Single DNA conformations and biological function

From a nanoscience perspective, cellular processes and their reduced in vitro imitations provide extraordinary examples for highly robust few or single molecule reaction pathways. A prime example are biochemical reactions involving DNA molecules, and the coupling of these reactions to the physical conformations of DNA. In this review, we summarise recent results on the following phenomena: We investigate the biophysical properties of DNA-looping and the equilibrium configurations of DNA-knots, whose relevance to biological processes are increasingly appreciated. We discuss how random DNA-looping may be related to the efficiency of the target search process of proteins for their specific binding site on the DNA molecule. And we dwell on the spontaneous formation of intermittent DNA nanobubbles and their importance for biological processes, such as transcription initiation. The physical properties of DNA may indeed turn out to be particularly suitable for the use of DNA in nanosensing applications.Comment: 53 pages, 45 figures. Slightly revised version of a review article, that is going to appear in the J. Comput. Theoret. Nanoscience; some typos correcte

Prä- und postoperative neuropsychiatrische Befunde bei Patienten mit primärem Hyperparathyreoidismus

Fragestellung vorliegender Untersuchung ist die Häufigkeit und die Veränderung neuropsychiatrischer Symptome bei Patienten mit primärem Hyperparathyreoidismus vor und nach Parathyreoidektomie. Es wurden die folgenden zwei Hypothesen überprüft und bestätigt. Erstens: Patienten mit pHPT zeigen mehr und stärkere neuropsychiatrische Symptome als nicht-pHPT-Patienten, die ebenfalls operativen Stressoren ausgesetzt sind und zweitens: pHPT-Patienten zeigen bereits wenige Tage nach Parathyreoidektomie eine Reduktion neuropsychiatrischer Befunde in Häufigkeit und Schweregrad. Untersucht wurden 39 zufällig ausgewählte pHPT-Patienten im mittleren Alter von 63 Jahren (Mittelwert 62,7; SD 9,9) und eine Kontrollgruppe aus 22 Patienten mit euthyreoter Struma im mittleren Alter von 52 Jahren (Mittelwert 51,8; SD 14,6) der Klinik für Allgemeinchirurgie des Zentrums für Operative Medizin I im Klinikum der Phillipps-Universität Marburg. Alle Studienteilnehmer wurden am Tage vor und drei Tage nach ihrer Operation mit Selbst- und Fremdbeurteilungsverfahren der Depressivität (HAMD, MADRS, BDI), der psychischen Beeinträchtigung (SCL-90-R) und kognitiven Leistungstests (Benton-Test, d2, KAI) in einer standardisierten Testsituation untersucht. Patienten mit pHPT zeigen präoperativ insgesamt mehr depressive Symptome in der Fremdbeurteilung (MADRS, HAMD), eine höhere psychische Beeinträchtigung (SCL-90-R) und geringere kognitive Leistungsfähigkeit (d2, KAI, Benton-Test) als Patienten mit euthyreoter Struma. Obwohl die Patienten mit pHPT postoperativ eine signifikante Reduktion auffälliger Befunde zeigen, bestehen weiterhin signifikante Unterschiede zu den Struma-Patienten in der psychischen Beeinträchtigung (SCL-90-R) und der kognitiven Leistungsfähigkeit (d2, KAI, Benton-Test)

Hydrogen-powered aviation in Germany: A macroeconomic perspective and methodological approach of fuel supply chain integration into an economy-wide dataset

The hydrogen (H2) momentum affects the aviation sector. However, a macroeconomic consideration is currently missing. To address this research gap, the paper derives a methodology for evaluating macroeconomic effects of H2 in aviation and applies this approach to Germany. Three goals are addressed: (1) Construction of a German macroeconomic database. (2) Translation of H2 supply chains to the system of national accounts. (3) Implementation of H2-powered aviation into the macroeconomic data framework. The article presents an economy-wide database for analyzing H2-powered aviation. Subsequently, the paper highlights three H2 supply pathways, provides an exemplary techno-economic cost break-down for ten H2 components and translates them into the data framework. Eight relevant macroeconomic sectors for H2-powered aviation are identified and quantified. Overall, the paper contributes on a suitable foundation to apply the macroeconomic dataset and to conduct macroeconomic analyses on H2-powered aviation. Finally, the article highlights further research potential on job effects related to future H2 demand

Blinking statistics of a molecular beacon triggered by end-denaturation of DNA

We use a master equation approach based on the Poland-Scheraga free energy for DNA denaturation to investigate the (un)zipping dynamics of a denaturation wedge in a stretch of DNA, that is clamped at one end. In particular, we quantify the blinking dynamics of a fluorophore-quencher pair mounted within the denaturation wedge. We also study the behavioural changes in the presence of proteins, that selectively bind to single-stranded DNA. We show that such a setup could be well-suited as an easy-to-implement nanodevice for sensing environmental conditions in small volumes.Comment: 14 pages, 5 figures, LaTeX, IOP style. Accepted to J Phys Cond Mat special issue on diffusio

Breathing dynamics in heteropolymer DNA

While the statistical mechanical description of DNA has a long tradition, renewed interest in DNA melting from a physics perspective is nourished by measurements of the fluctuation dynamics of local denaturation bubbles by single molecule spectroscopy. The dynamical opening of DNA bubbles (DNA breathing) is supposedly crucial for biological functioning during, for instance, transcription initiation and DNA's interaction with selectively single-stranded DNA binding proteins. Motivated by this, we consider the bubble breathing dynamics in a heteropolymer DNA based on a (2+1)-variable master equation and complementary stochastic Gillespie simulations, providing the bubble size and the position of the bubble along the sequence as a function of time. We utilize new experimental data that independently obtain stacking and hydrogen bonding contributions to DNA stability. We calculate the spectrum of relaxation times and the experimentally measurable autocorrelation function of a fluorophore-quencher tagged base-pair, and demonstrate good agreement with fluorescence correlation experiments. A significant dependence of opening probability and waiting time between bubble events on the local DNA sequence is revealed and quantified for a promoter sequence of the T7 phage. The strong dependence on sequence, temperature and salt concentration for the breathing dynamics of DNA found here points at a good potential for nanosensing applications by utilizing short fluorophore-quencher dressed DNA constructs.Comment: 11 pages, 8 figure

On the Importance of the Equation of State for the Neutrino-Driven Supernova Explosion Mechanism

By implementing widely-used equations of state (EOS) from Lattimer & Swesty (LS) and H. Shen et al. (SHEN) in core-collapse supernova simulations, we explore possible impacts of these EOS on the post-bounce dynamics prior to the onset of neutrino-driven explosions. Our spherically symmetric (1D) and axially symmetric (2D) models are based on neutrino radiation hydrodynamics including spectral transport, which is solved by the isotropic diffusion source approximation. We confirm that in 1D simulations neutrino-driven explosions cannot be obtained for any of the employed EOS. Impacts of the EOS on the post-bounce hydrodynamics are more clearly visible in 2D simulations. In 2D models of a 15 M_sun progenitor using the LS EOS, the stalled bounce shock expands to increasingly larger radii, which is not the case using the SHEN EOS. Keeping in mind that the omission of the energy drain by heavy-lepton neutrinos in the present scheme could facilitate explosions, we find that 2D models of an 11.2 M_sun progenitor produce neutrino-driven explosions for all the EOS under investigation. Models using the LS EOS are slightly more energetic compared to those with the SHEN EOS. The more efficient neutrino heating in the LS models coincides with a higher electron antineutrino luminosity and a larger mass that is enclosed within the gain region. The models based on the LS EOS also show a more vigorous and aspherical downflow of accreting matter to the surface of the protoneutron star (PNS). The accretion pattern is essential for the production and strength of outgoing pressure waves, that can push in turn the shock to larger radii and provide more favorable conditions for the explosion. [abbreviated]Comment: 21 pages, 22 figures, accepted for publication in Ap

Nature of unconventional pairing in the kagome superconductors AV3_3Sb5_5

The recent discovery of AV$_3$Sb$_5$ (A=K,Rb,Cs) has uncovered an intriguing arena for exotic Fermi surface instabilities in a kagome metal. Among them, superconductivity is found in the vicinity of multiple van Hove singularities, exhibiting indications of unconventional pairing. We show that the sublattice interference mechanism is central to understanding the formation of superconductivity in a kagome metal. Starting from an appropriately chosen minimal tight-binding model with multiple with multiple van Hove singularities close to the Fermi level for AV$_3$Sb$_5$, we provide a random phase approximation analysis of superconducting instabilities. Non-local Coulomb repulsion, the sublattice profile of the van Hove bands, and the bare interaction strength turn out to be the crucial parameters to determine the preferred pairing symmetry. Implications for potentially topological surface states are discussed, along with a proposal for additional measurements to pin down the nature of superconductivity in AV$_3$Sb$_5$.Comment: 6 page, 4 figure

Entropy loss in long-distance DNA looping

The entropy loss due to the formation of one or multiple loops in circular and linear DNA chains is calculated from a scaling approach in the limit of long chain segments. The analytical results allow to obtain a fast estimate for the entropy loss for a given configuration. Numerical values obtained for some examples suggest that the entropy loss encountered in loop closure in typical genetic switches may become a relevant factor which has to be overcome by the released bond energy between the looping contact sites.Comment: 7 pages, 3 figure

Handbuch methodischer Grundfragen zur Masterplan-Erstellung - Kommunale Masterpläne für 100 % Klimaschutz

Masterplan-Kommunen sind die Vorreiter unter den Klimaschutzkommunen und müssen über das bisher in der Breite bereits Begonnene hinausgehen. Sie stehen vor großen strukturellen und finanziellen Herausforderungen, aber auch vor großen Chancen. Die Chancen ergeben sich insbesondere für ein verbessertes und lebenswerteres Umfeld in der Kommune und damit auch für eine gesteigerte Lebensqualität. Die Einbindung aller Akteure in der Kommune, innerhalb und außerhalb der Verwaltung, ist ein wichtiger Baustein auf dem Weg zum Ziel „Null Emissionen“. Vor allem die Einbindung der Wirtschaft vor Ort und der Bürgerinnen und Bürger ist essenziell, wenn eine Transformation angestoßen und umgesetzt werden soll. Das Handbuch unterstützt die Masterplan-Kommunen mit der vorliegenden methodischen Herangehensweise auf ihrem Weg

Procalcitonin reflects bacteremia and bacterial load in urosepsis syndrome: a prospective observational study

Introduction: Guidelines recommend that two blood cultures be performed in patients with febrile urinary tract infection (UTI), to detect bacteremia and help diagnose urosepsis. The usefulness and cost-effectiveness of this practice have been criticized. This study aimed to evaluate clinical characteristics and the biomarker procalcitonin (PCT) as an aid in predicting bacteremia. Methods: A prospective observational multicenter cohort study included consecutive adults with febrile UTI in 35 primary care units and 8 emergency departments of 7 regional hospitals. Clinical and microbiological data were collected and PCT and time to positivity (TTP) of blood culture were measured. Results: Of 581 evaluable patients, 136 (23%) had bacteremia. The median age was 66 years (interquartile range 46 to 78 years) and 219 (38%) were male. We evaluated three different models: a clinical model including seven bedside characteristics, the clinical model plus PCT, and a PCT only model. The diagnostic abilities of these models as reflected by area under the curve of the receiver operating characteristic were 0.71 (95% confidence interval (CI): 0.66 to 0.76), 0.79 (95% CI: 0.75 to 0.83) and 0.73 (95% CI: 0.68 to 0.77) respectively. Calculating corresponding sensitivity and specificity for the presence of bacteremia after each step of adding a significant predictor in the model yielded that the PCT > 0.25 mu g/l only model had the best diagnostic performance (sensitivity 0.95; 95% CI: 0.89 to 0.98, specificity 0.50; 95% CI: 0.46 to 0.55). Using PCT as a single decision tool, this would result in 40% fewer blood cultures being taken, while still identifying 94 to 99% of patients with bacteremia. The TTP of E. coli positive blood cultures was linearly correlated with the PCT log value; the higher the PCT the shorter the TTP (R-2 = 0.278, P = 0.007). Conclusions: PCT accurately predicts the presence of bacteremia and bacterial load in patients with febrile UTI. This may be a helpful biomarker to limit use of blood culture resources.Immunogenetics and cellular immunology of bacterial infectious disease