Optoelectronic properties of CuPc thin films deposited at different substrate temperatures

Structural and optical characterization of copper phthalocyanine thin film thermally deposited at different substrate temperatures was the aim of this work. The morphology of the films shows strong dependence on temperature, as can be observed by atomic force microscopy and x-ray diffraction spectroscopy, specifically in the grain size and features of the grains. The increase in the crystal phase with substrate temperature is shown by x-ray diffractometry. Optical absorption coefficient measured by photothermal deflection spectroscopy and optical transmittance reveal a weak dependence on the substrate temperature. Besides, the electro-optical response measured by the external quantum efficiency of Schottky ITO/CuPc/Al diodes shows an optimized response for samples deposited at a substrate temperature of 60 °C, in correspondence to the I-V diode characteristics.

Substrate-selective repair and restart of replication forks by DNA translocases

Stalled replication forks are sources of genetic instability. Multiple fork-remodeling enzymes are recruited to stalled forks, but how they work to promote fork restart is poorly understood. By combining ensemble biochemical assays and single-molecule studies with magnetic tweezers, we show that SMARCAL1 branch migration and DNA-annealing activities are directed by the single-stranded DNA-binding protein RPA to selectively regress stalled replication forks caused by blockage to the leading-strand polymerase and to restore normal replication forks with a lagging-strand gap. We unveil the molecular mechanisms by which RPA enforces SMARCAL1 substrate preference. E. coli RecG acts similarly to SMARCAL1 in the presence of E. coli SSB, whereas the highly related human protein ZRANB3 has different substrate preferences. Our findings identify the important substrates of SMARCAL1 in fork repair, suggest that RecG and SMARCAL1 are functional orthologs, and provide a comprehensive model of fork repair by these DNA translocases.

Liquid fructose down-regulates liver insulin receptor substrate 2 and gluconeogeneic enzymes by modifying nutrient sensing factors in rats

High consumption of fructose-sweetened beverages has been linked to a high prevalence of chronic metabolic diseases. We have previously shown that a short course of fructose supplementation as a liquid solution induces glucose intolerance in female rats. In the present work, we characterized the fructose-driven changes in the liver and the molecular pathways involved. To this end, female rats were supplemented or not with liquid fructose (10%, w/v) for 7 or 14 days. Glucose and pyruvate tolerance tests were performed, and the expression of genes related to insulin signaling, gluconeogenesis and nutrient sensing pathways was evaluated. Fructose-supplemented rats showed increased plasma glucose excursions in glucose and pyruvate tolerance tests and reduced hepatic expression of several genes related to insulin signaling, including insulin receptor substrate 2 (IRS-2). However, the expression of key gluconeogenic enzymes, glucose-6-phosphatase and phosphoenolpyruvate carboxykinase, was reduced. These effects were caused by an inactivation of hepatic forkhead box O1 (FoxO1) due to an increase in its acetylation state driven by a reduced expression and activity of sirtuin 1 (SIRT1). Further contributing to FoxO1 inactivation, fructose consumption elevated liver expression of the spliced form of X-box-binding-protein-1 as a consequence of an increase in the activity of the mammalian target of rapamycin 1 and protein 38-mitogen activated protein kinase (p38-MAPK). Liquid fructose affects both insulin signaling (IRS-2 and FoxO1) and nutrient sensing pathways (p38-MAPK, mTOR and SIRT1), thus disrupting hepatic insulin signaling without increasing the expression of key gluconeogenic enzymes.

Can Orthopantomography be used as a tool for screening of carotid atheromatous pathology and thus be used to help reduce the prevalence of ischemic stroke within the population?

Objective: To assess the possibility of Dentists being able to screen patients with higher risk of vascular diseases. Materials: Kodak 8000C Orthopantomographer, eco-Doppler Logiq-500 General Electric at the Lisbon Hospital Particular. Methods: Assessment of orthopantomographies made to 142 patients aged 50 or more, as well as the existing risk factors. Conduction of carotid eco-Doppler to patients who appear to have calcified plaques of the atheroma. Results: Strong dependence between dichotomised age and having the pathology (p = 0.02).Smokers are twice more likely to present plaques (OR= 2). Being hypertensive increases in about 1.4 the likelihood of having a stroke (OR= 1.4). Of the 27 individuals who presented calcifications in the Orthopantomography, they were all submitted to an eco-Doppler and 21 had the pathology confirmed. 27 individuals, who did not show any plaques in the Orthopantomography, were randomly selected to be the control group. They were submitted to an eco-Doppler. And 23 confirmed the non-existence of plaques. Conclusions: Orthopantomography used for assessing the oral cavity reveals more information which should be the object of the Dentist"s attention

Characterization of human pancreatic orthotopic tumor xenografts suitable for drug screening

Background Efforts to identify novel therapeutic options for human pancreatic ductal adenocarcinoma (PDAC) have failed to result in a clear improvement in patient survival to date. Pancreatic cancer requires efficient therapies that must be designed and assayed in preclinical models with improved predictor ability. Among the available preclinical models, the orthotopic approach fits with this expectation, but its use is still occasional. Methods An in vivo platform of 11 orthotopic tumor xenografts has been generated by direct implantation of fresh surgical material. In addition, a frozen tumorgraft bank has been created, ensuring future model recovery and tumor tissue availability. Results Tissue microarray studies allow showing a high degree of original histology preservation and maintenance of protein expression patterns through passages. The models display stable growth kinetics and characteristic metastatic behavior. Moreover, the molecular diversity may facilitate the identification of tumor subtypes and comparison of drug responses that complement or confirm information obtained with other preclinical models. Conclusions This panel represents a useful preclinical tool for testing new agents and treatment protocols and for further exploration of the biological basis of drug responses.

Characterization of human pancreatic orthotopic tumor xenografts suitable for drug screening

Background Efforts to identify novel therapeutic options for human pancreatic ductal adenocarcinoma (PDAC) have failed to result in a clear improvement in patient survival to date. Pancreatic cancer requires efficient therapies that must be designed and assayed in preclinical models with improved predictor ability. Among the available preclinical models, the orthotopic approach fits with this expectation, but its use is still occasional. Methods An in vivo platform of 11 orthotopic tumor xenografts has been generated by direct implantation of fresh surgical material. In addition, a frozen tumorgraft bank has been created, ensuring future model recovery and tumor tissue availability. Results Tissue microarray studies allow showing a high degree of original histology preservation and maintenance of protein expression patterns through passages. The models display stable growth kinetics and characteristic metastatic behavior. Moreover, the molecular diversity may facilitate the identification of tumor subtypes and comparison of drug responses that complement or confirm information obtained with other preclinical models. Conclusions This panel represents a useful preclinical tool for testing new agents and treatment protocols and for further exploration of the biological basis of drug responses.

Diphenyl urea derivatives as inhibitors of transketolase: a structure-based virtual screening.

Transketolase is an enzyme involved in a critical step of the non-oxidative branch of the pentose phosphate pathway whose inhibition could lead to new anticancer drugs. Here, we report new human transketolase inhibitors, based on the phenyl urea scaffold, found by applying structure-based virtual screening. These inhibitors are designed to cover a hot spot in the dimerization interface of the homodimer of the enzyme, providing for the first time compounds with a suggested novel binding mode not based on mimicking the thiamine pyrophosphate cofactor.

PEN as substrate for new solar cell technologies

The possible use of polyethylene naphthalate as substrate for low-temperature deposited solar cells has been studied in this paper. The transparency of this polymer makes it a candidate to be used in both substrate and superstrate configurations. ZnO:Al has been deposited at room temperature on top of PEN. The resulting structure PEN/ZnO:Al presented good optical and electrical properties. PEN has been successfully textured (nanometer and micrometer random roughness) using hot-embossing lithography. Reflector structures have been built depositing Ag and ZnO:Al on top of the stamped polymer. The deposition of these layers did not affect the final roughness of the whole. The reflector structure has been morphologically and optically analysed to verify its suitability to be used in solar cells.

Substrate and depth preferences of macroinvertebrates along a transect in a Pyrenean high mountain lake (Estanh Redo, NE Spain)

Se estudia la composiciÛn y estructura de la comunidad de macroinvertebrados a lo largo de un transecto en profundidad en el lago Redó (Pirineos). Este estudio se enmarca dentro del proyecto de ámbito europeo MOLAR (Mountain Lake Research). Un equipo de buceadores muestreo dos tipos de substrato, piedras y fondos blandos, cada 2 m desde los 2 a los 20 m de profundidad. En la parte m·s profunda del lago las muestras se tomaron con draga Ekman (tres rÈplicas). Todas las muestras se tomaron el mismo día, el 15 de Julio de 1997. Los resultados, mediante un análisis de autocorrelación de Mantel, muestran que no existe un gradiente continuo en la sustituciÛn de unas especies por otras en la comunidad sobre substrato rocoso, sino que se distinguen dos discontinuidades claras, una a los 4 metros y otra a los 14 metros. La primera separa las especies propias de la zona litoral respecto a las de la zona sublitoral, mientras que la segunda coincide con la parte inferior de la termoclina, una zona siempre mas frÌa, con menos luz y con mayor acumulación de material fino sobre los sustratos duros a la vez que desaparece la cobertura algal que cubrÌa las piedras hasta esta profundidad. Respecto al sustrato existen especies que claramente prefieren el sustrato blando (oligoquetos, o los quironÛmidos Micropsectra radialis y Pseudodiamesa nivosa), mientras que otras eran más abundantes o exclusivas de los sustratos duros (Radix peregra, Plectrocnemia laetabilis, Psectrocladius octomaculatus). Estos resultados seran muy útiles para la interpretaciÛn de los datos paleolimnolÛgicos de los cores que actualmente se est·n estudiando en el lago.

Structure of a-Si:H/a-Si1-xCx:H multilayers deposited in a reactor with automated substrate holder

This paper deals with the structural properties of a-Si:H/a-Si1-xCx: H multilayers deposited by glow-discharge decomposition of SiH4 and SiH4 and CH4 mixtures. The main feature of the rf plasma reactor is an automated substrate holder. The plasma stabilization time and its influence on the multilayer obtained is discussed. A series of a-Si:H/a-Si1-xCx: H multilayers has been deposited and characterized by secondary ion mass spectrometry (SIMS), X-ray diffraction (XRD) and transmission electron microscopy (TEM). No asymmetry between the two types of interface has been observed. The results show that the multilayers present a very good periodicity and low roughness. The difficulty of determining the abruptness of the multilayer at the nanometer scale is discussed.

Screening premorbid metabolic syndrome in community pharmacies: a cross-sectional descriptive study

Background: Premorbid metabolic syndrome (pre-MetS) is a cluster of cardiometabolic risk factors characterised by central obesity, elevated fasting glucose, atherogenic dyslipidaemia and hypertension without established cardiovascular disease or diabetes. Community pharmacies are in an excellent position to develop screening programmes because of their direct contact with the population. The main aim of the study was to determine the prevalence of pre-MetS in people who visited community pharmacies for measurement of any of its five risk factors to detect the presence of other risk factors. The secondary aims were to study the presence of other cardiovascular risk factors and determine patients" cardiovascular risk. Methods: Cross-sectional, descriptive, multicentre study. Patients meeting selection criteria aged between 18 and 65 years who visited participating community pharmacies to check any of five pre-MetS diagnostic factors were included. The study involved 23 community pharmacies in Catalonia (Spain). Detection criteria for pre-MetS were based on the WHO proposal following IDF and AHA/NHBI consensus. Cardiovascular risk (CVR) was calculated by Regicor and Score methods. Other variables studied were smoking habit, physical activity, body mass index (BMI), and pharmacological treatment of dyslipidemia and hypertension. The data were collected and analysed with the SPSS programme. Comparisons of variables were carried out using the Student"s T-test, Chi-Squared test or ANOVA test. Level of significance was 5% (0.05). Results: The overall prevalence of pre-MetS was 21.9% [95% CI 18.7-25.2]. It was more prevalent in men, 25.5% [95% CI 22.1-28.9], than in women, 18.6% [95% CI 15.5-21.7], and distribution increased with age. The most common risk factors were high blood pressure and abdominal obesity. About 70% of people with pre-MetS were sedentary and over 85% had a BMI ≥25 Kg/m2 . Some 22.4% had two metabolic criteria and 27.2% of patients with pre-MetS had no previous diagnosis. Conclusions: The prevalence of pre-MetS in our study (21.9%) was similar to that found in other studies carried out in Primary Care in Spain. The results of this study confirm emergent cardiometabolic risk factors such as hypertension, obesity and physical inactivity. Our study highlights the strategic role of the community pharmacy in the detection of pre-MetS in the apparently healthy population.

Total synthesis and antiproliferative activity screening of (±)-aplicyanins A, B and E and related analogs

The first total synthesis of the indole alkaloids ()-aplicyanins A, B and E, plus seventeen analogs, all in racemic form is reported. Modifications to the parent compound included changing the number of bromine substituents on the indole, the groups on the indole nitrogen (H, Me or OMe), and/or the oxidation level of the heterocyclic core tetrahydropyrimidine. Each compound was screened against three human tumor cell lines, and fourteen of the newly synthesized compounds showed considerable cytotoxicity. The assay results were used to establish structure-activity relationships. These results suggest that the acetyl group moiety on the imine nitrogen, and the bromine at position 5 of the indole, are both critical to activity.

Analytical Dirac-Hartree-Fock-Slater screening function for atoms (Z=1-92)

An analytical approximation, depending on five parameters, for the atomic screening function is proposed. The corresponding electrostatic potential takes a simple analytical form (superposition of three Yukawa potentials) well suited to most practical applications. Parameters in the screening function, determined by an analytical fitting procedure to Dirac-Hartree-Fock-Slater (DHFS) self-consistent data, are given for Z=1¿92. The reliability of this analytical approach is demonstrated by showing that (a) Born cross sections for elastic scattering of fast charged particles by the present analytical field and by the DHFS field practically coincide and (b) one-electron binding energies computed from the independent-particle model with our analytical field (corrected for exchange and electrostatic self-interaction) agree closely with the DHFS energy eigenvalues.

Thioflavin-S staining of bacterial inclusion bodies for the fast, simple, and inexpensive screening of amyloid aggregation inhibitors

Amyloid aggregation is linked to a large number of human disorders, from neurodegenerative diseases as Alzheimer"s disease (AD) or spongiform encephalopathies to non-neuropathic localized diseases as type II diabetes and cataracts. Because the formation of insoluble inclusion bodies (IBs) during recombinant protein production in bacteria has been recently shown to share mechanistic features with amyloid self-assembly, bacteria have emerged as a tool to study amyloid aggregation. Herein we present a fast, simple, inexpensive and quantitative method for the screening of potential anti-aggregating drugs. This method is based on monitoring the changes in the binding of thioflavin-S to intracellular IBs in intact Eschericchia coli cells in the presence of small chemical compounds. This in vivo technique fairly recapitulates previous in vitro data. Here we mainly use the Alzheimer"s related beta-amyloid peptide as a model system, but the technique can be easily implemented for screening inhibitors relevant for other conformational diseases simply by changing the recombinant amyloid protein target. Indeed, we show that this methodology can be also applied to the evaluation of inhibitors of the aggregation of tau protein, another amyloidogenic protein with a key role in AD.

Thioflavin-S staining of bacterial inclusion bodies for the fast, simple, and inexpensive screening of amyloid aggregation inhibitors

Amyloid aggregation is linked to a large number of human disorders, from neurodegenerative diseases as Alzheimer"s disease (AD) or spongiform encephalopathies to non-neuropathic localized diseases as type II diabetes and cataracts. Because the formation of insoluble inclusion bodies (IBs) during recombinant protein production in bacteria has been recently shown to share mechanistic features with amyloid self-assembly, bacteria have emerged as a tool to study amyloid aggregation. Herein we present a fast, simple, inexpensive and quantitative method for the screening of potential anti-aggregating drugs. This method is based on monitoring the changes in the binding of thioflavin-S to intracellular IBs in intact Eschericchia coli cells in the presence of small chemical compounds. This in vivo technique fairly recapitulates previous in vitro data. Here we mainly use the Alzheimer"s related beta-amyloid peptide as a model system, but the technique can be easily implemented for screening inhibitors relevant for other conformational diseases simply by changing the recombinant amyloid protein target. Indeed, we show that this methodology can be also applied to the evaluation of inhibitors of the aggregation of tau protein, another amyloidogenic protein with a key role in AD.