Plasma total cell-free DNA (cfDNA) is a surrogate biomarker for tumour burden and a prognostic biomarker for survival in metastatic melanoma patients Valpione, S.; Gremel, G.; Mundra, P.; Middlehurst, P.; Galvani, E.; Girotti, Maria Romina; Lee, R.J.; Garner, G.; Dhomen, N.; Lorigan, P.C.; Marais, R. Introduction Tumour burden is a prognostic biomarker in metastatic melanoma. However, tumour burden is difficult to measure and there are currently no reliable surrogate biomarkers to easily and reliably determine it. The aim of this study was to assess the potential of plasma total cell free DNA as biomarker of tumour burden and prognosis in metastatic melanoma patients. Materials and methods A prospective biomarker cohort study for total plasma circulating cell-free DNA (cfDNA) concentration was performed in 43 metastatic melanoma patients. For 38 patients, paired blood collections and scan assessments were available before treatment and at first response evaluation. Tumour burden was calculated as the sum of volumes from three-dimensional radiological measurements of all metastatic lesions in individual patients. Results Baseline cfDNA concentration correlated with pre-treatment tumour burden (ρ = 0.52, P < 0.001). Baseline cfDNA levels correlated significantly with hazard of death and overall survival, and a cut off value of 89 pg/μl identified two distinct prognostic groups (HR = 2.22 for high cfDNA, P = 0.004). Patients with cfDNA ≥89 pg/μl had shorter OS (10.0 versus 22.7 months, P = 0.009; HR = 2.22 for high cfDNA, P = 0.004) and the significance was maintained when compared with lactic dehydrogenase (LDH) in a multivariate analysis. We also found a correlation between the changes of cfDNA and treatment-related changes in tumour burden (ρ = 0.49, P = 0.002). In addition, the ratio between baseline cfDNA and tumour burden was prognostic (HR = 2.7 for cfDNA/tumour volume ≥8 pg/(μl*cm3), P = 0.024). Conclusions We have demonstrated that cfDNA is a surrogate marker of tumour burden in metastatic melanoma patients, and that it is prognostic for overall survival.

Landslide change detection based on Multi-Temporal airborne LIDAR-derived DEMs Mora, Omar E.; Lenzano, María Gabriela; Toth, Charles Karoly; Grejner-Brzezinska, Dorota A.; Fayne, Jessica V. Remote sensing technologies have seen extraordinary improvements in both spatial resolution and accuracy recently. In particular, airborne laser scanning systems can now provide data for surface modeling with unprecedented resolution and accuracy, which can effectively support the detection of sub-meter surface features, vital for landslide mapping. Also, the easy repeatability of data acquisition offers the opportunity to monitor temporal surface changes, which are essential to identifying developing or active slides. Specific methods are needed to detect and map surface changes due to landslide activities. In this paper, we present a methodology that is based on fusing probabilistic change detection and landslide surface feature extraction utilizing multi-temporal Light Detection and Ranging (LiDAR) derived Digital Elevation Models (DEMs) to map surface changes demonstrating landslide activity. The proposed method was tested in an area with numerous slides ranging from 200 m2 to 27,000 m2 in area under low vegetation and tree cover, Zanesville, Ohio, USA. The surface changes observed are probabilistically evaluated to determine the likelihood of the changes being landslide activity related. Next, based on surface features, a Support Vector Machine (SVM) quantifies and maps the topographic signatures of landslides in the entire area. Finally, these two processes are fused to detect landslide prone changes. The results demonstrate that 53 out of 80 inventory mapped landslides were identified using this method. Additionally, some areas that were not mapped in the inventory map displayed changes that are likely to be developing landslides.

Sequential Bayesian Experimental Design for Process Optimization with Stochastic Binary Outcomes Luna, Martín Francisco; Martínez, Ernesto Carlos For innovative products, the issue of reproducibly obtaining their desired end-use properties at industrial scale is the main problem to be addressed and solved in process development. Lacking a reliable first-principles process model, a Bayesian optimization algorithm is proposed. On this basis, a short of sequence of experimental runs for pinpointing operating conditions that maximize the probability of successfully complying with end-use product properties is defined. Bayesian optimization is able to take advantage of the full information provided by the sequence of experiments made using a probabilistic model (Gaussian process) of the probability of success based on a one-class classification method. The metric which is maximized to decide the conditions for the next experiment is designed around the expected improvement for a binary response. The proposed algorithm's performance is demonstrated using simulation data from a fed-batch reactor for emulsion polymerization of styrene.

Goal-directed Design of Dynamic Experiments for Cybernetic Models of Bioreactors Luna, Martín Francisco; Martínez, Ernesto Carlos The distinctive feature of cybernetic models of bioreactors is their capacity to account for regulatory mechanisms in a cell metabolism by modeling the synthesis of enzymes and their activities. From a process engineering viewpoint, to guarantee its predictive capabilities regarding one or more process objective or goals (e.g. optimization, controllability, etc.), experimental data used to fit a cybernetic model parameters should be the most informative bearing in mind the adequacy of the resulting model to describe the specific objective of interest. To excite the most relevant metabolic modes in the cybernetic model, a dynamic experiment is optimally designed by accounting for the sensitivity of the chosen objective to operating conditions. The bioreactor feeding profile and sampling times are selected to maximize a global sensitivity index. As a case study, biomass production or fermentation to ethanol conversion in the fed-batch cultivation of Saccharomyces Cerevisiae are considered as alternative objectives.

Visualization of the Diffusion Pathway of Protons in (NH4)2Si0.5Ti0.5P4O13 as an Electrolyte for Intermediate-Temperature Fuel Cells Sun, Chunwen; Chen, Lanli; Shi, Siqi; Reeb, Berthold; Lopez, Carlos Alberto; Alonso, José Antonio; Stimming, Ulrich We demonstrate that (NH4)2Si0.5Ti0.5P4O13 is an excellent proton conductor. The crystallographic information concerning the hydrogen positions is unraveled from neutron-powder-diffraction (NPD) data for the first time. This study shows that all the hydrogen atoms are connected though H bonds, establishing a two-dimensional path between the [(Si0.5Ti0.5)P4O132-]n layers for proton diffusion across the crystal structure by breaking and reconstructing intermediate H-O=P bonds. This transient species probably reduces the potential energy of the H jump from an ammonium unit to the next neighboring NH4+ unit. Both theoretical and experimental results support an interstitial-proton-conduction mechanism. The proton conductivities of (NH4)2Si0.5Ti0.5P4O13 reach 0.0061 and 0.024 S cm-1 in humid air at 125 and 250 °C, respectively. This finding demonstrates that (NH4)2Si0.5Ti0.5P4O13 is a promising electrolyte material operating at 150-250 °C. This work opens up a new avenue for designing and fabricating high-performance inorganic electrolytes.

Políticas Estéticas: El caso Saer y la persistencia de la autonomía Abbate, Florencia El objetivo de es artículo será la revisión del concepto de autonomía del arte y su puesta en relación con la obra narrativa y ensayística de Juan José Saer. Se examinan de modo crítico aquellas lecturas que implícitamente han tendido a interpretarlo retomando de modo epigonal dicotomías como arte por el arte vs. arte comprometido o formalismo vs. realismo. Sostenemos que en este autor la defensa del pilar moderno de la autonomía estética no se opone a aquellas visiones que le atribuyen al arte una función social sino que, por el contrario, asume en su obra un valor político. Para ello, nos basamos en algunas nociones de J. Ranciére, cuya filosofía redefine la estética como algo no sólo perteneciente al campo de las formas sensibles sino también de lo social y lo político, y pensamos lo político como una "redistribución de lo sensible".

Galectins: key players at the frontiers of innate and adaptive immunity Martínez Allo, Verónica Candela; Toscano, Marta Alicia; Pinto, Nicolás Alejandro; Rabinovich, Gabriel Adrián The proper function of the immune system entails multiple regulatory pathways aimed at modulating immunogenic and tolero-genic functions of immune cells. Galectins, a family of carbohydrate-binding proteins, control a variety of biological processes involved in activation, differentiation, trafficking and survival of immune cells. In this review we summarize pioneer work and emerging findings highlighting selected functions of galectins as regulatory checkpoints that control innate and adaptive immune cell programs.

CSDC2, a cold shock domain RNA-binding protein in decidualization Vallejo, Griselda; Mestre Citrinovitz, Ana Cecilia; Winterhager, Elke; Saragueta, Patricia Esther RNA-binding proteins (RBPs) have been described for cancer cell progression and differentiation, although there is still much to learn about their mechanisms. Here, using in vivo decidualization as a model, we describe the role of RBP cold shock domain containing C2 (CSDC2) in the endometrium. Csdc2 messenger RNA expression was differentially regulated depending on time and areas of decidua development, with the most variation in antimesometrium (AM) and, to a lesser degree, in the junctional zone (JZ). Immunohistochemistry of CSDC2 showed a preferentially cytoplasmic localization at AM and JZ, and nuclear localization in underneath myometrium and mesometrium (M). Cytoplasmic localization coincided with differentiated, DESMIN-marked areas, while nuclear localization coincides with proliferative zones. Uterine suppression of CSDC2 through intrauterine-injected-specific small interfering RNA (siRNA) led to abnormal decidualization in early pregnancy, with more extended antimesometrial area and with poor M development if compared with control siRNA-injected animals. These results suggest that CSDC2 could be a regulator during decidua development.

Estudio de los mecanismos moleculares y celulares de la entrada y propagación del Virus de la Diarrea Viral Bovina Merwaiss, Fernando; Alvarez, Diego Ezequiel; Czibener, Cecilia El virus de la diarrea viral bovina (BVDV) es un pestivirus patógeno del ganado vacuno cercanamente relacionado al virus de la hepatitis C (HCV) dentro de la familia Flaviviridae. La infección con BVDV reduce la productividad causando pérdidas económicas para la industria ganadera. La partícula viral comprende una membrana lipídica asociada a las glicoproteínas de envoltura Erns, E1 y E2, que rodean a la nucleocápside que contiene el genoma viral, el cual consiste en una única molécula de ARN simple cadena de polaridad positiva. E2 es el principal determinante antigénico en el animal infectado y produce una respuesta inmune con anticuerpos neutralizantes contra BVDV. A su vez cumple un rolfundamental para la entrada del virus a la célula huésped dado que interacciona con receptores en la superficie de la célula que median la endocitosis de la partícula viral, y forma un complejo con E1 que es esencial en la fusión de la envoltura del virus con la membrana del endosoma en medio ácido para liberar el genoma de ARN en el citoplasmade la célula infectada. La reciente determinación de la estructura cristalina de E2 ha abierto nuevas perspectivas en el estudio del mecanismo molecular de la entrada de BVDV. En este trabajo de tesis se desarrollaron nuevas herramientas genéticas y moleculares con elobjetivo de estudiar el mecanismo de entrada y propagación de BVDV, haciendo foco fundamentalmente en el rol protagónico de la glicoproteína de envoltura E2.En la primera parte de este trabajo se empleo genética invesa para producir una versión recombinante de BVDV que expresa GFP en el citoplasma de células infectadas. Utilizando este virus desarrollamos ensayos basados en la detección de GFP por microscopia de fluorescenica y citometría de flujo mediante los que pudimos demostrar que la expresión de dicha proteina funciona como reportero de la replicación de BVDV. Por otro lado se desarrolló un sistema de expresión y marcación sitio específica con biotina in vivo para la proteína de envoltura viral E2 que permitió producir una proteína recombinante marcada homogéneamente. La unión especifica de esta proteína recombinante a células susceptibles y su capacidad de bloquear la entrada de BVDV,sugieren que la misma mantiene un plegamiento y funcionalidad correctos.A partir de la bibliografía referida a las funciones de E2 y basándose en un análisis de conservación de secuencias se identificaron en la estructura de la proteína posibles motivos funcionales. En particular, analizamos el rol de un motivo de estructura tipo β-hairpin expuesto al solvente como posible responsable de la interacción con receptores. Sediseñaron mutaciones en dicha region, las cuales en el contexto de la proteína soluble resultaron en una disminucion de su capacidad de bloquear la entrada de BVDV. A continuación, se generó un virus recombinante portando las mutaciones en el β-hairpin y se observó que la infectividad de dicho virus está severamente disminuida con respecto alvirus, indicando que dicha región está involucrada en la interacción con receptores celulares.En la segunda parte de este trabajo se construyó una pareja de virus recombinantes citopático y no citopático que expresa una versión de E2 en fase con la proteína fluorescente mCherry en su extremo amino terminal. A través de la detección de mCherry se pudieron identificar células infectadas y seguir así la propagación de la infección en células vivas. Empleando esta herramienta nos propusimos estudiar si BVDV tiene la capacidad de propagar en forma directa de célula a célula. Para esto se diseñaron ensayos de co-cultivo, donde se pudo observar la propagación de la infección viral desde células productoras de virus hacia células blanco aun en presencia de suero neutralizante en el medio. De esta forma demostramos por primera vez la existencia de propagación célula a célula en pestivirus. Con estas mismas herramientas comenzamos a estudiar cuales son los factores virales y celulares que median este tipo de propagación, hallando que la misma depende de la interacción de E2 con receptores específicos.

Theoretical modelling of chiral modifier/substrate interaction for Enantioselective Hydrogenation of p-Isobutylacetophenone Recupero, Francisco; Casella, Mónica Laura; Ruggera, José Fernando Se estudió a nivel DFT la interacción entre el modificador quiral y el sustrato para la reacción de hidrogenación enantioselectiva del tipo de Orito. Se realizó el modelado molecular a nivel DFT para estudiar la interacción entre el (R)-(-)-1-aminoindano y (S)-(+)-1-aminoindano como modificadores quirales y la p-isobutilacetofenona (intermediario en la síntesis del ibuprofeno). A partir de los cálculos teóricos e implementando un análisis de interacciones no covalentes, se demostró que la interacción responsable de la formación del complejo entre el modificador quiral y el sustrato es un enlace tipo puente de hidrógeno. Teniendo en cuenta las energías libres para la formación de cada complejo se calculó de forma teórica los excesos enantioméricos utilizando cada modificador quiral, encontrándose un exceso de alrededor del 30% del enantiómero R del producto cuando se utiliza el (R)-(-)-1-aminoindano, mientras que el exceso sería 30% pero para el enantiómero S del producto cuando se utiliza como modificador el (S)-(+)-1-aminoindano.; DFT level calculations were carried out to study the interaction between chiral modifier and substrate for Orito type enantioselective hydrogenation. Molecular modelling on a DFT level was developed to study the interaction between (R)-(-)-1-aminoindane and (S)-(+)-1-aminoindane as chiral modifiers and pisobutylacetophenone(intermediary the synthesis of Ibuprofen). Judging from theoretical calculations and implementing a non-covalent interaction analysis, it was shown that the interaction responsible for the formation of a complex between chiral modifier and substrate is a hydrogen bond. Taking into account the free energies of formation for each complex, a theoretical calculation was performed for the enantiomeric excess obtained from either chiral modifier, finding an excess of about 30% of the R enantiomer product when using (R)-(-)-1-aminoindane, while the excess would be of 30% for the S enantiomer product if the modifier is (S)-(+)-1-aminoindane.

Nuevos territorios: vida, literatura y subjetivación Cámara, Mario Cesar El trabajo aborda textos de Clarice Lispector, La hora de la estrella, de Mario Bellatín, Salón de Belleza, y de Joao Gilberto Noll, Lorde, a partir del concepto de "vidas precarias" desarrollado por Judith Butler en su libro homónimo. El recorrido plantea una breve historización del realismo literario y luego plantea las diferencias que estarían estableciendo con aquella tradición los textos literarios mencionados.

Nuevos territorios: vida, literatura y subjetivación Cámara, Mario Cesar El trabajo aborda textos de Clarice Lispector, La hora de la estrella, de Mario Bellatín, Salón de Belleza, y de Joao Gilberto Noll, Lorde, a partir del concepto de "vidas precarias" desarrollado por Judith Butler en su libro homónimo. El recorrido plantea una breve historización del realismo literario y luego plantea las diferencias que estarían estableciendo con aquella tradición los textos literarios mencionados.

A crustacean lobula plate: Morphology, connections, and retinotopic organization Bengochea, Mercedes; Berón de Astrada, Martín; Tomsic, Daniel; Sztarker, Julieta The lobula plate is part of the lobula complex, the third optic neuropil, in the optic lobes of insects. It has been extensively studied in dipterous insects, where its role in processing flow-field motion information used for controlling optomotor responses was discovered early. Recently, a lobula plate was also found in malacostracan crustaceans. Here, we provide the first detailed description of the neuroarchitecture, the input and output connections and the retinotopic organization of the lobula plate in a crustacean, the crab Neohelice granulata using a variety of histological methods that include silver reduced staining and mass staining with dextran-conjugated dyes. The lobula plate of this crab is a small elongated neuropil. It receives separated retinotopic inputs from columnar neurons of the medulla and the lobula. In the anteroposterior plane, the neuropil possesses four layers defined by the arborizations of such columnar inputs. Medulla projecting neurons arborize mainly in two of these layers, one on each side, while input neurons arriving from the lobula branch only in one. The neuropil contains at least two classes of tangential elements, one connecting with the lateral protocerebrum and the other that exits the optic lobes toward the supraesophageal ganglion. The number of layers in the crab's lobula plate, the retinotopic connections received from the medulla and from the lobula, and the presence of large tangential neurons exiting the neuropil, reflect the general structure of the insect lobula plate and, hence, provide support to the notion of an evolutionary conserved function for this neuropil.

First case of bacteraemia due to Acinetobacter schindleri harbouring blaNDM-1 in an immunocompromised patient Montaña, Sabrina Daiana; Palombarani, Susana; Carulla, M.; Kunst, A.; Rodriguez, C.H.; Nastro, Marcela; Vay, C.; Ramirez, M.S.; Almuzara, Marisa Clinically significant NDM-1-producing Acinetobacter schindleri has not yet been described in the literature. We report the first case of bacteraemia due to an A. schindleri strain harbouring blaNDM-1 recovered from an immunocompromised patient. Our report reinforces the fact that NDM-1 can easily be acquired by Acinetobacter species.

Staurosira patagonica sp. nov., a new diatom (Bacillariophyta) from southern Argentina, with a discussion on the genus Staurosira Ehrenberg García, María Luján; Maidana, Nora Irene; Ector, L.; Morales, E.A. We present a detailed morphological analysis by light and scanning electron microscopy of Staurosira patagonica sp. nov. from quaternary sediments of Maar Magallanes and recent sediments of the shallow lake Laguna Toro, both in Santa Cruz Province, Argentinian Patagonia. While the valve outline of this new taxon resembles Staurosira incerta, S. construens and Pseudostaurosira pseudoconstruens, it presents features (e.g., fl at valve surface, bifurcate volae and radiate striae) that set it apart from them. Staurosira patagonica sp. nov. is smaller than other small fragilarioids species. We also discuss the main characteristics of Staurosira, we provide a list of species currently included in it, and we propose several new combinations accordingly with current concepts of araphid diatom genera.

Cyclostephanos salsae and Placoneis patagonica, two new diatoms (Bacillariophyta) from Laguna Cháltel in southern Patagonia, Argentina Maidana, Nora Irene; Aponte, Gustavo A.; Fey, Michael; Schäbitz, F.; Morales, E.A. Two new diatom species, Cyclostephanos salsae and Placoneis patagonica found in plankton, superfi cial sediments and quaternary lacustrine sediment samples from Laguna Cháltel, Southern Argentina, are described. The detailed morphology of these two taxa is examined using both light (LM) and scanning electron microscopy (SEM). The main morphological features that distinguish C. salsae sp. nov. are the raised central area without fultoportulae and with scattered areolae, and the presence of some interstriae bifurcated on the valve mantle, bearing one fultoportulae in one of the forks. The variable, sometimes asymmetrical outline and the irregularly spaced central striae are the main morphological features of P. patagonica sp. nov. The relationships of these two new taxa with morphologically similar species and their ecological affi nities are discussed.

Acute toxicity of tributyltin to encapsulated embryos of a marine gastropod Averbuj, Andres; Primost, Monica Angelina; Giulianelli, Sebastian Jesus; Bigatti, Gregorio The marine gastropod Buccinanops globulosus is known to have high imposex incidence in areas moderately polluted by tributyltin (TBT). Acute toxicity was previously studied in adults but no information is known about embryonic intracapsular development. To estimate the potential effects of organotin pollution on the progeny of B. globulosus, acute toxicity tests were conducted on encapsulated and excapsulated pre-hatching embryos. The lethal median concentration estimated for 96 h (LC50 96 h) in B. globulosus excapsulated embryos was 196.70 µg TBTCl L−1, while in encapsulated embryos it was 2951.28 µg TBTCl L−1. The LC50 96 h was 15-fold higher for encapsulated embryos compared to excapsulated embryos, denoting egg capsule protection against pollutants from the external environment. Our results show that TBT pollution can have significant effects in molluscs other than the chronic effect of imposex.

Modeling the Impact of the Type of Cutting and Storage Temperature on the Bioactive Compound Content, Phenylpropanoid Metabolism Enzymes and Quality Attributes of Fresh-Cut Strawberries Van de Velde, Franco; Fenoglio, Cecilia Lorena; Piagentini, Andrea; Pirovani, Maria Elida The aim of this work was to model the effect of the type of cutting (whole without hull, halved, and quartered), storage temperature (2, 6, and 13 °C) and time on the changes of bioactive compounds, phenylpropanoid metabolism enzyme activities, and quality attributes of fresh-cut strawberries. The effect of increasing the intensity of wounding revealed an activation of the phenylalanine ammonia lyase (PAL) enzyme, with the consequent synthesis of phenolic compounds. Results revealed that quartered strawberries stored at 2 °C for 15 days accumulated up to 22% more phenolics than whole strawberries. The changes on quality parameters (soluble solids, pH, and color), total anthocyanins, and polyphenol oxidase were adequately fitted with zero order kinetic. All rate constants of these attributes, except for anthocyanins, fitted appropriately with Arrhenius equation. Changes on total phenolic contents and on PAL activity were fitted with a consecutive reaction mechanistic kinetic model. The rate constants of phenolics kinetic showed no dependence with temperature. However, rate constants of PAL activity fitted appropriately with Arrhenius equation. This global study offers a better understanding of the effects of processing and storage conditions on general quality, bioactive compounds, and phenylpropanoid metabolism enzymes of fresh-cut strawberries.

Classification of collaborative behavior from free text interactions Berdun, Franco Daniel; Armentano, Marcelo Gabriel; Berdun, Franco Daniel; Mineo, Martin In a computer-supported collaborative work (CSCW) environment, a group of people can work together to fulfill a given assignment. In this context, collaborative problems might naturally arise. The detection of these problems is extremely important for teachers or team leaders to help the team members to improve their collaborative skills and the resolution of the collaboration problems. The observation and analysis of the interaction process of several groups is a time-consuming and difficult task for any teacher or team leader. In this article, we propose a multi-phase classification approach to automatically classify free text observed form the chat of a CSCW environment into different collaborative categories of behavior. We obtained promising results that can be used to help teachers or team leaders with the interaction process analysis in order to focus only in the resolution's actions of the problems that might arise.

Experimental and theoretical study on the structural, electrical and optical properties of tantalum-doped ZnO nanoparticles prepared via sol-gel acetate route Richard, Diego; Romero, Mariano; Faccio Sgiorovello, Ricardo Juan Pure and Ta-doped ZnO were prepared by the sol-gel method in acetic medium using different annealing temperature treatments. The effects of low Ta doping on the crystallinity and electrical properties of ZnO nanoparticles were analyzed by means of X-ray diffraction and micro-Raman, UV–visible, and impedance spectroscopies. We also performed first principles calculations in order to study the predicted changes in the structural, vibrational and electronic properties induced by the inclusion of the impurities, and to complement the experimental measurements. We showed that above thermal treatments at 600 °C the precursor samples take the hexagonal wurtzite ZnO phase with high crystallinity. For the doped samples, we found that the synthesizing method has good Ta doping efficiency of the ZnO host structure. Also, Ta doping substantially decreases the resistivity compared to pure ZnO. These results confirm that Ta impurities can substitute Zn atoms and act as donor impurities in the host semiconductor.