14 research outputs found
On Becoming: An Autoethnography of a Language Professional
No full textThis autoethnography is a reflective self-reconstruction of a non-traditional learner’s path of professional development in the field of Teaching English to Speakers of Other Languages (TESOL) while in the University of Hawai`i’s Department of Second Language Studies (SLS) BA Program. In providing an academically oriented representation of experiences in undergraduate SLS/TESOL programs, the author provides examples of how steps towards professional development and the process of written reflection intersect with a personal philosophy of teaching that has helped him establish an identity as a globally aware language professional in the field of SLS and TESOL. This paper provides a reconstruction and reflection on the language learning experience while the author was participating in the 2009-2010 Freeman Vietnam study abroad program, attaining a CELTA certification and completing the Second Language Studies undergraduate program at the University of Hawai`i at Mānoa. The writer reflects on a variety of issues relevant to language learners as well as those entering the field of TESOL and how sociolinguistic frameworks are providing valuable insights that are bringing light on these institutional interactions, transforming the world of teaching in the modern landscape of Global English
Genetische und klinische Heterogenität bei LCA-Patienten
No full textBackground. Leber congenital amaurosis (LCA) usually describes patients with severely reduced vision due to a retinal dystrophy in early childhood. Methods. In 135 families in a case series with severely reduced vision due to a retinal dystrophy in early childhood a complete ophthalmologic examination was extended by two-color threshold perimetry, fundus autofluorescence (FAF), und optical coherence tomography (OCT). Mutation screening included AIPL1, CRB1, CRX, GUCY2D, LRAT, RPE65, RPGRIP, and TULP1. Results. GUCY2D mutations caused the most severe phenotype with severely reduced vision from birth but unremarkable fundus appearance. RPE65 mutations were correlated with an obvious lack of FAF. CRB1 mutations showed a significantly thickened retina on OCT. CRX mutations were associated with a progressive form of cone-rod dystrophy. Conclusion. A genotype-phenotype correlation for selected genes allows an optimized strategy for the molecular genetic work-up
Biallelic mutation of human SLC6A6 encoding the taurine transporter TAUT is linked to early retinal degeneration
No full textWe previously reported that inactivation of the transmembrane taurine transporter (TauT or solute carrier 6a6) causes early retinal degeneration in mice. Compatible with taurine’s indispensability for cell volume homeostasis, protein stabilization, cytoprotection, antioxidation, and immuno- and neuromodulation, mice develop multisystemic dysfunctions (hearing loss; liver fibrosis; and behavioral, heart, and skeletal muscle abnormalities) later on. Here, by genetic, cell biologic, in vivo1H–magnetic resonance spectroscopy and molecular dynamics simulation studies, we conducted in-depth characterization of a novel disorder: human TAUT deficiency. Loss of TAUT function due to a homozygous missense mutation caused panretinal degeneration in 2 brothers. TAUTp.A78E still localized in the plasma membrane but is predicted to impact structural stabilization. 3H-taurine uptake by peripheral blood mononuclear cells was reduced by 95%, and taurine levels were severely reduced in plasma, skeletal muscle, and brain. Extraocular dysfunctions were not yet detected, but significantly increased urinary excretion of 8-oxo-7,8-dihydroguanosine indicated generally enhanced (yet clinically unapparent) oxidative stress and RNA oxidation, warranting continuous broad surveillance.—Preising, M. N., Görg, B., Friedburg, C., Qvartskhava, N., Budde, B. S., Bonus, M., Toliat, M. R., Pfleger, C., Altmüller, J., Herebian, D., Beyer, M., Zöllner, H. J., Wittsack, H.-J., Schaper, J., Klee, D., Zechner, U., Nürnberg, P., Schipper, J., Schnitzler, A., Gohlke, H., Lorenz, B., Häussinger, D., Bolz, H. J. Biallelic mutation of human SLC6A6 encoding the taurine transporter TAUT is linked to early retinal degeneration
Influences of surface quality on the rolling contact fatique behaviour of ceramics
No full textA novel eccentric lapping machine was designed by the author and manufactured in-house, to serve as a test bench to investigate the finishing process parameters in relation to surface quality, as well as the feasibility of accelerating the finishing process of HIPed silicon nitride balls. The kinematics of the eccentric lapping were
analysed and discussed. Taguchi Methods were used to optimise the finishing parameters to achieve maximum material removal rate in lapping and to achieve minimum surface roughness value Ra in polishing. Two kinds of HIPed silicon nitride ball blanks were finished by this machine. A finishing rate of 68 µm/hour was achieved which is 15 times higher than the conventional concentric lapping (normally 3'-4µm/hour). The surface roughness and roundness of the polished ball were above grade 5, close to grade 3 precision bearing ball specification. The upper limits of
lapping load and lapping speed were determined by aggressive lapping tests. The effects of various finishing parameters on the surface quality generated were studied
by detailed surface analysis, including X-ray diffraction residual stress measurement. As a result, the relationship between the finishing process and surface quality has
been established. Accelerated rolling contact fatigue tests were performed both under a standard 4-ball and a modified 5-ball rolling configuration, with a ceramic ball as the upper ball and steel balls as lower balls. The tests were conducted at high speed and lubricated conditions under different loads and were run for up to 135-200 million
stress cycles. Tests were conducted on commercially finished balls with different surface roughness and with different surface integrity (heterogeneous porosity, star
defect, grinding defect and C-cracks). Tests were also conducted on self-finished balls with different finishing parameters and with different surface roughness. After
tests, the rolling tracks and failure areas were examined by detailed surface analysis. The residual stresses on the rolling tracks were measured. Finite Element Approaches
were also employed to describe the contact stress status. Failure modes in relation to surface quality were discussed. The research has provided an understanding of the finishing process, surface quality and rolling contact fatigue behaviour of HIPed silicon nitride balls
Predominant rod photoreceptor degeneration in Leber congenital amaurosis
No full textophthalmology, AIPL1 gene, immunocyte chemistry, microscopy, photoreceptor, Leber congenital amaurosis, opsin, lectin, recoverin, cone arresti
Comprehensive registration of DNA sequence variants associated with inherited retinal diseases in Leiden Open Variation Databases
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Mutations in RD3 are associated with an extremely rare and severe form of early onset retinal dystrophy
No full textPurpose: To identify the underlying mutation and describe the phenotype in a consanguineous Kurdish family with Leber's congenital amaurosis (LCA)/early onset severe retinal dystrophy (EOSRD). Methods: Members of the index family were followed up to 22 years by ophthalmological examinations, including best corrected visual acuity (BCVA), Goldmann visual field (GVF), two-color-threshold perimetry (2CTP) and Ganzfeld electroretinogram (ERG), fundus photographs, fundus autofluorescence (FAF), and optical coherence tomography (OCT). After excluding seven of nine known LCA/EOSRD genes in the index patient, linkage analysis was performed in the family using a microarray followed by microsatellite fine mapping and direct sequencing of candidate genes. RD3 was screened by direct sequencing of 85 independent patients with LCA/EOSRD presenting with a BCVA ≥ 1.0 LogMAR before the age of 2 years to assess the prevalence of RD3 mutations in LCA/EOSRD. Since RD3 and RetGC1 have a functional relation, study authors screened for a modifying effect of RD3 mutations in 17 independent patients with mutations in GUCY2D. Results: BCVA was severely reduced from the earliest examinations (as early as 3 months), never exceeding 1.3 LogMAR. The disease presented as cone-rod dystrophy with dystrophic changes in the macula and bone spicules in the periphery on progression. Linkage analysis narrowed the region of interest towards the LCA12 locus. Direct sequencing of RD3 revealed a homozygous nonsense mutation (c.180C > A) in all affected members tested. Screening of additional unrelated LCA/EOSRD patients revealed only polymorphisms in RD3. Conclusions: This is the second family reported so far with mutations in RD3. Mutations in RD3 are a very rare cause of LCA associated with an extremely severe form of retinal dystrophy
Autosomal Recessive Bestrophinopathy: New Observations on the Retinal Phenotype – Clinical and Molecular Report of an Italian Family
No full text<i>Purpose:</i> To describe the genotype and phenotype in a 9-year-old boy with bilateral retinopathy. <i>Methods:</i> The patient, his healthy (by history) nonconsanguineous parents and his sister were examined by best-corrected visual acuity, matrix frequency doubling technology, monocular static field analysis, fundus autofluorescence imaging, optical coherence tomography, Ganzfeld electroretinography (ERG), pattern ERG, multifocal ERG, electro-oculography and genotyping of the <i>BEST1</i> gene. <i>Results:</i> The patient presented with an Arden ratio of 1.25, an unremarkable ERG and fluorescent yellow deposits distributed throughout the fundus suggestive of autosomal recessive bestrophinopathy (ARB). Genotyping revealed a homozygous nonsense mutation in <i>BEST1</i> (p.R200X). The parents and the sister, who were heterozygous mutation carriers, presented with normal ophthalmological function. <i>Conclusions:</i> ARB is a rare retinal disorder. We contribute a novel patient report indicative of ARB, assessed by clinical examination and confirmed by genotyping of <i>BEST1,</i> to the short list of ARB cases in the literature.</jats:p
Congenital cataract and macular hypoplasia in humans associated with a de novo mutation in CRYAA and compound heterozygous mutations in P
No full textBackground: An isolated form of congenital cataract associated with macular hypoplasia and a generally hypopigmented fundus in infancy was observed in a German family. To test the hypothesis that a de-novo mutation had occurred in one of the parental germ lines, a functional candidate gene approach was applied. Methods: The family was carefully examined by a senior paediatric ophthalmologist according to routine procedures (slit lamp, funduscopy, ERG). Blood was taken from the proband and his parents, genomic DNA was isolated and some candidate genes for cataract (CRYAA, CRYBB2, GJA8) or macular hypoplasia (OA1, P) or both (PAX6) were analyzed. Results: The proband showed bilateral cataracts at the age of 4 months; the fundus appeared pale, the optic disc grayish, and macular reflexes were absent. After cataract surgery, the nystagmus persisted, and a control ERG at age 9 years showed essentially normal scotopic and photopic wave forms. An infectious aetiology as well as galactosemia were excluded. However, a heterozygous mutation was found in the proband in exon 1 of CRYAA (62 C -> T), which leads to an exchange from Arg to Leu at amino acid position 21 (R21L). This sequence alteration was not found in the parents and in 96 randomly selected DNA samples from ophthalmologically normal individuals of the KORA S4 study population. In addition, two heterozygous mutations in P were identified (R419Q and A481T); one of both was present in each of the unaffected parents. Conclusion: Based upon the unique finding of the mutation and the expression of CRYAA in the lens, this R21L mutation in the CRYAA is considered to be causative for the dominant cataract phenotype. Moreover, the macular hypoplasia has to be considered a concerted interaction with compound heterozygous mutations in the P gene manifesting a mild form of oculocutaneous albinism. Nevertheless, this combination is rare and future studies will focus on identifying similar phenotypes
