Exploiting HIV-1 protease and reverse transcriptase cross-resistance information for improved drug resistance prediction by means of multi-label classification

Gini impurity PIs. (PDF 8 kb

DNA watermarks: A proof of concept

<p>Abstract</p> <p>Background</p> <p>DNA-based watermarks are helpful tools to identify the unauthorized use of genetically modified organisms (GMOs) protected by patents. <it>In silico </it>analyses showed that in coding regions synonymous codons can be used to insert encrypted information into the genome of living organisms by using the DNA-Crypt algorithm.</p> <p>Results</p> <p>We integrated an authenticating watermark in the Vam7 sequence. For our investigations we used a mutant <it>Saccharomyces cerevisiae </it>strain, called CG783, which has an amber mutation within the Vam7 sequence. The CG783 cells are unable to sporulate and in addition display an abnormal vacuolar morphology. Transformation of CG783 with pRS314 Vam7 leads to a phenotype very similar to the wildtype yeast strain CG781. The integrated watermark did not influence the function of Vam7 and the resulting phenotype of the CG783 cells transformed with pRS314 Vam7-TB shows no significant differences compared to the CG783 cells transformed with pRS314 Vam7.</p> <p>Conclusion</p> <p>From our experiments we conclude that the DNA watermarks produced by DNA-Crypt do not influence the translation from mRNA into protein. By analyzing the vacuolar morphology, growth rate and ability to sporulate we confirmed that the resulting Vam7 protein was functionally active.</p

DNA watermarks in non-coding regulatory sequences

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Interactive polar diagrams for model comparison

Objective Evaluating the performance of multiple complex models, such as those found in biology, medicine, climatology, and machine learning, using conventional approaches is often challenging when using various evaluation metrics simultaneously. The traditional approach, which relies on presenting multi-model evaluation scores in the table, presents an obstacle when determining the similarities between the models and the order of performance. Methods By combining statistics, information theory, and data visualization, juxtaposed Taylor and Mutual Information Diagrams permit users to track and summarize the performance of one model or a collection of different models. To uncover linear and nonlinear relationships between models, users may visualize one or both charts. Results Our library presents the first publicly available implementation of the Mutual Information Diagram and its new interactive capabilities, as well as the first publicly available implementation of an interactive Taylor Diagram. Extensions have been implemented so that both diagrams can display temporality, multimodality, and multivariate data sets, and feature one scalar model property such as uncertainty. Our library, named polar-diagrams, supports both continuous and categorical attributes. Conclusion The library can be used to quickly and easily assess the performances of complex models, such as those found in machine learning, climate, or biomedical domains

Determinants of Consumers’ Willingness-to-pay for Fairly-produced, Locally Grown Dairy Products

At the end of the last decade, several regional marketing projects were launched in the dairy sectors of various Alpine countries with the aim of creating a higher added value for milk products and allowing fair prices for the dairy farmers involved. The projects wanted to offer an alternative marketing channel for the farms in these regions by marketing ‘fairly-produced, locally grown products’. The aim of this study is to analyze the determinants of consumers’ willingness-to-pay (WTP) for fairly-produced, locally grown products using two different WTP measures: the first one describes a more general willingness-to-pay (WTPGEN) and the second one quantifies the price premium (WTPQUAN) respondents are willing to pay. The influence of both person-related and environmental factors, which are known to have an impact on food-related consumption behavior, was determined introducing and using the Shapley value (SV) decomposition of R2. This concept is commonly used in the commercial marketing context, but until now it has rarely been applied in academic research on food-related consumption behavior, even though it provides interesting advantages. The results show that consumers’ WTP for fairly-produced, locally grown products is influenced by person-related factors as well as by environmental factors. In the case of WTPQUAN, a dominant influence by consumers’ price consciousness can be observed, while a higher relative importance of the more global constructs of norms, stated preferences, and values can be detected when ex-plaining WTPGEN

Structure of HIV-1 quasi-species as early indicator for switches of co-receptor tropism

Deep sequencing is able to generate a complete picture of the retroviral quasi-species in a patient. We demonstrate that the unprecedented power of deep sequencing in conjunction with computational data analysis has great potential for clinical diagnostics and basic research. Specifically, we analyzed longitudinal deep sequencing data from patients in a study with Vicriviroc, a drug that blocks the HIV-1 co-receptor CCR5. Sequences covered the V3-loop of gp120, known to be the main determinant of co-receptor tropism. First, we evaluated this data with a computational model for the interpretation of V3-sequences with respect to tropism, and we found complete agreement with results from phenotypic assays. Thus, the method could be applied in cases where phenotypic assays fail. Second, computational analysis led to the discovery of a characteristic pattern in the quasi-species that foreshadows switches of co-receptor tropism. This analysis could help to unravel the mechanism of tropism switches, and to predict these switches weeks to months before they can be detected by a phenotypic assay

Analyse von Ursachen und Co-Faktoren bei frustraner mechanischer Rekanalisation beim ischämischen Schlaganfall

In der vorliegenden Studie wurden die Ursachen der frustranen Thrombektomie bei Patienten mit akutem ischämischem Schlaganfall des vorderen Stromgebietes (A. carotis interna, A. cerebri media) untersucht. Die gesamte Studienpopulation umfasste 100 gescheiterte Interventionen und 100 zufällig ausgewählte Kontrollpatienten aus einer Gesamtheit von 596 am Universitätsklinikum des Saarlandes im Zeitraum Januar 2014 bis Oktober 2018 interventionell therapierten Patienten. Das Kollektiv der beiden Gruppen unterschied sich statistisch nicht in Alter, Geschlecht und der Symptomausprägung. Als erfolgreiche Intervention wurde ein postinterventioneller TICI-Score von 2b oder höher definiert. Es zeigte sich, dass das neurovaskuläre Zentrum in Homburg im Vergleich zur internationalen Literatur vergleichbare Erfolgsraten von etwa 83,2% aufweist. In der Studienpopulation erhöht die intravenöse Lysetherapie vor Intervention die Erfolgsrate signifikant. Außerdem ergab sich ein statistischer Zusammenhang zwischen der dauerhaften Einnahme von Nitraten und einer erfolgreichen Intervention. 20% der gescheiterten Interventionen sind auf technisch mechanische Hindernisse zurückzuführen. Beispielsweise war dabei kein arterieller Zugang zu etablieren oder die Verschlussstelle konnte aufgrund von Stenosen oder Elongationen nicht erreicht werden. In dieser Gruppe konnte eine deutliche Häufung von pAVK und der Einnahme von Acetylsalicylsäure dargelegt werden. Des Weiteren traten bei diesen Patienten technisch-mechanische Hindernisse häufiger bei Verschlüssen der A. carotis interna und seltener in der A. cerebri media, Segment M1 auf. Bei 80% der frustranen Thrombektomien gelang es zwar, den Verschluss zu erreichen, allerdings konnte das Gefäß aus anderen Gründen nicht oder nicht vollständig eröffnet werden. Vorhofflimmern trat bei diesen Patienten seltener auf als in der Kontrollgruppe. Eine Gerinnungsstörung liegt dagegen signifikant häufiger vor. Hinsichtlich der Gerinnungstherapie mit Cumarinen oder Direkten Oralen Antikoagulantien zeigte sich in keiner der Gruppen ein Unterschied. Auch Laborparameter für eine Entzündungsreaktion und die Gerinnung waren in beiden Gruppen vergleichbar. Zeitliche Faktoren bezogen auf Symptombeginn, Lyse und Intervention scheinen für den Rekanalisationserfolg keine Rolle zu spielen, obwohl aus der Literatur bekannt ist, dass sie das Outcome des Patienten stark beeinflussen. Histologische Untersuchungen gewonnener Thromben zeigten – bei einer Fallzahl von nur 6 Proben – keine Differenzen, ebenso wenig wie CT-morphologische Charakteristika des Thrombus. Zusammenfassend lässt sich feststellen, dass etwa 17% aller geplanten Interventionen nach obiger Definition frustran verlaufen. Bei 20% davon, liegt die Ursache in technisch-mechanischen Hindernissen und eine direkte Punktion der Carotiden könnte in einigen Fällen Abhilfe schaffen, um die Verschlussstelle zu erreichen. Bei den übrigen 80% der scheiternden Interventionen liegt die Ursache hauptsächlich in zwei Gründen: Entweder kann trotz erfolgreicher Platzierung des Stent-Retrievers kein Gerinnsel geborgen werden oder es bleibt ein Verschluss distal gelegener Gefäßäste bestehen. Komplikationen, wie Dissektionen und subarachnoidale Blutungen, sind insgesamt selten. Anzumerken ist, dass nur angiographische Daten und keine klinischen Parameter betreffend das Outcome erhoben wurden. Mit 200 Patienten war die untersuchte Fallzahl nicht sehr groß, sodass keine statistische Signifikanz erreicht werden konnte und sich bei vielen Parametern lediglich Tendenzen erkennen lassen. Eine Ausweitung der Studie auf andere Zentren oder eine Wiederholung zu einem späteren Zeitpunkt mit einer größeren Patientenzahl wäre daher wünschenswert.The present study investigated the causes of failing thrombectomy in patients with acute ischemic stroke of the anterior circulation (A. carotis interna, A. cerebri media). The entire study population comprised 100 failed interventions and 100 randomly selected control patients from a total of 596 interventionally treated patients at Saarland University Hospital between January 2014 and October 2018. The collective of the two groups did not differ statistically in age, sex and symptom severity. A postinterventional TICI score of 2b or higher was defined as a successful intervention. It was found that the neurovascular center in Homburg had comparable success rates to the international literature of about 83.2%. In the study population, intravenous thrombolysis before intervention significantly increases the success rate. Furthermore, there was a statistical correlation between the long-term intake of nitrates and a successful intervention. 20% of the failing interventions are due to technical mechanical obstacles. For example, no arterial access could be established, or the occlusion site could not be reached due to stenosis or elongation. In this group, an association with PAOD and the intake of acetylsalicylic acid could be demonstrated. In addition, technical and mechanical obstacles occurred more frequently in occlusions of the internal carotid artery and less frequently in the cerebral media artery, segment M1. In 80% of the frustrated thrombectomies it was possible to reach the occlusion site, but for other reasons the vessel could not or not completely be recanalized. In this group, atrial fibrillation is less frequent than in the control group. In addition, patients with a coagulation disorder have a significantly worse result. Regarding coagulation therapy with coumarins or direct oral anticoagulants, there was no difference in any of the groups. Laboratory parameters for inflammatory response and coagulation were also comparable in both groups. Time factors related to symptom onset, lysis and intervention do not seem to play a role in the success of recanalization, although it is known from the literature that they strongly influence the outcome of the patient. Histological examinations of thrombi obtained - with a case number of only 6 samples - showed no differences, nor did CT-morphological data of the thrombus. In summary, 17% of all interventions fail according to the definition above. In 20% of these, there are technical reasons for failure. Direct carotid puncture could be a solution to reach the occlusion site. In the remainig 80% there are two main causes for failure: On the one hand, no thrombus material can be extracted although the stent-retriever-device is correctly in place and on the other hand, distal vessel branches stay occluded. In total, complications such as subarachnoid hemorrhage or iatrogenic dissection are rare. It should be noted that only angiographic data and no clinical parameters concerning patient outcome were collected. With 200 patients, the investigated case number was not very large, so that no statistic significance could be proven and only tendencies can be identified for many parameters. An extension of the study to other centers or a repetition with a larger number of patients would therefore be necessary

Selective synthesis of primary amines by kinetic-based optimization of the ruthenium-Xantphos catalysed amination of alcohols with ammonia

The selective synthesis of primary amines directly from several alcohols and ammonia using a homogeneous catalyst based on HRuCl(CO)(PPh3)3 and Xantphos is presented. The key to success was the detailed understanding of all mutually influencing parameters such as temperature, ammonia excess, and substrate concentration. These studies were supported by the determination of the kinetics, which allowed the reaction order to be calculated as 0.7. Furthermore, the kinetic model derived from the mechanism was confirmed. After measuring reaction profiles for all influencing parameters, optimized conditions were obtained, which finally allowed the amination of aliphatic, cyclic, as well as primary and secondary alcohols with selectivities to the desired primary amine exceeding 90 % at quantitative alcohol conversion with only minimal formation of the undesired secondary amines. Furthermore, the catalytic activity of the commercially available and robust Xantphos system was drastically improved, corresponding to a turnover frequency (TOF)>60 h−1 after 30 minutes and a turnover number (TON) of 120