprung. Material y métodos: Se realizó un estudio descriptivo, retrospectivo, presentación de caso clínico sobre Enfermedad de Hirschsprung. Resultados: Se describe un caso de Enfermedad de Hirschsprung en paciente pediátrico con complicaciones y resolución quirpurgica satisfactoria. Conclusiones: La adecuada aplicación del método clínico permite un diagnóstico preciso y tratamiento oportuno de la Enfermedad de Hirschsprung

Controlled delivery of tauroursodeoxycholic acid from biodegradable microspheres slows retinal degeneration and vision loss in P23H rats

Successful drug therapies for treating ocular diseases require effective concentrations of neuroprotective compounds maintained over time at the site of action. The purpose of this work was to assess the efficacy of intravitreal controlled delivery of tauroursodeoxycholic acid (TUDCA) encapsulated in poly(D, L-lactic-co-glycolic acid) (PLGA) microspheres for the treatment of the retina in a rat model of retinitis pigmentosa. PLGA microspheres (MSs) containing TUDCA were produced by the O/W emulsion-solvent evaporation technique. Particle size and morphology were assessed by light scattering and scanning electronic microscopy, respectively. Homozygous P23H line 3 rats received a treatment of intravitreal injections of TUDCA-PLGA MSs. Retinal function was assessed by electroretinography at P30, P60, P90 and P120. The density, structure and synaptic contacts of retinal neurons were analyzed using immunofluorescence and confocal microscopy at P90 and P120. TUDCA-loaded PLGA MSs were spherical, with a smooth surface. The production yield was 78%, the MSs mean particle size was 23 mu m and the drug loading resulted 12.5 +/- 0.8 mu g TUDCA/mg MSs. MSs were able to deliver the loaded active compound in a gradual and progressive manner over the 28-day in vitro release study. Scotopic electroretinografic responses showed increased ERG a- and b-wave amplitudes in TUDCA-PLGA-MSstreated eyes as compared to those injected with unloaded PLGA particles.TUDCA-PLGAMSs- treated eyes showed more photoreceptor rows than controls. The synaptic contacts of photoreceptors with bipolar and horizontal cells were also preserved in P23H rats treated with TUDCA-PLGA MSs. This work indicates that the slow and continuous delivery of TUDCA from PLGA-MSs has potential neuroprotective effects that could constitute a suitable therapy to prevent neurodegeneration and visual loss in retinitis pigmentosa

Enfermedad de Hirschsprung, a propósito de un caso

Introduction: Hirschsprung's disease (HD) is within theclinical context one of Pediatric diseases that lowerIncidencehas, representing barely 2.7% of all of them, according todata from the American College of Pediatrics (ACP). However, its pathophysiologyand clinical behavior governed by the age of the patient are the main variablesthat complicate the diagnosis and give errors of up to 35%(ACP). The mortality of patients can amount up to 65% whenthe EH is complicated with a picture of Necrotizingenterocolitis, in a patient who has notbeen theeliminationof meconium within the first 12 hours of life must suspecteh, always takinginto account the patient's age and recallingthat preterm the same delay can be considered normal, while in the case oflarger aged patients the incidence of thedisease is lower, however the diagnostic probability should not be disregarded. Sepsis in abdominal origin andnecrotising enterocolitis are two of the major complicationsof which the physician should be prevented, even when, asreported in the present case, even patients who are opposedto the main factors of risk described in literature, such asage, can develop a HD box and a latent risk of complicationlikethe rest of patients that if shared these risk factors. Objective: To describe a case of Hirschsprung's disease. Material and methods: a descriptive, retrospective studyabout Hirschsprung's disease clinical case presenta-tion. Results: Describes a case of Hirschsprung's disease inpediatric patient with complications and resolution satisfactory quirurgica. Conclusions: The proper implementation of the clinicalmethod allows an accurate diagnosis and timely treatmentof Hirschsprung's disease.Introducción: La Enfermedad deHirschsprung (EH) es dentro del contexto clínico-quirúrgico una de las patologías pediátricas que menor incidencia posee, representando a penas el 2,7% de todas ellas según datos del Colegio Americano de Pediatría (ACP). Sin embargo, su fisiopatología y su comportamiento clínico regido por la edad del paciente son las principales variables que complican el diagnóstico y dan errores de hasta un 35% (ACP). La mortalidad de los pacientes puede ascender hasta un 65% cuando la EHse complica con un cuadro de enterocolitis necrotizante, en un paciente que no se ha conseguido la eliminación de meconio dentro de las 12 primeras horas de vida deberá sospecharse de EH, siempre tomando en cuenta la edad del pacientey recordando que en pretérminos el retraso del mismopuede considerarse normal, mientras que en el caso de pacientes más grandes de edadla incidencia de la patología es menor, sin embargo la probabilidad diagnóstica no debe de ser menospreciada. La sepsis de origen abdominal y enterocolitis necrotizante son dos de las grandes complicaciones de las cuales el médico debe estar prevenido, más aún, cuando, como se relata en el presente caso clínico, incluso pacientes que se contraponen a los principales factores de riesgo descritos por la literatura, como la edad, pueden desarrollar un cuadro de EH y tener un riesgo latente de complicación al igual que el resto de pacientes que si comparten dichos factores de riesgos. Objetivo: Describir un caso clínico de Enfermedad de Hirschsprung. Material y métodos: Se realizó un estudio descriptivo, retrospectivo, presentación de caso clínico sobre Enfermedad de Hirschsprung. Resultados: Se describe un caso de Enfermedad de Hirschsprung en paciente pediátrico con complicaciones y resolución quirpurgica satisfactoria. Conclusiones: La adecuada aplicación del método clínico permite un diagnóstico preciso y tratamiento oportuno de la Enfermedad de Hirschsprung

Combination of polymeric superplasticizers, water repellents and pozzolanic agents to improve air lime-based grouts for historic masonry repair

This paper presents the experimental procedure to develop air lime-based injection grouts including polymeric superplasticizers, a water repellent agent and pozzolanic agents as additives. Research focuses on the development of grouts to improve various characteristics simultaneously combining different additions and admixtures. Aiming to improve the injectability of the grouts, in this study different polymeric superplasticizers were added, namely polycarboxylated-ether derivative (PCE), polynaphthalene sulfonate (PNS) and condensate of melamine-formaldehyde sulfonate (SMFC). Sodium oleate was also used as a water repellent agent to reduce the water absorption. The enhancement of the strength and setting time was intended by using microsilica and metakaolin as pozzolanic mineral additions. Compatibility between the different admixtures and action mechanism of the different polymers were studied by means of zeta potential and adsorption isotherms measurements. Diverse grout mixtures were produced and investigated assessing their injectability, fluidity, stability, compressive strength, hydrophobicity and durability. This research leads to several suitable mixtures produced by using more than one component to enhance efficiency and to provide better performance of grouts. According to the results, the grout composed of air lime, metakaolin, sodium oleate and PCE was found the most effective composition improving the mechanical strength, injectability and hydrophobicity