bluuebunny/crossref_metadata_2025 huggingface dataset:
Remote sensing of Neptune's bow shock: Evidence for large‐scale shock motions
Authors: Cairns Iver H. , Smith Charles W. , Kurth William S. , Gurnett Donald A. , Lepping Ronald P.
Published: September 2012

The Voyager 2 spacecraft observed high levels of Langmuir waves before the inbound crossing of Neptune's bow shock, thereby signifying magnetic connection to the bow shock. The Langmuir waves occurred in multiple bursts throughout two distinct periods separated by an 85‐min absence of wave activity. We use the times of onsets, stable maxima, and disappearances of the waves, together with the magnetic field direction and spacecraft position, to perform a “remote‐sensing” analysis of the shape and location of Neptune's bow shock prior to the inbound bow shock crossing. The bow shock is assumed to have a paraboloidal shape (symmetric about the Sun‐Neptune line) with a standoff distance and flaring parameter determined independently for pairs of wave events. Our analyses show that published static models for the location of Neptune's bow shock cannot explain the wave data. Instead, the nose of Neptune's bow shock is located near 38‐43 RN during the first wave period and moves monotonically planetward from 38.5 RN to 34.5 RN during the second wave period. The remote‐sensing analysis gives a shock position consistent with the time of the inbound shock crossing and an average flaring parameter consistent with the inbound and outbound shock crossings. Location of the shock's nose near 38‐43 RN during the first wave period is consistent with the observed variations in the solar wind ram pressure. Measured variations in the magnetic field direction and ram pressure explain the magnetic disconnection of the spacecraft from the shock during the period without observed Langmuir waves. However, the analysis indicates that the shock's nose moved continuously planetward during the second wave period while the ram pressure remained effectively constant. As normalized by the ram pressure, the remotely sensed shock moves sunward during the first wave period and planetward in the second wave period. The maximum standoff distance occurs while the dipole's axis is close to being perpendicular to the Sun‐Neptune direction. One interpretation of these results is that the location of Neptune's bow shock is controlled by the rotation phase of Neptune's oblique, tilted dipole. Our analyses should permit testing of detailed theoretical models for changes in the position and shape of Neptune's bow shock with rotation phase and solar wind ram pressure variations.
A PBPK Model to Predict Disposition of CYP3A‐Metabolized Drugs in Pregnant Women: Verification and Discerning the Site of CYP3A Induction
Authors: Ke AB , Nallani SC , Zhao P , Rostami‐Hodjegan A , Unadkat JD
Published: September 2012

Besides logistical and ethical concerns, evaluation of safety and efficacy of medications in pregnant women is complicated by marked changes in pharmacokinetics (PK) of drugs. For example, CYP3A activity is induced during the third trimester (T3). We explored whether a previously published physiologically based pharmacokinetic (PBPK) model could quantitatively predict PK profiles of CYP3A‐metabolized drugs during T3, and discern the site of CYP3A induction (i.e., liver, intestine, or both). The model accounted for gestational age‐dependent changes in maternal physiological function and hepatic CYP3A activity. For model verification, mean plasma area under the curve (AUC), peak plasma concentration (Cmax), and trough plasma concentration (Cmin) of midazolam (MDZ), nifedipine (NIF), and indinavir (IDV) were predicted and compared with published studies. The PBPK model successfully predicted MDZ, NIF, and IDV disposition during T3. A sensitivity analysis suggested that CYP3A induction in T3 is most likely hepatic and not intestinal. Our PBPK model is a useful tool to evaluate different dosing regimens during T3 for drugs cleared primarily via CYP3A metabolism.

CPT: Pharmacometrics & Systems Pharmacology (2012) 1, e3; doi:10.1038/psp.2012.2; advance online publication 26 September 2012
Open Access: A New Model for Publishing in the Pharmacological Sciences
Authors: Conway M
Published: September 2012

CPT: Pharmacometrics & Systems Pharmacology (CPT:PSP) is an online‐only, open access (OA) journal, which means that anyone, anywhere in the world, can access, download, print out, and read articles published here immediately upon publication on the journal's website at Nature and simultaneous deposit in the public‐access repository, PubMed Central. Using a Creative Commons license for authors, CPT:PSP permits authors to retain copyright in their articles and permits readers to download and reuse (with attribution) tables, data, and other elements of a paper. This Perspective provides an introduction to authors and readers of this new ASCPT journal about this approach to publishing.

CPT: Pharmacometrics & Systems Pharmacology (2012) 1, e7; doi:10.1038/psp.2012.7; advance online publication 26 September 2012
Using Spaced Retrieval to Effectively Treat Dysphagia in Clients With Dementia
Authors: Camp Cameron , Antenucci Vincent , Brush Jennifer , Slominski Thomas
Published: September 2012

Spaced retrieval (SR) is an evidence-based memory intervention that can be effective for helping people with mild to moderate dementia. It can be used to help clients reach a variety of goals, such as less repetitive questioning, better orientation, greater engagement in activities, improved appointment keeping, safe ambulation, and, in particular, safe swallowing. Thus, therapists using SR can enable clients with dementia to reach dysphagia therapy goals. Achievement of these goals can promote independence and reduce anxiety, as well as improve client-staff interactions. SR has been proven to be effective across a variety of types of dementia. It has been used successfully with clients in their homes, adult day centers, and skilled nursing facilities. It can be implemented during treatment sessions with speech-language pathologists and then maintained by family caregivers or nursing care staff.
Gewebe-Doppler-Imaging durch Ultraschall zeigt keine Verzögerung der
Feedforward-Aktivität der Bauchmuskeln bei schnellen Armbewegungen bei Patienten mit
chronischen Kreuzschmerzen
Authors: Schiller Stefan
Published: September 2012

Fragestellung

Kann mithilfe von Gewebe-Doppler-Imaging (Tissue doppler imaging, TDI) durch Ultraschall
bei Patienten mit chronischen lumbalen Schmerzen (Chronic low back pain, cLBP) im
Vergleich zu schmerzfreien Personen eine Verzögerung der Aktivität der lateralen
Bauchmuskeln bei schnellen Armbewegungen nachgewiesen werden?
Unmittelbare Schmerzreduktion bei Low Back Pain nach lumbaler Gelenkmobilisation und
gestreckten Liegestützen korreliert mit erhöhter Wasserdiffusion in den Bandscheiben
L5–S1
Authors: Hirtz Frederick
Published: September 2012

Fragestellung

Am Department of Exercise Science, School of Public Health and Department of
Developmental Biology and Anatomy, School of Medicine der University of South
Carolina wurde von Oktober 2008 bis Mai 2009 bei Patienten (N = 10) mit
unspezifischen lumbalen Rückenschmerzen (Low back pain, LBP), die nach manueller
Mobilisation und anschließenden Extensionsübungen eine Schmerzlinderung um mindestens 2
Punkte auf einer 10 Punkte umfassenden numerischen Rating Skala (NRS) angaben, die
Flüssigkeitsaufnahme des Diskus L5–S1 untersucht. Im Anschluss erfolgte ein Vergleich mit
Patienten (N = 10), die nach derselben Intervention keine Schmerzlinderung aufwiesen.
Perpendicular and tangential angularly resolved multi-sight neutral particle analyzer system in LHD
Authors: Ozaki T. , Veshchev E. , Ido T. , Shimizu A. , Goncharov P. , Sudo S.
Published: September 2012

The particle loss in a helical plasma can be found by measuring the angular distribution of the energetic neutral particles using the angularly resolved multi-sightline neutral particle analyzer (ARMS). In ARMS, the AXUV detector with 20 segments usually used as UV monitor is utilized as the particle detector. Two ARMSs, which are installed with perpendicular and tangential views are operated for measuring the real time neutral particle distribution and investigating the particle loss.
Charge transport in poly(3-hexylthiophene):CdSe nanocrystals hybrid thin films investigated with time-of-flight measurements
Authors: Couderc Elsa , Bruyant Nicolas , Fiore Angela , Chandezon Frédéric , Djurado David , Reiss Peter , Faure-Vincent Jérôme
Published: September 2012

Charge carrier mobilities and transport dispersivity are studied in hybrid films composed of poly(3-hexylthiophene) and CdSe nanocrystals by the time-of-flight method, using a field range of 105–106 V/cm. It is found that charge transport parameters pass through an optimum for 75 wt. % (36 vol. %) of nanocrystals in the polymer matrix, yielding balanced hole and electron mobilities around 10−3 cm2/V s. Changing the nanocrystal shape from spherical to branched increases the intersite coupling disorder in the hybrid whereas changing the surface ligands from stearate/oleylamine to pyridine decreases it. Both these modifications have an impact on the electric field dependence of the measured mobilities.
Convergence rates of vanishing diffusion limit on nonlinear hyperbolic system with damping and diffusion
Authors: Ruan Lizhi , Yin Haiyan
Published: September 2012

The aim of this paper is to study the global unique solvability on C∞-solution to the Cauchy problem of a special 2 × 2 nonlinear hyperbolic system with damping and diffusion. Furthermore, we also investigate the convergence rates as the diffusion parameter β goes to zero. It is shown that the convergence rates in C∞-norm is of the order O(β). The novelty of analysis taken in the present article is to obtain the uniform-in-β a priori estimates on Hs-norm for any \documentclass[12pt]{minimal}\begin{document}$s\in \mathbb {N}$\end{document}s∈N, which are implemented by introducing induction. We focus on two cases in this paper: both α = β and α ≠ β since the uniform-in-β a prioriestimates obtained are distinctly different for different cases.
Record-low propagation losses of 154 dB/cm for substrate-type W1 photonic crystal waveguides by means of hole shape engineering
Authors: Kappeler R. , Kaspar P. , Jäckel H. , Hafner Ch.
Published: September 2012

Large propagation losses in the order 600-1000 dB/cm were reported in the past for planar line-defect photonic crystal waveguides with a weak vertical refractive index contrast (substrate-type). Loss-relevant factors are a well-suited design of the photonic crystal pattern and a high-quality fabrication technology. Here, the focus is on the latter. Two methods—a thermally driven mass transport process and an ultra-slow, selective wet-etching process—are assessed with respect to their capability of enabling low-loss waveguides. With the resulting hole shape, we experimentally demonstrate record-low propagation losses of 154 dB/cm for W1 photonic crystal waveguides in the InP/InGaAsP system.
Tunable magnetic states in hexagonal boron nitride sheets
Authors: Machado-Charry Eduardo , Boulanger Paul , Genovese Luigi , Mousseau Normand , Pochet Pascal
Published: September 2012

Magnetism in two dimensional atomic sheets has attracted considerable interest as its existence could allow the development of electronic and spintronic devices. The existence of magnetism is not sufficient for devices, however, as states must be addressable and modifiable through the application of an external drive. We show that defects in hexagonal boron nitride present a strong interplay between the N-N distance in the edge and the magnetic moments of the defects. By stress-induced geometry modifications, we change the ground state magnetic moment of the defects. This control is made possible by the triangular shape of the defects as well as the strong spin localisation in the magnetic state.
Position-displacement correlations in QELSS spectra of non-dilute colloids
Authors: Phillies George D. J.
Published: September 2012

This paper examines relationships between the quasielastic light scattering spectrum S(q, t) and the distribution functions for particle displacements over various times. For dilute probes in a complex, non-scattering fluid, S(q, t) is determined by the even moments ⟨X(t)2n⟩ of the one-particle displacement distribution function P(X, t). For concentrated scattering particles, S(q, t) is not determined by P(X, t). Instead, S(q, t) is determined in part by P(X, t) and in part by a spatial Fourier transform of the two particle displacement distribution function P2(X, t, R12). Here, X is the displacement of particle 1 during t, and R12 is the component (at t = 0), parallel to the scattering vector q, of the vector from particle 1 to a second particle 2.
Modification of Δ′ by magnetic feedback and kinetic effects
Authors: Liu Yueqiang , Hastie R. J. , Hender T. C.
Published: September 2012

Two possible ways of modifying the linear tearing mode index, by active magnetic feedback and by drift kinetic effects of deeply trapped particles, are analytically investigated. Magnetic feedback schemes, studied in this work, are found generally stabilizing for Δ′. The drift kinetic effects from both thermal particles and hot ions tend to reduce the power of the large solution from the outer region. This generally leads to a destabilization of Δ′ for the toroidal analytic equilibria considered here.
Thermal contact resistance across nanoscale silicon dioxide and silicon interface
Authors: Chen Jie , Zhang Gang , Li Baowen
Published: September 2012

Silicon dioxide and silicon (SiO2/Si) interface plays a very important role in semiconductor industry. However, at nanoscale, its interfacial thermal properties have not been well understood so far. In this paper, we systematically study the interfacial thermal resistance (Kapitza resistance) of a heterojunction composed of amorphous silicon dioxide and crystalline silicon by using molecular dynamics simulations. Numerical results have shown that Kapitza resistance at SiO2/Si interface depends on the interfacial coupling strength remarkably. In the weak interfacial coupling limit, Kapitza resistance depends on both the detailed interfacial structure and the length of the heterojunction, showing large fluctuation among different samples. In contrast, it is almost insensitive to the detailed interfacial structure or the length of the heterojunction in the strong interfacial coupling limit, giving rise to a nearly constant value around 0.9×10−9m2KW−1 at room temperature. Moreover, the temperature dependent Kapitza resistance in the strong interfacial coupling limit has also been examined. Our study provides useful guidance to the thermal management and heat dissipation across nanoscale SiO2/Si interface, in particular, for the design of silicon nanowire based nano electronics and photonics devices.
Strain dependent stabilization of metallic paramagnetic state in epitaxial NdNiO3 thin films
Authors: Kumar Yogesh , Choudhary R. J. , Sharma S. K. , Knobel M. , Kumar Ravi
Published: September 2012

We report here the strain dependent study of epitaxial NdNiO3 films deposited on LaAlO3 and SrTiO3 substrates using pulsed laser deposition. Electrical transport and magnetic properties of films are found to be controlled by the substrate induced strain. NdNiO3 film on SrTiO3 substrate exhibits behaviour similar to that of bulk NdNiO3, while stabilization of low temperature metallic paramagnetic phase has been observed for film deposited on LaAlO3 substrate. Invariance of Raman spectra, with temperature, of the film on LaAlO3 reveals that the melting of charge ordering under compressive strain is responsible for the stabilization of metallic phase at lower temperature.
A microfluidic platform for measuring electrical activity across cells
Authors: Bathany Cédric , Beahm Derek L. , Besch Steve , Sachs Frederick , Hua Susan Z.
Published: September 2012

In this paper, we present a microfluidic chip that is capable of measuring electrical conductance through gap junction channels in a 2-dimensional cell sheet. The chip utilizes a tri-stream laminar flow to create a non-conductive sucrose gap between the two conducting solutions so that electrical current can pass across the sucrose gap only through the cells. Using the chip, we tested the effect of a gap junction inhibitor, 2-APB, on the electrical coupling of connexin 43 (Cx43) gap junction channels in NRK-49F cells. We found that 2-APB reversibly blocks the conductivity in a dose-dependent manner. The tri-stream chip further allows us to simultaneously follow the conductance changes and dye diffusion in real time. We show that 2-APB affects both conductance and diffusion, supporting the interpretation that both sets of data reflect the same gap junction activity. The chip provides a generic platform to investigate gap junction properties and to screen drugs that may inhibit or potentiate gap junction transmission.
Cell-encapsulating droplet formation and freezing
Authors: Ryoun Youn Jae , Seok Song Young
Published: September 2012

Cell-encapsulating droplets are vitrified for biopreservation applications. The dynamics of micro-droplet formation and its freezing mechanism are analyzed numerically and experimentally. In addition, the microdroplet encapsulation technique is applied to cryopreserve cells.
Detecting single molecules inside a carbon nanotube to control molecular sequences using inertia trapping phenomenon
Authors: Hu Z. L. , Mårtensson Gustaf , Murugesan Murali , Fu Yifeng , Guo Xingming , Liu Johan
Published: September 2012

Here we show the detection of single gas molecules inside a carbon nanotube based on the change in resonance frequency and amplitude associated with the inertia trapping phenomenon. As its direct implication, a method for controlling the sequence of small molecule is then proposed to realize the concept of manoeuvring of matter atom by atom in one dimension. The detection as well as the implication is demonstrated numerically with the molecular dynamics method. It is theoretically assessed that it is possible for a physical model to be fabricated in the very near future.
Evidences for direct magnetic patterning via diffusive transformations using femtosecond laser interferometry
Authors: Polushkin N. I. , Oliveira V. , Conde O. , Vilar R. , Drozdov Yu. N. , Apolinário A. , García-García A. , Teixeira J. M. , Kakazei G. N.
Published: September 2012

The application of femtosecond laser interferometry to direct patterning of thin-film magnetic alloys is demonstrated. The formation of stripe gratings with submicron periodicities is achieved in Fe1−xVx (x = 18–34 wt. %) layers, with a difference in magnetic moments up to Δμ/μ ∼ 20 between adjacent stripes but without any significant development of the topographical relief (<1% of the film thickness). The produced gratings exhibit a robust effect of their anisotropy shape on magnetization curves in the film plane. The obtained data witness ultrafast diffusive transformations associated with the process of spinodal decomposition and demonstrate an opportunity for producing magnetic nanostructures with engineered properties upon this basis.
Water droplets on a hydrophobic insulator surface under high voltages: A thermal perspective
Authors: Xie Guoxin , Luo Jianbin , Yang Ye , Guo Dan , Si Lina
Published: September 2012

The thermal characteristics in the interaction process between water droplets on a hydrophobic insulator surface under high direct current voltages have been investigated with the infrared thermography. Discharge inception under a sufficiently high electric field resulted in the temperature rise between droplets and the formation of a liquid channel. The channel was transient for low conductivity droplets followed by their coalescence while stable for highly conductive ones. Asymmetric temperature distributions in the associated droplets appeared, and localized drying in the low conductivity droplet near the higher potential electrode initiated intermittent discharge. Mechanisms of these experimental phenomena have been discussed.
Suppression of m-plane and c-plane slip through Si and Mg doping in partially relaxed (202¯1) InGaN/GaN heterostructures
Authors: Hardy Matthew T. , Young Erin C. , Shan Hsu Po , Haeger Daniel A. , Koslow Ingrid L. , Nakamura Shuji , DenBaars Steven P. , Speck James S.
Published: September 2012

Several series of (202¯1) oriented InGaN/GaN heterostructures were grown to examine the impact of Si and Mg doping on stress relaxation by misfit dislocation formation. Si doping greatly reduced m-plane slip misfit dislocation lines as observed in cathodoluminescence, as well as reducing relaxation from c-plane slip as measured using x-ray diffraction reciprocal space maps. However, samples with the same degree of relaxation still showed reduced m-plane slip for the highly Si doped case. Mg doping showed a similar effect while experiments with Si–Mg co-doping reversed the effect.
Electrical and optical properties of vanadium dioxide containing gold nanoparticles deposited by pulsed laser deposition
Authors: Orlianges J.-C. , Leroy J. , Crunteanu A. , Mayet R. , Carles P. , Champeaux C.
Published: September 2012

Nanostructured vanadium dioxide is one of the most interesting and studied member of the vanadates family performing a reversible transition from an insulating state to a metallic state associated with a structural transition when heated above a temperature of 68 °C. On the other hand, noble metal nanoparticles (NPs) support localized surface plasmon resonance which causes selective absorption bands in the visible and near-IR regions. The purpose of this letter is to study structural, optical, and electrical properties of vanadium dioxide thin films containing gold nanoparticles synthetized using pulsed laser deposition process. Thus, we have performed x-ray diffraction, optical transmission, and four point probe electrical measurements to investigate the nanocomposite properties versus its temperature. Interestingly, we have observed switching behavior for VO2 film containing gold NPs with a resistivity contrast of four orders of magnitude and a decrease of its transition temperature.
Plasmon enhanced polymer solar cells by spin-coating Au nanoparticles on indium-tin-oxide substrate
Authors: Gao H. L. , Zhang X. W. , Yin Z. G. , Tan H. R. , Zhang S. G. , Meng J. H. , Liu X.
Published: September 2012

To enhance light absorption in polymer solar cells, the Au nanoparticles (NPs) with different sizes were incorporated to the devices by spin-coating Au colloid solution on the indium-tin-oxide substrates prior to deposition of buffer layer. It has been found that the power conversion efficiency of bulk heterojunction cells can be increased from 3.50% to 4.07% after incorporating the 60 nm Au NPs, corresponding to an improvement of 16%. The improved device performance is ascribed to the localized surface plasmon excitation of the Au NPs. The method we report herein is a kind of simple and quick solution process.
Fibre in late gestation gilt diets, glucose tolerance, and feed intake and bodyweight loss during subsequent lactation
Authors: Langendijk P. , Chen T.-Y.
Published: September 2012

Forty-nine crossbred gilts were fed one of three diets during the last month of their gestation: 2.5 kg of a standard diet (2.5C, n = 15), 3.5 kg of the same standard diet (3.5C, n = 17), or 3.5 kg of a high fibre diet, with 10.6% fibre compared with 4.4% fibre in the standard diet (3.5F, n = 17). The 3.5F and 3.5C gilts were fed at isocaloric and isonitrogenous levels. During the subsequent lactation, all gilts were fed the same lactation diet. Nineteen gilts (6 or 7 per treatment) were subjected to an oral glucose tolerance test around Day 110 of gestation. The high feed level (3.5C and 3.5F) resulted in a higher weight gain during gestation (P < 0.05). Gilts fed the high fibre diet tended to have (P < 0.10) piglets with a greater birthweight at farrowing (1535 g) than gilts fed the standard diet at 2.5 kg (1484 g). The 3.5C gilts (n.s.) and the 3.5F gilts (P < 0.05) had a lower feed intake and more bodyweight loss during lactation than gilts fed the 2.5-kg standard diet during gestation. Insulin profiles after the glucose tolerance test were higher for gilts fed the high fibre diet. Gilts fed the 2.5- or 3.5-kg standard diet had a similar insulin profile. Glucose profiles and insulin sensitivity were similar across treatments. Leptin around Day 110 was negatively correlated with feed intake during the third week of lactation (r = –0.28; P < 0.05). This study shows that a high feed level during late gestation reduces feed intake during lactation and that a high fibre diet during gestation does not negate this effect. The results suggest that feed level during gestation and the resulting body fat mass, rather than glucose tolerance, impacts on feed intake during lactation.
Synthesis of Diphenyl Carbonate from Carbon Dioxide, Phenol, and Carbon Tetrachloride Catalysed by ZnCl2 Using Trifluoromethanesulfonic Acid as Functional Co-Catalyst
Authors: Fan Guozhi , Wang Min , Duan Zhenxiao , Wan Minghai , Fang Tao
Published: September 2012

Diphenyl carbonate (DPC) was synthesised from carbon dioxide, phenol, and carbon tetrachloride catalysed by the Lewis acid ZnCl2 with the addition of co-catalyst. It was found that common bases are not effective co-catalysts for the production of DPC, and only slight enhancement in the catalytic activity of ZnCl2 was observed in the presence of inorganic additives such as inorganic carbonates and quaternary ammonium salts. Although poor conversion of phenol and yield of DPC were obtained using ZnCl2 or trifluoromethanesulfonic acid (CF3SO3H) as the sole catalyst, the catalytic activity of ZnCl2 was significantly improved by the addition of a catalytic amount of CF3SO3H. CF3SO3H has been proven to be an effective co-catalyst. The conversion of phenol and the yield of DPC were dependent on the amount of ZnCl2 and CF3SO3H, the reaction temperature, and the pressure of CO2. A possible reaction mechanism for the synthesis of DPC catalysed by the co-catalytic system including ZnCl2 and CF3SO3H was also proposed.
Ag Nanoparticle-Poly(acrylic acid) Composite Film with Dynamic Plasmonic Properties
Authors: Chegel Volodymyr , Lopatynskyi Andrii , Ishihara Shinsuke , Hill Jonathan P. , Ariga Katsuhiko
Published: September 2012

Poly(acrylic acid) (PAA) thin films with embedded Ag nanoparticles (AgNPs) prepared by UV photoreduction exhibited cyclically changeable optical absorbance properties during variation of ambient aqueous medium. The observed phenomenon is due to conformational changes in the polymer matrix which leads to variation in the 3D configuration of the AgNPs ensemble. Reversible variation of the distance between nanoparticles during swelling and shrinking processes within the PAA matrix changes the optical parameters of these plasmonic metamaterials and can be considered a useful feature for optoelectronic devices and sensors. The finite-difference time-domain method was used for modelling of light extinction of developed matrix structures in their swollen and shrunken states.
Combinatorics of distance-based tree inference
Authors: Pardi Fabio , Gascuel Olivier
Published: September 2012

Several popular methods for phylogenetic inference (or hierarchical clustering) are based on a matrix of pairwise distances between taxa (or any kind of objects): The objective is to construct a tree with branch lengths so that the distances between the leaves in that tree are as close as possible to the input distances. If we hold the structure (topology) of the tree fixed, in some relevant cases (e.g., ordinary least squares) the optimal values for the branch lengths can be expressed using simple combinatorial formulae. Here we define a general form for these formulae and show that they all have two desirable properties: First, the common tree reconstruction approaches (least squares, minimum evolution), when used in combination with these formulae, are guaranteed to infer the correct tree when given enough data (consistency); second, the branch lengths of all the simple (nearest neighbor interchange) rearrangements of a tree can be calculated, optimally, in quadratic time in the size of the tree, thus allowing the efficient application of hill climbing heuristics. The study presented here is a continuation of that by Mihaescu and Pachter on branch length estimation [Mihaescu R, Pachter L (2008)Proc Natl Acad Sci USA105:13206–13211]. The focus here is on the inference of the tree itself and on providing a basis for novel algorithms to reconstruct trees from distances.
Sequence-dependent sliding kinetics of p53
Authors: Leith Jason S. , Tafvizi Anahita , Huang Fang , Uspal William E. , Doyle Patrick S. , Fersht Alan R. , Mirny Leonid A. , van Oijen Antoine M.
Published: September 2012

Proper timing of gene expression requires that transcription factors (TFs) efficiently locate and bind their target sites within a genome. Theoretical studies have long proposed that one-dimensional sliding along DNA while simultaneously reading its sequence can accelerate TF’s location of target sites. Sliding by prokaryotic and eukaryotic TFs were subsequently observed. More recent theoretical investigations have argued that simultaneous reading and sliding is not possible for TFs without their possessing at least two DNA-binding modes. The tumor suppressor p53 has been shown to slide on DNA, and recent experiments have offered structural and single molecule support for a two-mode model for the protein. If the model is applicable to p53, then the requirement that TFs be able to read while sliding implies that noncognate sites will affect p53’s mobility on DNA, which will thus be generally sequence-dependent. Here, we confirm this prediction with single-molecule microscopy measurements of p53’s local diffusivity on noncognate DNA. We show how a two-mode model accurately predicts the variation in local diffusivity, while a single-mode model does not. We further determine that the best model of sequence-specific binding energy includes terms for “hemi-specific” binding, with one dimer of tetrameric p53 binding specifically to a half-site and the other binding nonspecifically to noncognate DNA. Our work provides evidence that the recognition by p53 of its targets and the timing thereof can depend on its noncognate binding properties and its ability to change between multiple modes of binding, in addition to the much better-studied effects of cognate-site binding.
Structural and functional insights into alphavirus polyprotein processing and pathogenesis
Authors: Shin Gyehwa , Yost Samantha A. , Miller Matthew T. , Elrod Elizabeth J. , Grakoui Arash , Marcotrigiano Joseph
Published: September 2012

Alphaviruses, a group of positive-sense RNA viruses, are globally distributed arboviruses capable of causing rash, arthritis, encephalitis, and death in humans. The viral replication machinery consists of four nonstructural proteins (nsP1–4) produced as a single polyprotein. Processing of the polyprotein occurs in a highly regulated manner, with cleavage at the P2/3 junction influencing RNA template use during genome replication. Here, we report the structure of P23 in a precleavage form. The proteins form an extensive interface and nsP3 creates a ring structure that encircles nsP2. The P2/3 cleavage site is located at the base of a narrow cleft and is not readily accessible, suggesting a highly regulated cleavage. The nsP2 protease active site is over 40 Å away from the P2/3 cleavage site, supporting a
trans
cleavage mechanism. nsP3 contains a previously uncharacterized protein fold with a zinc-coordination site. Known mutations in nsP2 that result in formation of noncytopathic viruses or a temperature sensitive phenotype cluster at the nsP2/nsP3 interface. Structure-based mutations in nsP3 opposite the location of the nsP2 noncytopathic mutations prevent efficient cleavage of P23, affect RNA infectivity, and alter viral RNA production levels, highlighting the importance of the nsP2/nsP3 interaction in pathogenesis. A potential RNA-binding surface, spanning both nsP2 and nsP3, is proposed based on the location of ion-binding sites and adaptive mutations. These results offer unexpected insights into viral protein processing and pathogenesis that may be applicable to other polyprotein-encoding viruses such as HIV, hepatitis C virus (HCV), and Dengue virus.
Uranium extremophily is an adaptive, rather than intrinsic, feature for extremely thermoacidophilic
Metallosphaera
species
Authors: Mukherjee Arpan , Wheaton Garrett H. , Blum Paul H. , Kelly Robert M.
Published: September 2012

Thermoacidophilic archaea are found in heavy metal-rich environments, and, in some cases, these microorganisms are causative agents of metal mobilization through cellular processes related to their bioenergetics. Given the nature of their habitats, these microorganisms must deal with the potentially toxic effect of heavy metals. Here, we show that two thermoacidophilic
Metallosphaera
species with nearly identical (99.99%) genomes differed significantly in their sensitivity and reactivity to uranium (U).
Metallosphaera prunae
, isolated from a smoldering heap on a uranium mine in Thüringen, Germany, could be viewed as a “spontaneous mutant” of
Metallosphaera sedula
, an isolate from Pisciarelli Solfatara near Naples.
Metallosphaera prunae
tolerated triuranium octaoxide (U
3
O
8
) and soluble uranium [U(VI)] to a much greater extent than
M. sedula
. Within 15 min following exposure to “U(VI) shock,”
M. sedula
, and not
M. prunae
, exhibited transcriptomic features associated with severe stress response. Furthermore, within 15 min post-U(VI) shock,
M. prunae
, and not
M. sedula
, showed evidence of substantial degradation of cellular RNA, suggesting that transcriptional and translational processes were aborted as a dynamic mechanism for resisting U toxicity; by 60 min post-U(VI) shock, RNA integrity in
M. prunae
recovered, and known modes for heavy metal resistance were activated. In addition,
M. sedula
rapidly oxidized solid U
3
O
8
to soluble U(VI) for bioenergetic purposes, a chemolithoautotrophic feature not previously reported.
M. prunae
, however, did not solubilize solid U
3
O
8
to any significant extent, thereby not exacerbating U(VI) toxicity. These results point to uranium extremophily as an adaptive, rather than intrinsic, feature for
Metallosphaera
species, driven by environmental factors.
Dicyanovinylnaphthalenes for neuroimaging of amyloids and relationships of electronic structures and geometries to binding affinities
Authors: Petrič Andrej , Johnson Scott A. , Pham Hung V. , Li Ying , Čeh Simon , Golobič Amalija , Agdeppa Eric D. , Timbol Gerald , Liu Jie , Keum Gyochang , Satyamurthy Nagichettiar , Kepe Vladimir , Houk Kendall N. , Barrio Jorge R.
Published: September 2012

The positron-emission tomography (PET) probe 2-(1-[6-[(2-fluoroethyl)(methyl)amino]-2-naphthyl]ethylidene) (FDDNP) is used for the noninvasive brain imaging of amyloid-β (Aβ) and other amyloid aggregates present in Alzheimer’s disease and other neurodegenerative diseases. A series of FDDNP analogs has been synthesized and characterized using spectroscopic and computational methods. The binding affinities of these molecules have been measured experimentally and explained through the use of a computational model. The analogs were created by systematically modifying the donor and the acceptor sides of FDDNP to learn the structural requirements for optimal binding to Aβ aggregates. FDDNP and its analogs are neutral, environmentally sensitive, fluorescent molecules with high dipole moments, as evidenced by their spectroscopic properties and dipole moment calculations. The preferred solution-state conformation of these compounds is directly related to the binding affinities. The extreme cases were a nonplanar analogt-butyl-FDDNP, which shows low binding affinity for Aβ aggregates (520 nMKi) in vitro and a nearly planar tricyclic analog cDDNP, which displayed the highest binding affinity (10 pMKi). Using a previously published X-ray crystallographic model of 1,1-dicyano-2-[6-(dimethylamino)naphthalen-2-yl]propene (DDNP) bound to an amyloidogenic Aβ peptide model, we show that the binding affinity is inversely related to the distortion energy necessary to avoid steric clashes along the internal surface of the binding channel.
Calcium with the β-tin structure at high pressure and low temperature
Authors: Li Bing , Ding Yang , Yang Wenge , Wang Lin , Zou Bo , Shu Jinfu , Sinogeikin Stas , Park Changyong , Zou Guangtian , Mao Ho-kwang
Published: September 2012

Using synchrotron high-pressure X-ray diffraction at cryogenic temperatures, we have established the phase diagram for calcium up to 110 GPa and 5–300 K. We discovered the long-sought for theoretically predicted β-tin structured calcium with
I
4
1
/amd symmetry at 35 GPa in a s mall low-temperature range below 10 K, thus resolving the enigma of absence of this lowest enthalpy phase. The stability and relations among various distorted simple-cubic phases in the Ca-III region have also been examined and clarified over a wide range of high pressures and low temperatures.
Potential consequences of climate change for primary production and fish production in large marine ecosystems
Authors: Blanchard Julia L. , Jennings Simon , Holmes Robert , Harle James , Merino Gorka , Allen J. Icarus , Holt Jason , Dulvy Nicholas K. , Barange Manuel
Published: September 2012

Existing methods to predict the effects of climate change on the biomass and production of marine communities are predicated on modelling the interactions and dynamics of individual species, a very challenging approach when interactions and distributions are changing and little is known about the ecological mechanisms driving the responses of many species. An informative parallel approach is to develop size-based methods. These capture the properties of food webs that describe energy flux and production at a particular size, independent of species' ecology. We couple a physical–biogeochemical model with a dynamic, size-based food web model to predict the future effects of climate change on fish biomass and production in 11 large regional shelf seas, with and without fishing effects. Changes in potential fish production are shown to most strongly mirror changes in phytoplankton production. We project declines of 30–60% in potential fish production across some important areas of tropical shelf and upwelling seas, most notably in the eastern Indo-Pacific, the northern Humboldt and the North Canary Current. Conversely, in some areas of the high latitude shelf seas, the production of pelagic predators was projected to increase by 28–89%.
Climate change in metacommunities: dispersal gives double-sided effects on persistence
Authors: Eklöf Anna , Kaneryd Linda , Münger Peter
Published: September 2012

Climate change is increasingly affecting the structure and dynamics of ecological communities both at local and at regional scales, and this can be expected to have important consequences for their robustness and long-term persistence. The aim of the present work is to analyse how the spatial structure of the landscape and dispersal patterns of species (dispersal rate and average dispersal distance) affects metacommunity response to two disturbances: (i) increased mortality during dispersal and (ii) local species extinction. We analyse the disturbances both in isolation and in combination. Using a spatially and dynamically explicit metacommunity model, we find that the effect of dispersal on metacommunity persistence is two-sided: on the one hand, high dispersal significantly reduces the risk of bottom-up extinction cascades following the local removal of a species; on the other hand, when dispersal imposes a risk to the dispersing individuals, high dispersal increases extinction risks, especially when dispersal is global. Large-bodied species with long generation times at the highest trophic level are particularly vulnerable to extinction when dispersal involves a risk. This suggests that decreasing the mortality risk of dispersing individuals by improving the quality of the habitat matrix may greatly increase the robustness of metacommunities.
Warming shifts top-down and bottom-up control of pond food web structure and function
Authors: Shurin Jonathan B. , Clasen Jessica L. , Greig Hamish S. , Kratina Pavel , Thompson Patrick L.
Published: September 2012

The effects of global and local environmental changes are transmitted through networks of interacting organisms to shape the structure of communities and the dynamics of ecosystems. We tested the impact of elevated temperature on the top-down and bottom-up forces structuring experimental freshwater pond food webs in western Canada over 16 months. Experimental warming was crossed with treatments manipulating the presence of planktivorous fish and eutrophication through enhanced nutrient supply. We found that higher temperatures produced top-heavy food webs with lower biomass of benthic and pelagic producers, equivalent biomass of zooplankton, zoobenthos and pelagic bacteria, and more pelagic viruses. Eutrophication increased the biomass of all organisms studied, while fish had cascading positive effects on periphyton, phytoplankton and bacteria, and reduced biomass of invertebrates. Surprisingly, virus biomass was reduced in the presence of fish, suggesting the possibility for complex mechanisms of top-down control of the lytic cycle. Warming reduced the effects of eutrophication on periphyton, and magnified the already strong effects of fish on phytoplankton and bacteria. Warming, fish and nutrients all increased whole-system rates of net production despite their distinct impacts on the distribution of biomass between producers and consumers, plankton and benthos, and microbes and macrobes. Our results indicate that warming exerts a host of indirect effects on aquatic food webs mediated through shifts in the magnitudes of top-down and bottom-up forcing.
Climate change impacts in multispecies systems: drought alters food web size structure in a field experiment
Authors: Woodward Guy , Brown Lee E. , Edwards Francois K. , Hudson Lawrence N. , Milner Alexander M. , Reuman Daniel C. , Ledger Mark E.
Published: September 2012

Experimental data from intergenerational field manipulations of entire food webs are scarce, yet such approaches are essential for gauging impacts of environmental change in natural systems. We imposed 2 years of intermittent drought on stream channels in a replicated field trial, to measure food web responses to simulated climate change. Drought triggered widespread losses of species and links, with larger taxa and those that were rare for their size, many of which were predatory, being especially vulnerable. Many network properties, including size–scaling relationships within food chains, changed in response to drought. Other properties, such as connectance, were unaffected. These findings highlight the need for detailed experimental data from different organizational levels, from pairwise links to the entire food web. The loss of not only large species, but also those that were rare for their size, provides a newly refined way to gauge likely impacts that may be applied more generally to other systems and/or impacts.
Differential effects of decoy receptor‐ and antibody‐mediated tumour necrosis factor blockage on FoxP3 expression in responsive arthritis patients
Authors: Ryder L. Rebekka , Ryder Lars P. , Bartels Else M. , Woetmann Anders , Madsen Hans O. , Ødum Niels , Danneskiold‐Samsøe Bente , Ribel‐Madsen Søren , Bliddal Henning
Published: September 2012

Our aim was to clarify if anti‐tumour necrosis factor (TNF) drugs have effect on expression of three splice forms of FoxP3 mRNA in blood CD4+ T cells from rheumatoid arthritis (RA) patients compared with healthy controls. Forty‐five rheumatoid arthritis patients treated with anti‐TNF therapy were investigated in a 12‐week prospective cohort study. FoxP3 isoforms, CD25 and CTLA‐4 mRNA in blood CD4+ T cells were measured with quantitative real‐time PCR. Patients benefitting from the treatment, based on changes in DAS28 scores, revealed a significant decrease in expression of full‐length FoxP3 following 12 weeks treatment with TNF receptor 2 fusion protein (Etanercept), but not following treatment with anti‐TNF antibodies (Adalimumab or Infliximab). A partial normalization of the CTLA‐4/FoxP3fl ratio and a correlation between clinical improvement and change in FoxP3 mRNA expression were also seen in Etanercept responders. These changes were not observed in responsive patients treated with the antibody therapies. Our data suggest that TNF decoy receptor and anti‐TNF antibodies differ in their effect on FoxP3 expression in responsive patients. As Etanercept binds both TNF‐α and Lymphotoxin‐α (LT‐α), whereas the antibodies only target TNF‐α, LT‐α may regulate FoxP3 expression in a subset of RA patients. Our findings support the view that anti‐TNF treatment is mainly symptomatic.
The role of lipocalins in airway disease
Authors: Dittrich A. M. , Meyer H. A. , Hamelmann E.
Published: September 2012

The pathogenesis of allergic airway inflammation and disease is complex and still not fully understood. Many cells, factors and mediators are involved in the different aspects of induction, maintenance and persistence of airway inflammation. The heterogeneity and redundancy of this system is one of the main reasons why novel therapeutic targets focusing on the pathogenesis of asthma only hesitantly reach the market and clinical application. Thus, it seems mandatory that we proceed in our efforts to better understand this micro cosmos to succeed in the development of safe and effective drugs for the treatment of more severe and refractory forms of asthma and chronic obstructive pulmonary disease. One of the more recently discovered mediators in the context of airway inflammation are the lipocalins (Lcns). They are a family of proteins that share functional and structural similarities and are involved in the transport of small hydrophobic molecules such as steroids and lipids into the cell. Lcns are found in many different cell types from plants and bacteria through invertebrate cells to cells of vertebrate origin. The purpose of this review is to summarize the role of Lcns in airway diseases, focusing on allergic and infectious inflammation. In particular, we will summarize the present knowledge about Lipocalin 1 and Lipocalin 2, where exciting new discoveries in the recent years have highlighted their role in pulmonary disease and infection. This new class of proteins is another putative candidate for the development of novel drugs against airway inflammation.
Implant placement under existing removable dental prostheses and its effect on oral health‐related quality of life
Authors: Wolfart Stefan , Moll Daniel , Hilgers Ralf‐Dieter , Wolfart Mona , Kern Matthias
Published: September 2012

Objective

One aim of this prospective clinical study was to measure the effects of strategicimplant placement under removable partial dental prostheses (RPDPs) and among removable complete dental prostheses (RCDPs) on oral health‐related quality of life (OHRQoL).

Materials and methods

Twenty‐three patients participated in this study restored with RCDPs (n = 12) or RPDPs retained by telescopic crowns with 1–2 abutment teeth (n = 11). The total number of abutments was increased to 5–6 (maxilla) or to 4 (mandible) by placing implants in strategically advantageous regions. Ball attachments were attached to the implants and integrated in the existing denture. The Oral Health Impact Profile (49 questions) was completed by patients before implant placement, at baseline (integration of ball attachments), and during 12‐ and 24‐month follow‐up visits.

Results

There were marked reductions of impacts in both groups when comparing pre‐treatment scores and scores at baseline (P < 0.0001), 12‐month (P < 0.0001), and 24‐month follow‐up visits (P < 0.0001), respectively. For none of the visits, a significant difference between the two groups was detected (P > 0.05).

Conclusion

It can be concluded that a strategic placement of implants under the existing dental prostheses improves OHRQoL in both treatment groups.