Tangle analysis of difference topology experiments: applications to a Mu protein-DNA complex

We develop topological methods for analyzing difference topology experiments involving 3-string tangles. Difference topology is a novel technique used to unveil the structure of stable protein-DNA complexes involving two or more DNA segments. We analyze such experiments for the Mu protein-DNA complex. We characterize the solutions to the corresponding tangle equations by certain knotted graphs. By investigating planarity conditions on these graphs we show that there is a unique biologically relevant solution. That is, we show there is a unique rational tangle solution, which is also the unique solution with small crossing number.Comment: 60 pages, 74 figure

Prospective evaluation of biomarkers for prediction of quality of life in community-acquired pneumonia

Most clinical research investigated prognostic biomarkers for their ability to predict cardiovascular events or mortality. It is unknown whether biomarkers allow prediction of quality of life (QoL) after survival of the acute event. Herein, we investigated the prognostic potential of well-established inflammatory/cardiovascular blood biomarkers including white blood cells (WBC), C-reactive protein (CRP), procalcitonin (PCT), pro-adrenomedullin (proADM) and pro-atrial natriuretic peptide (proANP) in regard to a decline in QoL in a well-defined cohort of patients with community-acquired pneumonia (CAP).; Within this secondary analysis including 753 patients with a final inpatient diagnosis of CAP from a multicenter trial, we investigated associations between admission biomarker levels and decline in QoL assessed by the EQ-5D health questionnaire from admission to day 30 and after 6 years.; Admission proADM and proANP levels significantly predicted decline of the weighted EQ-5D index after 30 days (n=753) with adjusted odds ratios (ORs) of 2.0 ([95% CI 1.1-3.8]; p=0.027) and 3.7 ([95% CI 2.2-6.0]; p>0.001). Results for 6-year outcomes (n=349) were similar with ORs of 3.3 ([95% CI 1.3-8.3]; p=0.012) and 6.2 ([95% CI 2.7-14.2]; p>0.001). The markers were associated with most of the different QoL dimensions including mobility, self-care, and usual activities, but not pain/discomfort and to a lesser degree anxiety/depression and the visual analogue scale (VAS). Initial WBC, PCT and CRP values did not well predict QoL at any time point.; ProADM and proANP accurately predict short- and long-term decline in QoL across most dimensions in CAP patients. It will be interesting to reveal underlying physiopathology in future studies

Activation of the tryptophan/serotonin pathway is associated with severity and predicts outcomes in pneumonia: results of a long-term cohort study

As part of the immune defense during infection, an increase in enzyme activity of indoleamine 2,3-dioxygenase (IDO) leads to a breakdown of tryptophan to kynurenine. In previous animal studies, therapeutic antagonism of IDO resulted in reduced sepsis mortality. We investigated the prognostic ability of tryptophan, serotonin, kynurenine and IDO (represented by the ratio of kynurenine/tryptophan) to predict adverse clinical outcomes in patients with community-acquired pneumonia (CAP).; We measured tryptophan, serotonin and kynurenine on admission plasma samples from CAP patients included in a previous multicenter trial by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). We studied their association with inflammation (C-reactive protein), infection (procalcitonin) and clinical outcome.; Mortality in the 268 included patients was 45% within 6 years of follow-up. IDO and kynurenine showed a strong positive correlation with markers of infection (procalcitonin) and inflammation (C-reactive protein) as well as sepsis and CAP severity scores. Tryptophan showed similar, but negative correlations. In a multivariate regression analysis adjusted for age and comorbidities, higher IDO activity and lower tryptophan levels were strongly associated with short-term adverse outcome defined as death and/or ICU admission within 30 days with adjusted odds ratios of 9.1 [95% confidence interval (CI) 1.4-59.5, p=0.021] and 0.11 (95% CI 0.02-0.70, p=0.021). Multivariate analysis did not reveal significant associations for kynurenine and serotonin.; In hospitalized CAP patients, higher IDO activity and lower tryptophan levels independently predicted disease severity and short-term adverse outcome. Whether therapeutic modulation of IDO has positive effects on outcome needs further investigation

Vergleich verschiedener Verhaltenstherapieformen bei aggressiven Hunden

Ziel der Studie war es, drei verschiedene Verhaltenstherapieformen bei aggressiven Hunden auf ihren Behandlungserfolg hin zu vergleichen

An Architecture for Peer-to-Peer Integration of Interorganizational Information Systems

On the business case of independent sales agencies we discuss the requirements of tiny sized enterprises for data integration. If a multitude of independent enterprises need to be integrated, we argue that those are best represented by equal peers and describe the Architecture of VIANA: a Peer-to-Peer architecture for materialized integration of information systems, both in the interas well as the intraorganizational domain. VIANA propagates updates on data between peers and continuously monitors data quality. We argue that this type of integration can be accomplished with ideally no alteration of the participating information systems and that the integration may benefit substantially from existing data exchange formats. To this end we formulate the architecture in a way that existing XML technologies and standards may be utilized without the need for alterations

Towards a Design Science Research Process for Legal Compliance by Design

The increasing complexity of IT-related laws and regulations pushes IS research to better integrate compliance into IS design processes. One key issue is the presence of often multiple legal provisions relevant to the same artifact. This generates tensions that can only be resolved through legal reasoning. Building on design science research and interdisciplinary literature, we explore features of a holistic design process based on legal reasoning to support legal compliance. We focus on the early stages of the design process - i.e., problem identification and definition of the objectives - and introduce two novel design activities: (1) analyzing the nature of requirements and (2) identifying and defining design trade-offs. Thereby, we develop a preliminary guideline to engage with legal experts. Our emerging method eases the transition into the design phase by putting legal reasoning before the definition of design objectives

With or Without Blockchain? Towards a Decentralized, SSI-based eRoaming Architecture

Fragmentation and limited accessibility of charging infrastructure impede the adoption of electric vehicles. To improve the availability of charging infrastructure independent of providers, eRoaming offers a promising solution. Yet, current eRoaming systems are typically centralized, which raises concerns of market power concentration. While the use of blockchain technology can obviate such concerns, it comes with significant privacy challenges. To address these challenges, we explore a combination of blockchain with self-sovereign identity. Specifically, we apply a design science research approach, which helps us to identify requirements, derive a conceptual architecture, and deduce design principles for decentralized eRoaming and beyond. We find that blockchain may best leverage its benefits when it takes a backseat as a public registry for legal entities. Moreover, we find that the use of self-sovereign identities could improve compliance with privacy regulations, but they should not be overused

With or Without Blockchain? Towards a Decentralized, SSI-based eRoaming Architecture

Fragmentation and limited accessibility of charging infrastructure impede the adoption of electric vehicles. To improve the availability of charging infrastructure independent of providers, eRoaming offers a promising solution. Yet, current eRoaming systems are typically centralized, which raises concerns of market power concentration. While the use of blockchain technology can obviate such concerns, it comes with significant privacy challenges. To address these challenges, we explore a combination of blockchain with self-sovereign identity. Specifically, we apply a design science research approach, which helps us to identify requirements, derive a conceptual architecture, and deduce design principles for decentralized eRoaming and beyond. We find that blockchain may best leverage its benefits when it takes a backseat as a public registry for legal entities. Moreover, we find that the use of self-sovereign identities could improve compliance with privacy regulations, but they should not be overused