Density functional theory and DFT+U study of transition metal porphines adsorbed on Au(111) surfaces and effects of applied electric fields

We apply Density Functional Theory (DFT) and the DFT+U technique to study the adsorption of transition metal porphine molecules on atomistically flat Au(111) surfaces. DFT calculations using the Perdew-Burke-Ernzerhof (PBE) exchange correlation functional correctly predict the palladium porphine (PdP) low-spin ground state. PdP is found to adsorb preferentially on gold in a flat geometry, not in an edgewise geometry, in qualitative agreement with experiments on substituted porphyrins. It exhibits no covalent bonding to Au(111), and the binding energy is a small fraction of an eV. The DFT+U technique, parameterized to B3LYP predicted spin state ordering of the Mn d-electrons, is found to be crucial for reproducing the correct magnetic moment and geometry of the isolated manganese porphine (MnP) molecule. Adsorption of Mn(II)P on Au(111) substantially alters the Mn ion spin state. Its interaction with the gold substrate is stronger and more site-specific than PdP. The binding can be partially reversed by applying an electric potential, which leads to significant changes in the electronic and magnetic properties of adsorbed MnP, and ~ 0.1 Angstrom, changes in the Mn-nitrogen distances within the porphine macrocycle. We conjecture that this DFT+U approach may be a useful general method for modeling first row transition metal ion complexes in a condensed-matter setting.Comment: 14 pages, 6 figure

RNA Metabolism and Therapeutics in Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a progressive neuromuscular disorder characterized by the selective death of upper and lowers motor neurons in spinal cord, brain stem, and motor cortex, which leads to paralysis and death within 2–3 years of onset. Deeply sequencing technologies, to simultaneously analyze the transcriptional expression of thousands of genes, offered new possibilities to focus on ALS pathogenesis and, most notably, to find new potential targets for novel treatments. The present book chapter illustrates recent advances in transcriptomic studies in animal models and human samples and in new molecular targets related to ALS pathogenesis and disease progression. Additionally, new insights into the involvement of altered transcriptional profiles of noncoding RNAs (microRNA and lncRNA) and ALS-associated ribosomal binding proteins have been investigated, to understand the functional consequences of extensive RNA dysregulation in ALS. Attention has been also turned on how transcriptome alterations could highlight new molecular targets for drug development

Alguns Tópicos e Problemas de tradução da Língua Chinesa

Consideramos, de forma resumida, alguns pontos básicos da tradução do chinês para o português: de problemas teóricos a práticos; apresentamos alguns tradutores chineses famosos; mencionamos a práxis milenar chinesa com seus centros especializados de tradução; damos alguns exemplos práticos de nossa própria atividade de tradutor; e concluímos com a tradução de um poema clássico chinês.We have considered briefly some basic topics of translation from the chinese into the portuguese: theoretical and practical problems; we have also presented some famous chinese translators; we have also related the millenary chinese praxis with its specialized centers of translation; we have given some practical examples of our own activity of translator, and concluded with the translation of a classic chinese poem

Theoretical EXAFS studies of a model of the oxygen-evolving complex of photosystem II obtained with the quantum cluster approach

The oxygen-evolving complex (OEC) of photosystem II is the only natural system that can form O2 from water and sunlight and it consists of a Mn4Ca cluster. In a series of publications, Siegbahn has developed a model of the OEC with the quantum mechanical (QM) cluster approach that is compatible with available crystal structures, able to form O2 with a reasonable energetic barrier, and has a significantly lower energy than alternative models. In this investigation, we present a method to restrain a QM geometry optimization toward experimental polarized extended X-ray absorption fine structure (EXAFS) data. With this method, we show that the cluster model is compatible with the EXAFS data and we obtain a refined cluster model that is an optimum compromise between QM and polarized EXAFS data. (C) 2012 Wiley Periodicals, Inc

RESTORING LEGITIMACY IN THE AFTERMATH OF CORPORATE SCANDALS: A MULTIPLE CASE-STUDY ANALYSIS ON CSR INITIATIVES

Corporate scandals undermine integrity and reputation, in that generating a legitimacy gap. Through a multiple-case study analysis, this paper provides qualitative evidence on the CSR initiatives undertaken by Multinational Enterprises (MNEs) in response to CSR-related scandals, in order to restore their legitimacy to operate. We consider four scandals in the apparel industry that \u201chit the headlines\u201d, namely Walmart, Moncler, Nike, and H&M. We classify CSR initiatives according to the dimensions of corporate behaviour framed by Sethi (1975) and interpret them through the lens of the legitimacy theory. Our findings show that all MNEs undertook several CSR initiatives, primarily acting on ethical norms, operating strategies and social accountability. They tended to issue or revise code of conducts, develop new relational approaches with the suppliers, and publish the CSR report, while neglected or made limited reference to the external assurance of CSR reports. Some MNEs also accepted investigations by Non-Governmental Organizations (NGOs) on their initiatives. Besides such common behaviours, some differences arise, especially with respect to the MNEs attitude towards the refusal or admission of their responsibility in the scandals. Our study confirms previous arguments suggested by CSR literature by providing evidence that MNEs shape both the internal and external environment to make it more favourable to ethical behaviours, and rely on social and environmental accountability to pursue legitimacy, even in a peculiar situation like a corporate scandal. The study contributes to the scant but growing literature on CSR in the aftermath of corporate scandals

DNAscan: personal computer compatible NGS analysis, annotation and visualisation.

BACKGROUND: Next Generation Sequencing (NGS) is a commonly used technology for studying the genetic basis of biological processes and it underpins the aspirations of precision medicine. However, there are significant challenges when dealing with NGS data. Firstly, a huge number of bioinformatics tools for a wide range of uses exist, therefore it is challenging to design an analysis pipeline. Secondly, NGS analysis is computationally intensive, requiring expensive infrastructure, and many medical and research centres do not have adequate high performance computing facilities and cloud computing is not always an option due to privacy and ownership issues. Finally, the interpretation of the results is not trivial and most available pipelines lack the utilities to favour this crucial step. RESULTS: We have therefore developed a fast and efficient bioinformatics pipeline that allows for the analysis of DNA sequencing data, while requiring little computational effort and memory usage. DNAscan can analyse a whole exome sequencing sample in 1 h and a 40x whole genome sequencing sample in 13 h, on a midrange computer. The pipeline can look for single nucleotide variants, small indels, structural variants, repeat expansions and viral genetic material (or any other organism). Its results are annotated using a customisable variety of databases and are available for an on-the-fly visualisation with a local deployment of the gene.iobio platform. DNAscan is implemented in Python. Its code and documentation are available on GitHub: https://github.com/KHP-Informatics/DNAscan . Instructions for an easy and fast deployment with Docker and Singularity are also provided on GitHub. CONCLUSIONS: DNAscan is an extremely fast and computationally efficient pipeline for analysis, visualization and interpretation of NGS data. It is designed to provide a powerful and easy-to-use tool for applications in biomedical research and diagnostic medicine, at minimal computational cost. Its comprehensive approach will maximise the potential audience of users, bringing such analyses within the reach of non-specialist laboratories, and those from centres with limited funding available

The role of extracellular vesicles in the removal of aggregated TDP43 responsible for ALS/FTD diseases

Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD) are two related neurodegenerative diseases. ALS is caused by the death of both upper and lower motoneurons, while FTD is characterized predominantly by circumscribed atrophy of the frontal and temporal lobes. ALS and FTD overlap each other. This is demonstrated by the presence of cognitive and behavioral dysfunction in up to 50% of ALS patients and by the presence of frontotemporal atrophy in patients with ALS. Moreover, these diseases are both characterize by the presence of TAR DNA binding protein 43 (TDP43) inclusions in affected cells. These inclusions, observed in 97% of patients with ALS and 50% of patients with FTD, are composed by TDP43 and its C-terminal fragments of 35 kDa (TDP35) and 25 kDa (TDP25). These fragments are highly aggregation-prone and probably neurotoxic. Thus, their removal is protective for cells. The mechanism responsible for the clearance of aggregates and misfolded proteins is the intracellular protein quality control (PQC) system. It consists of molecular chaperones/co- chaperones and the degradative pathways. PQC controls the folding status of proteins and prevents the aggregation of misfolded proteins by refolding them or degrading. Recent data demonstrated that also extracellular secretory pathway, represented especially by exosomes (EXOs) and microvesicles (MVs), might be involved in the removal of misfolded proteins from affected cells. Thus, we evaluated the role of EXOs and MVs in the secretion of TDP43 and its C-terminal fragments, using neuronal cell models. We used ultracentrifugation, that allowed us to separate MVs from EXOs on the basis of their dimension. Then we analyzed them through i) Nanoparticle Tracking Analysis (NanoSight) to establish their number and sizes, and ii) western blot analysis, to characterize their protein content. Our preliminary results show that TDP43, TDP35 and TDP25 are all secreted, mainly by MVs. In particular, we found that MVs are enriched of insoluble forms of TDPs and also of superoxide dismutase 1 (SOD1), another ALS-related protein. Finally, both in EXOs and in MVs, we observed the presence of some important PQC-components, suggesting an interplay between the two pathways. GRANTS: Fondazione Cariplo, Italy (n. 2017_0747); Universit\ue0 degli Studi di Milano e piano di sviluppo UNIMI - linea B

Sistemas de generacion por autorregulacion aleatoria : Estrategias proyectuales para territorios urbanos dinamicos

El ejercicio práctico que se presenta aquí corresponde al proyecto de cien viviendas, espacio público y equipamientos en el morro Itararé, Río de Janeiro. El ejercicio tiene por objetivo re-pensar la favela y su arquitectura, y, por tanto la ciudad como artefactos de la naturaleza, es decir, como organismos vivos. Para ello hemos adoptado definiciones, herramientas y estrategias de disciplinas ocupadas del estudio de las condiciones dinámicas de la naturaleza. El paradigma actual de la ecología−la resiliencia−estudia el proceso de evolución de fenómenos tales como adaptación, modificación, e incluso, disrupción. La metodología de trabajo consistió en 3 etapas transformativas: 1. identificación de patrones físicos, lugares intersticiales entre el tejido existente, y terrazas de las construcciones existentes con posibilidades de soportar ampliaciones. 2. Construcción de artefactos a esc. 1:1 a partir de un sistema generativo aleatorio. Para facilitar a los estudiantes el desarrollo de los artefactos se fijaron los siguientes prototipos: funguis, mutantes, aliens y rizomas. 3. los prototipos fueron sometidos a una secuencia de transformación como dispositivo “interfaz” entre la experimentación a escala 1:1 y la especulación a escala 1:100. Se espera producir futuras derivaciones que contribuyan a la enseñanza-aprendizaje del proceso proyectual en territorios urbanos dinámicos.Área temática 1: Proyecto Arquitectónico y Urbano - Eje EnseñanzaFacultad de Arquitectura y Urbanism

Sistemas de generacion por autorregulacion aleatoria : Estrategias proyectuales para territorios urbanos dinamicos

El ejercicio práctico que se presenta aquí corresponde al proyecto de cien viviendas, espacio público y equipamientos en el morro Itararé, Río de Janeiro. El ejercicio tiene por objetivo re-pensar la favela y su arquitectura, y, por tanto la ciudad como artefactos de la naturaleza, es decir, como organismos vivos. Para ello hemos adoptado definiciones, herramientas y estrategias de disciplinas ocupadas del estudio de las condiciones dinámicas de la naturaleza. El paradigma actual de la ecología−la resiliencia−estudia el proceso de evolución de fenómenos tales como adaptación, modificación, e incluso, disrupción. La metodología de trabajo consistió en 3 etapas transformativas: 1. identificación de patrones físicos, lugares intersticiales entre el tejido existente, y terrazas de las construcciones existentes con posibilidades de soportar ampliaciones. 2. Construcción de artefactos a esc. 1:1 a partir de un sistema generativo aleatorio. Para facilitar a los estudiantes el desarrollo de los artefactos se fijaron los siguientes prototipos: funguis, mutantes, aliens y rizomas. 3. los prototipos fueron sometidos a una secuencia de transformación como dispositivo “interfaz” entre la experimentación a escala 1:1 y la especulación a escala 1:100. Se espera producir futuras derivaciones que contribuyan a la enseñanza-aprendizaje del proceso proyectual en territorios urbanos dinámicos.Área temática 1: Proyecto Arquitectónico y Urbano - Eje EnseñanzaFacultad de Arquitectura y Urbanism

Sistemas de generacion por autorregulacion aleatoria : Estrategias proyectuales para territorios urbanos dinamicos

El ejercicio práctico que se presenta aquí corresponde al proyecto de cien viviendas, espacio público y equipamientos en el morro Itararé, Río de Janeiro. El ejercicio tiene por objetivo re-pensar la favela y su arquitectura, y, por tanto la ciudad como artefactos de la naturaleza, es decir, como organismos vivos. Para ello hemos adoptado definiciones, herramientas y estrategias de disciplinas ocupadas del estudio de las condiciones dinámicas de la naturaleza. El paradigma actual de la ecología−la resiliencia−estudia el proceso de evolución de fenómenos tales como adaptación, modificación, e incluso, disrupción. La metodología de trabajo consistió en 3 etapas transformativas: 1. identificación de patrones físicos, lugares intersticiales entre el tejido existente, y terrazas de las construcciones existentes con posibilidades de soportar ampliaciones. 2. Construcción de artefactos a esc. 1:1 a partir de un sistema generativo aleatorio. Para facilitar a los estudiantes el desarrollo de los artefactos se fijaron los siguientes prototipos: funguis, mutantes, aliens y rizomas. 3. los prototipos fueron sometidos a una secuencia de transformación como dispositivo “interfaz” entre la experimentación a escala 1:1 y la especulación a escala 1:100. Se espera producir futuras derivaciones que contribuyan a la enseñanza-aprendizaje del proceso proyectual en territorios urbanos dinámicos.Área temática 1: Proyecto Arquitectónico y Urbano - Eje EnseñanzaFacultad de Arquitectura y Urbanism