Torsional Directed Walks, Entropic Elasticity, and DNA Twist Stiffness

DNA and other biopolymers differ from classical polymers due to their torsional stiffness. This property changes the statistical character of their conformations under tension from a classical random walk to a problem we call the `torsional directed walk'. Motivated by a recent experiment on single lambda-DNA molecules [Strick et al., Science 271 (1996) 1835], we formulate the torsional directed walk problem and solve it analytically in the appropriate force regime. Our technique affords a direct physical determination of the microscopic twist stiffness C and twist-stretch coupling D relevant for DNA functionality. The theory quantitatively fits existing experimental data for relative extension as a function of overtwist over a wide range of applied force; fitting to the experimental data yields the numerical values C=120nm and D=50nm. Future experiments will refine these values. We also predict that the phenomenon of reduction of effective twist stiffness by bend fluctuations should be testable in future single-molecule experiments, and we give its analytic form.Comment: Plain TeX, harvmac, epsf; postscript available at http://dept.physics.upenn.edu/~nelson/index.shtm

Sequence Effects on DNA Entropic Elasticity

DNA stretching experiments are usually interpreted using the worm-like chain model; the persistence length A appearing in the model is then interpreted as the elastic stiffness of the double helix. In fact the persistence length obtained by this method is a combination of bend stiffness and intrinsic bend effects reflecting sequence information, just as at zero stretching force. This observation resolves the discrepancy between the value of A measured in these experiments and the larger ``dynamic persistence length'' measured by other means. On the other hand, the twist persistence length deduced from torsionally-constrained stretching experiments suffers no such correction. Our calculation is very simple and analytic; it applies to DNA and other polymers with weak intrinsic disorder.Comment: LaTeX; postscript available at http://dept.physics.upenn.edu/~nelson/index.shtm

Mechanical response of plectonemic DNA: an analytical solution

We consider an elastic rod model for twisted DNA in the plectonemic regime. The molecule is treated as an impenetrable tube with an effective, adjustable radius. The model is solved analytically and we derive formulas for the contact pressure, twisting moment and geometrical parameters of the supercoiled region. We apply our model to magnetic tweezer experiments of a DNA molecule subjected to a tensile force and a torque, and extract mechanical and geometrical quantities from the linear part of the experimental response curve. These reconstructed values are derived in a self-contained manner, and are found to be consistent with those available in the literature.Comment: 14 pages, 4 figure

Fluctuating Filaments I: Statistical Mechanics of Helices

We examine the effects of thermal fluctuations on thin elastic filaments with non-circular cross-section and arbitrary spontaneous curvature and torsion. Analytical expressions for orientational correlation functions and for the persistence length of helices are derived, and it is found that this length varies non-monotonically with the strength of thermal fluctuations. In the weak fluctuation regime, the local helical structure is preserved and the statistical properties are dominated by long wavelength bending and torsion modes. As the amplitude of fluctuations is increased, the helix ``melts'' and all memory of intrinsic helical structure is lost. Spontaneous twist of the cross--section leads to resonant dependence of the persistence length on the twist rate.Comment: 5 figure

Governments, decentralisation, and the risk of electoral defeat

<p>In the last three decades several countries around the world have transferred authority from their national to their regional governments. However, not all their regions have been empowered to the same degree and important differences can be observed between and within countries. Why do some regions obtain more power than others? Current literature argues that variation in the redistribution of power and resources between regions is introduced by demand. Yet these explanations are conditional on the presence of strong regionalist parties or territorial cleavages. This article proposes instead a theory that links the government’s risk of future electoral defeat with heterogeneous decentralisation, and tests its effects using data from 15 European countries and 141 regions. The results provide evidence that parties in government protect themselves against the risk of electoral defeat by selectively targeting decentralisation towards regions in which they are politically strong. The findings challenge previous research that overestimates the importance of regionalist parties while overlooking differences between regions.</p

Enhancement of Magneto-Optic Effects via Large Atomic Coherence

We utilize the generation of large atomic coherence to enhance the resonant nonlinear magneto-optic effect by several orders of magnitude, thereby eliminating power broadening and improving the fundamental signal-to-noise ratio. A proof-of-principle experiment is carried out in a dense vapor of Rb atoms. Detailed numerical calculations are in good agreement with the experimental results. Applications such as optical magnetometry or the search for violations of parity and time reversal symmetry are feasible

Chromatin: a tunable spring at work inside chromosomes

This paper focuses on mechanical aspects of chromatin biological functioning. Within a basic geometric modeling of the chromatin assembly, we give for the first time the complete set of elastic constants (twist and bend persistence lengths, stretch modulus and twist-stretch coupling constant) of the so-called 30-nm chromatin fiber, in terms of DNA elastic properties and geometric properties of the fiber assembly. The computation naturally embeds the fiber within a current analytical model known as the ``extensible worm-like rope'', allowing a straightforward prediction of the force-extension curves. We show that these elastic constants are strongly sensitive to the linker length, up to 1 bp, or equivalently to its twist, and might locally reach very low values, yielding a highly flexible and extensible domain in the fiber. In particular, the twist-stretch coupling constant, reflecting the chirality of the chromatin fiber, exhibits steep variations and sign changes when the linker length is varied. We argue that this tunable elasticity might be a key feature for chromatin function, for instance in the initiation and regulation of transcription.Comment: 38 pages 15 figure

Use of the Behavior Assessment Tool in 18 Pilot Residency Programs

Background: The purpose of this study was to determine the feasibility and evaluate the effectiveness of the American Board of Orthopaedic Surgery Behavior Tool (ABOSBT) for measuring professionalism. Methods: Through collaboration between the American Board of Orthopaedic Surgery and American Orthopaedic Association\u27s Council of Residency Directors, 18 residency programs piloted the use of the ABOSBT. Residents requested assessments from faculty at the end of their clinical rotations, and a 360° request was performed near the end of the academic year. Program Directors (PDs) rated individual resident professionalism (based on historical observation) at the outset of the study, for comparison to the ABOSBT results. Results: Nine thousand eight hundred ninety-two evaluations were completed using the ABOSBT for 449 different residents by 1,012 evaluators. 97.6% of all evaluations were scored level 4 or 5 (high levels of professional behavior) across all of the 5 domains. In total, 2.4% of all evaluations scored level 3 or below reflecting poorer performance. Of 431 residents, the ABOSBT identified 26 of 32 residents who were low performers (2 or more \u3c level 3 scores in a domain) and who also scored below expectations by the PD at the start of the pilot project (81% sensitivity and 57% specificity), including 13 of these residents scoring poorly in all 5 domains. Evaluators found the ABOSBT was easy to use (96%) and that it was an effective tool to assess resident professional behavior (81%). Conclusions: The ABOSBT was able to identify 2.4% low score evaluations ( Level of Evidence: Level II

Colonial Heritage and Economic Development

While the importance of institutions for explaining cross-country income differences is widely recognized, comparatively little is known about the origins of economic institutions. One strand of the literature emphasizes cultural differences while another points at exogenous environmental factors such as mortality and climate. Both are supported by some empirical evidence. I reconcile the two schools of institutional origins by proposing a theory of self-selection of colonists to different geographic destinations. Exogenous characteristics such as climate, mortality and factor differences determine which type of settler decides to move to a particular colony. Settler type, in turn, shapes the institutional quality of the new country. The model is used to confirm observed regularities reported by previous researchers. Furthermore, robust new evidence is presented in support of this selection process. The results suggest that any theory of colonial development that does not take selection into account will be incomplete

Mechanism Based Design of Efficient PET Hydrolases

Polyethylene terephthalate PET is the most widespread synthetic polyester, having been utilized in textile fibers and packaging materials for beverages and food, contributing considerably to the global solid waste stream and environmental plastic pollution. While enzymatic PET recycling and upcycling have recently emerged as viable disposal methods for a circular plastic economy, only a handful of benchmark enzymes have been thoroughly described and subjected to protein engineering for improved properties over the last 16 years. By analyzing the specific material properties of PET and the reaction mechanisms in the context of interfacial biocatalysis, this Perspective identifies several limitations in current enzymatic PET degradation approaches. Unbalanced enzyme substrate interactions, limited thermostability, and low catalytic efficiency at elevated reaction temperatures, and inhibition caused by oligomeric degradation intermediates still hamper industrial applications that require high catalytic efficiency. To overcome these limitations, successful protein engineering studies using innovative experimental and computational approaches have been published extensively in recent years in this thriving research field and are summarized and discussed in detail here. The acquired knowledge and experience will be applied in the near future to address plastic waste contributed by other mass produced polymer types e.g., polyamides and polyurethanes that should also be properly disposed by biotechnological approache