Identification of Amino Acid Sequences with Good Folding Properties in an Off-Lattice Model

Folding properties of a two-dimensional toy protein model containing only two amino-acid types, hydrophobic and hydrophilic, respectively, are analyzed. An efficient Monte Carlo procedure is employed to ensure that the ground states are found. The thermodynamic properties are found to be strongly sequence dependent in contrast to the kinetic ones. Hence, criteria for good folders are defined entirely in terms of thermodynamic fluctuations. With these criteria sequence patterns that fold well are isolated. For 300 chains with 20 randomly chosen binary residues approximately 10% meet these criteria. Also, an analysis is performed by means of statistical and artificial neural network methods from which it is concluded that the folding properties can be predicted to a certain degree given the binary numbers characterizing the sequences.Comment: 15 pages, 8 Postscript figures. Minor change

New observations of the NGC 1275 phenomenon

Wetensch. publicatieFaculteit der Wiskunde en Natuurwetenschappe

Enhanced Fusion-Evaporation Cross Sections in Neutron-Rich 132^{132}Sn on 64^{64}Ni

Evaporation residue cross sections have been measured with neutron-rich radioactive $^{132}$Sn beams on $^{64}$Ni in the vicinity of the Coulomb barrier. The average beam intensity was $2\times 10^{4}$ particles per second and the smallest cross section measured was less than 5 mb. Large subbarrier fusion enhancement was observed. Coupled-channels calculations taking into account inelastic excitation and neutron transfer underpredict the measured cross sections below the barrier.Comment: 4 pages including 1 table and 3 figure

Designing a therapeutic hepatitis B vaccine to circumvent immune tolerance

An effective prophylactic hepatitis B virus (HBV) vaccine has long been available but is ineffective for chronic infection. The primary cause of chronic hepatitis B (CHB) and greatest impediment for a therapeutic vaccine is the direct and indirect effects of immune tolerance to HBV antigens. The resulting defective CD4+/CD8+ T cell response, poor cytokine production, insufficient neutralizing anti-body (nAb) and poor response to HBsAg vaccination characterize CHB infection. The objective of this study was to develop virus-like-particles (VLPs) that elicit nAb to prevent viral spread and prime CD4+/CD8+ T cells to eradicate intracellular HBV. Eight neutralizing B cell epitopes from the envelope PreS1 region were consolidated onto a species-variant of the HBV core protein, the woodchuck hepatitis core antigen (WHcAg). PreS1-specific B cell epitopes were chosen because of preferential expression on HBV virions. Because WHcAg and HBcAg are not crossreactive at the B cell level and only partially cross-reactive at the CD4+/CD8+ T cell level, CD4+ T cells specific for WHcAg-unique T cell sites can provide cognate T-B cell help for anti-PreS1 Ab production that is not curtailed by immune tolerance. Immunization of immune tolerant HBV transgenic (Tg) mice with PreS1-WHc VLPs elicited levels of high titer anti-PreS1 nAbs equivalent to wildtype mice. Passive transfer of PreS1 nAbs into human-liver chimeric mice prevented acute infection and cleared serum HBV from mice previously infected with HBV in a model of CHB. At the T cell level, PreS1-WHc VLPs and hybrid WHcAg/HBcAg DNA immunogens elicited HBcAg-specific CD4+ Th and CD8+ CTL responses

Marketing and public policy: Transformative research in developing markets

Developing markets are a challenge for researchers who study them and for governments, business leaders, and citizens who strive to improve the quality of life in them. The limitations of the dominant development paradigm coupled with the need to focus on consumers provide tremendous opportunities to engage in truly transformative research. Toward this outcome, several interactive forces must be understood and addressed during research design, management, and implementation. The purpose of this essay is to provide a synthesis-that is, a framework in the form of a conceptual model-with practical applications to transformative research in developing markets and, ultimately, with the broader objective to stimulate new conceptualizations, research, and best practices to transform consumer well-being. © 2012, American Marketing Association

The Interrelationships of Placental Mammals and the Limits of Phylogenetic Inference

Placental mammals comprise three principal clades: Afrotheria (e.g., elephants and tenrecs), Xenarthra (e.g., armadillos and sloths), and Boreoeutheria (all other placental mammals), the relationships among which are the subject of controversy and a touchstone for debate on the limits of phylogenetic inference. Previous analyses have found support for all three hypotheses, leading some to conclude that this phylogenetic problem might be impossible to resolve due to the compounded effects of incomplete lineage sorting (ILS) and a rapid radiation. Here we show, using a genome scale nucleotide data set, microRNAs, and the reanalysis of the three largest previously published amino acid data sets, that the root of Placentalia lies between Atlantogenata and Boreoeutheria. Although we found evidence for ILS in early placental evolution, we are able to reject previous conclusions that the placental root is a hard polytomy that cannot be resolved. Reanalyses of previous data sets recover Atlantogenata + Boreoeutheria and show that contradictory results are a consequence of poorly fitting evolutionary models; instead, when the evolutionary process is better-modeled, all data sets converge on Atlantogenata. Our Bayesian molecular clock analysis estimates that marsupials diverged from placentals 157-170 Ma, crown Placentalia diverged 86-100 Ma, and crown Atlantogenata diverged 84-97 Ma. Our results are compatible with placental diversification being driven by dispersal rather than vicariance mechanisms, postdating early phases in the protracted opening of the Atlantic Ocean

Anti-Search for the Glueball Candidate f_J(2220) in Two-Photon Interactions

Using 13.3 fb^{-1} of e^+e^- data recorded with the CLEO II and CLEO II.V detector configurations at CESR, we have searched for f_J(2220) decays to K^0_{S} K^0_{S} in untagged two-photon interactions. We report an upper limit on the product of the two-photon partial width and the branching fraction, Gamma_gamma gamma cdot B (f_J(2220) to K^0_{S} K^0_{S}) of less than 1.1 eV at the 95% C.L: systematic uncertainties are included. This dataset is four times larger than that used in the previous CLEO publication.Comment: 10 pages postscript, also available through http://w4.lns.cornell.edu/public/CLNS, Submitted to PRD (R

Velocity-resolved Reverberation Mapping of Five Bright Seyfert 1 Galaxies

We present the first results from a reverberation-mapping campaign undertaken during the first half of 2012, with additional data on one active galactic nucleus (AGN) (NGC 3227) from a 2014 campaign. Our main goals are (1) to determine the black hole masses from continuum-Hβ reverberation signatures, and (2) to look for velocity-dependent time delays that might be indicators of the gross kinematics of the broad-line region. We successfully measure Hβ time delays and black hole masses for five AGNs, four of which have previous reverberation mass measurements. The values measured here are in agreement with earlier estimates, though there is some intrinsic scatter beyond the formal measurement errors. We observe velocity-dependent Hβ lags in each case, and find that the patterns have changed in the intervening five years for three AGNs that were also observed in 2007.G.D.R., C.J.G., B.M.P., and R.W.P. are grateful for the support of the National Science Foundation through grant AST-1008882 to The Ohio State University. K.D.D., B.J.S., C.B.H., and J.L.V. acknowledge support by NSF Fellowships. M.C.B. gratefully acknowledges support from the NSF through CAREER grant AST-1253702. A.M.M. and D.M.S. acknowledge the support of NSF grants AST-1004756 and AST1009756. C.S.K. is supported by NSF grant AST-1515876. S.K. is supported at the Technion by the Kitzman Fellowship and by a grant from the Israel-Niedersachsen collaboration program. S.R. is supported at Technion by the Zeff Fellowship. S.G.S. acknowledges the support to CrAO in the frame of the “CosmoMicroPhysics” Target Scientific Research Complex Programme of the National Academy of Sciences of Ukraine (2007–2012). M.V. gratefully acknowledges support from the Danish Council for Independent Research via grant no. DFF 4002-00275. V.T.D. acknowledges the support of the Russian Foundation of Research (RF project no. 12-02-01237-a). The CrAO CCD cameras were purchased through the US Civilian Research and Development for Independent States of the Former Soviet Union (CRDF) awards UP1-2116 and UP1- 2549-CR-03. This research has been partly supported by the Grants-in-Aid of Scientific Research (17104002, 20041003, 21018003, 21018005, 22253002, and 22540247) of the Ministry of Education, Science, Culture and Sports of Japan. This research has made use of the NASA/IPAC Extragalactic Database (NED), which is operated by the Jet Propulsion Laboratory, California Institute of Technology, under contract with the National Aeronautics and Space Administratio