Was heißt hier „Web 2.0“? Überlegungen zu ei-nem Grundbegriff in der geschichtsdidaktischen Diskussion um den „digitalen Wandel“

Christopher Friedburg versucht zu Beginn seines Beitrags „Was heißt hier „Web 2.0“?“ anhand von 10 Aspekten eine Definition des komplexen Web 2.0. Anschließend betrachtet er den partizipativen Charakter und das Social Web als Teil des Web 2.0 unter dem Gesichtspunkt der Anwendbarkeit für die Geschichtsdidaktik. In seinem Fazit fordert er sowohl einen differenzierten Umgang mit Medienbegriffen, als auch die Entwicklung von Theorien aus der Praxis heraus

Nachnutzung der gemeinsamen JOIN2^2 –Repository-Infrastruktur für den KDSF-Objektbereich Publikation?

Im Rahmen des JOIN2-Projekts haben Bibliotheks- & Dokumentationseinheiten (Deutsches Elektronensynchrotron DESY Hamburg/Zeuten, Deutsches Krebsforschungszentrum DKFZ Heidelberg, Forschungszentrum Jülich, GSI Helmholtzzentrum für Schwerionenforschung Darmstadt, Maier-Leibnitz-Zentrum Garching, Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen, KIT Institut für experimentelle Kernphysik Karlsruhe) eine gemeinsame Repository-Infrastruktur für ihre Wissenschaftler und Wissenschaftlerinnen geschaffen. Das Poster dokumentiert Überlegungen, welche Anforderungen des Kerndatensatzes Forschung im Objektbereich abgebildet werden können, wo Probleme und fehlende Normierungen in der Praxis auftauchen könnten und vor allem, an welchen Stellen Kompromisse in Hinblick auf die JOIN2-Serviceorientierung für den Wissenschaftsbereich eingegangen werden müssen.Schlagwörter: Repositorium; VeröffentlichungsdatenbankSchwerpunktbereich: Identifikatoren & Anbindung von Drittsystemen, z.B. von Repositorie

Diffusion with random distribution of static traps

The random walk problem is studied in two and three dimensions in the presence of a random distribution of static traps. An efficient Monte Carlo method, based on a mapping onto a polymer model, is used to measure the survival probability P(c,t) as a function of the trap concentration c and the time t. Theoretical arguments are presented, based on earlier work of Donsker and Varadhan and of Rosenstock, why in two dimensions one expects a data collapse if -ln[P(c,t)]/ln(t) is plotted as a function of (lambda t)^{1/2}/ln(t) (with lambda=-ln(1-c)), whereas in three dimensions one expects a data collapse if -t^{-1/3}ln[P(c,t)] is plotted as a function of t^{2/3}lambda. These arguments are supported by the Monte Carlo results. Both data collapses show a clear crossover from the early-time Rosenstock behavior to Donsker-Varadhan behavior at long times.Comment: 4 pages, 6 figure

A comprehensive clinical and biochemical functional study of a novel RPE65 hypomorphic mutation

PURPOSE. Later onset and progression of retinal dystrophy occur with some RPE65 missense mutations. The functional consequences of the novel P25L RPE65 mutation was correlated with its early-childhood phenotype and compared with other pathogenic missense mutations. METHODS. In addition to typical clinical tests, fundus autofluorescence (FAF), optical coherence tomography (OCT), and two-color threshold perimetry (2CTP) were measured. RPE65 mutations were screened by SSCP and direct sequencing. Isomerase activity of mutant RPE65 was assayed in 293F cells and quantified by HPLC analysis of retinoids. RESULTS. A very mild phenotype was detected in a now 7-yearold boy homozygous for the P25L mutation in RPE65. Although abnormal dark adaptation was noticed early, best corrected visual acuity was 20/20 at age 5 years and 20/30 at age 7 years. Nystagmus was absent. Cone electroretinogram (ERG) was measurable, rod ERG severely reduced, and FAF very low. 2CTP detected mainly cone-mediated responses in scotopic conditions, and light-adapted cone responses were approximately 1.5 log units below normal. High-resolution spectral domain OCT revealed morphologic changes. Isomerase activity in 293F cells transfected with RPE65/P25L was reduced to 7.7% of wild-type RPE65-transfected cells, whereas RPE65/ L22P-transfected cells had 13.5%. CONCLUSIONS. The mild clinical phenotype observed is consistent with the residual activity of a severely hypomorphic mutant RPE65. Reduction to Ͻ10% of wild-type RPE65 activity by homozygous P25L correlates with almost complete rod function loss and cone amplitude reduction. Functional survival of cones is possible in patients with residual RPE65 isomerase activity. This patient should profit most from gene therapy. (Invest Ophthalmol Vis Sci. 2008;49:5235-5242) DOI: 10.1167/iovs.07-1671 H uman mutations in the gene for the highly preferentially expressed RPE protein RPE65 are associated with a spectrum of retinal dystrophies ranging from more severe earlyonset conditions, variously described as Leber congenital amaurosis type 2/autosomal recessive childhood-onset severe retinal dystrophy or early-onset severe retinal dystrophy (LCA2/arCSR, EOSRD) to later onset conditions described as autosomal recessive retinitis pigmentosa (arRP). 1-7 Recently, RPE65 has been established as the isomerase central to the retinoid visual cycle. 8 -10 This cycle 11 is crucial for supply of the chromophore 11-cis retinal for visual pigment regeneration. Animal models have contributed greatly to our understanding of the role of RPE65 in the visual cycle, regeneration, and retinal dystrophy. Rpe65 knockout mice display a biochemical phenotype consisting of extreme chromophore starvation (no rhodopsin) in the photoreceptors concurrent with overaccumulation of all-trans retinyl esters in the RPE 10 and are extremely insensitive to light. This insensitivity to light protects Rpe65 Ϫ/Ϫ mice from light damage, establishing rhodopsin as the mediator of light-induced retinal damage. 12 There is also a natural mutation in mouse Rpe65 called rd12. 14,15 The utility of gene therapy was established by preclinical trials in these dogs. 21 This level appears to be more than enough to maintain near-normal function. In contrast, human RPE65 EOSRD displays a wide spectrum of severity, age of onset, and progression not seen in animal models. In this article, we present the mild phenotypic consequences of a homozygous P25L missense mutation in a young patient and correlate these with the biochemical effect of this mutation on RPE65 activity. We show that even though the isomerase activity of the mutant RPE65 was quite impaired, the patient had near-normal visual acuity. However, rod function was extremely impaired. In addition, short-wavelength cones appeared more impaired than long-wavelength cones, consistent with findings in other patients with RPE65 mutations that blue color vision is much more and earlier impaired than is red vision, opposite to the usual case in cone dystrophies. These From th

Real-world clinical experience with Idebenone in the treatment of Leber hereditary optic neuropathy

Background: Leber hereditary optic neuropathy (LHON) leads to bilateral central vision loss. In a clinical trial setting, idebenone has been shown to be safe and to provide a trend toward improved visual acuity, but long-term evidence of effectiveness in real-world clinical practice is sparse. Methods: Open-label, multicenter, retrospective, noncontrolled analysis of long-term visual acuity and safety in 111 LHON patients treated with idebenone (900 mg/day) in an expanded access program. Eligible patients had a confirmed mitochondrial DNA mutation and had experienced the onset of symptoms (most recent eye) within 1 year before enrollment. Data on visual acuity and adverse events were collected as per normal clinical practice. Efficacy was assessed as the proportion of patients with either a clinically relevant recovery (CRR) or a clinically relevant stabilization (CRS) of visual acuity. In the case of CRR, time to and magnitude of recovery over the course of time were also assessed. Results: At time of analysis, 87 patients had provided longitudinal efficacy data. Average treatment duration was 25.6 months. CRR was observed in 46.0% of patients. Analysis of treatment effect by duration showed that the proportion of patients with recovery and the magnitude of recovery increased with treatment duration. Average gain in best-corrected visual acuity for responders was 0.72 logarithm of the minimal angle of resolution (logMAR), equivalent to more than 7 lines on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. Furthermore, 50% of patients who had a visual acuity below 1.0 logMAR in at least one eye at initiation of treatment successfully maintained their vision below this threshold by last observation. Idebenone was well tolerated, with most adverse events classified as minor. Conclusions: These data demonstrate the benefit of idebenone treatment in recovering lost vision and maintaining good residual vision in a real-world setting. Together, these findings indicate that idebenone treatment should be initiated early and be maintained more than 24 months to maximize efficacy. Safety results were consistent with the known safety profile of idebenone

Detection of early age-related macular degeneration using novel functional parameters of the focal cone electroretinogram

The focal cone electroretinogram is a sensitive marker for macular disease, but have we unlocked its full potential? Typically assessment of waveform parameters is subjective and focuses on a small number of locations (e.g. the a-wave). This study evaluated the discriminatory and diagnostic potential of 4 conventional and 15 novel, objectively determined, parameters in patients with early Age-related Macular Degeneration. Focal cone electroretinograms were recorded in 54 participants with early Age-related Macular Degeneration (72.9±8.2 years) and 54 healthy controls (69±7.7 years). Conventional a and b wave amplitudes and implicit times were measured and compared to novel parameters derived from both the 1st and 2nd derivatives and the frequency-domain power spectrum of the electroretinogram.Statistically significant differences between groups were shown for all conventional parameters, the majority of 1st and 2nd derivative parameters and the power spectrum at 25 and 30 Hz. Receiver operating characteristics showed that both conventional and 1st and 2nd derivative implicit times had provided the best diagnostic potential. A regression model showed a small improvement over any individual parameter investigated. The non-conventional parameters enhanced the objective evaluation of the focal electroretinogram, especially when the amplitude was low. Furthermore, the novel parameters described here allow the implicit time of the electroretinogram to be probed at points other than the peaks of the a and b waves. Consequently these novel analysis techniques could prove valuable in future electrophysiological investigation, detection and monitoring of Age-related Macular Degeneration

Full field electroretinogram in autism spectrum disorder

Purpose To explore early findings that individuals with autism spectrum disorder (ASD) have reduced scotopic ERG b-wave amplitudes. Methods Dark adapted (DA) ERGs were acquired to a range of flash strengths, (-4.0 to 2.3 log phot cd.s.m-2), including and extending the ISCEV standard, from two subject groups: (ASD) N=11 and (Control) N=15 for DA and N=14 for light adapted (LA) ERGs who were matched for mean age and range. Naka-Rushton curves were fitted to DA b-wave amplitude growth over the first limb (-4.0 to -1.0 log phot cd.s.m-2). The derived parameters (Vmax, Km and n) were compared between groups. Scotopic 15 Hz flicker ERGs (14.93Hz) were recorded to 10 flash strengths presented in ascending order from -3.0 to 0.5 log Td.s to assess the slow and fast rod pathways respectively. LA ERGs were acquired to a range of flash strengths, (-0.5 to 1.0 log phot cd.s.m-2). Photopic 30 Hz, flicker ERGs, oscillatory potentials (OPs) and the responses to prolonged 120 ms ON- OFF stimuli were also recorded. Results For some individuals the DA b-wave amplitudes fell below the control 5th centile of the controls with up to four ASD participants (36%) at the 1.5 log phot cd.s.m-2 flash strength and two (18%) ASD participants at the lower -2 log phot cd.s.m-2 flash strength. However, across the thirteen flash strengths there were no significant group differences for b-wave amplitude’s growth (repeated measures ANOVA p=0.83). Nor were there any significant differences between the groups for the Naka-Rushton parameters (p>0.09). No group differences were observed in the 15Hz scotopic flicker phase or amplitude (p>0.1), DA ERG a- wave amplitude or time to peak (p>26). The DA b-wave time to peak at 0.5 log phot cd.s.m-2 were longer in the ASD group (corrected p=0.04). The single ISCEV LA 0.5 log phot cd.s.m-2 (p0.08) to the single flash stimuli although there was a significant interaction between group and flash strength for the b-wave amplitude (corrected p=0.006). The prolonged 120 ms ON-responses were smaller in the ASD group (corrected p=0.003), but the OFF response amplitude (p>0.6) and ON and OFF times to peaks (p>0.4) were similar between groups. The LA OPs showed an earlier bifurcation of OP2 in the younger ASD participants, however no other differences were apparent in the OPs or 30Hz flicker waveforms. Conclusion Some ASD individuals show subnormal DA ERG b-wave amplitudes. Under LA conditions the b-wave is reduced across the ASD group along with the ON response of the ERG. These exploratory findings, suggest there is altered cone-ON bipolar signalling in ASD

A Politico-Communal Reading of the Rose

Lettura del Fiore in rapporto alle fonti retoriche e politiche di ambiente comunal

Income-Tested College Financial Aid and Labor Disincentives

Working has become commonplace among college students; however, this activity can have unexpected financial consequences. Federal formulas implicitly tax the amount of financial aid students are eligible to receive by as much as 50 cents for each marginal dollar of income. This tax creates an incentive for college students to reduce income, though abstruse formulas and the timing of financial aid receipt are likely to limit responses. Using data from a national sample of financially independent college students in the United States, I do not find that students bunch below earnings protection thresholds in a manner that would indicate attempts to avoid reductions in financial aid in total or grants specifically. Moreover, I do not find evidence that implicit income taxes predict lower earnings in a manner that suggests that students meaningfully reduce earnings in response to the tax. Therefore, while economically efficient, the reduction in aid has the potential to burden low-income students who need to both work and receive financial aid in order to afford college expenses