Die Paradoxie der unerlösten Erlösung: Überlegungen zu Wolframs Neutralen Engeln

Zweitveröffentlichun

Log-multiplikative Modelle zur Bestimmung der Assoziation zwischen qualitativen Variablen mit inkonsistent geordneten Kategorien

'Variablen, deren Kategorien nur teilweise eine konsistente Rangfolge beschreiben, kommen in sozialwissenschaftlichen Untersuchungen häufig vor. Eine Möglichkeit, noch diesen 'Rest' an ordinaler Information ausschöpfen zu können, bieten log-multiplikative Analyseverfahren. Es können simultan multivariate Abhängigkeiten sparsam bestimmt und die interessierenden Variablen skaliert werden. Da log-multiplikative Modelle bisher nur sehr selten angewendet wurden, soll in diesem Beitrag ihre Brauchbarkeit demonstriert werden.' (Autorenreferat)'Variables whose categories only partly describe a consistent order often occur in social science inquiries. Log-multiplicative models provide a method to analyze even the remaining ordinal information found in these variables. Such models are able to parsimoniously determine multivariate dependencies and simultaneously scale the variables of interest. Since log-multiplicative models habe rarely been used, this article is intended to demonstrate their effectiveness.' (author's abstract)

Sammelrezension: GoT in Kürze

Jan Söffner: Nachdenken über ‚Game of Thrones’:George R.R. Martins ‚A Song of Ice and Fire’Paderborn: Wilhelm Fink 2017, 152 S., ISBN 9783770562091,EUR 24,90 Kerstin Stutterheim: ‚Game of Thrones‘ sehen: Dramaturgie einer TV-SeriePaderborn: Wilhelm Fink 2017, 132 S., ISBN 9783770562046,EUR 24,9

Das allgemeine Assoziationsmodell 'ANOAS'

'Während der Beitrag des gleichen Autors in Heft 33 der ZA-Informationen in die statistischen Grundlagen log-multiplikativer Modelle einführt, behandelt die folgende Arbeit die Verallgemeinerung dieser Modelle zum allgemeinen Assoziationsmodell 'ANOAS'. An Hand eines Beispiels aus der Transformationsforschung werden einige unterschiedlich restriktive Versionen des ANOAS-Modells erläutert.' (Autorenreferat)'As the article of the same author in No. 33 of the ZA-Informationen introduced the statistical basis of log-multiplicative models, the following work will only deal with the extension of these models to the 'ANOAS'-model. Using an example from transformation research, several different restrictive versions of the ANOAS-model will be explained.' (author's abstract)

Error correction of next-generation sequencing data and reliable estimation of HIV quasispecies

Next-generation sequencing technologies can be used to analyse genetically heterogeneous samples at unprecedented detail. The high coverage achievable with these methods enables the detection of many low-frequency variants. However, sequencing errors complicate the analysis of mixed populations and result in inflated estimates of genetic diversity. We developed a probabilistic Bayesian approach to minimize the effect of errors on the detection of minority variants. We applied it to pyrosequencing data obtained from a 1.5‐kb-fragment of the HIV-1 gag/pol gene in two control and two clinical samples. The effect of PCR amplification was analysed. Error correction resulted in a two- and five-fold decrease of the pyrosequencing base substitution rate, from 0.05% to 0.03% and from 0.25% to 0.05% in the non-PCR and PCR-amplified samples, respectively. We were able to detect viral clones as rare as 0.1% with perfect sequence reconstruction. Probabilistic haplotype inference outperforms the counting-based calling method in both precision and recall. Genetic diversity observed within and between two clinical samples resulted in various patterns of phenotypic drug resistance and suggests a close epidemiological link. We conclude that pyrosequencing can be used to investigate genetically diverse samples with high accuracy if technical errors are properly treate

Error correction of next-generation sequencing data and reliable estimation of HIV quasispecies

Next-generation sequencing technologies can be used to analyse genetically heterogeneous samples at unprecedented detail. The high coverage achievable with these methods enables the detection of many low-frequency variants. However, sequencing errors complicate the analysis of mixed populations and result in inflated estimates of genetic diversity. We developed a probabilistic Bayesian approach to minimize the effect of errors on the detection of minority variants. We applied it to pyrosequencing data obtained from a 1.5‐kb-fragment of the HIV-1 gag/pol gene in two control and two clinical samples. The effect of PCR amplification was analysed. Error correction resulted in a two- and five-fold decrease of the pyrosequencing base substitution rate, from 0.05% to 0.03% and from 0.25% to 0.05% in the non-PCR and PCR-amplified samples, respectively. We were able to detect viral clones as rare as 0.1% with perfect sequence reconstruction. Probabilistic haplotype inference outperforms the counting-based calling method in both precision and recall. Genetic diversity observed within and between two clinical samples resulted in various patterns of phenotypic drug resistance and suggests a close epidemiological link. We conclude that pyrosequencing can be used to investigate genetically diverse samples with high accuracy if technical errors are properly treated

HIV-1 diversity in viral reservoirs obtained from circulating T-cell subsets during early ART and beyond

Even during extended periods of effective immunological control, a substantial dynamic of the viral genome can be observed in different cellular compartments in HIV-1 positive individuals, indicating the persistence of active viral reservoirs. To obtain further insights, we studied changes in the proviral as well as in the viral HIV-1 envelope (Env) sequence along with transcriptional, translational and viral outgrowth activity as indicators for viral dynamics and genomic intactness. Our study identified distinct reservoir patterns that either represented highly sequence-diverse HIV-1 populations or only a single / few persisting virus variants. The single dominating variants were more often found in individuals starting ART during early infection phases, indicating that early treatment might limit reservoir diversification. At the same time, more sequence-diverse HIV reservoirs correlated with a poorer immune status, indicated by lower CD4 count, a higher number of regimen changes and more co-morbidities. Furthermore, we noted that in T-cell populations in the peripheral blood, replication-competent HIV-1 is predominantly present in Lymph node homing TN (naïve) and TCM (central memory) T cells. Provirus genomes archived in TTM (transitional memory) and TEM (effector memory) T cells more frequently tended to carry inactivating mutations and, population-wise, possess changes in the genetic diversity. These discriminating properties of the viral reservoir in T-cell subsets may have important implications for new early therapy strategies, underscoring the critical role of early therapy in preserving robust immune surveillance and constraining the viral reservoir

The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage?

Background: Although being considered as a rarely observed HIV-1 protease mutation in clinical isolates, the L76V-prevalence increased 1998-2008 in some European countries most likely due to the approval of Lopinavir, Amprenavir and Darunavir which can select L76V. Beside an enhancement of resistance, L76V is also discussed to confer hypersusceptibility to the drugs Atazanavir and Saquinavir which might enable new treatment strategies by trying to take advantage of particular mutations. Results: Based on a cohort of 47 L76V-positive patients, we examined if there might exist a clinical advantage for L76V-positive patients concerning long-term success of PI-containing regimens in patients with limited therapy options. Genotypic- and phenotypic HIV-resistance tests from 47 mostly multi-resistant, L76V-positive patients throughout Germany were accomplished retrospectively 1999-2009. Five genotype-based drug-susceptibility predictions received from online interpretation-tools for Atazanavir, Saquinavir, Amprenavir and Lopinavir, were compared to phenotype-based predictions that were determined by using a recombinant virus assay along with a Virtual Phenotype™(Virco). The clinical outcome of the L76V-adapted follow-up therapy was determined by monitoring viral load for 96 weeks. Conclusions: In this analysis, the mostly used interpretation systems overestimated the L76V-mutation concerning Atazanavir- and SQV resistance. In fact, a clear benefit in drug susceptibility for these drugs was observed in phenotype analysis after establishment of L76V. More importantly, long-term therapy success was significantly higher in patients receiving Atazanavir and/or Saquinavir plus one L76V-selecting drug compared to patients without L76V-selecting agents (p = 0.002). In case of L76V-occurrence ATV and/or SQV may represent encouraging options for patients in deep salvage situations