An alternative formulation of classical electromagnetic duality

By introducing a doublet of electromagnetic four dimensional vector potentials, we set up a manifestly Lorentz covariant and SO(2) duality invariant classical field theory of electric and magnetic charges. In our formulation one does not need to introduce the concept of Dirac string.Comment: 14 pages, no figures, Latex, minor corrections, references and acknowledgements adde

A generalized theory of semiflexible polymers

DNA bending on length scales shorter than a persistence length plays an integral role in the translation of genetic information from DNA to cellular function. Quantitative experimental studies of these biological systems have led to a renewed interest in the polymer mechanics relevant for describing the conformational free energy of DNA bending induced by protein-DNA complexes. Recent experimental results from DNA cyclization studies have cast doubt on the applicability of the canonical semiflexible polymer theory, the wormlike chain (WLC) model, to DNA bending on biological length scales. This paper develops a theory of the chain statistics of a class of generalized semiflexible polymer models. Our focus is on the theoretical development of these models and the calculation of experimental observables. To illustrate our methods, we focus on a specific toy model of DNA bending. We show that the WLC model generically describes the long-length-scale chain statistics of semiflexible polymers, as predicted by the Renormalization Group. In particular, we show that either the WLC or our new model adequate describes force-extension, solution scattering, and long-contour-length cyclization experiments, regardless of the details of DNA bend elasticity. In contrast, experiments sensitive to short-length-scale chain behavior can in principle reveal dramatic departures from the linear elastic behavior assumed in the WLC model. We demonstrate this explicitly by showing that our toy model can reproduce the anomalously large short-contour-length cyclization J factors observed by Cloutier and Widom. Finally, we discuss the applicability of these models to DNA chain statistics in the context of future experiments

Research frontiers in the analysis of coupled biogeochemical cycles

Author Posting. © Ecological Society of America, 2011. This article is posted here by permission of Ecological Society of America for personal use, not for redistribution. The definitive version was published in Frontiers in Ecology and the Environment 9 (2011): 74–80, doi:10.1890/100137.The analysis of coupled biogeochemical cycles (CBCs) addresses the scientific basis for some of today's major environmental problems. Drawing from information presented at a series of sessions on CBCs held at the 2009 Annual Meeting of the Ecological Society of America and from the research community's expertise, we identify several principal research themes that justify action and investment. Critical areas for research include: coupling of major element cycles to less studied yet equally important trace element cycles; analyzing CBCs across ecosystem boundaries; integrating experimental results into regional- and global-scale models; and expanding the analysis of human interactions with CBCs arising from human population growth, urbanization, and geoengineering. To advance the current understanding of CBCs and to address the environmental challenges of the 21st century, scientists must maintain and synthesize data from existing observational and experimental networks, develop new instrumentation networks, and adopt emerging technologies.We thank the National Science Foundation (NSF) and the Ecological Society of America (ESA) for their financial and logistical support of the Coupled Biogeochemical Cycles sessions held at the 2009 ESA Annual Meeting, and the publication of this special feature issue of Frontiers. ACF was supported by the NSF (DEB- 0743564) and the US Department of Energy’s (DOE’s) Office of Biological and Environmental Research (10- DOE-1053). SCD was supported by the Center for Microbial Oceanography, Research and Education (NSF EF-0424599). RBJ was supported by the NSF (DEB #0717191) and by the DOE’s National Institute for Climate Change Research

An Inducible Cell-Cell Fusion System with Integrated Ability to Measure the Efficiency and Specificity of HIV-1 Entry Inhibitors

HIV-1 envelope glycoproteins (Envs) mediate virus entry by fusing the viral and target cell membranes, a multi-step process that represents an attractive target for inhibition. Entry inhibitors with broad-range activity against diverse isolates of HIV-1 may be extremely useful as lead compounds for the development of therapies or prophylactic microbicides. To facilitate the identification of such inhibitors, we have constructed a cell-cell fusion system capable of simultaneously monitoring inhibition efficiency and specificity. In this system, effector cells stably express a tetracycline-controlled transactivator (tTA) that enables tightly inducible expression of both HIV-1 Env and the Renilla luciferase (R-Luc) reporter protein. Target cells express the HIV-1 receptors, CD4 and CCR5, and carry the firefly luciferase (F-Luc) reporter gene under the control of a tTA-responsive promoter. Thus, Env-mediated fusion of these two cell types allows the tTA to diffuse to the target cell and activate the expression of the F-Luc protein. The efficiency with which an inhibitor blocks cell-cell fusion is measured by a decrease in the F-Luc activity, while the specificity of the inhibitor is evaluated by its effect on the R-Luc activity. The system exhibited a high dynamic range and high Z'-factor values. The assay was validated with a reference panel of inhibitors that target different steps in HIV-1 entry, yielding inhibitory concentrations comparable to published virus inhibition data. Our system is suitable for large-scale screening of chemical libraries and can also be used for detailed characterization of inhibitory and cytotoxic properties of known entry inhibitors

Stepwise bending of DNA by a single TATA-box Binding Protein

The TATA-box Binding Protein (TBP) is required by all three eukaryotic RNA polymerases for the initiation of transcription from most promoters. TBP recognizes, binds to, and bends promoter sequences called ``TATA-boxes'' in the DNA. We present results from the study of individual Saccharomyces cerevisia TBPs interacting with single DNA molecules containing a TATA-box. Using video microscopy, we observed the Brownian motion of beads tethered by short surface-bound DNA. When TBP binds to and bends the DNA, the conformation of the DNA changes and the amplitude of Brownian motion of the tethered bead is reduced compared to that of unbent DNA. We detected individual binding and dissociation events and derived kinetic parameters for the process. Dissociation was induced by increasing the salt concentration or by directly pulling on the tethered bead using optical tweezers. In addition to the well-defined free and bound classes of Brownian motion, we observed another two classes of motion. These extra classes were identified with intermediate states on a three-step, linear binding pathway. Biological implications of the intermediate states are discussed.Comment: Accepted for publication in: Biophysical Journa

Elevated CO₂ does not increase eucalypt forest productivity on a low-phosphorus soil

Rising atmospheric CO2 stimulates photosynthesis and productivity of forests, offsetting CO2 emissions. Elevated CO2 experiments in temperate planted forests yielded ~23% increases in productivity over the initial years. Whether similar CO2 stimulation occurs in mature evergreen broadleaved forests on low-phosphorus (P) soils is unknown, largely due to lack of experimental evidence. This knowledge gap creates major uncertainties in future climate projections as a large part of the tropics is P-limited. Here,we increased atmospheric CO2 concentration in a mature broadleaved evergreen eucalypt forest for three years, in the first large-scale experiment on a P-limited site. We show that tree growth and other aboveground productivity components did not significantly increase in response to elevated CO2 in three years, despite a sustained 19% increase in leaf photosynthesis. Moreover, tree growth in ambient CO2 was strongly P-limited and increased by ~35% with added phosphorus. The findings suggest that P availability may potentially constrain CO2-enhanced productivity in P-limited forests; hence, future atmospheric CO2 trajectories may be higher than predicted by some models. As a result, coupled climate-carbon models should incorporate both nitrogen and phosphorus limitations to vegetation productivity in estimating future carbon sinks

Astrophysical Constraints on Modifying Gravity at Large Distances

Recently, several interesting proposals were made modifying the law of gravity on large scales, within a sensible relativistic formulation. This allows a precise formulation of the idea that such a modification might account for galaxy rotation curves, instead of the usual interpretation of these curves as evidence for dark matter. We here summarize several observational constraints which any such modification must satisfy, and which we believe make more challenging any interpretation of galaxy rotation curves in terms of new gravitational physics.Comment: References added, submitted to Classical & Quantum Gravit

Dark matter and non-Newtonian gravity from General Relativity coupled to a fluid of strings

An exact solution of Einstein's field equations for a point mass surrounded by a static, spherically symmetric fluid of strings is presented. The solution is singular at the origin. Near the string cloud limit there is a $1/r$ correction to Newton's force law. It is noted that at large distances and small accelerations, this law coincides with the phenomenological force law invented by Milgrom in order to explain the flat rotation curves of galaxies without introducing dark matter. When interpreted in the context of a cosmological model with a string fluid, the new solution naturally explains why the critical acceleration of Milgrom is of the same order of magnitude as the Hubble parameter.Comment: 12 pages, REVTeX, no figure

Novel structurally related compounds reactivate latent HIV-1 in a bcl-2-transduced primary CD4+ T cell model without inducing global T cell activation

Background: The latent reservoir of HIV-1 in resting memory CD4+ T cells is a major barrier to curing HIV-1 infection. Eradication strategies involve reactivation of this latent reservoir; however, agents that reactivate latent HIV-1 through non-specific T cell activation are toxic. Methods: Using latently infected Bcl-2-transduced primary CD4+ T cells, we screened the MicroSource Spectrum library for compounds that reactivate latent HIV-1 without global T cell activation. Based on the structures of the initial hits, we assembled 50 derivatives from commercial sources and mostly by synthesis. The doseresponse relationships of these derivatives were established in a primary cell model. Activities were confirmed with another model of latency (J-Lat). Cellular toxicity and cytokine secretion were tested using freshly isolated human CD4+ T cells. Results: We identified two classes of quinolines that reactivate latent HIV-1. Class I compounds are the Mannich adducts of 5-chloroquinolin-8-ol. Class II compounds are quinolin-8-yl carbamates. Most EC 50 values were in the 0.5 -10 mM range. HIV-1 reactivation ranged from 25% to 70% for anti-CD3+ anti-CD28 co-stimulation. All quinolin-8-ol derivatives that reactivate latent HIV-1 follow Lipinski's Rule of Five, and most follow the stricter rule of three for leads. After 48 h of treatment, none of the analogues induced detectable cytokine secretion in primary resting CD4+ T cells. Conclusions: We discovered a group of quinolin-8-ol derivatives that can induce latent HIV-1 in a primary cell model without causing global T cell activation. This work expands the number of latency-reversing agents and provides new possible scaffolds for further drug development research