Transcriptomic Profiles of CD47 in Breast Tumors Predict Outcome and Are Associated with Immune Activation

Targeting the innate immune system has attracted attention with the development of anti- CD47 antibodies. Anti-CD47 antibodies block the inhibition of the phagocytic activity of macrophages caused by the up-regulation of CD47 on tumor cells. In this study, public genomic data was used to identify genes highly expressed in breast tumors with elevated CD47 expression and analyzed the association between the presence of tumor immune infiltrates and the expression of the selected genes. We found that 142 genes positively correlated with CD47, of which 83 predicted favorable and 32 detrimental relapse-free survival (RFS). From those associated with favorable RFS, we selected the genes with immunologic biological functions and defined a CD47-immune signature composed of PTPRC, HLA-E, TGFBR2, PTGER4, ETS1, and OPTN. In the basal-like and HER2+ breast cancer subtypes, the expression of the CD47-immune signature predicted favorable outcome, correlated with the presence of tumor immune infiltrates, and with gene expression signatures of T cell activation. Moreover, CD47 up-regulated genes associated with favorable survival correlated with pro-tumoral macrophages. In summary, we described a CD47-immune gene signature composed of 6 genes associated with favorable prognosis, T cell activation, and pro-tumoral macrophages in breast cancer tumors expressing high levels of CD47.     

Ethylene and Nitric Oxide Involvement in the Regulation of Fe and P Deficiency Responses in Dicotyledonous Plants

Iron (Fe) and phosphorus (P) are two essential elements for plant growth. Both elements are abundant in soils but with poor availability for plants, which favor their acquisition by developing morphological and physiological responses in their roots. Although the regulation of the genes related to these responses is not totally known, ethylene (ET) and nitric oxide (NO) have been involved in the activation of both Fe-related and P-related genes. The common involvement of ET and NO suggests that they must act in conjunction with other specific signals, more closely related to each deficiency. Among the specific signals involved in the regulation of Fe- or P-related genes have been proposed Fe-peptides (or Fe ion itself) and microRNAs, like miR399 (P), moving through the phloem. These Fe- or P-related phloem signals could interact with ET/NO and confer specificity to the responses to each deficiency, avoiding the induction of the specific responses when ET/NO increase due to other nutrient deficiencies or stresses. Besides the specificity conferred by these signals, ET itself could confer specificity to the responses to Fe- or P-deficiency by acting through different signaling pathways in each case. Given the above considerations, there are preliminary results suggesting that ET could regulate different nutrient responses by acting both in conjunction with other signals and through different signaling pathways. Because of the close relationship among these two elements, a better knowledge of the physiological and molecular basis of their interaction is necessary to improve their nutrition and to avoid the problems associated with their misuse. As examples of this interaction, it is known that Fe chlorosis can be induced, under certain circumstances, by a P over- fertilization. On the other hand, Fe oxides can have a role in the immobilization of P in soils. Qualitative and quantitative assessment of the dynamic of known Fe- and P-related genes expression, selected ad hoc and involved in each of these deficiencies, would allow us to get a profound knowledge of the processes that regulate the responses to both deficiencies. The better knowledge of the regulation by ET of the responses to these deficiencies is necessary to properly understand the interactions between Fe and P. This will allow the obtention of more efficient varieties in the absorption of P and Fe, and the use of more rational management techniques for P and Fe fertilization. This will contribute to minimize the environmental impacts caused by the use of P and Fe fertilizers (Fe chelates) in agriculture and to adjust the costs for farmers, due to the high prices and/or scarcity of Fe and P fertilizers. This review aims to summarize the latest advances in the knowledge about Fe and P deficiency responses, analyzing the similarities and differences among them and considering the interactions among their main regulators, including some hormones (ethylene) and signaling substances (NO and GSNO) as well as other P- and Fe-related signals.     

Computational modeling of cathodic limitations on localized corrosion of wetted SS 316L at room temperature

The ability of a SS 316L surface wetted with a thin electrolyte layer to serve as an effective cathode for an active localized corrosion site was studied computationally. The dependence of the total net cathodic current, I_net, supplied at the repassivation potential E_rp (of the anodic crevice) on relevant physical parameters including water layer thickness (WL), chloride concentration ([Cl⁻]) and length of cathode (Lc) were investigated using a three-level, full factorial design. The effects of kinetic parameters including the exchange current density (i_o,c) and Tafel slope (β_c) of oxygen reduction, the anodic passive current density (i_p) (on the cathodic surface), and E_rp were studied as well using three-level full factorial designs of [Cl⁻] and Lc with a fixed WL of 25 μm. The study found that all the three parameters WL, [Cl⁻] and Lc as well as the interactions of Lc × WL and Lc × [Cl⁻] had significant impact on I_net. A five-factor regression equation was obtained which fits the computation results reasonably well, but demonstrated that interactions are more complicated than can be explained with a simple linear model. Significant effects on I_net were found upon varying either i_o,c, β_c, or E_rp, whereas i_p in the studied range was found to have little impact. It was observed that I_net asymptotically approached maximum values (I_max) when Lc increased to critical minimum values. I_max can be used to determine the stability of coupled localized corrosion and the critical Lc provides important information for experimental design and corrosion protection.     

In vivo aging of gutta‐percha dental cone

Gutta‐percha cone is the most widely used material for root canal filling. The in vivo aging of this cone focus on the degradation of its main organic component, trans‐1,4‐polyisoprene, was studied. Aged cones (25 samples) from 2 to 30 years of root canal filling were extracted from different patients in the occasion of retreatment by mechanical way. The information about the aging time was given by the patients. Gel‐permeation chromatography (GPC) and infrared spectroscopy (FTIR) were the analytical techniques used. Polyisoprene degrades with time of aging, but in a slow process. Decrease in polymer molar mass from 5.7 × 10⁵ to 1.7 × 10⁵ g/mol was observed in polyisoprene from cone after 30 years of root canal filling and inside a noninfected tooth. In tooth with caries and periodontal infection, the decrease in molar mass is higher (4.6 × 10⁴ g/mol in cone with 10 years of aging). The production of carbonyl and hydroxyl groups in the aged material indicates that the process is oxidative, even in closed teeth. In these cases, the oxygen could be provided from tissue fluid. The degradation mechanism is complex and depends on many factors, besides time of root canal filling. The dental problem caused by the aging could be the production and migration of cytotoxic substances to periodontal ligament and the reduction on the canal sealing property due to the polymer weight loss. Both of them could contribute to the root canal treatment failure. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 100:4082–4088, 2006     

Observability of linear systems with commensurate delays and unknown inputs

This paper investigates the observability analysis for linear time systems whose outputs are affected by unknown inputs. Three different definitions of observability are proposed. By introducing the Smith form and comparing the invariant factors, a sufficient condition is deduced for each proposed observability definition. Three examples are given for the purpose of highlighting the effectiveness of the proposed approach.     

Mechanisms of hydrocarbon conversion reactions on heterogeneous catalysts: analogies with organometallic chemistry

Catalysis is central to most industrial processes for chemical manufacturing. As catalytic processes have become more complex and more demanding, selectivity has become the central issue in their design. Selectivity is defined by the relative rates of competing reaction pathways available to crucial intermediates, and can be controlled by subtle changes in the nature of the catalyst, the reactants, and/or the reaction conditions. In order to be able to do this in a systematic manner, a good understanding of the catalytic reaction mechanisms is needed. Here a connection is drawn between the key elementary steps comprising hydrocarbon conversion reactions on surfaces and those known to occur on discrete organometallic complexes. This way, the hydrogenation, dehydrogenation, hydrogenolysis, chain growth, and isomerization reactions typical in heterogeneous catalysis are redefined in terms of hydride elimination, oxidative addition, reductive elimination, migratory insertion, and 1, 2-shift elementary steps, among others. It is suggested that the knowledge already available from organometallic chemistry can be used to further advance the understanding of the surface science involved in heterogeneous catalysis. Thanks to the commonality of the chemistry involved, a better synergy could also be established between homogeneous and heterogeneous catalytic development. These ideas are discussed in this article in a critical and personal way.*Invited contribution to the special volume entitled The Interface between Heterogeneous and Homogeneous Catalysis, stemming from contributions at the recent International Symposium on Relations between Heterogeneous and Homogeneous Catalysis, and dedicated to the memory of Robert L. Burwell.     

Vessel Inspection: A Micro-Aerial Vehicle-based Approach

Vessel maintenance entails periodic visual inspections of the internal and external parts of the hull in order to detect the typical defective situations affecting metallic structures, such as coating breakdown, corrosion, cracks, etc. The main goal of project MINOAS is the automation of the inspection process, currently undertaken by human surveyors, by means of a fleet of robotic agents. This paper overviews an approach to the inspection problem based on an autonomous Micro Aerial Vehicle (MAV) which, as part of this fleet, is in charge of regularly supplying images that can teleport the surveyor from a base station to the areas of the hull to be inspected. The control software approach adopted for the MAV is fully described, with a special emphasis on the self-localization capabilities of the vehicle. Experimental results showing the suitability of the platform to the application are as well reported and discussed.     

Change detection by probabilistic segmentation from monocular view

We present a method for foreground/background video segmentation (change detection) in real-time that can be used, in applications such as background subtraction or analysis of surveillance cameras. Our approach implements a probabilistic segmentation based on the Quadratic Markov Measure Field models. This framework regularizes the likelihood of each pixel belonging to each one of the classes (background or foreground). We propose a new likelihood that takes into account two cases: the first one is when the background is static and the foreground might be static or moving (Static Background Subtraction), the second one is when the background is unstable and the foreground is moving (Unstable Background Subtraction). Moreover, our likelihood is robust to illumination changes, cast shadows and camouflage situations. We implement a parallel version of our algorithm in CUDA using a NVIDIA Graphics Processing Unit in order to fulfill real-time execution requirements.     

Agricultural use of three organic residues: effect on orange production and on properties of a soil of the ‘Comarca Costa de Huelva’ (SW Spain)

Disposal of urban, agricultural and industrial organic residues impliesan increasing problem because of all the economic and environmentalrepercussions involved. One of the most adequate ways of managing this problemis the agricultural use of these wastes as organic amendments. Three organicresidues (AC, olive mill waste water sludge compost; MWC, municipal solid wastecompost; and PS, paper mill sludge) were used in a 3-year field experimentinvolving orange production. The effect of their application on crop productionand on soil quality was investigated. Soil samples (0–20 cm depth)collected 11 months after the last soil amendment were analysed for: pH and EC,Kjeldahl-N, available-P, available-K, total organic carbon, humic substances,dehydrogenase, phosphatase, -glucosidase, urease andbenzoyl-argininamidehydrolysing protease (BAA-protease) activities. Generally, the application of the MWC and PSincreased orange yield when compared to control. Moreover, total organic carbonand humic substances significantly increased in soils treated with all theorganic amendments. Organic fertilisation increased the Kjeldahl-N andavailable-P contents of the soil. The application of the organic residues also causedsignificant increases in dehydrogenase, -glucosidase, urease andBAA-protease activities of the soil. Significant positive correlations (p <0.01) between these enzymatic activities and total organic carbon were foundforall treatments. Significant positive correlation between dehydrogenase, urease,-glucosidase, and BAA-protease and orange yield was also found. However,a clear inhibition of phosphatase activity was observed in soils treated withPS. The results indicate that the repeated application to the soil of moderateamounts of organic amendments has positive effects on the chemical andbiochemical properties of the soil, as well as on the orange yield.     

Synthesis of deuterated cyclopropene fatty esters structurally related to palmitic and myristic acids

To develop a synthesis of tritiated cyclopropene fatty acids (CPFA), compounds that should prove useful for affinity labeling of desaturases in insect pheromone biosynthetic studies, a series of novel, selectively deuterated CPFA analogues was prepared and characterized. In methyl [16-²H]12,13-methylene-12-hexadecenoate, the incorporation of deuterium was achieved by treatment of the corresponding ω-chloro derivative with sodium borodeuteride in dimethylsulfoxide at 70°C for 24 h (67% yield) following conventional procedures. Alkylation of the tetrahydropyranyl derivative of 13-tridecynol in the presence of lithium diisopropylamide in tetrahydrofuran at −20°C with 1-chloro-3-iodopropane in hexamethylphosphoramide, followed by Jones oxidation of the crude product, yielded 16-chloro-12-hexadecynoic acid (54%), which was esterified to the corresponding methyl ester by treatment with potassium carbonate and methyl iodide in dimethylformamide. Treatment of this acetylenic ester with ethyldiazoacetate in the presence of activated copper-bronze as catalyst followed by hydrolysis in KOH solution at room temperature yielded 16-chloro-12,13-(carboxymethylene)-12-hexadecenoic acid. This diacid was treated with excess oxalyl chloride to give the corresponding diacyl chloride, which was decarbonylated in a diethyl ether solution with zinc chloride, and the cyclopropenium ions thus formed were added at −40°C to a methanolic sodium hydroxide solution of sodium borohydride to give methyl 16-chloro-12,13-methylene-12-hexadecenoate. Analogous procedures were followed to prepare methyl [17-²H]10,11-methylene-10-hexadecenoate, methyl [17-²H]11,12-methylene-11-hexadecenoate and methyl [17-²H]12,13-methylene-12-hexadecenoate from the corresponding diacids using sodium borodeuteride in the reduction of the cyclopropenium ions. Alternatively, methyl [2,2,3,3-²H₄]hexadecynoate, prepared by reaction of methyl 2,11-hexadecadiynoate with magnesium in deuterated methanol at room temperature, was submitted to the above cyclopropenylation and reductive decarbonylation sequence to give methyl [2,2,3,3,17-²H₅]-11,12-methylene-11-hexadecenoate. In summary, complementary methods for the selective incorporation of one to five deuterium atoms into cyclopropene fatty acids, at different sites, in moderate to high yields have been developed. The methods should easily be applicable to the preparation of the corresponding tritiated analogues.