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No full textNumerous brain regions have been shown to have neural correlates of gradually accumulating evidence for decision-making, but the causal roles of these regions in decisions driven by accumulation of evidence have yet to be determined. Here, in rats performing an auditory evidence accumulation task, we inactivated the frontal orienting fields (FOF) and posterior parietal cortex (PPC), two rat cortical regions that have neural correlates of accumulating evidence and that have been proposed as central to decision-making. We used a detailed model of the decision process to analyze the effect of inactivations. Inactivation of the FOF induced substantial performance impairments that were quantitatively best described as an impairment in the output pathway of an evidence accumulator with a long integration time constant (>240 ms). In contrast, we found a minimal role for PPC in decisions guided by accumulating auditory evidence, even while finding a strong role for PPC in internally-guided decisions
Uncovering the variability, regulatory roles and mutation rates of short tandem repeats
No full textThesis: Ph. D., Massachusetts Institute of Technology, Computational and Systems Biology Program, 2016.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Cataloged from student-submitted PDF version of thesis.Includes bibliographical references (pages 163-186).Over the past decade, the advent of next-generation DNA sequencing technologies has ushered in an exciting era of biological research. Through large-scale sequencing projects, scientists have begun to unveil the variability and function of millions of DNA mutations called single nucleotide polymorphisms. Despite this rapid growth in understanding, short tandem repeats (STRs), genomic elements consisting of a repeating pattern of 2-6 bases, have remained poorly understood. Mutating orders of magnitude more rapidly than most of the human genome, STRs have been identified as the causal variants in diseases such as Fragile X syndrome and Huntington's disease. However, in spite of their potentially profound biological consequences, STRs remain systematically understudied due to difficulties associated with obtaining accurate genotypes. To address this issue, we developed a series of bioinformatics approaches and applied them to population-scale whole-genome sequencing data sets. Using data from the 1000 Genomes Project, we performed the first genome-wide characterization of STR variability by analyzing over 700,000 loci in more than 1000 individuals. Next, we integrated these genotypes with expression data to assess the contribution of STRs to gene expression in humans, uncovering their substantial regulatory role. We then developed a state-of-the-art algorithm to genotype STRs, resulting in vastly improved accuracy and uncovering hundreds of replicable de novo mutations in a deeply sequenced trio. Lastly, we developed a novel approach to estimate mutation rates for STRs on the Y-chromosome (Y-STR), resulting in rates for hundreds of previously uncharacterized markers. Collectively, these analyses highlight the extreme variability of STRs and provide a framework for incorporating them into future studies.by Thomas F. Willems.Ph. D
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Developing self-efficacy and self-regulated learning in academic planning : applying social cognitive theory in academic advising to assess student learning outcomes
No full textThis dissertation demonstrates how Social Cognitive Theory (Bandura, 1986,
1997) can be successfully applied to Counselor academic advising interventions, in
order to increase students' self-efficacy and self-regulated learning (Zimmerman,
2000) in academic planning as learned outcomes. This was accomplished by (a)
reviewing the academic advising literature and showing the current existing gap for
assessing learning outcomes in academic advising; (b) evaluating the validity and
reliability of three assessment instruments, designed by this author, to measure self efficacy
and self-regulated learning constructs in academic planning; (c) testing three
hypotheses to determine whether pre-post increases in self-efficacy and self-regulated
learning occurred following academic advising interventions, and whether a positive
reciprocal relationship existed between self-efficacy and self-regulated learning; and
finally (d) demonstrating how these changes were influenced by Counselor
interventions (based in social cognitive learning principles), with students' learned
outcomes.
One hundred twenty California Community College students individually
participated in a 30-minute academic advising session. The results show strong
validity and reliability for using these three assessment instruments for measuring
students' self-efficacy and self-regulated learning in academic planning. Significant
mean increases were found between pre-post measures following Counselor
interventions, as well as a positive, reciprocal relationship existing between selfefficacy
and self-regulated learning in academic planning. Increased correlations were
found within forethought and self-reflection phases following Counselor interventions
using Zimmerman's (2000) cyclical self-regulated learning model. These findings lent
support to Zimmerman's model and the relational influences between Counselor
intervention processes with students' learned outcomes.Keywords: self-efficacy, social cognitive theory, academic advising, self-regulated learnin
Translating cognitive behavioral interventions from bench to bedside: The feasibility and acceptability of cognitive remediation in research as compared to clinical settings
No full textInternational audienc
Studies on polymorphic alu insertions and genomic diversity within the major histocompatibility complex
No full textAfter the initiation of the human genome sequencing project and the introduction of the field of 'bioinformatics', interest in human genetic diversity studies has been increased. Sequence diversity has helped define differences between genes and genomic regions that were previously unknown or difficult to determine. In this thesis I have undertaken to study sequence diversity in the human genome in three areas; 1) investigated diversity in the MHC as represented by the MICA alleles with respect to the known HLA alleles, 2) investigated the structure and diversity in the intergenic region from an MHC related (paralogous) genomic region and related the structural and diversity findings to the knowledge available on the MHC and the wider genome, and 3) described the identification of three and characterization of five new MHC class I polymorphic markers (Alu) and their polymorphic characteristics in worldwide populations and their associations with skin cancer.
1. Phylogenetic analysis of MICA alpha-domain (extracellular) sequences demonstrated relationships with HLA-B cross-reactive serogroups. The HLA-B and MICA loci are in linkage disequilibrium. The data indicated that MICA and HLA-B have evolved in concert from their common ancestors and that the transmembrane polymorphisms have arisen independently and more recently.
2. Sequence analysis of the CD1 genomic region confirmed the presence of five CD1 genes and revealed that there are four unrelated intergenic regions (IGRs). The IGRs are composed mostly of retroelements including five full-length L1 PA sequences and various pseudogenes. Genomic and phylogenetic analyses support the view that the human CD1 gene copies were duplicated prior to the evolution of primates and the bulk of the HLA class I genes found in humans.
3. Five polymorphic Alu insertions (POALINs) were identified (two from previous studies) and located within the 1.8 megabase of the MHC class I genomic region. All five POALINs are polymorphic, and are positively associated with the HLA-A and HLA-B alleles. The AluyHJ insertion was found most frequently associated with HLA-A1 or A24, AluyHG with HLA-A2, AluyHF with HLA-A2, A-10 or -A26 and AluyTF showed a marginal association with HLA-A29. The AluyMICB insertion was strongly associated with HLA-B17 (HLA-B57, HLA-B58) and HLA-B13. The presence of three Alu insertions (AluyHJ, AluyHG and AluyHF) was found in only one HLA class I haplotype (HLA-A1, -B57, -Cw6) in the 10th IHW cell lines. A novel positive association between the presence of AluyMICB and the 'MICAdel/MICBnull/HLA-B48' haplotype was determined. The AluyMICB insertion was also associated with at least three different MICB alleles (*0102, *0107N and *0105) and three different HLA-B alleles (B13, B48 and B57). Based on the analysis of associations between different polymorphic markers within the beta block, the MICB*0102 allele was inferred to be the ancestral form of the MICB*0105 and MICB*0107N alleles. The AluyMICB polymorphism can be used to further investigate haplotype relationship and consequently their lineage origins. Some of the MHC POALINs are haplospecific and associate strongly with certain groups of HLA class I alleles and MHC ancestral haplotypes. The AluyTF frequency was significantly associated with skin cancer (p<0.005).
MICA gene diversity is derived from two different evolving paths, therefore one or the other alone cannot reliably mark an ancestral haplotype. The CD1 duplicons originated well before the HLA class I duplicons. The MHC POALINs provide new lineage and linkage markers for the fine mapping study of different haplotypes and variations in linkage groups across 1.8 Mb of the MHC class I region. The POALINs may also prove useful in investigating the origins and history of human populations and in determining the role of human genetic diversity in disease risk
Art and the artist in the literary works of Elsa Triolet
No full textThis thesis takes a representative selection of Triolet's works to study the themes of writing and creativity as they are presented in the novels. These are all portraits of artists and the accounts of the search for a synthesis of aesthetic freedom and ethical responsibility. It considers Triolet's importance as a foreign writer, adopting a new creative language to be adopted by a different cultural
environment, to be essential in understanding her importance to the French literary tradition. By emphasising her formative years in the avant-garde circles of prerevolutionary Russia, my study demonstrates her considerable contribution to the meeting of Russian and French aesthetic theories. I extend this with close textual
readings of certain works to demonstrate her techniques in novelistic construction which reveal many Formalist practices before Formalist works in translation made
their official influence on creative methods.
The introduction considers the reasons for Triolet's neglect as a writer. It then considers various contemporary and recent critical appraisals which indicate
the interest she has received until present and which allow me to define my own critical approach. Part One traces Triolet's literary evolution from her formative
years in Russia, through exile to her first publications in Russian. It then considers her insertion into French literary activity, and her association with the schools of
socialist realism and the "nouveau roman".
Part Two examines two traditional novels which portray the creative and metaphorical roles of the artist and his work, showing the constant conflict between private and public lives. In Part Three, I show how aspects of novelistic
traditionalism are gradually foregrounded so that the work develops a dual-sided character where it both narrates and examines the processes of its own narration. In Part Four, this move to highly self-conscious aesthetics demonstrates an idiosyncratic exploration of new paths for the novel that bring visual, auditive and cinematographic media into the traditional domain of written art. Accompanying
the very post-modernist experimentation, I show how this research within the novel into the novel's own future has an ethical and redemptive purpose whose final conclusion is that creativity and human freedom are inexorably interwoven
Cognitive remediation in large systems of psychiatric care
No full textIntroductionWith the increasing enthusiasm to provide cognitive remediation (CR) as an evidence-based practice, questions arise as to what is involved in implementing CR in a large system of care. This article describes the first statewide implementation of CR in the USA, with the goal of documenting the implementation issues that care providers are likely to face when bringing CR services to their patients.MethodsIn 2014, the New York State Office of Mental Health set up a Cognitive Health Service that could be implemented throughout the state-operated system of care. This service was intended to broadly address cognitive health, to assure that the cognitive deficits commonly associated with psychiatric illnesses are recognized and addressed, and that cognitive health is embedded in the vocabulary of wellness. It involved creating a mechanism to train staff to recognize how cognitive health could be prioritized in treatment planning as well as implementing CR in state-operated adult outpatient psychiatry clinics.ResultsBy 2017, CR was available at clinics serving people with serious mental illness in 13 of 16 adult Psychiatric Centers, located in rural and urban settings throughout New York state. The embedded quality assurance program evaluation tools indicated that CR was acceptable, sustainable, and effective.ConclusionsCognitive remediation can be feasibly implemented in large systems of care that provide a multilevel system of supports, a training program that educates broadly about cognitive health and specifically about the delivery of CR, and embedded, ongoing program evaluation that is linked to staff supervision.</jats:sec
Taxonomy, phylogenetic and biogeographical relationships of African grassland Francolins (Genus: Scleroptila)
No full textBibliography: leaves 23-28.The potential for using a combination of molecular and whole-organismal data has opened up new avenues for avian taxonomy, phylogenetics and biogeography. Such a multifaceted approach is used here to identify diagnosable taxa within the Orange River Francolin Scleroptila levaillanloides species complex and resolve evolutionary relationships between these taxa and other mono-and polytypic forms within the Red-winged Group of francolins (= genus Scleroplila sensli lalo). Mitochondrial cytochrome-b DNA sequence data (±250 b.p.) from 50 individuals and 19 morphological characters extracted from reports in published literature were employed to achieve these aims. These characters were analysed separately and also in combination using maximum parsimony (DNA sequences and organismal data), maximum likelihood (DNA sequences) and distance (DNA sequences) analyses. Monophyly of the Red-winged Group plus the Ring-necked Francolin Dendroperdix slreptophorus was supported by all the analyses (bootstrap support ranged from 50%-94%) except distance analysis. The Orange River Francolin complex was found to be non-monophyletic. Two distinct clades were identified, one comprising taxa from southwestern and the other from northeastern Africa. Morphological analysis yielded a distinct clade of the southwestern Orange River Francolin. The other polytypic species and assemblages thereof show poor resolution. The results of this study clearly demonstrate a need for further assessment of the taxonomic status of Scleroptila spp. and their phylogenetic relationships
Barthes, Bakhtin, Structuralism: A Reassessment
No full textPhDThe thesis is a comparative analysis of the shared ideas and concerns in the works of
Mikhail Bakhtin and Roland Barthes from the point of view of differences between
French and Slavic literary structuralisms. Its background argument is that the
structuralism developed in the later works of the Russian Formalists and by Prague
Structuralists and Soviet Semioticians is more historically and socially oriented than its
French version, defining the structure of a literary work as a system of all of its
elements and effects (even those that take us outside of the text, like literary tradition
and historical and political circumstances). In this sense, Bakhtin can be seen as a part
of the Slavic structuralist tradition (and not opposed to it as is often claimed), and
Barthes (seen throughout his career) is on the whole perhaps closer to the Slavic
structuralism than he is to the French.
The particular problems discussed are those of the relationship between
literature and ideology, the notions of intertextuality, heteroglossia, dialogism and
polyphony and the differences between them, and the role of the author.
Barthes and Bakhtin shared a lifelong interest in the role of ideology in literature
and the influence of authoritarian language or myth on culture in general and the literary
text in particular. They looked for ways in which the deadening effect of the
mythological (epic, monological) thought and word can be counteracted through
literature, and different versions of what Kristeva termed 'intertextuality' played an
important part in their treatment of the subject. They also both discussed the role of the
author and their voice in the literary text, and the question of their power over the text,
its characters (Bakhtin) and the reader (Barthes).
The main thread of Barthes and Bakhtin's thought focuses on the problem of
counteracting authoritarian language through literature, and the solutions they proposed
can fruitfully be seen in the light of Slavic structuralism's notions of literary structure
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