Computational approaches for improving treatment and prevention of viral infections

The treatment of infections with HIV or HCV is challenging. Thus, novel drugs and new computational approaches that support the selection of therapies are required. This work presents methods that support therapy selection as well as methods that advance novel antiviral treatments. geno2pheno[ngs-freq] identifies drug resistance from HIV-1 or HCV samples that were subjected to next-generation sequencing by interpreting their sequences either via support vector machines or a rules-based approach. geno2pheno[coreceptor-hiv2] determines the coreceptor that is used for viral cell entry by analyzing a segment of the HIV-2 surface protein with a support vector machine. openPrimeR is capable of finding optimal combinations of primers for multiplex polymerase chain reaction by solving a set cover problem and accessing a new logistic regression model for determining amplification events arising from polymerase chain reaction. geno2pheno[ngs-freq] and geno2pheno[coreceptor-hiv2] enable the personalization of antiviral treatments and support clinical decision making. The application of openPrimeR on human immunoglobulin sequences has resulted in novel primer sets that improve the isolation of broadly neutralizing antibodies against HIV-1. The methods that were developed in this work thus constitute important contributions towards improving the prevention and treatment of viral infectious diseases.Die Behandlung von HIV- oder HCV-Infektionen ist herausfordernd. Daher werden neue Wirkstoffe, sowie neue computerbasierte Verfahren benötigt, welche die Therapie verbessern. In dieser Arbeit wurden Methoden zur Unterstützung der Therapieauswahl entwickelt, aber auch solche, welche neuartige Therapien vorantreiben. geno2pheno[ngs-freq] bestimmt, ob Resistenzen gegen Medikamente vorliegen, indem es Hochdurchsatzsequenzierungsdaten von HIV-1 oder HCV Proben mittels Support Vector Machines oder einem regelbasierten Ansatz interpretiert. geno2pheno[coreceptor-hiv2] bestimmt den HIV-2 Korezeptorgebrauch dadurch, dass es einen Abschnitt des viralen Oberflächenproteins mit einer Support Vector Machine analysiert. openPrimeR kann optimale Kombinationen von Primern für die Multiplex-Polymerasekettenreaktion finden, indem es ein Mengenüberdeckungsproblem löst und auf ein neues logistisches Regressionsmodell für die Vorhersage von Amplifizierungsereignissen zurückgreift. geno2pheno[ngs-freq] und geno2pheno[coreceptor-hiv2] ermöglichen die Personalisierung antiviraler Therapien und unterstützen die klinische Entscheidungsfindung. Durch den Einsatz von openPrimeR auf humanen Immunoglobulinsequenzen konnten Primersätze generiert werden, welche die Isolierung von breit neutralisierenden Antikörpern gegen HIV-1 verbessern. Die in dieser Arbeit entwickelten Methoden leisten somit einen wichtigen Beitrag zur Verbesserung der Prävention und Therapie viraler Infektionskrankheiten

Color Screening and Quark-Quark Interactions in Finite Temperature QCD

We analyze the screening of static diquark sources in 2-flavor QCD and compare results with the screening of static quark-antiquark pairs. We show that a two quark system in a fixed color representations is screened at short distances like a single quark source in the same color representation whereas at large distances the two quarks are screened independently. At high temperatures we observe that the relative strength of the interaction in diquark and quark-antiquark systems, respectively, obeys Casimir scaling. We use this result to examine the possible existence of heavy quark-quark bound states in the high temperature phase of QCD. We find support for the existence of $bb$ states up to about $2T_c$ while $cc$ states are unlikely to be formed above $T_c$.Comment: 8 pages, 6 figure

Experiences with an Emotional Sales Agent

With COSIMA B2B we demonstrate a prototype of a complex and visionary e-procurement application. The embodied character agent named COSIMA is able to respect a customer's preferences and deals with him or her via natural speech. She expresses various emotions via mimic, gesture, combined with speech output, and COSIMA is even able to consider the customer's emotions via mimic recognition. As first observations show, this is a very promising approach to improve the bargaining with the customer or the recommendation of products

Wüchsigkeit und physiologische Aktivität der Rebe in Abhängigkeit von verschiedenen weinbaulichen Bewirtschaftungssystemen

Based on a field trial, the impact of three different viticultural management strategies on vigour and grapevine physiology of Vitis vinifera cv. Riesling was compared. The vines were planted in 1991 at Geisenheim (Rheingau, Germany) and three different management strategies i.e. integrated (code of good practice), organic (European Union Regulation 834/07 and ECOVIN standard) and biodynamic (European Union Regulation 834/07 and DEMETER standard) were established in 2006. Even though all treatments received the same level of nutrients and water a decline in vigour, expressed as lateral growth, was observed for the organic and biodynamic treatment during three seasons (2010 to 2012). During dryer conditions (2011) a reduction of physiological activity expressed as stomatal conductance gs, assimilation rate A and transpiration E two weeks after full-bloom and a reduction in pre-dawn water potential at veraison were assessed for the biological treatments. In 2012 under wetter growing conditions neither differences in physiological activity nor in pre-dawn water potential were observed. Therefore changes in physiological activity and pre-dawn water potential are just partially responsible for the reduced vigour in the biological treatments

Future Developments in German Fish Market – Integration of Market Expert Knowledge into a Modelling System

Globally fish has become more important in the human nutrition, thus global consumption is expected to highly increase in the future years. Business-as-usual projections for fish market are limited by availability of reliable data that hinders the differentiation on fish category level on the supply and demand side and across EU member states. The Fishmodul in AGEMEMOD provides long term predictions for the fish market by fish categories at EU member state level. For this, a status-quo simulation to the year 2030 is developed in AGMEMOD. Additionally, opinions of market experts from private sector and research institutions through interviews and an elaborated questionnaire is integrated into the model to deal with the insufficient information. Thus, expertise knowledge provides better and accurate information of the sector for market projections. As results, baseline projections were adjusted, showing a slowly increase over the years, but higher production level by 2030

Accurate Transponder Calibrations with the Novel Three-Transponder Method

Transponders are, besides trihedral corner reflectors, the most commonly used measurement standards in radiometric SAR calibration. They allow signal recording for the reconstruction of the azimuth pattern of the SAR system, adjustments of the backscattering matrix for polarimetric applications, and radar cross sections (RCSs) which are potentially much larger than those of passive point targets. These advantages led DLR to develop, manufacture, and install three new, accurate C-band “Kalibri” transponders in South Germany, which are now being used for the calibration and monitoring of the Copernicus Sentinel-1A satellite. Before the transponders could be used as radiometric measurement standards, they needed to be calibrated themselves. In an effort to find the most accurate RCS calibration approach for the given transponder design, several existing methods were compared [1], and a new, potentially highly accurate method, devised which exploits the specific design of the Kalibri transponders [2]. The new “three-transponder method” is similar in principle to the known “three-antenna method”, but is based on the radar equation instead of the Friis transmission formula. The approach exploits the fact that modern transponders like the “Kalibri” device can also be operated as radars because of the integrated digital sub-system (which is needed to implement a digital delay line and incorporates an AD and DA converter). To conduct a complete measurement, three transponders and three measurements (with one transponder pair each) are required; refined measurement schemas are also possible. In comparison to existing methods, no additional radiometric measurement standard is needed, which so far has been one of the limiting factors in accomplishing lower calibration uncertainties. Measurement traceability is achieved by tracing a comparatively simple length measurement back to a national realization of the meter. Such a length measurements can be performed with high accuracy. The presentation will include the setup and the measurement results of a first demonstration measurement campaign. Despite remaining challenges in the practical implementation, the uncertainty analysis shows that the method is a good candidate for highly accurate transponder RCS calibrations in the future

Future Developments in German Fish Market – Integration of Market Expert Knowledge into a Modelling System

Globally, fish has become more important in human nutrition, thus global consumption is expected to highly increase in the future years. Business-as-usual projections for fish market are limited by availability of reliable data at fish category level that hinders the differentiation in more detail on supply and demand as well as across EU member states. The new fish module in AGMEMOD provides midterm projections for the fish category markets in EU member states. For this, a status-quo simulation to the year 2030 is developed in AGMEMOD. In order to deal with the poor data availability, the model employs expert opinions about the German market, obtained through an elaborate questionnaire. Thus, expertise knowledge provides more detailed and accurate information on the German fish sector that helps to improve the insights in future German market developments. Based on this, AGMEMOD shows somewhat higher production development up to 2030, than in the original projections

Multimorbidity and health-related quality of life in the older population: results from the German KORA-Age study

<p>Abstract</p> <p>Background</p> <p>Multimorbidity in the older population is well acknowledged to negatively affect health-related quality of life (HRQL). Several studies have examined the independent effects of single diseases; however, little research has focused on interaction between diseases. The purpose of this study was to assess the impact of six self-reported major conditions and their combinations on HRQL measured by the EQ-5D.</p> <p>Methods</p> <p>The EQ-5D was administered in the population-based KORA-Age study of 4,565 Germans aged 65 years or older. A generalised additive regression model was used to assess the effects of chronic conditions on HRQL and to account for the nonlinear associations with age and body mass index (BMI). Disease interactions were identified by a forward variable selection method.</p> <p>Results</p> <p>The conditions with the greatest negative impact on the EQ-5D index were the history of a stroke (regression coefficient -11.3, p < 0.0001) and chronic bronchitis (regression coefficient -8.1, p < 0.0001). Patients with both diabetes and coronary disorders showed more impaired HRQL than could be expected from their separate effects (coefficient of interaction term -8.1, p < 0.0001). A synergistic effect on HRQL was also found for the combination of coronary disorders and stroke. The effect of BMI on the mean EQ-5D index was inverse U-shaped with a maximum at around 24.8 kg/m².</p> <p>Conclusions</p> <p>There are important interactions between coronary problems, diabetes mellitus, and the history of a stroke that negatively affect HRQL in the older German population. Not only high but also low BMI is associated with impairments in health status.</p