Conformational Properties of Angiotensin II and Its Active and Inactive TOAC-Labeled Analogs in the Presence of Micelles. Electron Paramagnetic Resonance, Fluorescence, and Circular Dichroism Studies

The interaction between angiotensin II (AII, DRVYIHPF) and its analogs carrying 2,2,6,6-tetramethylpiperidine-1-oxyl-4-amino-4-carboxylic acid (TOAC) and detergents-negatively charged sodium dodecyl sulfate (SDS) and zwitterionic N-hexadecyl-N,N-dimethyl-3-ammonio-1-propanesulfonate (HPS)-was examined by means of EPR, CD, and fluorescence. EPR spectra of partially active TOAC(1)-AII and inactive TOAC(3)-AII in aqueous solution indicated fast tumbling, the freedom of motion being greater at the N-terminus. Line broadening occurred upon interaction with micelles. Below SDS critical micelle concentration, broader lines indicated complex formation with tighter molecular packing than in micelles. Small changes in hyperfine splittings evinced TOAC location at the micelle-water interface. The interaction with anionic micelles was more effective than with zwitterionic micelles. Peptide-micelle interaction caused fluorescence increase. The TOAC-promoted intramolecular fluorescence quenching was more, pronounced for TOAC(3)-AII because of the proximity between the nitroxide and Tyr(4). CD spectra showed that although both AII and TOAC(1)-AII presented flexible conformations in water, TOAC(3)-AII displayed conformational restriction because of the TOAC-imposed bend (Schreier et al., Biopolymers 2004, 74, 389). In HPS, conformational changes were observed for the labeled peptides at neutral and basic pH. In SDS, all peptides underwent pH-dependent conformational changes. Although the spectra suggested similar folds for All and TOAC(1)-AII, different conformations were acquired by TOAC(3)-AII. The membrane environment has been hypothesized to shift conformational equilibria so as to stabilize the receptor-bound conformation of ligands. The fact that TOAC(3)-AII is unable to acquire conformations similar to those of native AII and partially active TOAC(1)-AII is probably the explanation for its lack of biological activity. (C) 2009 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 92: 525-537, 2009.

Classification of Parkinson’s Disease using MultiPass Lvq,Logistic Model Tree,K-Star for Audio Data set : Classification of Parkinson Disease using Audio Dataset

Parkinson's disease (PD) is a degenerative illness whose cardinal symptoms include rigidity, tremor, and slowness of movement. In addition to its widely recognized effects PD can have a profound effect on speech and voice.The speech symptoms most commonly demonstrated by patients with PD are reduced vocal loudness, monopitch, disruptions of voice quality, and abnormally fast rate of speech. This cluster of speech symptoms is often termed Hypokinetic Dysarthria.The disease can be difficult to diagnose accurately, especially in its early stages, due to this reason, automatic techniques based on Artificial Intelligence should increase the diagnosing accuracy and to help the doctors make better decisions. The aim of the thesis work is to predict the PD based on the audio files collected from various patients.Audio files are preprocessed in order to attain the features.The preprocessed data contains 23 attributes and 195 instances. On an average there are six voice recordings per person, By using data compression technique such as Discrete Cosine Transform (DCT) number of instances can be minimized, after data compression, attribute selection is done using several WEKA build in methods such as ChiSquared, GainRatio, Infogain after identifying the important attributes, we evaluate attributes one by one by using stepwise regression.Based on the selected attributes we process in WEKA by using cost sensitive classifier with various algorithms like MultiPass LVQ, Logistic Model Tree(LMT), K-Star.The classified results shows on an average 80%.By using this features 95% approximate classification of PD is acheived.This shows that using the audio dataset, PD could be predicted with a higher level of accuracy.

A corpus approach to discursive constructions of a hip-hop identity

This chapter is an analysis of a 100,000-word corpus consisting of message-board postings on hip-hop websites. A discourse analysis of this corpus reveals three strategies employed by the posters to identify themselves as members of the hip-hop community in the otherwise anonymous setting of the internet: (1) defined openings and closings, (2) repeated use of slang and taboo terms, and (3) performance of verbal art. Each strategy is characterized by the codification of non-standard grammar and pronunciations characteristic of speech, as well as by the use of non-standard orthography. The purpose of the discourse is shown to be a performance of identity, whereby language is used and recognized as the discursive construction of one’s hip-hop identity.

Immigration, security and the public debate on US language policy : a critical discourse analysis of language attitudes in the United States of America

The narrative of the United States is of a "nation of immigrants" in which the language shift patterns of earlier ethnolinguistic groups have tended towards linguistic assimilation through English. In recent years, however, changes in the demographic landscape and language maintenance by non-English speaking immigrants, particularly Hispanics, have been perceived as threats and have led to calls for an official English language policy.This thesis aims to contribute to the study of language policy making from a societal security perspective as expressed in attitudes regarding language and identity originating in the daily interaction between language groups. The focus is on the role of language and American identity in relation to immigration. The study takes an interdisciplinary approach combining language policy studies, security theory, and critical discourse analysis. The material consists of articles collected from four newspapers, namely USA Today, The New York Times, Los Angeles Times, and San Francisco Chronicle between April 2006 and December 2007.Two discourse types are evident from the analysis namely Loyalty and Efficiency. The former is mainly marked by concerns of national identity and contains speech acts of security related to language shift, choice and English for unity. Immigrants are represented as dehumanised, and harmful. Immigration is given as sovereignty-related, racial, and as war. The discourse type of Efficiency is mainly instrumental and contains speech acts of security related to cost, provision of services, health and safety, and social mobility. Immigrants are further represented as a labour resource. These discourse types reflect how the construction of the linguistic 'we' is expected to be maintained. Loyalty is triggered by arguments that the collective identity is threatened and is itself used in reproducing the collective 'we' through hegemonic expressions of monolingualism in the public space and semi-public space. The denigration of immigrants is used as a tool for enhancing societal security through solidarity and as a possible justification for the denial of minority rights. Also, although language acquisition patterns still follow the historical trend of language shift, factors indicating cultural separateness such as the appearance of speech communities or the use of minority languages in the public space and semi-public space have led to manifestations of intolerance. Examples of discrimination and prejudice towards minority groups indicate that the perception of worth of a shared language differs from the actual worth of dominant language acquisition for integration purposes. The study further indicates that the efficient working of the free market by using minority languages to sell services or buy labour is perceived as conflicting with nation-building notions since it may create separately functioning sub-communities with a new cultural capital recognised as legitimate competence. The discourse types mainly represent securitising moves constructing existential threats. The perception of threat and ideas of national belonging are primarily based on a zero-sum notion favouring monolingualism. Further, the identity of the immigrant individual is seen as dynamic and adaptable to assimilationist measures whereas the identity of the state and its members are perceived as static. Also, the study shows that debates concerning language status are linked to extra-linguistic matters. To conclude, policy makers in the US need to consider the relationship between four factors, namely societal security based on collective identity, individual/human security, human rights, and a changing linguistic demography, for proposed language intervention measures to be successful.

La confrontation de la laideur avec la beauté dans lesromans Mercure et Attentat. Une étude sur lareprésentation de la dualité thématique laideur-beautéchez Amélie Nothomb. : "Where there is Quasimodo, there is also Esmeralda." The confrontationbetween ugliness and beauty in the novels Mercure and Attentat. Astudy on the representation of the duality beauty-ugliness in the worksof Amélie Nothomb.

This paper studies one of the recurrent topics of writing found in Amélie Nothomb’snovels: beauty and ugliness. The novels Mercure and Attentat are analyzed in detail,with respect to figures of speech used to describe the extreme physical appearance ofthe protagonists and the role of the duality beauty-ugliness in the advancement of theplot.

First-principle data-driven models for assessment of motor disorders in Parkinson’s disease

Parkinson’s disease (PD) is an increasing neurological disorder in an aging society. The motor and non-motor symptoms of PD advance with the disease progression and occur in varying frequency and duration. In order to affirm the full extent of a patient’s condition, repeated assessments are necessary to adjust medical prescription. In clinical studies, symptoms are assessed using the unified Parkinson’s disease rating scale (UPDRS). On one hand, the subjective rating using UPDRS relies on clinical expertise. On the other hand, it requires the physical presence of patients in clinics which implies high logistical costs. Another limitation of clinical assessment is that the observation in hospital may not accurately represent a patient’s situation at home. For such reasons, the practical frequency of tracking PD symptoms may under-represent the true time scale of PD fluctuations and may result in an overall inaccurate assessment. Current technologies for at-home PD treatment are based on data-driven approaches for which the interpretation and reproduction of results are problematic.  The overall objective of this thesis is to develop and evaluate unobtrusive computer methods for enabling remote monitoring of patients with PD. It investigates first-principle data-driven model based novel signal and image processing techniques for extraction of clinically useful information from audio recordings of speech (in texts read aloud) and video recordings of gait and finger-tapping motor examinations. The aim is to map between PD symptoms severities estimated using novel computer methods and the clinical ratings based on UPDRS part-III (motor examination). A web-based test battery system consisting of self-assessment of symptoms and motor function tests was previously constructed for a touch screen mobile device. A comprehensive speech framework has been developed for this device to analyze text-dependent running speech by: (1) extracting novel signal features that are able to represent PD deficits in each individual component of the speech system, (2) mapping between clinical ratings and feature estimates of speech symptom severity, and (3) classifying between UPDRS part-III severity levels using speech features and statistical machine learning tools. A novel speech processing method called cepstral separation difference showed stronger ability to classify between speech symptom severities as compared to existing features of PD speech. In the case of finger tapping, the recorded videos of rapid finger tapping examination were processed using a novel computer-vision (CV) algorithm that extracts symptom information from video-based tapping signals using motion analysis of the index-finger which incorporates a face detection module for signal calibration. This algorithm was able to discriminate between UPDRS part III severity levels of finger tapping with high classification rates. Further analysis was performed on novel CV based gait features constructed using a standard human model to discriminate between a healthy gait and a Parkinsonian gait. The findings of this study suggest that the symptom severity levels in PD can be discriminated with high accuracies by involving a combination of first-principle (features) and data-driven (classification) approaches. The processing of audio and video recordings on one hand allows remote monitoring of speech, gait and finger-tapping examinations by the clinical staff. On the other hand, the first-principles approach eases the understanding of symptom estimates for clinicians. We have demonstrated that the selected features of speech, gait and finger tapping were able to discriminate between symptom severity levels, as well as, between healthy controls and PD patients with high classification rates. The findings support suitability of these methods to be used as decision support tools in the context of PD assessment.

Understanding older people’s experiences of home care through the capability approach

The core concepts of CA In the theoretical framework of CA, well-being is constituted by a person’s unique way of functioning and capabilities. This means that a person's well-being is personal and involves freedom of choice which in turn means they have a number of options. Although many people may have the same resources, it is of importance to study how these resources are converted into how they function. Thus, wellbeing is about the person's freedom to achieve in general and the capabilities to function in particular (Sen, 1995). Strength of the capability approach The capability approach is a useful tool for matching objective evaluations with subjective metrics. Furthermore, although one’s individual abilities are in focus, contextual factors, and subjective perceptions and experiences, are taken into consideration. Critiques against the CA The capability approach has been criticized for being too individual-centered and not taking sufficient account to social structures in society. It is difficult to know what a person would choose to do if other options were available. Therefore, to operationalize abilities involves uncertainties.

The relative perceptual weight of two Swedish prosodic contrasts

Abstract. In addition to 9 vowel and 18 consonant phonemes, Swedish has three prosodic phonemic contrasts: word stress, quantity and tonal word accent. There are also examples of distinctive phrase or sentence stress, where a verb can be followed by either an unstressed preposition or a stressed particle. This study focuses on word level and more specifically on word stress and tonal word accent in disyllabic words. When making curriculums for second language learners, teachers are helped by knowing which phonetic or phonological features are more or less crucial for the intelligibility of speech and there are some structural and anecdotal evidence that word stress should play a more important role for intelligibility of Swedish, than the tonal word accent. The Swedish word stress is about prominence contrasts between syllables, mainly signaled by syllable duration, while the tonal word accent is signaled mainly by pitch contour. The word stress contrast, as in armen [´arːmən] ‘the arm’ - armén [ar´meːn] ‘the army’, the first word trochaic and the second iambic, is present in all regional varieties of Swedish, and realized with roughly the same acoustic cues, while the tonal word accent, as in anden [´anːdən] ‘the duck’ - anden [`anːdən] ‘the spirit’ is absent in some dialects (as well as in singing), and also signaled with a variety of tonal patterns depending on region. The present study aims at comparing the respective perceptual weight of the two mentioned contrasts. Two lexical decision tests were carried out where in total 34 native Swedish listeners should decide whether a stimulus was a real word or a non-word. Real words of all mentioned categories were mixed with nonsense words and words that were mispronounced with opposite stress pattern or opposite tonal word accent category. The results show that distorted word stress caused more non-word judgments and more loss, than distorted word accent. Our conclusion is that intelligibility of Swedish is more sensitive to distorted word stress pattern than to distorted tonal word accent pattern. This is in compliance with the structural arguments presented above, and also with our own intuition.

Verdi's Settings of Shakespeare : from Play to Liberetto to Opera

As a Senior Scholar pursuing the topic, Verdi's Settings of Shakespeare: From Play to Libretto to Opera, I have endeavoured to study a project relevant to my majors, Music and English. During first semester, I carefully analysed Shakespeare's plays, Macbeth, Othello and Falstaff. The highlight of my project was in January when I travelled to New York City and spent the day working with the Metropolitan Opera Guild. I was also able to see a performance of Verdi's Othello with Jon Vickers in the lead role. During the second semester, I studied the musical aspects of the compositions. I spent time analysing musical passages and relating them to the plays and the operas. I was also able to continue my study of Italian, which I find extremely beneficial while studying Verdi's libretti. On Monday, 13th May, 1974, I gave a lecture presentation of my project. At this time, I showed slides of Metropolitan productions of the operas, presented my own rendition of five arias (in costume) and talked about comparisions between the plays and the operas. I applied for a Rotary Fellowship to take my project to Europe and am presently waiting to hear the results. If I do receive the fellowship, I am planning to spend a year studying the plays and operas in England and Italy. Afterwards, I hope to publish a paper explaining my findings. The paper is divided into six sections. The first section is an introduction which explains the period of Romanticism and its relationship to Shakespeare and Verdi. The second section is devoted to discussing the librettist for Macbeth, Francesco Piave. Following this section the opera Macbeth is discussed. Arrigo Boito, the librettist for Otello and Falstaff is discussed in the fourth section. The last two sections deal with Otello and Falstaff. I have also included a number of musical selections to better explain certain passages. My project has been invaluable to me. My Senior Scholar project has allowed me the freedom of independent study as well as a means of tying my majors together.

A produção da subjetividade no contexto institucional de um seminário católico

Esta pesquisa visa estudar a produção da subjetividade no contexto institucional de um Seminário Católico. Este estabelecimento funciona em regime de internato no qual atualmente 70 seminaristas estudam Filosofia durante 3 anos, numa etapa preparatória para o sacerdócio. Pesquisamos o funcionamento da vida institucional através da observação participante e utilizamos entrevistas semi-estruturadas para entender como o seminarista experiencia sua vida. Os resultados preliminares indicam que a vida no contexto institucional do Seminário produz diversas modalizações da subjetividade nos seminaristas internados no estabelecimento: há uma perda considerável de autonomia pessoal, da liberdade de ir e vir, agir e decidir, originando comportamentos de dependência excessiva, de resistência à mudança, de conversão ao papel proposto, de rivalidade fraterna. A contradição detectada entre o aparelho repressivo e o discurso participativo parece produzir nos indivíduos características marcadas pela clivagem e pela recusa.

Identification of a Microdeletion at the 7q33-q35 Disrupting the CNTNAP2 Gene in a Brazilian Stuttering Case

Speech and language disorders are some of the most common referral reasons to child development centers accounting for approximately 40% of cases. Stuttering is a disorder in which involuntary repetition, prolongation, or cessation of the sound precludes the flow of speech. About 5% of individuals in the general population have a stuttering problem, and about 80% of the affected children recover naturally. The causal factors of stuttering remain uncertain in most cases; studies suggest that genetic factors are responsible for 70% of the variance in liability for stuttering, whereas the remaining 30% is due to environmental effects supporting a complex cause of the disorder. The use of high-resolution genome wide array comparative genomic hybridization has proven to be a powerful strategy to narrow down candidate regions for complex disorders. We report on a case with a complex set of speech and language difficulties including stuttering who presented with a 10Mb deletion of chromosome region 7q33-35 causing the deletion of several genes and the disruption of CNTNAP2 by deleting the first three exons of the gene. CNTNAP2 is known to be involved in the cause of language and speech disorders and autism spectrum disorder and is in the same pathway as FOXP2, another important language gene, which makes it a candidate gene for causal studies speech and language disorders such as stuttering. (C) 2010 Wiley-Liss, Inc.

Extension of the Nambu-Jona-Lasinio model predictions at high densities and temperatures using an implicit regularization scheme

Traditional cutoff regularization schemes of the Nambu-Jona-Lasinio model limit the applicability of the model to energy-momentum scales much below the value of the regularizing cutoff. In particular, the model cannot be used to study quark matter with Fermi momenta larger than the cutoff. In the present work, an extension of the model to high temperatures and densities recently proposed by Casalbuoni, Gatto, Nardulli, and Ruggieri is used in connection with an implicit regularization scheme. This is done by making use of scaling relations of the divergent one-loop integrals that relate these integrals at different energy-momentum scales. Fixing the pion decay constant at the chiral symmetry breaking scale in the vacuum, the scaling relations predict a running coupling constant that decreases as the regularization scale increases, implementing in a schematic way the property of asymptotic freedom of quantum chromodynamics. If the regularization scale is allowed to increase with density and temperature, the coupling will decrease with density and temperature, extending in this way the applicability of the model to high densities and temperatures. These results are obtained without specifying an explicit regularization. As an illustration of the formalism, numerical results are obtained for the finite density and finite temperature quark condensate and applied to the problem of color superconductivity at high quark densities and finite temperature.

Are Working Memory Measures Free of Socioeconomic Influence?

Purpose: This study evaluated the impact of socioeconomic factors on children's performance on tests of working memory and vocabulary.Method: Twenty Brazilian children, aged 6 and 7 years, from low-income families, completed tests of working memory ( verbal short-term memory and verbal complex span) and vocabulary ( expressive and receptive). A further group of Brazilian children from families of higher socioeconomic status matched for age, gender, and nonverbal ability also participated in the study.Results: Children from the low socioeconomic group obtained significantly lower scores on measures of expressive and receptive vocabulary than their higher income peers but no significant group differences were found on the working memory measures.Conclusion: Measures of working memory provide assessments of cognitive abilities that appear to be impervious to substantial differences in socioeconomic background. As these measures are highly sensitive to language ability and learning in general, they appear to provide useful methods for diagnosing specific learning difficulties that are independent of environmental opportunity.

Para onde caminha a ciência politica?

The purpose of this paper is to analyze the challenges to Political Sciences at the moment when many authors emphasize the usage of democratic paradigm as the only way to the rational building of speech in pluralist societies. At the end of one century of the consolidation of modern liberal thought, both in right and left versions (Wallerstein, 1995), the democracy as research tradition(Ball, 1987) fades away its ethical meaning, based upon equality and freedom, and lacks room for discussions about rules for implementing it. The analytical method seeks to historically rebuild the different levels of modern state-nation upbringing and the consolidation of competitive party democracy in the 20th century, which is the explanation key for the political organizational phenomenon of globalized societies. The result of this analysis opens new perspectives to Political Sciences advance in discussing the nature of democratic paradigm since it needs to face challenges to survive, such as: the fight against the structural violence of our society; the fight against despotism; and the adjustment to the meaning of the word freedom. The facing of the mentioned challenges may open explanation keys that will lead to a change in Political Sciences ways.

Conformational basis for the biological activity of TOAC-labeled angiotensin II and bradykinin: Electron paramagnetic resonance, circular dichroism, and fluorescence studies

N-Terminally and internally labeled analogues of the hormones angiotensin (AII, DRVYIHPF) and bradykinin (BK, RPPGFSPFR) were synthesized containing the paramagnetic amino acid 2,2,6,6-tetramethylpiperidine-1-oxyl-4-amino-4- carboxylic acid (TOAC). TOAC replaced Asp 1 (TOAC 1-AII) and Val 3 (TOAC 3-AII) in AII and was inserted prior to Arg 1 (TOAC 0-BK) and replacing Pro 3 (TOAC 3-BK) in BK. The peptide conformational properties were examined as a function of trifluoroethanol (TFE) content and pH. Electron paramagnetic resonance spectra were sensitive to both variables and showed that internally labeled analogues yielded rotational correlation times (TC) considerably larger than N-terminally labeled ones, evincing the greater freedom of motion of the N-terminus. In TFE, τ C increased due to viscosity effects. Calculation of τ Cpeptide/τ CTOAC ratios indicated that the peptides acquired more folded conformations. Circular dichroism spectra showed that, except for TOAC 1-AII in TFE, the N-terminally labeled analogues displayed a conformational behavior similar to that of the parent peptides. In contrast, under all conditions, the TOAC 3 derivatives acquired more restricted conformations. Fluorescence spectra of All and its derivatives were especially sensitive to the ionization of Tyr 4. Fluorescence quenching by the nitroxide moiety was much more pronounced for TOAC 3-AII The conformational behavior of the TOAC derivatives bears excellent correlation with their biological activity, since, while the N-terminally labeled peptides were partially active, their internally labeled counterparts were inactive [Nakaie, C. R., et al., Peptides 2002, 23, 65-70]. The data demonstrate that insertion of TOAC in the middle of the peptide chain induces conformational restrictions that lead to loss of backbone flexibility, not allowing the peptides to acquire their receptor-bound conformation. © 2004 Wiley Periodicals, Inc.