Current Status of Angiogenic Cell Therapy and Related Strategies Applied in Critical Limb Ischemia

Critical limb ischemia (CLI) constitutes the most severe form of peripheral arterial disease (PAD), it is characterized by progressive blockade of arterial vessels, commonly correlated to atherosclerosis. Currently, revascularization strategies (bypass grafting, angioplasty) remain the first option for CLI patients, although less than 45% of them are eligible for surgical intervention mainly due to associated comorbidities. Moreover, patients usually require amputation in the short-term. Angiogenic cell therapy has arisen as a promising alternative for these “no-option” patients, with many studies demonstrating the potential of stem cells to enhance revascularization by promoting vessel formation and blood flow recovery in ischemic tissues. Herein, we provide an overview of studies focused on the use of angiogenic cell therapies in CLI in the last years, from approaches testing different cell types in animal/pre-clinical models of CLI, to the clinical trials currently under evaluation. Furthermore, recent alternatives related to stem cell therapies such as the use of secretomes, exosomes, or even microRNA, will be also described.     

Indoor heterogeneous photochemistry of furfural drives emissions of nitrous acid

People spend approximately 80% of their time indoor, making the understanding of the indoor chemistry an important task for safety. The high surface-area-to-volume ratio characteristic of indoor environments leads the semi-volatile organic compounds (sVOCs) to deposit on the surfaces. Using a long path absorption photometer (LOPAP), this work investigates the formation of nitrous acid (HONO) through the photochemistry of adsorbed nitrate anions and its enhancement by the presence of furfural. Using a high-resolution proton-transfer-reaction time-of-flight mass spectrometer (PTR-TOF-MS), this work also investigates the surface emissions of VOCs from irradiated films of furfural and a mix of furfural and nitrate anions. Among the emitted VOCs, 2(5H)-furanone/2-Butenedial was observed at high concentrations, leading to maleic anhydride formation after UV irradiation. Moreover, the addition of potassium nitrate to the film formed NO_x and HONO concentrations up to 10 ppb, which scales to ca. 4 ppb for realistic indoor conditions. This work helps to understand the high levels of HONO and NO_x measured indoors.     

Interaction of triton X-100 on silica: A relationship between surface characteristics and adsorption isotherms

Adsorption of Triton X-100 on various silica substrates has been investigated. A number of solids, including a natural quartz, this quartz washed with HCl acid and subsequently heated at 1273 K; two aerosils and one Kieselgel silicas were studied. These solids exhibit surface areas in the range of 5 to 430 m² g^?1. All the Triton adsorption isotherms display an S-shape at the adsorption temperatures studied (298 and 308 K). It has been found that the pretreatments of natural quartz (by water washing, impurities removed by acid and/or high temperature calcination) affect considerably the amounts of TX-100 adsorbed. Measurements of surface composition have been made by X-ray photoelectron spectroscopy (XPS) with particular emphasis on the presence of impurities and on the number of OH groups at the surface of the samples. The nature of the surface hydroxyl has also been studied by infrared spectroscopy. Furthermore, the specific number of hydroxyl groups on the surface of the silica samples has been determined by thermogravimetric analysis. Finally an attempt to correlate solid surface characteristics with adsorption isotherms has been developed.     

Assessing continuous bivariate effects among different groups through nonparametric regression models: An application to breast cancer detection

In many applications, the joint effect of two continuous covariates on the target binary response may vary across groups defined by levels of a given factor. A testing procedure that would enable this type of surface-by-factor interactions to be detected has been designed. To accomplish this goal, a logistic generalized additive model (GAM) with bivariate continuous interactions varying across groups defined by levels of a factor is considered. A local scoring algorithm based on local linear kernel smoothers was implemented to estimate the proposed logistic GAM. Bootstrap resampling techniques were used for the purpose of testing for factor-by-surface interactions. Given the high computational cost involved, binning techniques were used to speed up computation in the estimation and testing processes. The adequacy of the bootstrap-based test was assessed by means of a simulation study. If a factor-by-surface interaction is detected in the model, it is then established that the use of the odds-ratio curves is very useful in obtaining a direct interpretation of the fitted model. The benefits of using this methodology when analyzing real data are illustrated by applying the technique to the outputs produced by a computerized system dedicated to the early detection of breast cancer.     

Membrane-bound calmodulin in Xenopus laevis oocytes as a novel binding site for melatonin

Melatonin has been suggested as a physiological antagonist of calmodulin. In this work, we have characterized melatonin binding sites in Xenopus laevis oocyte membranes. Binding of [125I]melatonin by X. laevis oocyte membranes fulfills all criteria for binding to a receptor site. Binding was dependent on time, temperature, and membrane concentration and was stable, reversible, saturable, and specific. The binding site was also pharmacologically characterized. Stoichiometric studies showed a high-affinity binding site with a Kd of 1.18 nM. These data are in close agreement with data obtained from kinetic studies (Kd=0.12 nM). In competition studies, we observed a low-affinity binding site (Kd=63.41 microM). Moreover, the binding site was characterized as calmodulin. Thus, binding was dependent on calcium and blocked by anti-CaM antibodies in a concentration-dependent manner. Calmodulin inhibitor chlorpromazine also inhibited binding of the tracer. From these results, it is suggested that membrane-bound calmodulin acts as a melatonin binding site in Xenopus laevis oocytes, where it might couple cellular activities to rhythmic circulating levels of melatonin. This hypothesis correlates with the previous findings describing melatonin as a physiological antagonist of calmodulin.     

Standardizing formats of corporate source data

This paper describe an approach for improving the data quality of corporate sources when databases are used for bibliometric purposes. Research management relies on bibliographic databases and citation index systems as analytical tools, yet the raw resources for bibliometric studies are plagued by a lack of consistency in fied formatting for institution data. The present contribution puts forth a Natural Language Processing (NLP)-oriented method for the identification of the structures guiding corporate data and their mapping into a standardized format. The proposed unification process is based on the definition of address patterns and the ensuing application of Enhanced Finite-State Transducers (E-FST). Our procedure was tested on address formats downloaded from the INSPEC, MEDLINE and CAB Abstracts. The results demonstrate the helpfulness of the method as long as close control of errors is exercised as far as the formats to be unified. The computational efficacy of the model is noteworthy, due to the fact that it is firmly guided by the definition of data in the application domain.     

Metric analysis of the information visibility and diffusion about the European Higher Education Area on Spanish University websites

The purpose of the study proposed in this paper is to evaluate the Spanish public university websites dedicated to the European Higher Education Area (EHEA). To do so, the quality of these resources has been analysed in the light of data provided by a series of indicators grouped in seven criteria, most of which were used to determine what information is made available and in what way. The criteria used in our analysis are: visibility, authority, updatedness, accesibility, correctness and completeness, quality assessment and navigability. All in all, the results allow us to carry out an overall diagnosis of the situation and also provide us with information about the situation at each university, thus revealing their main strengths, namely authority and navegability, and also their chief shortcomings: updatedness, accessibility and quality assessment. In this way it is possible to detect the best practices in each of the aspects evaluated so that they can serve as an example and guide for universities with greater deficiencies and thus help them to improve their EHEA websites.     

Effect of Crude Oil Composition and Blending on Flowing Properties

The effect of crude oil n-paraffin molecular weight distribution on wax crystallization risk was studied. Sixteen highly paraffinic crude oils from Eastern Venezuela were characterized, in terms of hydrocarbon family distribution, by High Temperature Simulate Distillation (HTSD), Gel Permeation Chromatography (GPC), and wax content. n-Paraffin chain length was correlated with crude oil cloud point and pour point. It was demonstrated that high molecular weight linear paraffins are responsible for crude oil wax precipitation. A quantitative correlation between molecular weight distribution and crude oil flowing properties was also obtained. It was found that the wider the molecular weight distribution, the lower is the wax crystallization risk. Blends of different paraffinic crude oils were prepared and their flowing properties were evaluated in comparison with the original crudes. Cloud points below the mean value were obtained. In some cases, a synergistic effect was observed (cloud points below the minimum of the two crude oils). Blends of some of these crudes with condensates afforded improvements on crude oil flow and a reduction of wax crystallization tendency (cloud point). This phenomenon can be attributed to a combination of two factors: I. increases in C24-n-paraffins, and II. a wider molecular weight distribution.     

Immunoexpression of epidermal growth factor in odontogenesis of the offspring of alcoholic mice

Several forms of cell perturbation have been associated with ethanol ingestion. Fetal alcohol syndrome (FAS) as well as diminished maxillofacial development and inhibition of cell regeneration in vitro and in vivo have been described. Epidermal growth factor (EGF) stimulates maxillofacial growth, DNA synthesis, and it is a potent mitogen for a number of various cell types. EGF exerts its effects on cells through binding to a specific cell surface receptor which leads to activation of a thyrosine kinase in the intracellular part of the receptor. The inhibitory effect of alcohol on EGF in the mouse dental follicle was studied in the offspring of alcoholic mothers using immunocytochemistry. Adult female mice were given 22% alcohol in their drinking water and fed a pelleted diet before and during pregnancy. Maternal blood alcohol levels were 262 +/- 1.3 mg/100 ml on gestation day 12.5. The offspring of the alcoholic and control mice were sacrificed on postnatal day 1.5, their mandibles were dissected, weighed and processed by routine immunocytochemistry with the following results. 1) Significant differences were found in mandible weight p < 0.01 after parturition. 2) The tooth germs in the offspring of ethanol treated mice were morphometrically smaller than those of control littermates. 3) Immunoexpression of EGF in the mandibular first molar of the control group was strong and homogeneous while in the experimental group the expression was light and heterogeneous. It is concluded that maternal alcoholism reduces EGF in the offspring.