Y-box binding protein 1 (YB-1) relevance in estrogen receptor-positive (ER+) breast cancer

Tese de mestrado, Biologia Molecular e Genética, Universidade de Lisboa, Faculdade de Ciências, 2016

Évaluation électrophysiologique auditive et examen du langage et de l’attention chez l’enfant né prématurément et l’enfant né à terme

L’objectif de cette thèse est l’étude du développement de l’attention auditive et des capacités de discrimination langagière chez l’enfant né prématurément ou à terme. Les derniers mois de grossesse sont particulièrement importants pour le développement cérébral de l’enfant et les conséquences d’une naissance prématurée sur le développement peuvent être considérables. Les enfants nés prématurément sont plus à risque de développer une variété de troubles neurodéveloppementaux que les enfants nés à terme. Même en l’absence de dommages cérébraux visibles, de nombreux enfants nés avant terme sont à risque de présenter des troubles tels que des retards langagiers ou des difficultés attentionnelles. Dans cette thèse, nous proposons donc une méthode d’investigation des processus préattentionnels auditifs et de discrimination langagière, à l’aide de l’électrophysiologie à haute densité et des potentiels évoqués auditifs (PEAs). Deux études ont été réalisées. La première visait à mettre sur pied un protocole d’évaluation de l’attention auditive et de la discrimination langagière chez l’enfant en santé, couvrant différents stades de développement (3 à 7 ans, 8 à 13 ans, adultes ; N = 40). Pour ce faire, nous avons analysé la composante de Mismatch Negativity (MMN) évoquée par la présentation de sons verbaux (syllabes /Ba/ et /Da/) et non verbaux (tons synthétisés, Ba : 1578 Hz/2800 Hz ; Da : 1788 Hz/2932 Hz). Les résultats ont révélé des patrons d’activation distincts en fonction de l’âge et du type de stimulus présenté. Chez tous les groupes d’âge, la présentation des stimuli non verbaux a évoqué une MMN de plus grande amplitude et de latence plus rapide que la présentation des stimuli verbaux. De plus, en réponse aux stimuli verbaux, les deux groupes d’enfants (3 à 7 ans, 8 à 13 ans) ont démontré une MMN de latence plus tardive que celle mesurée dans le groupe d’adultes. En revanche, en réponse aux stimuli non verbaux, seulement le groupe d’enfants de 3 à 7 ans a démontré une MMN de latence plus tardive que le groupe d’adulte. Les processus de discrimination verbaux semblent donc se développer plus tardivement dans l’enfance que les processus de discrimination non verbaux. Dans la deuxième étude, nous visions à d’identifier les marqueurs prédictifs de déficits attentionnels et langagiers pouvant découler d’une naissance prématurée à l’aide des PEAs et de la MMN. Nous avons utilisé le même protocole auprès de 74 enfants âgés de 3, 12 et 36 mois, nés prématurément (avant 34 semaines de gestation) ou nés à terme (au moins 37 semaines de gestation). Les résultats ont révélé que les enfants nés prématurément de tous les âges démontraient un délai significatif dans la latence de la réponse MMN et de la P150 par rapport aux enfants nés à terme lors de la présentation des sons verbaux. De plus, les latences plus tardives de la MMN et de la P150 étaient également corrélées à des performances langagières plus faibles lors d’une évaluation neurodéveloppementale. Toutefois, aucune différence n’a été observée entre les enfants nés à terme ou prématurément lors de la discrimination des stimuli non verbaux, suggérant des capacités préattentionnelles auditives préservées chez les enfants prématurés. Dans l’ensemble, les résultats de cette thèse indiquent que les processus préattentionnels auditifs se développent plus tôt dans l'enfance que ceux associés à la discrimination langagière. Les réseaux neuronaux impliqués dans la discrimination verbale sont encore immatures à la fin de l'enfance. De plus, ceux-ci semblent être particulièrement vulnérables aux impacts physiologiques liés à la prématurité. L’utilisation des PEAs et de la MMN en réponse aux stimuli verbaux en bas âge peut fournir des marqueurs prédictifs des difficultés langagières fréquemment observées chez l’enfant prématuré.

Évaluation électrophysiologique auditive et examen du langage et de l’attention chez l’enfant né prématurément et l’enfant né à terme

L’objectif de cette thèse est l’étude du développement de l’attention auditive et des capacités de discrimination langagière chez l’enfant né prématurément ou à terme. Les derniers mois de grossesse sont particulièrement importants pour le développement cérébral de l’enfant et les conséquences d’une naissance prématurée sur le développement peuvent être considérables. Les enfants nés prématurément sont plus à risque de développer une variété de troubles neurodéveloppementaux que les enfants nés à terme. Même en l’absence de dommages cérébraux visibles, de nombreux enfants nés avant terme sont à risque de présenter des troubles tels que des retards langagiers ou des difficultés attentionnelles. Dans cette thèse, nous proposons donc une méthode d’investigation des processus préattentionnels auditifs et de discrimination langagière, à l’aide de l’électrophysiologie à haute densité et des potentiels évoqués auditifs (PEAs). Deux études ont été réalisées. La première visait à mettre sur pied un protocole d’évaluation de l’attention auditive et de la discrimination langagière chez l’enfant en santé, couvrant différents stades de développement (3 à 7 ans, 8 à 13 ans, adultes ; N = 40). Pour ce faire, nous avons analysé la composante de Mismatch Negativity (MMN) évoquée par la présentation de sons verbaux (syllabes /Ba/ et /Da/) et non verbaux (tons synthétisés, Ba : 1578 Hz/2800 Hz ; Da : 1788 Hz/2932 Hz). Les résultats ont révélé des patrons d’activation distincts en fonction de l’âge et du type de stimulus présenté. Chez tous les groupes d’âge, la présentation des stimuli non verbaux a évoqué une MMN de plus grande amplitude et de latence plus rapide que la présentation des stimuli verbaux. De plus, en réponse aux stimuli verbaux, les deux groupes d’enfants (3 à 7 ans, 8 à 13 ans) ont démontré une MMN de latence plus tardive que celle mesurée dans le groupe d’adultes. En revanche, en réponse aux stimuli non verbaux, seulement le groupe d’enfants de 3 à 7 ans a démontré une MMN de latence plus tardive que le groupe d’adulte. Les processus de discrimination verbaux semblent donc se développer plus tardivement dans l’enfance que les processus de discrimination non verbaux. Dans la deuxième étude, nous visions à d’identifier les marqueurs prédictifs de déficits attentionnels et langagiers pouvant découler d’une naissance prématurée à l’aide des PEAs et de la MMN. Nous avons utilisé le même protocole auprès de 74 enfants âgés de 3, 12 et 36 mois, nés prématurément (avant 34 semaines de gestation) ou nés à terme (au moins 37 semaines de gestation). Les résultats ont révélé que les enfants nés prématurément de tous les âges démontraient un délai significatif dans la latence de la réponse MMN et de la P150 par rapport aux enfants nés à terme lors de la présentation des sons verbaux. De plus, les latences plus tardives de la MMN et de la P150 étaient également corrélées à des performances langagières plus faibles lors d’une évaluation neurodéveloppementale. Toutefois, aucune différence n’a été observée entre les enfants nés à terme ou prématurément lors de la discrimination des stimuli non verbaux, suggérant des capacités préattentionnelles auditives préservées chez les enfants prématurés. Dans l’ensemble, les résultats de cette thèse indiquent que les processus préattentionnels auditifs se développent plus tôt dans l'enfance que ceux associés à la discrimination langagière. Les réseaux neuronaux impliqués dans la discrimination verbale sont encore immatures à la fin de l'enfance. De plus, ceux-ci semblent être particulièrement vulnérables aux impacts physiologiques liés à la prématurité. L’utilisation des PEAs et de la MMN en réponse aux stimuli verbaux en bas âge peut fournir des marqueurs prédictifs des difficultés langagières fréquemment observées chez l’enfant prématuré.

Disturbances of agency and ownership in schizophrenia: An auditory verbal event related potentials study

A ‘sense of self’ is essentially the ability to distinguish between self-generated and external stimuli. It consists of at least two very basic senses: a sense of agency and a sense of ownership. Disturbances seem to provide a basic deficit in many psychiatric diseases. The aim of our study was to manipulate those qualities separately in 28 patients with schizophrenia (14 auditory hallucinators and 14 non-hallucinators) and 28 healthy controls (HC) and to investigate the effects on the topographies and the power of the event-related potential (ERP). We performed a 76-channel EEG while the participants performed the task as in our previous paper. We computed ERPs and difference maps for the conditions and compared the amount of agency and ownership between the HC and the patients. Furthermore, we compared the global field power and the topographies of these effects. Our data showed effects of agency and ownership in the healthy controls and the hallucinator group and to a lesser degree in the non-hallucinator group. We found a reduction of the N100 during the presence of agency, and a bilateral temporal negativity related to the presence of ownership. For the agency effects, we found significant differences between HC and the patients. Contrary to the expectations, our findings were more pronounced in non-hallucinators, suggesting a more profoundly disturbed sense of agency compared to hallucinators. A contemporary increase of global field power in both patient groups indicates a compensatory recruitment of other mechanisms not normally associated with the processing of agency and ownership.

Spin squeezing as a measure of entanglement in a two-qubit system

We show that the two definitions of spin squeezing extensively used in the literature [M. Kitagawa and M. Ueda, Phys. Rev. A 47, 5138 (1993) and D.J. Wineland , Phys. Rev. A 50, 67 (1994)] give different predictions of entanglement in the two-atom Dicke system. We analyze differences between the definitions and show that the spin squeezing parameter of Kitagawa and Ueda is a better measure of entanglement than the commonly used spectroscopic spin squeezing parameter. We illustrate this relation by examining different examples of a driven two-atom Dicke system in which spin squeezing and entanglement arise dynamically. We give an explanation of the source of the difference using the negativity criterion for entanglement.

Event-related potential correlates of impaired visuospatial working memory in schizophrenia

Previous studies have reported that patients with schizophrenia demonstrate impaired performance during working memory (WM) tasks. The current study aimed to determine whether WM impairments in schizophrenia are accompanied by reduced slow wave (SW) activity during on-line maintenance of mnemonic information. Event-related potentials were obtained from patients with schizophrenia and well controls as they performed a visuospatial delayed response task. On 50% of trials, a distractor stimulus was introduced during the delay. Compared with controls, patients with schizophrenia produced less SW memory negativity, particularly over the right hemisphere, together with reduced frontal enhancement of SW memory negativity in response to distraction. The results indicate that patients with schizophrenia generate less maintenance phase neuronal activity during WM performance, especially under conditions of distraction.

Entangling two atoms via spontaneous emission

We discuss the creation of entanglement between two two-level atoms in the dissipative process of spontaneous emission. It is shown that spontaneous emission can lead to a transient entanglement between the atoms even if the atoms were prepared initially in an unentangled state. The amount of entanglement created in the system is quantified by using two different measures: concurrence and negativity. We find analytical formulae for the evolution of concurrence and negativity in the system. We also find the analytical relation between the two measures of entanglement. The system consists of two two-level atoms which are separated by an arbitrary distance r(12) and interact with each other via the dipole-dipole interaction, and the antisymmetric state of the system is included throughout, even for small interatomic separations, in contrast to the small-sample model. It is shown that for sufficiently large values of the dipole-dipole interaction initially the entanglement exhibits oscillatory behaviour with considerable entanglement in the peaks. For longer times the amount of entanglement is directly related to the population of the slowly decaying antisymmetric state.

Reinforcing the glass ceiling: The consequences of hostile sexism for female managerial candidates

Previous research has established that benevolent sexism is related to the negative evaluation of women who violate specific norms for behavior. Research has yet to document the causal impact of hostile sexism on evaluations of individual targets. Correlational evidence and ambivalent sexism theory led us to predict that hostile sexism would be associated with negative evaluations of a female candidate for a masculine-typed occupational role. Participants completed the ASI (P. Glick & S. T. Fiske, 1996) and evaluated a curriculum vitae from either a male or female candidate. Higher hostile sexism was significantly associated with more negative evaluations of the female candidate and with lower recommendations that she be employed as a manager. Conversely, higher hostile sexism was significantly associated with higher recommendations that a male candidate should be employed as a manager. Benevolent sexism was unrelated to evaluations and recommendations in this context. The findings support the hypothesis that hostile, but not benevolent, sexism results in negativity toward individual women who pose a threat to men's status in the workplace.

Production of superpositions of coherent states in traveling optical fields with inefficient photon detection

We develop an all-optical scheme to generate superpositions of macroscopically distinguishable coherent states in traveling optical fields. It nondeterministically distills coherent-state superpositions (CSS's) with large amplitudes out of CSS's with small amplitudes using inefficient photon detection. The small CSS's required to produce CSS's with larger amplitudes are extremely well approximated by squeezed single photons. We discuss some remarkable features of this scheme: it effectively purifies mixed initial states emitted from inefficient single-photon sources and boosts negativity of Wigner functions of quantum states.

Typical medullary breast carcinomas have a basal/myoepithelial phenotype

Medullary breast cancer (MBC) is a rare, diagnostically difficult, pathological subtype. Despite being high grade, it has a good prognosis. MBC patients have an excess of BRCA1 germ-fine mutation and reliable identification of MBC could help to identify patients at risk of carrying germline BRCA1 mutations or in whom chemotherapy could be avoided. The aim of this study was therefore to improve diagnosis by establishing an MBC protein expression profile using immunohistochemistry (IHC) on tissue-microarrays (TMA). Using a series of 779 breast carcinomas ('EC' set), diagnosed initially as MBC, a double-reading session was carried out by several pathologists on all of the histological material to establish the diagnosis as firmly as possible using a 'medullary score'. Only MBCs with high scores, i.e. typical MBC (TMBC) (n = 44) and non-TMBC grade III with no or low scores (n = 160), were included in the IHC study. To validate the results obtained on this first set, a control series of TMBC (n = 17) and non-MBC grade III cases (n = 140) ('IPC' set) was studied. The expression of 18 proteins was studied in the 61 TMBCs and 300 grade III cases from the two sets. The global intra-observer concordance of the first reading for the diagnosis of TMBC was 94%, with almost perfect kappa (kappa) of 0.815. TMBC was characterized by a high degree of basal/myoepithelial differentiation. In multivariate analysis with logistic regression, TMBC was defined by the association of P-cadherin (R = 2.29), MIB1 > 50 (R = 3.80), ERBB2 negativity (R = 2.24) and p53 positivity (RR = 1.45). Copyright (c) 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Nonclassicality of a photon-subtracted Gaussian field

We investigate the nonclassicality of a photon-subtracted Gaussian field, which was produced in a recent experiment, using negativity of the Wigner function and the nonexistence of well-behaved positive P function. We obtain the condition to see negativity of the Wigner function for the case including the mixed Gaussian incoming field, the threshold photodetection and the inefficient homodyne measurement. We show how similar the photon-subtracted state is to a superposition of coherent states.

Quantum entanglement in the two-impurity Kondo model

In order to quantify quantum entanglement in two-impurity Kondo systems, we calculate the concurrence, negativity, and von Neumann entropy. The entanglement of the two Kondo impurities is shown to be determined by two competing many-body effects, namely the Kondo effect and the Ruderman-Kittel-Kasuya-Yosida (RKKY) interaction, I. Due to the spin-rotational invariance of the ground state, the concurrence and negativity are uniquely determined by the spin-spin correlation between the impurities. It is found that there exists a critical minimum value of the antiferromagnetic correlation between the impurity spins which is necessary for entanglement of the two impurity spins. The critical value is discussed in relation with the unstable fixed point in the two-impurity Kondo problem. Specifically, at the fixed point there is no entanglement between the impurity spins. Entanglement will only be created [and quantum information processing (QIP) will only be possible] if the RKKY interaction exchange energy, I, is at least several times larger than the Kondo temperature, T-K. Quantitative criteria for QIP are given in terms of the impurity spin-spin correlation.

Microarray-based comparative genomic hybridisation of breast cancer patients receiving neoadjuvant chemotherapy

We analysed the molecular genetic profiles of breast cancer samples before and after neoadjuvant chemotherapy with combination doxorubicin and cyclophosphamide (AC). DNA was obtained from microdissected frozen breast core biopsies from 44 patients before chemotherapy. Additional samples were obtained before the second course of chemotherapy (D21) and after the completion of the treatment (surgical specimens) in 17 and 21 patients, respectively. Microarray-based comparative genome hybridisation was performed using a platform containing approx5800 bacterial artificial chromosome clones (genome-wide resolution: 0.9 Mb). Analysis of the 44 pretreatment biopsies revealed that losses of 4p, 4q, 5q, 12q13.11–12q13.12, 17p11.2 and 17q11.2; and gains of 1p, 2p, 7q, 9p, 11q, 19p and 19q were significantly associated with oestrogen receptor negativity. 16q21–q22.1 losses were associated with lobular and 8q24 gains with ductal types. Losses of 5q33.3–q4 and 18p11.31 and gains of 6p25.1–p25.2 and Xp11.4 were associated with HER2 amplification. No correlations between DNA copy number changes and clinical response to AC were found. Microarray-based comparative genome hybridisation analysis of matched pretreatment and D21 biopsies failed to identify statistically significant differences, whereas a comparison between matched pretreatment and surgical samples revealed a statistically significant acquired copy number gain on 11p15.2–11p15.5. The modest chemotherapy-driven genomic changes, despite profound loss of cell numbers, suggest that there is little therapeutic selection of resistant non-modal cell lineages.

British lesbian, gay and bisexual psychologies:theory, research and practice

Gain insight into crucial British mental health approaches for LGB individuals. There is very little collaborative literature between LGB-affirmative psychologists and psychotherapists in the United States and the United Kingdom. British Lesbian, Gay, and Bisexual Psychologies: Theory, Research, and Practice may well be a crucial beginning step in building dialogue between these two countries on important LGB psychotherapy developments. Leading authorities comprehensively examine the latest studies and effective therapies for LGB individuals in the United Kingdom. Practitioners will discover an extensive survey of the most current developments to supplement their own work, while educators and students will find diverse expert perspectives on which to consider and broaden their own viewpoints. This unique book offers an informative introduction to British psychosocial perspectives on theory, research, and practice. British Lesbian, Gay, and Bisexual Psychologies provides a critical exploration of the recent history of LGB psychology and psychotherapy in the United Kingdom, focusing on key publications and outlining the current terrain. Other chapters are organized into two thematic sections. The first section explores theoretical frameworks in United Kingdom therapeutic practice, while the second section examines sexual minority identities and their needs for support and community. Topics in British Lesbian, Gay, and Bisexual Psychologies include: - similarities and differences between LGBT psychology and psychotherapy in the United States and United Kingdom - gay affirmative therapy (GAT) as a positive framework - existential-phenomenological approach to psychotherapy - core issues in the anxiety about whether or not to “come out” - object relations theory - exploring homo-negativity in the therapeutic process - aspects of psychotherapy that lesbians and gay men find helpful - research into how the mainstreaming of lesbian and gay culture has affected the lives of LGB individuals - study into LGB youth issues - difficulties of gay men with learning disabilities—with suggestions on how to offer the best psychological service - a study on gay athletes’ experiences of coming out in a heterosexist world British Lesbian, Gay, and Bisexual Psychologies takes a needed step toward sharing valuable psychosocial perspectives between countries. This useful, enlightening text is perfect for educators, students, psychologists, psychotherapists, and counselors working in the field of sexuality.

Topographic mapping and source localization of the pattern onset visual evoked magnetic response

The topography of the visual evoked magnetic response (VEMR) to a pattern onset stimulus was investigated using 4 check sizes and 3 contrast levels. The pattern onset response consists of three early components within the first 200ms, CIm, CIIm and CIIIm. The CIIm is usually of high amplitude and is very consistent in latency within a subject. Half field (HF) stimuli produce their strongest response over the contralateral hemisphere; the RHF stimulus exhibiting a lower positivity (outgoing field) and an upper negativity (ingoing field), rotated towards the midline. LHF stimulation produced the opposite response, a lower negative and an upper positive. Larger check sizes produce a single area of ingoing and outgoing field while smaller checks produce on area of ingoing and outgoing field over each hemisphere. Latency did not appear to vary with change in contrast but amplitudes increased with increasing contrast. A more detailed topographic study incorporating source localisation procedures suggested a source for CIIm - 4cm below the scalp, close to the midline with current flowing towards the lateral surface. Similar depth and position estimates but with opposite polarity were obtained for the pattern shift P100m previously. Hence, the P100m and the CIIm may originate in similar areas of visual cortex but reveal different aspects of visual processing. © 1992 Human Sciences Press, Inc.