Conformational effects on the pro-S hydrogen abstraction reaction in cyclooxygenase-1: an integrated QM/MM and MD study

A key step in the cyclooxygenase reaction cycle of cyclooxygenase 1 (COX-1) is abstraction of the pro-S hydrogen atom of the arachidonic acid by a radical that is formed at the protein residue Tyr-385. Here we investigate this reaction step by a quantum-mechanics/molecular-mechanics approach in combination with molecular-dynamics simulations. The simulations identify the hydrogen abstraction angle as a crucial geometric determinant of the reaction, thus revealing the importance of the cyclooxygenase active site for calculating the potential energy surface of the reaction

El votante argentino

Este trabajo proporciona un análisis crítico de los aportes que han contribuido a configurar el área de estudios sobre comportamiento electoral en Argentina durante el actual período democrático. ¿Qué se ha estudiado concretamente en los últimos treinta años? ¿Qué preguntas se han intentado responder y cómo? ¿Es posible identificar patrones de comportamiento del votante argentino? ¿Cuál es el vínculo entre estos patrones y la dinámica más general que asumió la democracia? Los trabajos que aquí se examinan pueden ser divididos en dos diferentes, aunque no enteramente excluyentes ni exhaustivas, categorías1. La primera categoría está compuesta por estudios que analizan si, y en qué medida, las divisiones de clase organizan la política electoral en nuestro país. Me refiero a estos trabajos como centrados en "factores estructurales". La segunda categoría comprende estudios que indagan acerca del potencial impacto de las percepciones, actitudes y experiencias individuales sobre las decisiones de voto. Denomino a estos aportes como centrados en "factores de comportamiento". Cada una de las secciones que compone esta nota está dedicada al examen particular de estas categorías analíticas. La sección final discute brevemente algunas limitaciones de los estudios electorales en Argentina y sugiere posibles soluciones para superar estos déficits.Fil: Lodola, Germán Jorge. Universidad Torcuato Di Tella; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

The Dual Logic of Intergovernmental Transfers: Presidents, Governors, and the Politics of Coalition-Building in Argentina

How do fiscal institutions shape the ability of presidents and state governors in a federation to manipulate federal money with coalition building goals? This article proposes a two-level theory of intergovernmental transfers based upon variation in the level of discretionality over the use of federal money that fiscal institutions grant to national and subnational executives. We use subnational level data in Argentina to show that not taking discretionality into account leads to wrong inferences about the electoral returns of intergovernmental transfers. We find that presidents extract different political utility from discretionary and nondiscretionary transfers. While discretionary transfers enable them to directly target voters bypassing opposition provincial governors, nondiscretionary transfers pay off more to co-partisan governors by guaranteeing security in the reception of transfer monies.Fil: Bonvecchi, Alejandro. Universidad Torcuato Di Tella. Departamento de Ciencia Política y Estudios Internacionales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Lodola, Germán Jorge. Universidad Torcuato Di Tella. Departamento de Ciencia Política y Estudios Internacionales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Theoretical Model of EphA2-Ephrin A1 Inhibition

This work aims at the theoretical description of EphA2-ephrin A1 inhibition by small molecules. Recently proposed ab initio-based scoring models, comprising long-range components of interaction energy, is tested on lithocholic acid class inhibitors of this protein⁻protein interaction (PPI) against common empirical descriptors. We show that, although limited to compounds with similar solvation energy, the ab initio model is able to rank the set of selected inhibitors more effectively than empirical scoring functions, aiding the design of novel compounds

Further Mediterranean expansion of the non-indigenous bryozoan <em>Celleporaria brunnea</em>: multiple records along the Italian coasts

In the framework of a wider systematic survey aimed at studying non-indigenous species in Italian harbours and marinas, the ascophoran bryozoan Celleporaria brunnea was detected for the first time in the western Mediterranean Sea. The species is presumably native to the Pacific coasts of North America and is distributed from British Columbia to the Galapagos Islands (Ecuador). In the Mediterranean Sea, C. brunnea was first recorded in 2004 in the inner part of Izmir Bay near Alsancak harbour (Turkey) and later reported along the Lebanese coasts. The species was recently detected in Cascais marina in Portugal and in the Arcachon Basin (France), documenting the first records in the eastern Atlantic. The finding in the Italian harbours of La Spezia (Liguria), Olbia (Sardinia) and Lampedusa (off Sicily) marks its western and northernmost occurrence within the Mediterranean basin. Pathways of introduction into the western Mediterranean Sea are discussed, concluding that hull fouling is the most likely vector. The species may be expected to appear soon in other harbours of the Mediterranean basin

Characterization of a PET scanner prototype for the on-line monitoring of hadrontherapy treatments

In the last decades, the interest in charged hadrontherapy (also known as particles therapy) as cancer treatment has greatly increased, leading to a rapid growth of dedicated facilities. Currently there are 55 operating structures and 35 more are under construction. In most of these facilities hadrontherapy is performed using proton beams and can be also referred to as proton therapy. Typical energy values for therapeutical protons beams are in the interval 3-300 MeV, corresponding to a range in water from 0.014 to 51.45 cm. With respect to standard radiotherapy employing photons in the gamma-rays energy range, hadrontherapy shows a superior physical selectivity, which allows to deliver a radiation dose more specifically to the tumour volume, while less damaging the surrounding healthy tissues. At the same time this kind of therapy requires a precise monitoring of the location of the delivered dose, both to ensure an efficient irradiation of the tumour and to safeguard patients health, avoiding the development of severe side-effect due to the overdosing of radiosensitive organs. Over the years, a number of particles range verification methods have been proposed: the most consolidated and mature for the clinical application is the one based on the Positron Emission Tomography (PET). When passing through tissues, impinging particles may be subjected to nuclear interactions with atomic nuclei, which result in the creation of positron emitting isotopes all along the beam path. The detection by a PET-scanner of the back-to-back photons, coming from the annihilation of the positron with an atomic electron, allows obtaining the spatial distribution of the activity induced in the irradiated tissues. The activation profile is characterised by a constant or slowly rising trend with depth, followed by a sudden drop to zero few millimeters in front of the Bragg peak. The particles range is usually determined through a comparison of the experimental activity profile with the one calculated with a Monte Carlo simulation. Among the proposed methods for the particles treatment monitoring, one of the most promising, even though still in development, is the one based on the detection of charged particles or prompt-gammas emitted during the irradiation. The particles range is then estimated by exploiting its correlation with the prompt-particles emission point. This thesis has been carried out in the framework of the INSIDE project, which aims at developing a multimodal system for the on-line monitoring of the dose delivered to a patient during an hadrontherapy treatment, both in case of proton and carbon ion beams. The system will be installed at the the National Centre of Oncological Hadrontherapy (CNAO) in Pavia, a clinical facility specifically dedicated to hadrontherapy treatments, and it will be composed of a dual head PET scanner and a charged particle tracker for the detection of prompt secondary particles. In particular, the main subject of this work is the characterization of a prototype of the INSIDE PET-scanner. The document is organised as follows: chapter 1 is dedicated to a general description of particles therapy and, in particular, of the clinical particles beams characteristics. Moreover, the National Centre of Oncological Hadrontherapy in Pavia, the particles therapy-dedicated facility where the INSIDE system is going to be installed, is also described. Chapter 2 is dedicated to a review of the existing techniques for the particles range verification, paying particular attention to the PET one. The third chapter presents the main characteristics of the INSIDE system, with the PET-scanner described with more details. The PET scanner will feature two planar heads (10x5 cm^2 each) constituted by 5x2 matrices of pixelated LFS scintillating crystals. Each pixel is coupled one to one with a Silicon Photomultiplier, which represents the latest technology of the solid state photo-detectors. The front-end electronics is constituted by 64 channels Integrated Circuits, with timing resolution at the state of the art. The final goal of the PET scanner is to provide a verification of the particels range with a spatial resolution of about 1 mm in less than 5 minutes after the begininng of irradiation, using only a fraction of the total dose. Chapter 4 is devoted to the characterization of a prototype of the PET scanner, made up by two LFS matrices facing each other. Specifically, it has been verified the correct functioning of the different SiPMs and their gain uniformity. Moreover it has been monitored the system performances stability over time. In May of this year, the prototypal PET system has been moved to CNAO for a test beam session. During the test, a PMMA phantom had been irradiated with proton beams at four different energies (68, 72, 84 and 100 MeV). Chapter 5 reports the analysis of the data acquired during the test and a discussion on the achieved results. In particular, it has been verified the capability of the system to detect the coincidence signals both during inter-spill and in-spill phases of the irradiation and it has been measured the achieved timing resolution. The standard deviation of the coincidence distribution or Coincidence Time Resolution (CTR) is 620 ps in the inter-spills and 700 ps in the in-spill one. Finally, the image reconstruction algorithm employed is described and the images of the activity distribution obtained are presented

Identification of pore type and origin in a Lower Cretaceous carbonate reservoir using NMR T2 relaxation times

Determining the distribution of porosity and permeability is one of the main challenges in carbonate petroleum reservoir characterization and requires a thorough understanding of pore type and origin, as well as their spatial distributions. Conventional studies of carbonate reservoirs require interpretation and analysis of cores to understand porosity. This study investigates the use of NMR logs in the determination of pore type and origin. This study is based on the analysis of both thin section petrographic and NMR data from a single well that cored the Lower Cretaceous (Aptian) shelf carbonates belonging to the Shuaiba Formation of the Middle East. Photographs of thin sections were used to determine pore type and origin according to Ahr's genetic classification of carbonate porosity. Descriptive statistics and modeling were used to analyze the NMR T2relaxation time distributions. Descriptive statistical analyses included estimating arithmetic average, standard deviation, skewness, median, mode and 90th percentile. T2modeling was performed by fitting multiple log-normal distributions to the measured T2distribution. Data from thin section petrography and from NMR measurements were then compared using conditional probabilities. As expected, thin section analysis revealed the predominance of mud-supported fabrics and micropores between matrix grains Vugs and dissolved rudistid fragments account for most of the macro porosity. Descriptive statistics showed that the mode and th percentile of the T2distribution had the greatest power to discriminate pores by origin. The first principal component (PC1) of the mode-90th percentile system was then used to compute the probabilities of having each pore origin, knowing that PC1 belongs to a given interval. Results were good, with each origin being predictable within a certain range of PC1. Decomposition of the T2distributions was performed using up to 3 log-normal component distributions. Samples of different pore origin behaved distinctively. Depositional porosity showed no increase in fit quality with increasing number of distributions whereas facies selective and diagenetic porosity did, with diagenetic porosity showing the greatest increase

The physics of plasma membrane photostimulation

Cell membrane perturbation is a common way to stimulate cells by using external actuators. Recently, nanotechnology has added a number of new strategies for doing this, enlarging the scope and the range of mechanisms involved. Here, we describe a number of possible perturbation actions that are driven by light, and we try to capture the underlying phenomena. The discussion is based on the simple equivalent circuit model for the cell membrane