Hypermethylated 14-3-3-sigma and ESR1 gene promoters in serum as candidate biomarkers for the diagnosis and treatment efficacy of breast cancer metastasis

Background: Numerous hypermethylated genes have been reported in breast cancer, and the silencing of these genes plays an important role in carcinogenesis, tumor progression and diagnosis. These hypermethylated promoters are very rarely found in normal breast. It has been suggested that aberrant hypermethylation may be useful as a biomarker, with implications for breast cancer etiology, diagnosis, and management. The relationship between primary neoplasm and metastasis remains largely unknown. There has been no comprehensive comparative study on the clinical usefulness of tumor-associated methylated DNA biomarkers in primary breast carcinoma and metastatic breast carcinoma. The objective of the present study was to investigate the association between clinical extension of breast cancer and methylation status of Estrogen Receptor1 (ESR1) and Stratifin (14-3-3-σ) gene promoters in disease-free and metastatic breast cancer patients. Methods: We studied two cohorts of patients: 77 patients treated for breast cancer with no signs of disease, and 34 patients with metastatic breast cancer. DNA was obtained from serum samples, and promoter methylation status was determined by using DNA bisulfite modification and quantitative methylation-specific PCR. Results: Serum levels of methylated gene promoter 14-3-3-σ significantly differed between Control and Metastatic Breast Cancer groups (P < 0.001), and between Disease-Free and Metastatic Breast Cancer groups (P < 0.001). The ratio of the 14-3-3-σ level before the first chemotherapy cycle to the level just before administration of the second chemotherapy cycle was defined as the Biomarker Response Ratio [BRR]. We calculated BRR values for the "continuous decline" and "rise-and-fall" groups. Subsequent ROC analysis showed a sensitivity of 75% (95% CI: 47.6 - 86.7) and a specificity of 66.7% (95% CI: 41.0 - 86.7) to discriminate between the groups for a cut-off level of BRR = 2.39. The area under the ROC curve (Z = 0.804 ± 0.074) indicates that this test is a good approach to post-treatment prognosis. Conclusions: The relationship of 14-3-3-σ with breast cancer metastasis and progression found in this study suggests a possible application of 14-3-3-σ as a biomarker to screen for metastasis and to follow up patients treated for metastatic breast cancer, monitoring their disease status and treatment response.

Quality Assessment of Cardiac Magnetic Resonance Images at 1.5/3.0 T: Description and Validation of Standardized Criteria

PURPOSE: Cardiovascular magnetic resonance (CMR) has become a robust and important diagnostic imaging modality in cardiovascular medicine. However,insufficient image quality may compromise its diagnostic accuracy. No standardized criteria are available to assess the quality of CMR studies. We aimed todescribe and validate standardized criteria to evaluate the quality of CMR studies including: a) cine steady-state free precession, b) delayed gadoliniumenhancement, and c) adenosine stress first-pass perfusion. These criteria will serve for the assessment of the image quality in the setting of the Euro-CMR registry.METHOD AND MATERIALS: First, a total of 45 quality criteria were defined (35 qualitative criteria with a score from 0-3, and 10 quantitative criteria). Thequalitative score ranged from 0 to 105. The lower the qualitative score, the better the quality. The quantitative criteria were based on the absolute signal intensity (delayed enhancement) and on the signal increase (perfusion) of the anterior/posterior left ventricular wall after gadolinium injection. These criteria were then applied in 30 patients scanned with a 1.5T system and in 15 patients scanned with a 3.0T system. The examinations were jointly interpreted by 3 CMR experts and 1 study nurse. In these 45 patients the correlation between the results of the quality assessment obtained by the different readers was calculated.RESULTS: On the 1.5T machine, the mean quality score was 3.5. The mean difference between each pair of observers was 0.2 (5.7%) with a mean standarddeviation of 1.4. On the 3.0T machine, the mean quality score was 4.4. The mean difference between each pair of onservers was 0.3 (6.4%) with a meanstandard deviation of 1.6. The quantitative quality assessments between observers were well correlated for the 1.5T machine: R was between 0.78 and 0.99 (pCONCLUSION: The described criteria for the assessment of CMR image quality are robust and have a low inter-observer variability, especially on 1.5T systems.CLINICAL RELEVANCE/APPLICATION: These criteria will allow the standardization of CMR examinations. They will help to improve the overall quality ofexaminations and the comparison between clinical studies.

Immigration and contested nation-building : explaining the political salience of immigration in multi-national societies

Multi-national societies present a complex setting for the politics of immigration, as migration’s linguistic, economic and cultural effects may coincide with existing contestation over nationhood between sub-units and the central state. Empirically, though, political actors only sometimes, and in some places, explicitly connect the politics of immigration to the stakes of multi-level politics. With reference to Canada, Belgium and the United Kingdom, this paper examines the conditions under which political leaders link immigration to ongoing debate about governance in multi-national societies. The paper argues that the distribution of policy competencies in the multi-level system is less important for shaping immigration and integration politics than is the perceived impact (positive or negative) on the sub-unit’s societal culture or its power relationship with the center. Immigration and integration are more often politicized where center and sub-unit hold divergent views on migration and its place in national identity.

Post-mortem cardiac 3-T magnetic resonance imaging: visualization of sudden cardiac death?

OBJECTIVES: This study aimed to investigate post-mortem magnetic resonance imaging (pmMRI) for the assessment of myocardial infarction and hypointensities on post-mortem T2-weighted images as a possible method for visualizing the myocardial origin of arrhythmic sudden cardiac death. BACKGROUND: Sudden cardiac death has challenged clinical and forensic pathologists for decades because verification on post-mortem autopsy is not possible. pmMRI as an autopsy-supporting examination technique has been shown to visualize different stages of myocardial infarction. METHODS: In 136 human forensic corpses, a post-mortem cardiac MR examination was carried out prior to forensic autopsy. Short-axis and horizontal long-axis images were acquired in situ on a 3-T system. RESULTS: In 76 cases, myocardial findings could be documented and correlated to the autopsy findings. Within these 76 study cases, a total of 124 myocardial lesions were detected on pmMRI (chronic: 25; subacute: 16; acute: 30; and peracute: 53). Chronic, subacute, and acute infarction cases correlated excellently to the myocardial findings on autopsy. Peracute infarctions (age range: minutes to approximately 1 h) were not visible on macroscopic autopsy or histological examination. Peracute infarction areas detected on pmMRI could be verified in targeted histological investigations in 62.3% of cases and could be related to a matching coronary finding in 84.9%. A total of 15.1% of peracute lesions on pmMRI lacked a matching coronary finding but presented with severe myocardial hypertrophy or cocaine intoxication facilitating a cardiac death without verifiable coronary stenosis. CONCLUSIONS: 3-T pmMRI visualizes chronic, subacute, and acute myocardial infarction in situ. In peracute infarction as a possible cause of sudden cardiac death, it demonstrates affected myocardial areas not visible on autopsy. pmMRI should be considered as a feasible post-mortem investigation technique for the deceased patient if no consent for a clinical autopsy is obtained.

Accounting system for activity standard costs formulation in ERP environment

Toiminnanohjausjärjestelmän implementointi ja sen mukanaan tuomat muutokset tuotekustannuslaskentaan asettavat haasteita yritykselle. Metallitoimialalla toimivassa yrityksessä on havaittu samat haasteet implementoitaessa SAP R/3 toiminnanohjausjärjestelmää ja sen tuotekustannuslaskentatoiminnallisuutta. SAP R/3 tuotekustannuslogiikka tarvitsee tietoa järjestelmän ulkopuolelta, minkä huomioimatta jättäminen vaikuttaa suoraan laskentatarkkuuteen. Diplomityössä kehitetään sekä standardoitu prosessi että laskentajärjestelmä, joiden avulla pystytään laskemaan tarvittavat niin toimintokustannukset eri teräspalvelukeskuksen kuormituspisteille kuin kustannustenvyörytysarvot. Lasketut arvot muodostavat tarvittavat tekijät SAP R/3 tuotekustannuslaskennan master dataan. Tavoitteena on edesauttaa läpinäkyvän kustannustiedon muodostumista. Diplomityö pohjautuu ns. vesiputousmalliin (SDLC). Ensin tunnistetaan reunaehdot ympäristöstä, jossa tuotekustannuslaskenta toteutetaan. Tämä asettaa joustamattomia komponentteja kehitettävälle laskentajärjestelmälle. Joustavat komponentit sen sijaan antavat vapautta laskentajärjestelmälle. Yhdistämällä joustamattomat ja joustavat komponentit saavutetaan järjestelmä, jolla voidaan täydentää SAP R/3 tuotekustannuslaskennan puutteellisuutta.

Visualization of communication system testing logs

During the past decades testing has matured from ad-hoc activity into being an integral part of the development process. The benefits of testing are obvious for modern communication systems, which operate in heterogeneous environments amongst devices from various manufacturers. The increased demand for testing also creates demand for tools and technologies that support and automate testing activities. This thesis discusses applicability of visualization techniques in the result analysis part of the testing process. Particularly, the primary focus of this work is visualization of test execution logs produced by a TTCN-3 test system. TTCN-3 is an internationally standardized test specification and implementation language. The TTCN-3 standard suite includes specification of a test logging interface and a graphical presentation format, but no immediate relationship between them. This thesis presents a technique for mapping the log events to the graphical presentation format along with a concrete implementation, which is integrated with the Eclipse Platform and the OpenTTCN Tester toolchain. Results of this work indicate that for majority of the log events, a visual representation may be derived from the TTCN-3 standard suite. The remaining events were analysed and three categories relevant in either log analysis or implementation of the visualization tool were identified: events indicating insertion of something into the incoming queue of a port, events indicating a mismatch and events describing the control flow during the execution. Applicability of the results is limited into the domain of TTCN-3, but the developed mapping and the implementation may be utilized with any TTCN-3 tool that is able to produce the execution log in the standardized XML format.

Studies on the Multifaceted Interaction of Atoms and an Electromagnetic Field

In this Thesis the interaction of an electromagnetic field and matter is studied from various aspects in the general framework of cold atoms. Our subjects cover a wide spectrum of phenomena ranging from semiclassical few-level models to fully quantum mechanical interaction with structured reservoirs leading to non-Markovian open quantum system dynamics. Within closed quantum systems, we propose a selective method to manipulate the motional state of atoms in a time-dependent double-well potential and interpret the method in terms of adiabatic processes. Also, we derive a simple wave-packet model, based on distributions of generalized eigenstates, explaining the finite visibility of interference in overlapping continuous-wave atom lasers. In the context of open quantum systems, we develop an unraveling of non-Markovian dynamics in terms of piecewise deterministic quantum jump processes confined in the Hilbert space of the reduced system - the non-Markovian quantum jump method. As examples, we apply it for simple 2- and 3-level systems interacting with a structured reservoir. Also, in the context of ion-cavity QED we study the entanglement generation based on collective Dicke modes in experimentally realistic conditions including photonic losses and an atomic spontaneous decay.

Emotion and anticipation in an enactive framework for cognition (response to Andy Clark)

Undeniably, anticipation plays a crucial role in cognition. By what means, to what extent, and what it achieves remain open questions. In a recent BBS target article, Clark (in press) depicts an integrative model of the brain that builds on hierarchical Bayesian models of neural processing (Rao and Ballard, 1999; Friston, 2005; Brown et al., 2011), and their most recent formulation using the free-energy principle borrowed from thermodynamics (Feldman and Friston, 2010; Friston, 2010; Friston et al., 2010). Hierarchical generative models of cognition, such as those described by Clark, presuppose the manipulation of representations and internal models of the world, in as much detail as is perceptually available. Perhaps surprisingly, Clark acknowledges the existence of a “virtual version of the sensory data” (p. 4), but with no reference to some of the historical debates that shaped cognitive science, related to the storage, manipulation, and retrieval of representations in a cognitive system (Shanahan, 1997), or accounting for the emergence of intentionality within such a system (Searle, 1980; Preston and Bishop, 2002). Instead of demonstrating how this Bayesian framework responds to these foundational questions, Clark describes the structure and the functional properties of an action-oriented, multi-level system that is meant to combine perception, learning, and experience (Niedenthal, 2007).

Four-level systems and a universal quantum gate

We discuss the possibility of implementing a universal quantum XOR gate by using two coupled quantum dots subject to external magnetic fields that are parallel and slightly different. We consider this system in two different field configurations. In the first case, parallel external fields with the intensity difference at each spin being proportional to the time-dependent interaction between the spins. A general exact solution describing this system is presented and analyzed to adjust field parameters. Then we consider parallel fields with intensity difference at each spin being constant and the interaction between the spins switching on and off adiabatically. In both cases we adjust characteristics of the external fields (their intensities and duration) in order to have the parallel pulse adequate for constructing the XOR gate. In order to provide a complete theoretical description of all the cases, we derive relations between the spin interaction, the inter-dot distance, and the external field. (C) 2008 WILEYNCH Verlag GmbH & Co. KGaA. Weinheim.

NUCLEAR SPIN 3/2 ELECTRIC QUADRUPOLE RELAXATION AS A QUANTUM COMPUTATION PROCESS

In this work we applied a quantum circuit treatment to describe the nuclear spin relaxation. From the Redfield theory, we obtain a description of the quadrupolar relaxation as a computational process in a spin 3/2 system, through a model in which the environment is comprised by five qubits and three different quantum noise channels. The interaction between the environment and the spin 3/2 nuclei is described by a quantum circuit fully compatible with the Redfield theory of relaxation. Theoretical predictions are compared to experimental data, a short review of quantum channels and relaxation in NMR qubits is also present.

Dietary fish oil replacement with lard and soybean oil affects triacylglycerol and phospholipid muscle and liver docosahexaenoic acid content but not in the brain and eyes of surubim juveniles Pseudoplatystoma sp

Triplicate groups of juvenile suribim were fed for 183 days one of four different isonitrogenous (47.6% crude protein) and isolipidic (18.7% lipid) diets formulated using three different lipid sources: 100% fish oil (FO, diet 1); 100% pig lard (L, diet 2); 100% soybean oil (SO, diet 3), and FO/L/SO (1:1:1, w/w/w; diet 4). The tissue levels of fatty acids 18:2n - 6 and 18:3n - 3 decreased relative to corresponding dietary fatty acid values. The 20:5n - 3 and 22:6n - 3 composition of muscle and liver neutral lipids were linearly correlated with corresponding dietary fatty acid composition. In contrast, the 22:6n - 3 composition of the brain and eye were similar among treatments. The 22:6n - 3 level was enriched in all tissues, particularly in the neural tissues. Similar results were observed for tissue polar lipids: fatty acids content reflected dietary composition, with the exception of the 22:6n - 3 level, which showed enrichment and no differences between groups. Given these results, the importance of the biochemical functions (transport and/or metabolism) of 22:6n - 3 in the development of the neural system of surubim warrants further investigation. © Springer Science+Business Media B.V. 2008.

Dissection of the role of pili and type 2 and 3 secretion systems in adherence and biofilm formation of an atypical enteropathogenic escherichia coli strain

Atypical enteropathogenic Escherichia coli (aEPEC) strains are diarrheal pathogens that lack bundle-forming pilus production but possess the virulence-associated locus of enterocyte effacement. aEPEC strain 1551-2 produces localized adherence (LA) on HeLa cells; however, its isogenic intimin (eae) mutant produces a diffuse-adherence (DA) pattern. In this study, we aimed to identify the DA-associated adhesin of the 1551-2 eae mutant. Electron microscopy of 1551-2 identified rigid rod-like pili composed of an 18-kDa protein, which was identified as the major pilin subunit of type 1 pilus (T1P) by mass spectrometry analysis. Deletion of fimA in 1551-2 affected biofilm formation but had no effect on adherence properties. Analysis of secreted proteins in supernatants of this strain identified a 150-kDa protein corresponding to SslE, a type 2 secreted protein that was recently reported to be involved in biofilm formation of rabbit and human EPEC strains. However, neither adherence nor biofilm formation was affected in a 1551-2 sslE mutant. We then investigated the role of the EspA filament associated with the type 3 secretion system (T3SS) in DA by generating a double eae espA mutant. This strain was no longer adherent, strongly suggesting that the T3SS translocon is the DA adhesin. In agreement with these results, specific anti-EspA antibodies blocked adherence of the 1551-2 eae mutant. Our data support a role for intimin in LA, for the T3SS translocon in DA, and for T1P in biofilm formation, all of which may act in concert to facilitate host intestinal colonization by aEPEC strains. ©2013, American Society for Microbiology.

Deposição e caracterização de filmes finos de GaAs e 'Al IND. 2''O IND. 3' para potencial utilizado em transistores

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Non-Markovianity through flow of information between a system and an environment

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Correlation of the Physicochemical and Structural Properties of pDNA/Cationic Liposome Complexes with Their in Vitro Transfection

In this study, we characterized the conventional physicochemical properties of the complexes formed by plasmid DNA (pDNA) and cationic liposomes (CL) composed of egg phosphatidylcholine (EPC), 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), and 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) (50/25/25% molar ratio). We found that these properties are nearly unaffected at the studied ranges when the molar charge ratio (R-+/-) between the positive charge from the CL and negative charge from pDNA is not close to the isoneutrality region (R-+/- = 1). However, the results from in vitro transfection of HeLa cells showed important differences when R-+/- is varied, indicating that the relationships between the physicochemical and biological characteristics were not completely elucidated. To obtain information regarding possible liposome structural modifications, small-angle X-ray scattering (SAXS) experiments were performed as a function of R-+/- to obtain correlations between structural, physicochemical, and transfection properties. The SAXS results revealed that pDNA/CL complexes can be described as being composed of single bilayers, double bilayers, and multiple bilayers, depending on the R-+/- value. Interestingly, for R-+/- = 9, 6, and 3, the system is composed of single and double bilayers, and the fraction of the latter increases with the amount of DNA (or a decreasing R-+/-) in the system. This information is used to explain the transfection differences observed at an R-+/- = 9 as compared to R-+/- = 3 and 6. Close to the isoneutrality region (R-+/- = 1.8), there was an excess of pDNA, which induced the formation of a fraction of aggregates with multiple bilayers. These aggregates likely provide additional resistance against the release of pDNA during the transfection phenomenon, reflected as a decrease in the transfection level. The obtained results permitted proper correlation of the physicochemical and structural properties of pDNA/CL complexes with the in vitro transfection of HeLa cells by these complexes, contributing to a better understanding of the gene delivery process.