ATPase cycle and DNA unwinding kinetics of RecG helicase

The superfamily 2 bacterial helicase, RecG, is a monomeric enzyme with a role in DNA repair by reversing stalled replication forks. The helicase must act specifically and rapidly to prevent replication fork collapse. We have shown that RecG binds tightly and rapidly to four-strand oligonucleotide junctions, which mimic a stalled replication fork. The helicase unwinds such DNA junctions with a step-size of approximately four bases per ATP hydrolyzed. To gain an insight into this mechanism, we used fluorescent stopped-flow and quenched-flow to measure individual steps within the ATPase cycle of RecG, when bound to a DNA junction. The fluorescent ATP analogue, mantATP, was used throughout to determine the rate limiting steps, effects due to DNA and the main states in the cycle. Measurements, when possible, were also performed with unlabeled ATP to confirm the mechanism. The data show that the chemical step of hydrolysis is the rate limiting step in the cycle and that this step is greatly accelerated by bound DNA. The ADP release rate is similar to the cleavage rate, so that bound ATP and ADP would be the main states during the ATP cycle. Evidence is provided that the main structural rearrangements, which bring about DNA unwinding, are linked to these states

When social scientists disagree: comments on the Butler-van den Besselaar debate

In 2003, Linda Butler found evidence that as a result of “the increased culture of evaluation faced by the [Australian higher education] sector … [in which] significant funds are distributed to universities, and within universities, on the basis of aggregate publication counts, with little attention paid to the impact or quality of that output … journal publication productivity has increased significantly in the last decade [the 1990s], but its impact has declined” (Butler, 2003a, p.143). More recently, however, Peter van den Besselaar, Ulf Heyman and Ulf Sandström (hereafter BHS) have concluded from their bibliometric analysis that “Australia not only improved its share of research output but also increased research quality, implying that total impact was greatly increased”, and hence “Butler’s main conclusions are not correct” (van den Besselaar et al., 2017, p.1 ). How can we explain this disagreement

What's happening to our universities?

In recent decades, many universities have been moving in the direction of a more hierarchical and centralised structure, with top-down planning and reduced local autonomy for departments. Yet, the management literature over this period has stressed the numerous benefits of flatter organisational structures, decentralisation and local autonomy for sections or departments. What might explain this paradox? And why have academics remained strangely quiet about this, meekly accepting their fate? This proposition paper critically examines the dangers of centralised top-down management, increasingly bureaucratic procedures, teaching to a prescribed formula, and research driven by assessment and performance targets, illustrating these with a number of specific examples. It discusses a number of possible forces driving these worrying developments, and concludes by asking whether academics may be in danger of suffering the fate of the boiled frog

Twenty challenges to innovation studies

With the field of innovation studies now half a century old, the occasion has been marked by several studies looking back to identify the main advances made over its lifetime. Starting from a list of 20 advances over the field’s history, this discussion paper sets out 20 challenges for coming decades. At a conference in 1900, David Hilbert put forward a list of 23 unsolved mathematical problems that were to have a profound influence on the work of mathematicians during the 20th Century. The intention here is to prompt a debate within the innovation studies community on what are, or should be, the key challenges for us to take up, and more generally on what sort of field we aspire to be. It is argued that the empirical focus of our studies has not kept pace with the fast changing world and economy, especially the shift from manufacturing to services and the growing need for sustainability. Moreover, the very way we conceptualise, define, operationalise and analyse ‘innovation’ seems rooted in the past, leaving us less able to grapple with other less visible or ‘dark’ forms of innovation

The future of science policy and innovation studies: some challenges and the factors underlying them

The field of science policy and innovation studies (SPIS) is now over half a century old. Although relatively well established, it is confronted with various major challenges, as the author has set out in previous papers. In this chapter, we examine what factors might be underlying those challenges. The aim is to understand those factors so that we are better positioned to tackle and eventually overcome these challenges to the field of SPIS

The Forecasting Performance of German Stock Option Densities

In this paper we will be estimating risk-neutral densities (RND) for the largest euro area stock market (the index of which is the German DAX), reporting their statistical properties, and evaluating their forecasting performance. We have applied an innovative test procedure to a new, rich, and accurate data set. We have two main results. First, we have recorded strong negative skewness in the densities. Second, we find evidence for significant differences between the actual density and the risk-neutral density, leading to the conclusion that market participants were surprised by the extent of both the rise and the fall of the DAX. -- In dieser Arbeit werden "risikoneutrale" Dichtefunktionen über künftige DAXIndexstände aus täglich beobachteten Preisen europäischer Kauf- und Verkaufsoptionen mit verschiedenen Restlaufzeiten abgeleitet. Das hierbei verwendete Berechnungsverfahren beruht auf der Mischung von zwei Log-Normalverteilung, bei dem fünf Parameter (der Mischungsparameter, zwei Mittelwerte und zwei Standardabweichungen) so bestimmt werden, dass der quadratische Abstand zwischen beobachteten und impliziten Optionspreisen minimal ist. Die Preisnotierungen für die Derivative werden der Eurex entnommen und der Untersuchungszeitraum erstreckt sich von Dezember 1995 bis Mai 2002, also sowohl über die Boom- als auch über die Niedergangsphase des DAX. Die Vorhersagehorizonte der Dichten sind auf Grund der Datenlage auf sechs bis acht Wochen begrenzt. Die Vorhersagegüte dieser Dichten wird über verschiedene neuartige statistische Evaluierungsverfahren abgeschätzt. Im Ergebnis stellt sich folgendes heraus: Erstens: Die Dichten weisen im Durchschnitt eine negative Schiefe (negatives drittes Moment) auf, so dass das linke Ende der Dichte "dicker" ist als das rechte und die Marktteilnehmer somit einen bestimmten prozentualen Kursverlust als wahrscheinlicher einschätzten als einen Kursgewinn. Zweitens: Die Evaluierungstests für die Dichten machen deutlich, dass die tatsächlichen Dichten im Mittel deutlich von den risikoneutralen Dichten abweichen. Dabei kann ausgeschlossen werden, dass es sich lediglich um einen "Mittelwert"fehler handelt. Vielmehr scheinen die Markteilnehmer sowohl in der Aufschwung- als auch in der Abschwungphase von den Kursbewegungen des DAX überrascht worden zu.option prices,risk-neutral density,density evaluation,overlapping data

Idealized Multigrid Algorithm for Staggered Fermions

An idealized multigrid algorithm for the computation of propagators of staggered fermions is investigated. Exemplified in four-dimensional $SU(2)$ gauge fields, it is shown that the idealized algorithm preserves criticality under coarsening. The same is not true when the coarse grid operator is defined by the Galerkin prescription. Relaxation times in computations of propagators are small, and critical slowing is strongly reduced (or eliminated) in the idealized algorithm. Unfortunately, this algorithm is not practical for production runs, but the investigations presented here answer important questions of principle.Comment: 11 pages, no figures, DESY 93-046; can be formatted with plain LaTeX article styl

On high energy tails in inelastic gases

We study the formation of high energy tails in a one-dimensional kinetic model for granular gases, the so-called Inelastic Maxwell Model. We introduce a time- discretized version of the stochastic process, and show that continuous time implies larger fluctuations of the particles energies. This is due to a statistical relation between the number of inelastic collisions undergone by a particle and its average energy. This feature is responsible for the high energy tails in the model, as shown by computer simulations and by analytical calculations on a linear Lorentz model.Comment: 8 pages, 2 figures, submitted to physica

Supergravity Higgs Inflation and Shift Symmetry in Electroweak Theory

We present a model of inflation in a supergravity framework in the Einstein frame where the Higgs field of the next to minimal supersymmetric standard model (NMSSM) plays the role of the inflaton. Previous attempts which assumed non-minimal coupling to gravity failed due to a tachyonic instability of the singlet field during inflation. A canonical K\"{a}hler potential with \textit{minimal coupling} to gravity can resolve the tachyonic instability but runs into the $\eta$-problem. We suggest a model which is free of the $\eta$-problem due to an additional coupling in the K\"{a}hler potential which is allowed by the Standard Model gauge group. This induces directions in the potential which we call K-flat. For a certain value of the new coupling in the (N)MSSM, the K\"{a}hler potential is special, because it can be associated with a certain shift symmetry for the Higgs doublets, a generalization of the shift symmetry for singlets in earlier models. We find that K-flat direction has $H_u^0=-H_d^{0*}.$ This shift symmetry is broken by interactions coming from the superpotential and gauge fields. This direction fails to produce successful inflation in the MSSM but produces a viable model in the NMSSM. The model is specifically interesting in the Peccei-Quinn (PQ) limit of the NMSSM. In this limit the model can be confirmed or ruled-out not just by cosmic microwave background observations but also by axion searches.Comment: matches the published version at JCA

Stochastic Aggregation: Scaling Properties

We study scaling properties of stochastic aggregation processes in one dimension. Numerical simulations for both diffusive and ballistic transport show that the mass distribution is characterized by two independent nontrivial exponents corresponding to the survival probability of particles and monomers. The overall behavior agrees qualitatively with the mean-field theory. This theory also provides a useful approximation for the decay exponents, as well as the limiting mass distribution.Comment: 6 pages, 7 figure