Structural and Functional Analysis of the Caspase –dependent and –independent Domains of the X-linked Inhibitor of Apoptosis Protein in Inflammatory Breast Cancer Tumor Biology

Inflammatory breast cancer (IBC) is an extremely rare but highly aggressive form of breast cancer characterized by the rapid development of therapeutic resistance leading to particularly poor survival. Our previous work focused on the elucidation of factors that mediate therapeutic resistance in IBC and identified increased expression of the anti-apoptotic protein, X-linked inhibitor of apoptosis protein (XIAP), to correlate with the development of resistance to chemotherapeutics. Although XIAP is classically thought of as an inhibitor of caspase activation, multiple studies have revealed that XIAP can also function as a signaling intermediate in numerous pathways. Based on preliminary evidence revealing high expression of XIAP in pre-treatment IBC cells rather than only subsequent to the development of resistance, we hypothesized that XIAP could play an important signaling role in IBC pathobiology outside of its heavily published apoptotic inhibition function. Further, based on our discovery of inhibition of chemotherapeutic efficacy, we postulated that XIAP overexpression might also play a role in resistance to other forms of therapy, such as immunotherapy. Finally, we posited that targeting of specific redox adaptive mechanisms, which are observed to be a significant barrier to successful treatment of IBC, could overcome therapeutic resistance and enhance the efficacy of chemo-, radio-, and immuno- therapies. To address these hypotheses our objectives were: 1. to determine a role for XIAP in IBC pathobiology and to elucidate the upstream regulators and downstream effectors of XIAP; 2. to evaluate and describe a role for XIAP in the inhibition of immunotherapy; and 3. to develop and characterize novel redox modulatory strategies that target identified mechanisms to prevent or reverse therapeutic resistance.

Using various genomic and proteomic approaches, combined with analysis of cellular viability, proliferation, and growth parameters both in vitro and in vivo, we demonstrate that XIAP plays a central role in both IBC pathobiology in a manner mostly independent of its role as a caspase-binding protein. Modulation of XIAP expression in cells derived from patients prior to any therapeutic intervention significantly altered key aspects IBC biology including, but not limited to: IBC-specific gene signatures; the tumorigenic capacity of tumor cells; and the metastatic phenotype of IBC, all of which are revealed to functionally hinge on XIAP-mediated NFκB activation, a robust molecular determinant of IBC. Identification of the mechanism of XIAP-mediated NFκB activation led to the characterization of novel peptide-based antagonist which was further used to identify that increased NFκB activation was responsible for redox adaptation previously observed in therapy-resistant IBC cells. Lastly, we describe the targeting of this XIAP-NFκB-ROS axis using a novel redox modulatory strategy both in vitro and in vivo. Together, the data presented here characterize a novel and crucial role for XIAP both in therapeutic resistance and the pathobiology of IBC; these results confirm our previous work in acquired therapeutic resistance and establish the feasibility of targeting XIAP-NFκB and the redox adaptive phenotype of IBC as a means to enhance survival of patients.

Numerical detection of the Gardner transition in a mean-field glass former.

Recent theoretical advances predict the existence, deep into the glass phase, of a novel phase transition, the so-called Gardner transition. This transition is associated with the emergence of a complex free energy landscape composed of many marginally stable sub-basins within a glass metabasin. In this study, we explore several methods to detect numerically the Gardner transition in a simple structural glass former, the infinite-range Mari-Kurchan model. The transition point is robustly located from three independent approaches: (i) the divergence of the characteristic relaxation time, (ii) the divergence of the caging susceptibility, and (iii) the abnormal tail in the probability distribution function of cage order parameters. We show that the numerical results are fully consistent with the theoretical expectation. The methods we propose may also be generalized to more realistic numerical models as well as to experimental systems.

Toddlers' prosocial behavior: from instrumental to empathic to altruistic helping.

The study explored how the meaning of prosocial behavior changes over toddlerhood. Sixty-five 18- and 30-month-olds could help an adult in 3 contexts: instrumental (action based), empathic (emotion based), and altruistic (costly). Children at both ages helped readily in instrumental tasks. For 18-month-olds, empathic helping was significantly more difficult than instrumental helping and required greater communication from the adult about her needs. Altruistic helping, which involved giving up an object of the child's own, was the most difficult for children at both ages. Findings suggest that over the 2nd year of life, prosocial behavior develops from relying on action understanding and explicit communications to understanding others' emotions from subtle cues. Developmental trajectories of social-cognitive and motivational components of early helping are discussed.

Expressing Sentiments in Game Reviews

Opinion mining and sentiment analysis are important research areas of Natural Language Processing (NLP) tools and have become viable alternatives for automatically extracting the affective information found in texts. Our aim is to build an NLP model to analyze gamers’ sentiments and opinions expressed in a corpus of 9750 game reviews. A Principal Component Analysis using sentiment analysis features explained 51.2 % of the variance of the reviews and provides an integrated view of the major sentiment and topic related dimensions expressed in game reviews. A Discriminant Function Analysis based on the emerging components classified game reviews into positive, neutral and negative ratings with a 55 % accuracy.

A mãe nas ações de acompanhamento do crescimento e desenvolvimento infantil

ARAÚJO, Marluce Oliveira de; ENDERS, Bertha Cruz. A mãe nas ações de acompanhamento do crescimento e desenvolvimento infantil. Revista Baiana de enfermagem, Salvador, v.19,n.1/2/3,p.93-103, jan./dez. 2004, jann./dez.2005.

Sobre (vivência) e mortalidade de pequenos negócios: o caso de mercados varejistas potiguares

This paper‟s starting point was the objective of understanding the relation between the reasons pointed out by small businesses owners for the continuity or shutdown of their businesses, and the reasons presented by the Environmental Theories. The paper discusses the Environmental Theories understand that it is supported by a systemic metaphor speech, discussing the theme in terms of organizational survival and mortality . The text reviews the literature showing the changes in the administrative thinking regarding the organization versus environment relation, and presenting general ideas about the micro and small businesses. In methodological terms, the qualitative approach was used in the research. Regarding the data collection technique, an in-depth thematic interview was used. It was carried out considering the elements of the techniques of life history and oral history, always giving priority to real world related narratives told by the interviewed subjects. The empirical corpus of the research was made up of seven owners of small retail businesses in two Potiguar cities: Natal and Mossoró. The interpretative and analytical process focused, at first, on the reflexive dialogue with each one of the owners‟ professional life history and business management experience, constituting the first level of analysis: reflections on individual narratives; and, afterwards, the interpretative process was developed through the analysis of all the subjects‟ statements, identifying the recurring themes and constituting the second level of analysis: reflection on the totalizing narrative. The themes identified in the totalizing narrative, that refer to the continuity of the businesses are: evolution, control, fidelity, liking what one does for a living. The themes that came up as reasons for shutdown are: lack of empathy with the business, lack of evolution, competition problems, suppliers and the government. The text synthesizes its comprehensions affirming that the reasons associated with continuity and shutdown of small markets, for this group of owners specifically, come up as a permanent tension between the volunteerism (quite human) and the determinism (systemic). The tension is shown in testimonies that at the same time evoke the organicist systemic logic through the themes evolution/no evolution, and also counterpoints with themes related to the interested human action, based on desires, feelings and personal convictions such as: liking what one does/ lack of empathy. As for the reflexive dialogue between the postulates of the Environmental Theories and the narratives, the results make it possible to affirm that, differently from the tension expressed by the subjects while talking about their reasons, the reasons associated with survival and mortality of businesses according to the Environmental Theories are theoretically polarized, seeming to preach options that are stagnated and shaping towards the subjects involved in the organization-environment relation

Elaboração e aplicação de um Programa de Treino de Técnica de Pontas para os alunos do 3º ano de Dança, da Academia de Dança do Vale do Sousa, com vista à preparação de Variações de Repertório Clássico

Relatório Final de Estágio apresentado à Escola Superior de Dança, com vista à obtenção do grau de Mestre em Ensino de Dança.

A mãe nas ações de acompanhamento do crescimento e desenvolvimento infantil

ARAÚJO, Marluce Oliveira de; ENDERS, Bertha Cruz. A mãe nas ações de acompanhamento do crescimento e desenvolvimento infantil. Revista Baiana de enfermagem, Salvador, v.19,n.1/2/3,p.93-103, jan./dez. 2004, jann./dez.2005.

Wind wave prediction in the Caspian Sea

In this thesis, wind wave prediction and analysis in the Southern Caspian Sea are surveyed. Because of very much importance and application of this matter in reducing vital and financial damages or marine activities, such as monitoring marine pollution, designing marine structure, shipping, fishing, offshore industry, tourism and etc, gave attention by some marine activities. In this study are used the Caspian Sea topography data that are extracted from the Caspian Sea Hydrography map of Iran Armed Forces Geographical Organization and the I 0 meter wind field data that are extracted from the transmitted GTS synoptic data of regional centers to Forecasting Center of Iran Meteorological Organization for wave prediction and is used the 20012 wave are recorded by the oil company's buoy that was located at distance 28 Kilometers from Neka shore for wave analysis. The results of this research are as follows: - Because of disagreement between the prediction results of SMB method in the Caspian sea and wave data of the Anzali and Neka buoys. The SMB method isn't able to Predict wave characteristics in the Southern Caspian Sea. - Because of good relativity agreement between the WAM model output in the Caspian Sea and wave data of the Anzali buoy. The WAM model is able to predict wave characteristics in the southern Caspian Sea with high relativity accuracy. The extreme wave height distribution function for fitting to the Southern Caspian Sea wave data is obtained by determining free parameters of Poisson-Gumbel function through moment method. These parameters are as below: A=2.41, B=0.33. The maximum relative error between the estimated 4-year return value of the Southern Caspian Sea significant wave height by above function with the wave data of Neka buoy is about %35. The 100-year return value of the Southern Caspian Sea significant height wave is about 4.97 meter. The maximum relative error between the estimated 4-year return value of the Southern Caspian Sea significant wave height by statistical model of peak over threshold with the wave data of Neka buoy is about %2.28. The parametric relation for fitting to the Southern Caspian Sea frequency spectra is obtained by determining free parameters of the Strekalov, Massel and Krylov etal_ multipeak spectra through mathematical method. These parameters are as below: A = 2.9 B=26.26, C=0.0016 m=0.19 and n=3.69. The maximum relative error between calculated free parameters of the Southern Caspian Sea multipeak spectrum with the proposed free parameters of double-peaked spectrum by Massel and Strekalov on the experimental data from the Caspian Sea is about 36.1 % in spectrum energetic part and is about 74M% in spectrum high frequency part. The peak over threshold waverose of the Southern Caspian Sea shows that maximum occurrence probability of wave height is relevant to waves with 2-2.5 meters wave fhe error sources in the statistical analysis are mainly due to: l) the missing wave data in 2 years duration through battery discharge of Neka buoy. 2) the deportation %15 of significant height annual mean in single year than long period average value that is caused by lack of adequate measurement on oceanic waves, and the error sources in the spectral analysis are mainly due to above- mentioned items and low accurate of the proposed free parameters of double-peaked spectrum on the experimental data from the Caspian Sea.

Aprender numa relação dialógica sustentada pela ação

Relatório de Estágio apresentado à Escola Superior de Educação de Paula Frassinetti para obtenção de grau Mestre em Educação Pré-Escolar e Ensino 1º ciclo do Ensino Básico.

Zastosowanie modelu hantli w badaniach właściwości fizykochemicznych i strukturalnych układów homo- i heterogenicznych metodą Monte Carlo

Wydział Chemii

Coagulation equations with mass loss

We derive and solve models for coagulation with mass loss arising, for example, from industrial processes in which growing inclusions are lost from the melt by colliding with the wall of the vessel. We consider a variety of loss laws and a variety of coagulation kernels, deriving exact results where possible, and more generally reducing the equations to similarity solutions valid in the large-time limit. One notable result is the effect that mass removal has on gelation: for small loss rates, gelation is delayed, whilst above a critical threshold, gelation is completely prevented. Finally, by forming an exact explicit solution for a more general initial cluster size distribution function, we illustrate how numerical results from earlier work can be interpreted in the light of the theory presented herein.

Sobre (vivência) e mortalidade de pequenos negócios: o caso de mercados varejistas potiguares

This paper‟s starting point was the objective of understanding the relation between the reasons pointed out by small businesses owners for the continuity or shutdown of their businesses, and the reasons presented by the Environmental Theories. The paper discusses the Environmental Theories understand that it is supported by a systemic metaphor speech, discussing the theme in terms of organizational survival and mortality . The text reviews the literature showing the changes in the administrative thinking regarding the organization versus environment relation, and presenting general ideas about the micro and small businesses. In methodological terms, the qualitative approach was used in the research. Regarding the data collection technique, an in-depth thematic interview was used. It was carried out considering the elements of the techniques of life history and oral history, always giving priority to real world related narratives told by the interviewed subjects. The empirical corpus of the research was made up of seven owners of small retail businesses in two Potiguar cities: Natal and Mossoró. The interpretative and analytical process focused, at first, on the reflexive dialogue with each one of the owners‟ professional life history and business management experience, constituting the first level of analysis: reflections on individual narratives; and, afterwards, the interpretative process was developed through the analysis of all the subjects‟ statements, identifying the recurring themes and constituting the second level of analysis: reflection on the totalizing narrative. The themes identified in the totalizing narrative, that refer to the continuity of the businesses are: evolution, control, fidelity, liking what one does for a living. The themes that came up as reasons for shutdown are: lack of empathy with the business, lack of evolution, competition problems, suppliers and the government. The text synthesizes its comprehensions affirming that the reasons associated with continuity and shutdown of small markets, for this group of owners specifically, come up as a permanent tension between the volunteerism (quite human) and the determinism (systemic). The tension is shown in testimonies that at the same time evoke the organicist systemic logic through the themes evolution/no evolution, and also counterpoints with themes related to the interested human action, based on desires, feelings and personal convictions such as: liking what one does/ lack of empathy. As for the reflexive dialogue between the postulates of the Environmental Theories and the narratives, the results make it possible to affirm that, differently from the tension expressed by the subjects while talking about their reasons, the reasons associated with survival and mortality of businesses according to the Environmental Theories are theoretically polarized, seeming to preach options that are stagnated and shaping towards the subjects involved in the organization-environment relation

Análise por meio de espectroscopia de emissão óptica das espécies ativas em nitretação iônica e gaiola catódica

Plasma process like ionic nitriding and cathodic cage plasma nitriding are utilized in order to become hard surface of steels. The ionic nitriding is already accepted in the industry while cathodic cage plasma nitriding process is in industrial implementation stage. Those process depend of plasma parameters like electronic and ionic temperature (Te, Ti), species density (ne, ni) and of distribution function of these species. In the present work, the plasma used to those two processes has been observed through Optical Emission Spectroscopy OES technique in order to identify presents species in the treatment ambient and relatively quantify them. So plasma of typical mixtures like N2 H2 has been monitored through in order to study evolution of those species during the process. Moreover, it has been realized a systematic study about leaks, also thought OES, that accomplish the evolution of contaminant species arising because there is flux of atmosphere to inside nitriding chamber and in what conditions the species are sufficiently reduced. Finally, to describe the physic mechanism that acts on both coating techniques ionic nitriding and cathodic cage plasma nitriding

X-Ray powder diffraction laboratory @ University of Málaga (UMA)

X-Ray Powder Diffraction (XRPD) laboratory is a facility placed at Servicios Centrales de apoyo a la Investigación (SCAI) at University of Malaga (UMA) http://www.scai.uma.es/. This facility has three XRPD diffractometers and a diffractometer to measure high-resolution thin-films. X´Pert PRO MPD from PANalytical. This is a bragg-brentano (theta/2theta) with reflection geometry diffractometer which allows to obtain high resolution XRPD data with strictly monochromatic CuKα1 radiation (λ=1.54059Å) [Ge(111) primary monochromator] and an automatic sample charger. Moreover, it has parallel monochromatic CuKα1 radiation (λ=1.54059Å) with an hybrid Ge(220) monochromator for capillary and multiproposal (bulk samples up to 1 Kg) sample holders. The HTK1200N chamber from Anton Paar allows collecting high resolution high temperature patterns. EMPYREAN from PANalytical. This diffractometer works in reflection and transmission geometries with theta/theta goniometer, using CuKα1,2 radiation (λ=1.5418Å), a focusing X-ray mirror and a ultra-fast PIXCEL 3D detector with 1D and 2D collection data modes (microstructural and preferred orientation analysis). Moreover, the TTK450N chamber allows low temperature and up to 450ºC studies. A D8 ADVANCE (BRUKER) was installed in April 2014. It is the first diffractometer in Europe equipped with a Johansson Ge(111) primary monochromator, which gives a strictly monochromatic Mo radiation (λ=0.7093 Å) [1]. It works in transmission mode (with a sample charger) with this high resolution configuration. XRPD data suitable for PDF (Pair Distribution Function) analysis can be collected with a capillary sample holder, due to the high energy and high resolution capabilities of this diffractometer. Moreover, it has a humidity chamber MHC-trans from Anton Paar working on transmission mode with MoKα1 (measurements can be collected at 5 to 95% of relative humidity (from 20 to 80 ºC) and up to 150ºC [2]). Furthermore, this diffractometer also has a reaction chamber XRK900 from Anton Paar (which uses CuKα1,2 radiation in reflection mode), which allows data collection from room temperature to 900ºC with up to 10 bar of different gases. Finally, a D8 DISVOVER A25 from BRUKER was installed on December 2014. It has a five axis Euler cradler and optics devices suitable for high resolution thin film data collection collected in in-plane and out-of-plane modes. To sum up, high-resolution thin films, microstructural, rocking-curve, Small Angle X-ray Scattering (SAXS), Grazing incident SAXS (GISAXS), Ultra Grazing incident diffraction (Ultra-GID) and microdiffraction measurements can be performed with the appropriated optics and sample holders. [1] L. León-Reina, M. García-Maté, G. Álvarez-Pinazo, I. Santacruz, O. Vallcorba, A.G. De la Torre, M.A.G. Aranda “Accuracy in Rietveld quantitative phase analysis: a comparative study of strictly monochromatic Mo and Cu radiations” J. Appl. Crystallogr. 2016, 49, 722-735. [2] J. Aríñez-Soriano, J. Albalad, C. Vila-Parrondo, J. Pérez-Carvajal, S. Rodríguez-Hermida, A. Cabeza, F. Busqué, J. Juanhuix, I. Imaz, Daniel Maspoch “Single-crystal and humidity-controlled powder diffraction study of the breathing effect in a metal-organic framework upon water adsorption/desorption” Chem. Commun., 2016, DOI: 10.1039/C6CC02908F.