Doctor of Philosophy / Biochemistry Interdepartmental Program / Antje Philine Wangemann / Mutations of SLC26A4 are the most common cause of the hearing loss associated with enlargement of the vestibular aqueduct. SLC26A4 encodes pendrin, an anion exchanger expressed in the cochlea, the vestibular labyrinth, and the endolymphatic sac of the inner ear. Slc26a4Δ/Δ mice, devoid of pendrin expression, develop an enlarged membranous labyrinth which leads to the failure to develop hearing, thereby recapitulating the human disease. Identifying the ionic composition of the endolymph and evaluating the importance of pendrin expression at various sites are initial steps towards developing strategies for preventing enlargement of the endolymph volume and subsequently restoring the inner ear functions. The major aims of the present study are 1) To determine the ionic composition of inner ear fluids during the developmental phase in which the enlargement of the endolymph volume occurs; 2) To test the hypothesis that pendrin expression in the endolymphatic sac is more important than its expression in the cochlea and the vestibular labyrinth. Here, we determined the Na+ and K⁺ concentrations in the cochlea and the endolymphatic sac with double-barreled ion-selective electrodes and generated a mouse model that restores pendrin expression in the endolymphatic sac while lacking expression in the cochlea and the vestibular labyrinth. High Na⁺ and low K⁺ concentrations were found in the cochlear endolymph during the embryonic stage. A rise of the K⁺ concentration along with a decline of the Na⁺ concentration occurred shortly before birth. The site-specific restoration of pendrin to the endolymphatic sac prevented enlargement and rescued hearing and balance. In conclusion, these data demonstrate that endolymph, in the phase of luminal enlargement during the embryonic development, is a Na⁺-rich fluid that is modified into a K⁺-rich fluid just before birth; restoration of pendrin in the endolymphatic sac is sufficient for developing normal inner ear function. Furthermore, these data suggest enlargement of endolymph volume caused by the loss of Slc26a4 is a consequence of disrupted Na⁺ absorption. Moreover, pharmacological strategies that correct fluid transport, as well as spatially and temporally limited restorations of pendrin, might restore normal inner ear functions in humans carrying mutations of SLC26A4.

Master of Science / Department of Anatomy and Physiology / A. Philine Wangemann / SLC26A4 and its murine ortholog Slc26a4 code for pendrin, an anion-exchanger that is expressed in the inner ear. Patients with mutations in SLC26A4 have syndromic or nonsyndromic hearing loss that is associated with a prenatal enlargement of the membranous labyrinth. The mouse model Slc26a4[superscript]Δ/Δ recapitulates the enlargement, develops an enlargement of the inner ear and fails to acquire hearing. The vestibular labyrinth secretes fluid, accounting for enlargement of the membranous labyrinth. The objective of the current study was to measure K⁺ concentrations in the utricular endolymph of Slc26a4[superscript]Δ/+ and Slc26a4[superscript]Δ/Δ mice as a first step toward a mechanistic understanding of fluid secretion during perinatal development. Doublebarreled K⁺-selective electrodes were used to measure K⁺ concentrations of the utricular endolymph in vitro. Potassium concentrations were ~10 mM in both genotypes at embryonic (E) day 16.5. The K⁺ concentrations started to rise at E17.5 in Slc26a4[superscript]Δ/+ mice. There was a 1-day delay in Slc26a4[superscript]Δ/Δ mice. This delay may be the consequence of a larger fluid volume. K⁺ concentrations rose to 150 mM and 132 mM in Slc26a4[superscript]Δ/+ and Slc26a4[superscript]Δ/Δ adult mice, respectively. Consistently, expression of KCNQ1 and the Na⁺/2Cl⁻/K⁺ cotransporter SLC12A2 was found in the utricle at E19.5 in Slc26a4[superscript]Δ/+ and Slc26a4[superscript]Δ/Δ mice. In conclusion, the data suggest that K⁺ secretion is not the major driving force of fluid secretion in the utricle of the developing mouse inner ear.

The thesis deals with the change of marketing mix components at polygraphic company. Its aim is to increase the competitiveness of the enterprise in printing industry market. The thesis is divided into three parts. The theoretical part focuses on explaining terms customer, marketing, enlarged marketing mix and basic market analysis. The analytical part compares theoretical knowledge with reality at polygraphic company. The proposal part contains factual suggestions how to improve the actual situation of polygraphic company in terms of market competitiveness. These were compiled on the basis of the analytical part.

Lacunar stroke accounts for one quarter of all ischaemic stroke and in the long term carries a greater risk of death and disability than was previously realised. Much of our current knowledge originated from neuropathological studies in the 1950s and 1960s. In the last thirty years, brain computed tomography (CT) and magnetic resonance imaging (MRI) have revolutionised our understanding of lacunar stroke and associated features of cerebral small vessel disease (SVD), namely white matter lesions (WML), enlarged perivascular spaces (EPVS) and brain microbleeds (BMB). The purpose of the projects which led to the writing of this thesis was to improve understanding of imaging characteristics of cerebral SVD. We aimed to assess (i) clinical and imaging features which might explain misclassification of lacunar infarcts as cortical infarcts and vice versa, (ii) the proportion of symptomatic lacunar infarcts progressing to lacunar cavities and associations of cavitation, (iii) completeness of reporting of lacunar lesions in the lacunar stroke literature, (iv) definitions and detection of lacunar lesions amongst SVD researchers, (v) the relationship between WML and carotid stenosis, (vi) clinical and imaging associations of EPVS and, (vii) observer variability in the assessment of EPVS and BMB, in order to develop visual rating scales. Section one describes neuroimaging of lacunar stroke. To investigate features which might explain clinical stroke subtype misclassification (‘clinical-imaging dissociation’), I used data from a stroke study. The main factor associated with clinical-imaging dissociation was diabetes, and in patients with acute lacunar infarction, proximity of the lacunar infarct to the cortex, age, diabetes and left hemisphere location. To investigate the proportion of symptomatic lacunar infarcts progressing to cavities, I used data from two stroke studies. A fifth of patients with acute lacunar ischaemic stroke showed definite cavitation on follow-up imaging at a median of 227 days; cavitation was associated with increasing time to follow-up. To assess completeness of reporting of lacunar lesions in the lacunar stroke literature, I reviewed 50 articles from three journals with a stroke focus. There was marked variation in terminology and descriptions of imaging definitions of lacunar lesions. To assess lacunar lesion definitions and detection amongst SVD researchers, I used an online survey consisting of case-based and non-case-based questions. There was marked variation in definitions and descriptions. Cavitated lesions were detected with the highest degree of confidence. Section two describes neuroimaging of associated features of cerebral SVD. Using data from two stroke studies, I examined the relationship between WML and ipsilateral carotid artery stenosis. There was no association between carotid stenosis and WML. I tested the association of EPVS with WML and lacunar stroke subtype using data from a stroke study. Total EPVS were associated with age and deep WML; basal ganglia (BG) EPVS were associated with age, centrum semiovale (CS) EPVS, cerebral atrophy and lacunar stroke subtype. Quantification of observer variability in EPVS rating was assessed on 60 MRI scans selected from a stroke study and an ageing cohort. Intrarater agreement was good and interrater agreement was moderate. Main reasons for interrater disagreement included the visualisation of very small EPVS and the presence of concomitant WML and lacunar lesions. Observer variability in BMB rating was quantified using MRI scans from a stroke study. Interrater agreement was moderate but improved following modification of the pilot rating scale (BOMBS; Brain Observer MicroBleed Scale), which had its main effect by differentiating ‘certain’ BMB from ‘uncertain’ BMB and BMB ‘mimics’. In conclusion, neuroimaging, particularly MRI, is a valuable tool for the investigation of lacunar stroke and associated features of cerebral SVD. With recent technological advances in both CT and MRI, neuroimaging will remain central to future SVD studies, hopefully leading to a much improved understanding of this important disease.

Le troisième tome de La vie de l’esprit, ultime œuvre de Hannah Arendt, aurait dû être consacré à la faculté de juger. Notre recherche débute par la reconstitution partielle de cette théorie du jugement non écrite, mais dont on trouve des traces dans l’ensemble du corpus arendtien. En nous appuyant principalement sur les conférences données par Arendt sur la troisième Critique de Kant et sur les écrits non destinés à la publication comme le Journal de Pensée, notre travail soutient la thèse d’une unité profonde entre toutes les positions d’Arendt sur le jugement : faculté mentale et politique, fondement de la conscience morale. La prise en compte d’une multiplicité de perspectives, grâce au processus de la « mentalité élargie » exposé par Kant, confère au jugement une dimension de pluralité qui en fait le trait d’union entre pensée et action. Le désintéressement du sujet, rendu possible par l’imagination, fonde cette capacité. Nous discutons alors cette dernière affirmation, en confrontant la théorie arendtienne à la perspective pragmatiste incarnée par John Dewey. Par son analyse de la pensée comme enquête (inquiry), et de la valuation, Dewey met en lumière la dimension expérimentale présente dans la formation de nos jugements, sans pour autant les réduire à des décisions instrumentales. L’interaction individu/environnement efface ainsi la frontière artificielle qui subsiste chez Arendt entre intériorité du soi et extériorité des apparences. Nous pouvons alors mettre en évidence l’usage possible de la théorie arendtienne dans l’analyse des problèmes politiques contemporains : le rôle du jugement dans l’espace public démocratique, et les conditions de son éducation. / The third volume of The Life of the Mind, Hannah Arendt’s final work, was to be dedicated to the faculty of judging. Our research begins by partially reconstructing this unformulated theory of judgment, fragments of which can be traced back throughout Arendt’s works. Taking as our principal basis the lectures Arendt gave on Kant's third Critique, as well as her writings not destined for publication, such as the Thinking Diary (Denktagebuch), our thesis supports the existence of a profound unity of all of Arendt’s affirmations on judgment: a mental and political faculty, which at the same time forms the moral conscience. The awareness of a diversity of perspectives, thanks to the process of the “enlarged mentality” displayed by Kant, confers to judgment a dimension of pluralism, rendering it a link between thought and action; and the subject’s disinterestedness, made possible by imagination, sets the foundation for this ability. We then deliberate this last affirmation juxtaposing Arendt’s theory with the pragmatist perspective embodied in John Dewey. Through his analysis of thought as inquiry, and of valuation, Dewey brings to light the experimental dimension present in the formation of our judgments without, nevertheless, reducing them to instrumental decisions. Thus, the individual/environment interaction erases Arendt’s enduring artificial boundaries between the inwardness of the self and the outwardness of appearances. This way we can exhibit the possible uses of Arendt’s theory in the analysis of contemporary political issues: the role of judgment within the democratic public sphere and the conditions of its education.

Regular education teachers are sometimes at a disadvantage when required to instruct learners with a visual impairment or other special needs in the classroom. A problem exists with reduced support and training for regular education teachers responsible for meeting literacy needs of students with visual impairment. The purpose of this qualitative interpretive case study was to explore regular education instructors' perceptions of their self-efficacy and ability to modify literature for learners with visual impairment. The research questions targeted this purpose, specifically in the areas of training opportunities and technology use. The social cognitive theory, a model emphasizing learning occurring through social contexts and observations, was used as the conceptual framework for this study. Data were collected from 1-on-1 interviews with 10 volunteer regular education teachers teaching students at the elementary level. The resulting data were analyzed via color-coding transcripts, NVivo running word-frequency queries, and manual review of each transcript. The results revealed the participants did not have training, awareness for the literacy needs of students with visual impairment, or knowledge of the different types of technology used to access and create literacy materials. Although they lacked training and current knowledge of providing literacy instruction, the participants expressed confidence in their ability to research, collaborate, and gain the knowledge needed to effectively do so. The implications for positive social change include implementation of training and/or an education cycle for more efficient instruction when serving a student with visual impairment in the local school district. Efficient instruction can facilitate an improvement in the academic performance of students with visual impairment.

No description available.

By enlarging the spatial and temporal spectral problems within a certain Lie algebra, a hierarchy of integrable couplings of the Kaup-Newell soliton equations is constructed. The recursion operator of the resulting hierarchy of integrable couplings is explicitly computed. The integrability of the new coupling hierarchy is exhibited by showing the existence of infinitely many commuting symmetries.

[pt] Nosso trabalho buscou apresentar a concepção de juízo na obra de Hannah Arendt, cuja compreensão se apoia em uma livre interpretação do juízo reflexionante estético de Kant. As razões pelas quais Arendt teria se voltado para o tema refletem sua preocupação com o obscurecimento do mundo, cuja pluralidade esteve visivelmente ameaçada com o advento do totalitarismo. Para a pensadora, os acontecimentos sem precedentes decorrentes do totalitarismo fazem parte de um contexto em que a ausência de reflexão e uma consequente inabilidade para julgar o que se passava fizeram do século XX um dos mais sombrios períodos da história da humanidade. A faculdade do juízo reflexionante estético, capaz de refletir sobre o particular sem que exista um universal dado, foi pensada por Arendt em um contexto político, e suas características apontam para a necessidade de compreender sem corrimãos os assuntos mundanos que se apresentam na contemporaneidade. Poderíamos considerar uma teoria do juízo arendtiana apenas de um modo fragmentado, uma vez que esse foi um projeto de uma pesquisa teórica que não foi realizado integralmente por ela, e do qual temos um quebra-cabeça a ser montado. Suas peças podem ser resgatadas desde os seus primeiros ensaios, quando a ação política era o seu leit motif intelectual. Posteriormente, a partir do julgamento de Eichmann, quando ao cunhar a expressão banalidade do mal ela própria se tornou exemplar em seu juízo reflexionante. Julgar prospectivamente com uma mentalidade alargada ou retrospectivamente com desinteresse são, pois, lados possíveis da mesma moeda: o juízo de gosto, cujo resgate Arendt se esforçou em trazer à luz. Tal juízo possui as características da comunicabilidade e intersubjetividade que possibilitam a existência do mundo, entendido como o espaço entre homens e espaço de visibilidade do pensamento reflexivo. Por essa razão, a atividade de julgar assim compreendida é a única faculdade espiritual do homem capaz de estabelecer o horizonte da pluralidade. / [en] Our work intended to present the notion of judgment in the writings of Hannah Arendt, whose comprehension supports itself on a free interpretation of Kantian aesthetic reflective judgment. The reasons why Arendt would have turned herself to the theme reflect her concern about the darkening of the world, whose plurality had been visibly threatened by the advent of totalitarianism. For philosopher, the unprecedented events that came from totalitarianism are part of a context in which the lack of deliberation and a subsequent inability to judge what was happening made the 20th century one of the darkest periods of human history. Arendt studied the faculty of aesthetic reflective judgment, capable of deliberating about the particular without a given universal, in a political context, and its characteristics point to the necessity of comprehending without handrails the mundane topics that present themselves on contemporaneity. We are able to consider only a fragmented Arendtian theory of judgment, since this was a research project not done solely by herself, and of which we have a whole puzzle to assemble. The pieces of this puzzle can be found beginning on her first essays, when the political action was her intellectual leit motif. Later, from Eichmann s judgment on, when she became an example on her own reflective judgment after coining the expression banality of evil. Judging prospectively with an enlarged mentality or retrospectively with disinterest are, then, two possible sides of the same coin: the judgment of taste, something Arendt tried to rescue and bring to light. This judgment holds the same characteristics of communicability and intersubjectivity that make possible the existence of the world, understood as the space between men and space of visibility of reflective judgment. For this reason, the activity of judging, comprehended this way, is the only spiritual faculty of men capable of establishing the horizon of plurality.

The thesis deals with creating and verifying of a set of compensatory excercises for children of younger school-age devoted to modern gymnastics. The experiment ran with two gymnastic groups from Prachatice and Volary. Every girl underwent an examination of hyperlordosis degree and a muscle strength and stretch level. Finally, it was proved that these girls suffer from hyperlordosis indeed. Therefore a set of excercises had been created and later applied on the girl gymnasts. Five months later the second measuring was realised and proved that the experiment was a success.