Age, microbiota, and T cells shape diverse individual IgA repertoires in the intestine

Intestinal immunoglobulin A (IgA) ensures host defense and symbiosis with our commensal microbiota. Yet previous studies hint at a surprisingly low diversity of intestinal IgA, and it is unknown to what extent the diverse Ig arsenal generated by somatic recombination and diversification is actually used. In this study, we analyze more than one million mouse IgA sequences to describe the shaping of the intestinal IgA repertoire, its determinants, and stability over time. We show that expanded and infrequent clones combine to form highly diverse polyclonal IgA repertoires with very little overlap between individual mice. Selective homing allows expanded clones to evenly seed the small but not large intestine. Repertoire diversity increases during aging in a dual process. On the one hand, microbiota-, T cell-, and transcription factor RORγt-dependent but Peyer's patch-independent somatic mutations drive the diversification of expanded clones, and on the other hand, new clones are introduced into the repertoire of aged mice. An individual's IgA repertoire is stable and recalled after plasma cell depletion, which is indicative of functional memory. These data provide a conceptual framework to understand the dynamic changes in the IgA repertoires to match environmental and intrinsic stimuli.

A Comparative Study of Two Semantic Systems: Body Russian and Russian Phraseology

Grigorij Kreidlin (Russia). A Comparative Study of Two Semantic Systems: Body Russian and Russian Phraseology. Mr. Kreidlin teaches in the Department of Theoretical and Applied Linguistics of the State University of Humanities in Moscow and worked on this project from August 1996 to July 1998. The classical approach to non-verbal and verbal oral communication is based on a traditional separation of body and mind. Linguists studied words and phrasemes, the products of mind activities, while gestures, facial expressions, postures and other forms of body language were left to anthropologists, psychologists, physiologists, and indeed to anyone but linguists. Only recently have linguists begun to turn their attention to gestures and semiotic and cognitive paradigms are now appearing that raise the question of designing an integral model for the unified description of non-verbal and verbal communicative behaviour. This project attempted to elaborate lexical and semantic fragments of such a model, producing a co-ordinated semantic description of the main Russian gestures (including gestures proper, postures and facial expressions) and their natural language analogues. The concept of emblematic gestures and gestural phrasemes and of their semantic links permitted an appropriate description of the transformation of a body as a purely physical substance into a body as a carrier of essential attributes of Russian culture - the semiotic process called the culturalisation of the human body. Here the human body embodies a system of cultural values and displays them in a text within the area of phraseology and some other important language domains. The goal of this research was to develop a theory that would account for the fundamental peculiarities of the process. The model proposed is based on the unified lexicographic representation of verbal and non-verbal units in the Dictionary of Russian Gestures, which the Mr. Kreidlin had earlier complied in collaboration with a group of his students. The Dictionary was originally oriented only towards reflecting how the lexical competence of Russian body language is represented in the Russian mind. Now a special type of phraseological zone has been designed to reflect explicitly semantic relationships between the gestures in the entries and phrasemes and to provide the necessary information for a detailed description of these. All the definitions, rules of usage and the established correlations are written in a semantic meta-language. Several classes of Russian gestural phrasemes were identified, including those phrasemes and idioms with semantic definitions close to those of the corresponding gestures, those phraseological units that have lost touch with the related gestures (although etymologically they are derived from gestures that have gone out of use), and phrasemes and idioms which have semantic traces or reflexes inherited from the meaning of the related gestures. The basic assumptions and practical considerations underlying the work were as follows. (1) To compare meanings one has to be able to state them. To state the meaning of a gesture or a phraseological expression, one needs a formal semantic meta-language of propositional character that represents the cognitive and mental aspects of the codes. (2) The semantic contrastive analysis of any semiotic codes used in person-to-person communication also requires a single semantic meta-language, i.e. a formal semantic language of description,. This language must be as linguistically and culturally independent as possible and yet must be open to interpretation through any culture and code. Another possible method of conducting comparative verbal-non-verbal semantic research is to work with different semantic meta-languages and semantic nets and to learn how to combine them, translate from one to another, etc. in order to reach a common basis for the subsequent comparison of units. (3) The practical work in defining phraseological units and organising the phraseological zone in the Dictionary of Russian Gestures unexpectedly showed that semantic links between gestures and gestural phrasemes are reflected not only in common semantic elements and syntactic structure of semantic propositions, but also in general and partial cognitive operations that are made over semantic definitions. (4) In comparative semantic analysis one should take into account different values and roles of inner form and image components in the semantic representation of non-verbal and verbal units. (5) For the most part, gestural phrasemes are direct semantic derivatives of gestures. The cognitive and formal techniques can be regarded as typological features for the future functional-semantic classification of gestural phrasemes: two phrasemes whose meaning can be obtained by the same cognitive or purely syntactic operations (or types of operations) over the meanings of the corresponding gestures, belong by definition to one and the same class. The nature of many cognitive operations has not been studied well so far, but the first steps towards its comprehension and description have been taken. The research identified 25 logically possible classes of relationships between a gesture and a gestural phraseme. The calculation is based on theoretically possible formal (set-theory) correlations between signifiers and signified of the non-verbal and verbal units. However, in order to examine which of them are realised in practice a complete semantic and lexicographic description of all (not only central) everyday emblems and gestural phrasemes is required and this unfortunately does not yet exist. Mr. Kreidlin suggests that the results of the comparative analysis of verbal and non-verbal units could also be used in other research areas such as the lexicography of emotions.

Affective and linguistic processing of speech prosody: DC potential studies

Speech melody or prosody subserves linguistic, emotional, and pragmatic functions in speech communication. Prosodic perception is based on the decoding of acoustic cues with a predominant function of frequency-related information perceived as speaker's pitch. Evaluation of prosodic meaning is a cognitive function implemented in cortical and subcortical networks that generate continuously updated affective or linguistic speaker impressions. Various brain-imaging methods allow delineation of neural structures involved in prosody processing. In contrast to functional magnetic resonance imaging techniques, DC (direct current, slow) components of the EEG directly measure cortical activation without temporal delay. Activation patterns obtained with this method are highly task specific and intraindividually reproducible. Studies presented here investigated the topography of prosodic stimulus processing in dependence on acoustic stimulus structure and linguistic or affective task demands, respectively. Data obtained from measuring DC potentials demonstrated that the right hemisphere has a predominant role in processing emotions from the tone of voice, irrespective of emotional valence. However, right hemisphere involvement is modulated by diverse speech and language-related conditions that are associated with a left hemisphere participation in prosody processing. The degree of left hemisphere involvement depends on several factors such as (i) articulatory demands on the perceiver of prosody (possibly, also the poser), (ii) a relative left hemisphere specialization in processing temporal cues mediating prosodic meaning, and (iii) the propensity of prosody to act on the segment level in order to modulate word or sentence meaning. The specific role of top-down effects in terms of either linguistically or affectively oriented attention on lateralization of stimulus processing is not clear and requires further investigations.

Characterization of legacy organic carbon in a culturally eutrophic lake : the role of the historic carbon deposition in the time course and extent of lake recovery

The time course of lake recovery after a reduction in external loading of nutrients is often controlled by conditions in the sediment. Remediation of eutrophication is hindered by the presence of legacy organic carbon deposits, that exert a demand on the terminal electron acceptors of the lake and contribute to problems such as internal nutrient recycling, absence of sediment macrofauna, and flux of toxic metal species into the water column. Being able to quantify the timing of a lake’s response requires determination of the magnitude and lability, i.e., the susceptibility to biodegradation, of the organic carbon within the legacy deposit. This characterization is problematic for organic carbon in sediments because of the presence of different fractions of carbon, which vary from highly labile to refractory. The lability of carbon under varied conditions was tested with a bioassay approach. It was found that the majority of the organic material found in the sediments is conditionally-labile, where mineralization potential is dependent on prevailing conditions. High labilities were noted under oxygenated conditions and a favorable temperature of 30 °C. Lability decreased when oxygen was removed, and was further reduced when the temperature was dropped to the hypolimnetic average of 8° C . These results indicate that reversible preservation mechanisms exist in the sediment, and are able to protect otherwise labile material from being mineralized under in situ conditions. The concept of an active sediment layer, a region in the sediments in which diagenetic reactions occur (with nothing occurring below it), was examined through three lines of evidence. Initially, porewater profiles of oxygen, nitrate, sulfate/total sulfide, ETSA (Electron Transport System Activity- the activity of oxygen, nitrate, iron/manganese, and sulfate), and methane were considered. It was found through examination of the porewater profiles that the edge of diagenesis occurred around 15-20 cm. Secondly, historical and contemporary TOC profiles were compared to find the point at which the profiles were coincident, indicating the depth at which no change has occurred over the (13 year) interval between core collections. This analysis suggested that no diagenesis has occurred in Onondaga Lake sediment below a depth of 15 cm. Finally, the time to 99% mineralization, the t99, was viewed by using a literature estimate of the kinetic rate constant for diagenesis. A t99 of 34 years, or approximately 30 cm of sediment depth, resulted for the slowly decaying carbon fraction. Based on these three lines of evidence , an active sediment layer of 15-20 cm is proposed for Onondaga Lake, corresponding to a time since deposition of 15-20 years. While a large legacy deposit of conditionally-labile organic material remains in the sediments of Onondaga Lake, it becomes clear that preservation, mechanisms that act to shield labile organic carbon from being degraded, protects this material from being mineralized and exerting a demand on the terminal electron acceptors of the lake. This has major implications for management of the lake, as it defines the time course of lake recovery following a reduction in nutrient loading.

Sulfoxides as an intramolecular sulfenylating agent for indoles and diverse applications of the sulfide-sulfoxide redox cycle in organic chemistry

This dissertation involves study of various aspects of sulfoxide chemistry. Specifically designed t-butyl and propanenitrile sulfoxides tethered to indole-2-carboxamide were used as a source of intramolecular sulfenylating agents to synthesize novel indolo[3,2-b]-1-5-benzothiazepinones which are structurally analogous to the other biologically active benzothiazepinones. This study reveals that the intramolecular cyclization of sulfoxide follows an electrophilic sulfenylation (Sulfoxide Electrophilic Sulfenylation, SES) reaction pathway. Evidence of the absence of sulfenic acid as a transient reactive intermediate in such intramolecular cyclization is also provided. In another study, sulfoxide was used as a “protecting group” of thioether to synthesize 8-membered, indole substituted, thiazocine-2-acetic acid derivative via Ring Closing Metathesis (RCM). Protection (oxidation) of inert (to RCM) sulfide to sulfoxide followed by RCM produced cyclized product in good yields. Deprotection (reduction) of sulfoxide was achieved using Lawessons Reagent (L.R.). Application of the sulfide-sulfoxide redox cycle to solve the existing difficulties in using RCM methodology to thioethers is illustrated. A new design of a “molecular brake”, based on the sulfide-sulfoxide redox cycle is described. N-Ar rotation in simple isoindolines is controlled by the oxidation state of the proximate sulfur atom. Sulfide [S(II)] shows “free” [brake OFF] N-Ar rotation whereas sulfoxide displayed hindered [brake ON] N-Ar rotation. The semi-empirical molecular orbital (PM3) calculations revealed concerted pyramidalization of amidic nitrogen with N-Ar rotation.

Becoming most fully ourselves : gender, voice, and ritual in dissertations

The writing and defense of the dissertation serve both as demonstration one is able to do the work of a scholar and as a rite of initiation. In contrast to much academic writing, dissertations generally adhere to narrowly conceived notions of academic discourse. I explore this within the context of an academic community in which under-representation remains a serious issue. This dissertation is about women writing dissertations. I draw from conversations with fifteen women, in or beyond, the process; friends’ anecdotes; published accounts; and, autobiographically, my experience. I suggest the dissertation’s initiatory role is at least as important as its scholarly role; during the process one establishes a sense of self as scholar, writer, and researcher. Students come to the dissertation with some notion of self as writer and scholar – a culturally negotiated sense that is more, or less, congruent with the culturally established self required for successful completion of the dissertation. The degree of congruence (or alternatively, harmony and dissonance) shapes the process of doing a dissertation. I argue that both the community and the language in which dissertations must generally be written are gendered masculine. Negotiating a voice that is acceptable in a dissertation while maintain fidelity to a sense of who one is seems more problematic as one’s distance from the center of dominant culture increases. Believing that agency lies in altering the reiteration of such processes, I worked with my committee to find ways to alter the process yet still do a dissertation I write in a variety of voices – essay and poetry as well as analytical – play with visual qualities of text, and experiment with non-verbal interpretations. These don’t exhaust possibilities, but do give a sense of how the rich variety of expression found in academe cam be brought into the dissertation. I thus demonstrate that one need not reconstitute herself through characteristic academic discourse in order to be initiated into the community of scholars. I suggest both the desirability of encouraging flexibility in the language, form, and process, of dissertations, and the theoretical necessity for such flexibility if the academic community is to become diverse. The writing and defense of the dissertation serve both as demonstration one is able to do the work of a scholar and as a rite of initiation. In contrast to much academic writing, dissertations generally adhere to narrowly conceived notions of academic discourse. I explore this within the context of an academic community in which under-representation remains a serious issue. This dissertation is about women writing dissertations. I draw from conversations with fifteen women, in or beyond, the process; friends’ anecdotes; published accounts; and, autobiographically, my experience. I suggest the dissertation’s initiatory role is at least as important as its scholarly role; during the process one establishes a sense of self as scholar, writer, and researcher Students come to the dissertation with some notion of self as writer and scholar – a culturally negotiated sense that is more, or less, congruent with the culturally established self required for successful completion of the dissertation. The degree of congruence (or alternatively, harmony and dissonance) shapes the process of doing a dissertation. I argue that both the community and the language in which dissertations must generally be written are gendered masculine. Negotiating a voice that is acceptable in a dissertation while maintain fidelity to a sense of who one is seems more problematic as one’s distance from the center of dominant culture increases. Believing that agency lies in altering the reiteration of such processes, I worked with my committee to find ways to alter the process yet still do a dissertation I write in a variety of voices – essay and poetry as well as analytical – play with visual qualities of text, and experiment with non-verbal interpretations. These don’t exhaust possibilities, but do give a sense of how the rich variety of expression found in academe cam be brought into the dissertation. I thus demonstrate that one need not reconstitute herself through characteristic academic discourse in order to be initiated into the community of scholars. I suggest both the desirability of encouraging flexibility in the language, form, and process, of dissertations, and the theoretical necessity for such flexibility if the academic community is to become diverse. The writing and defense of the dissertation serve both as demonstration one is able to do the work of a scholar and as a rite of initiation. In contrast to much academic writing, dissertations generally adhere to narrowly conceived notions of academic discourse. I explore this within the context of an academic community in which under-representation remains a serious issue. This dissertation is about women writing dissertations. I draw from conversations with fifteen women, in or beyond, the process; friends’ anecdotes; published accounts; and, autobiographically, my experience. I suggest the dissertation’s initiatory role is at least as important as its scholarly role; during the process one establishes a sense of self as scholar, writer, and researcher Students come to the dissertation with some notion of self as writer and scholar – a culturally negotiated sense that is more, or less, congruent with the culturally established self required for successful completion of the dissertation. The degree of congruence (or alternatively, harmony and dissonance) shapes the process of doing a dissertation. I argue that both the community and the language in which dissertations must generally be written are gendered masculine. Negotiating a voice that is acceptable in a dissertation while maintain fidelity to a sense of who one is seems more problematic as one’s distance from the center of dominant culture increases. Believing that agency lies in altering the reiteration of such processes, I worked with my committee to find ways to alter the process yet still do a dissertation I write in a variety of voices – essay and poetry as well as analytical – play with visual qualities of text, and experiment with non-verbal interpretations. These don’t exhaust possibilities, but do give a sense of how the rich variety of expression found in academe cam be brought into the dissertation. I thus demonstrate that one need not reconstitute herself through characteristic academic discourse in order to be initiated into the community of scholars. I suggest both the desirability of encouraging flexibility in the language, form, and process, of dissertations, and the theoretical necessity for such flexibility if the academic community is to become diverse. The writing and defense of the dissertation serve both as demonstration one is able to do the work of a scholar and as a rite of initiation. In contrast to much academic writing, dissertations generally adhere to narrowly conceived notions of academic discourse. I explore this within the context of an academic community in which under-representation remains a serious issue. This dissertation is about women writing dissertations. I draw from conversations with fifteen women, in or beyond, the process; friends’ anecdotes; published accounts; and, autobiographically, my experience. I suggest the dissertation’s initiatory role is at least as important as its scholarly role; during the process one establishes a sense of self as scholar, writer, and researcher Students come to the dissertation with some notion of self as writer and scholar – a culturally negotiated sense that is more, or less, congruent with the culturally established self required for successful completion of the dissertation. The degree of congruence (or alternatively, harmony and dissonance) shapes the process of doing a dissertation. I argue that both the community and the language in which dissertations must generally be written are gendered masculine. Negotiating a voice that is acceptable in a dissertation while maintain fidelity to a sense of who one is seems more problematic as one’s distance from the center of dominant culture increases. Believing that agency lies in altering the reiteration of such processes, I worked with my committee to find ways to alter the process yet still do a dissertation I write in a variety of voices – essay and poetry as well as analytical – play with visual qualities of text, and experiment with non-verbal interpretations. These don’t exhaust possibilities, but do give a sense of how the rich variety of expression found in academe cam be brought into the dissertation. I thus demonstrate that one need not reconstitute herself through characteristic academic discourse in order to be initiated into the community of scholars. I suggest both the desirability of encouraging flexibility in the language, form, and process, of dissertations, and the theoretical necessity for such flexibility if the academic community is to become diverse.

The Diverse Impacts of the Neo-liberal Social Policies on Children’s Welfare and Social Work with Young People: The Finnish Perspective

This article discusses the impacts of globalization, neo-liberal social policies and the Finnish economic recession of the 1990s on children's and young people's welfare. It summarises some of the impacts of Finnish social policies on the everyday lives of families with children and highlights some of the features of the recent and current debates surrounding youth delinquency and the societal reactions to young generations. All this contributes to a contradictory and conflicting societal context which challenges experts in the field of child welfare social work experts to operate - as expected - at the right moment, legally and effectively. Instead of being overly-defensive for the ‘good old’ ways of practicing social work with children, the authors invite social work scholars and practitioners to reconceptualise both the concept of children's citizenship and its position both in child welfare theory and practice in the context of children's global rights.

Book Review of “Indigenous Social Work around the World. Towards Culturally Relevant Education and Practice”, 2008, edited by Mel Gray, John Coates and Michael Yellow Bird

One could be seduced into a critique of this volume that focuses on its potential to overstate the momentum for a shift in Western social work ideology when faced with the conundrum of cultural difference. One could posit that the discussion is too broad, the topics covered too numerous, the opportunity for detail missed, the urgency of the messages unnecessarily exaggerated, the “proof” not beyond anecdote and so forth. I reject this temptation to conform to the dominant professional dynamic most emphatically and offer that what Gray, Coates and Yellow Bird have presented to the social work field in this volume is the first tangible step towards an alternative paradigm for an occupation afflicted with unsustainable hypocrisy and thus at the brink of irrelevancy.

Alarm systems and catastrophes from a diverse point of view

Using a chain of urns, we build a Bayesian nonparametric alarm system to predict catastrophic events, such as epidemics, black outs, etc. Differently from other alarm systems in the literature, our model is constantly updated on the basis of the available information, according to the Bayesian paradigm. The papers contains both theoretical and empirical results. In particular, we test our alarm system on a well-known time series of sunspots.

Tailored instructional methods for students with diverse levels of computer knowledge and skills

The purpose of this online course is to ensure new nursing graduate students know how to use computer technologies required to complete academic and research activities. Powerful computers, high speed internet, digitalized resources and databases are widely available in educational institutes. New renovation and updates are being released at faster pace than ever. All these developments are necessary for a student to utilize computer programs and synthesize large amount of data in a limited time for any given academic research project. [See PDF for complete abstract]

Communication Across Cultures - Use of Video to Promote Culturally Competent Patient Management

Diverse belief systems exist among dental and medical patients related to health, healing and wellness. Culturally competent health care may be defined as the ability to provide care to patients with diverse values, beliefs and behaviors, including modifying delivery of care to meet patients’ social and cultural needs. [See PDF for complete abstract]

Smooth Muscle Hyperplasia due to ACTA2/MYH11 Mutations: Identification of Novel Pathology and Pathways Leading to Aneurysms and Diverse Vascular Occlusive Diseases

Missense mutations in smooth muscle cell (SMC) specific ACTA2 (á-actin) and MYH11 (â-myosin heavy chain) cause diffuse and diverse vascular diseases, including thoracic aortic aneurysms and dissections (TAAD) and early onset coronary artery disease and stroke. The mechanism by which these mutations lead to dilatation of some arteries but occlusion of others is unknown. We hypothesized that the mutations act through two distinct mechanisms to cause varied vascular diseases: a loss of function, leading to decreased SMC contraction and aneurysms, and a gain of function, leading to increased SMC proliferation and occlusive disease. To test this hypothesis, ACTA2 mutant SMCs and myofibroblasts were assessed and found to not form á-actin filaments whereas control cells did, suggesting a dominant negative effect of ACTA2 mutations on filament formation. A loss of á-actin filaments would be predicted to cause decreased SMC contractility. Histological examination of vascular tissues from patients revealed SMC hyperplasia leading to arterial stenosis and occlusion, supporting a gain of function associated with the mutant gene. Furthermore, ACTA2 mutant SMCs and myofibroblasts proliferated more rapidly in static culture than control cells (p<0.05). We also determined that Acta2-/- mice have ascending aortic aneurysms. Histological examination revealed aortic medial SMC hyperplasia, but minimal features of medial degeneration. Acta2-/- SMCs proliferated more rapidly in culture than wildtype (p<0.05), and microarray analysis of Acta2-/- SMCs revealed increased expression of Actg2, 15 collagen genes, and multiple focal adhesion genes. Acta2-/- SMCs showed altered localization of vinculin and zyxin and increased phosphorylated focal adhesion kinase (FAK) in focal adhesions. A specific FAK inhibitor decreased Acta2-/- SMC proliferation to levels equal to wildtype SMCs (p<0.05), suggesting that FAK activation leads to the increased proliferation. We have described a unique pathology associated with ACTA2 and MYH11 mutations, as well as an aneurysm phenotype in Acta2-/- mice. Additionally, we identified a novel pathogenic pathway for vascular occlusive disease due to loss of SMC contractile filaments, alterations in focal adhesions, and activation of FAK signaling in SMCs with ACTA2 mutations.

Adherence to host extracellular matrix and serum components by Enterococcus faecium isolates of diverse origin.

Enterococcus faecium has emerged as an important cause of nosocomial infections over the last two decades. We recently demonstrated collagen type I (CI) as a common adherence target for some E. faecium isolates and a significant correlation was found to exist between acm-mediated CI adherence and clinical origin. Here, we evaluated 60 diverse E. faecium isolates for their adherence to up to 15 immobilized host extracellular matrix and serum components. Adherence phenotypes were most commonly observed to fibronectin (Fn) (20% of the 60 isolates), fibrinogen (17%) and laminin (Ln) (13%), while only one or two of the isolates adhered to collagen type V (CV), transferrin or lactoferrin and none to the other host components tested. Adherence to Fn and Ln was almost exclusively restricted to clinical isolates, especially the endocarditis-enriched nosocomial genogroup clonal complex 17 (CC17). Thus, the ability to adhere to Fn and Ln, in addition to CI, may have contributed to the emergence and adaptation of E. faecium, in particular CC17, as a nosocomial pathogen.