bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation der psychosozialen Betreuung Opiatabhängiger in Substitutionsbehandlung
Authors: Boywitt C. Dennis , Zwingmann Christian , Behrendt Regina , Schneitler Heiko
Published: August 2012

Fragestellung: Ziel dieser Arbeit war es, die Wirksamkeit der psychosozialen Betreuung (PSB) von Klienten in Substitutionsbehandlung anhand verschiedener Kriterien wie psychosoziale Belastung, individuelle Zielerreichung und Beikonsum zu untersuchen. Methodik: Zu diesem Zweck wurde eine Stichprobe von Klienten, die zu diesem Zeitpunkt in psychosozialer Betreuung war, zu zwei Zeitpunkten befragt. Der Abstand zwischen den beiden Befragungen betrug etwa zwölf Monate, um kurz- bis mittelfristige Entwicklungen im Rahmen der PSB abbilden zu können. Ergebnisse: Auf der zentralen Variablen der psychosozialen Belastung zeigen sich im Rahmen der PSB deutlich positive Entwicklungen. Auch das Ausmaß der individuellen Zielerreichung ist positiv. Weiterhin zeigt sich eine deutliche Übereinstimmung zwischen Klienten und Betreuern in der Einschätzung der Lage der Klienten und deren Entwicklung. Allerdings lässt sich praktisch keine Veränderung im Bereich des Beikonsums feststellen. Schlussfolgerungen: Die psychosoziale Betreuung stabilisiert die psychosoziale Situation der Klienten und ist damit ein günstiger Bestandteil im Hilfesystem der Substitutionsbehandlung opiatabhängiger Patienten.
Trampolin – Entwicklung eines Programms für Kinder aus suchtbelasteten Familien
Authors: Moesgen Diana , Bröning Sonja , Ruths Sylvia , Wiedow Annika , Wartberg Lutz , Pflug Ellen , Schaunig-Busch Ines , Thomasius Rainer , Klein Michael
Published: August 2012

Hintergrund: Kinder aus suchtbelasteten Familien besitzen ein hohes Risiko, später eine Suchtstörung oder andere psychische Auffälligkeiten zu entwickeln. Trotz ihres Hilfebedarfs existieren nur wenige, auf Wirksamkeit überprüfte Präventionsprogramme. Programmbeschreibung: Das neu entwickelte Gruppenprogramm „Trampolin“ bietet eine innovative, wissenschaftlich fundierte und praxisorientierte Intervention für die Zielgruppe. „Trampolin“ ist theoriegeleitet und fußt auf internationalen Forschungsergebnissen. Ebenfalls eine Rolle bei der Entwicklung spielte der fachliche Dialog mit Institutionen aus der Praxis. Es entstand ein Manual für die Durchführung von insgesamt neun Kinder-Modulen, welches im hohen Maße suchtspezifisch und ressourcenorientiert gestaltet ist. Didaktisch enthält es u. a. Psychoedukation, (Rollen‐) Spiele und Entspannungsübungen. Ein Eltern-Modul ist integriert. Evaluation: Das Programm wurde in verschiedenen ambulanten Einrichtungen bundesweit durchgeführt und wird derzeit im Rahmen einer randomisiert-kontrollierten Multicenter-Studie evaluiert.
The observed variation in cloud‐induced longwave radiation in response to sea surface temperature over the Pacific warm pool from MTSAT‐1R imagery
Authors: Cho Heeje , Ho Chang‐Hoi , Choi Yong‐Sang
Published: August 2012

This study investigated variations in outgoing longwave radiation (OLR) in response to changes in sea surface temperature (SST) over the Pacific warm pool area (20°N–20°S, 130°E–170°W). OLR values were obtained from recent (January 2008–June 2010) geostationary window channel imagery at hourly resolution, which resolves processes associated with tropical convective clouds. We used linear regression analysis with the domain‐averaged OLR and SST anomalies (i.e., ΔOLR, ΔSST; deviations from their 90‐day moving averages). Results show that the regression slope appears to be significant only with SST least‐affected by cloud radiative forcing, for which SST needs to be obtained as daily average over cloud‐free regions (ΔSSTclear). The estimated value of ΔOLR/ΔSSTclear is 15.72 W m−2 K−1, indicating the presence of strong outgoing longwave radiation in response to surface warming. This atmospheric cooling effect is found to be primarily associated with reduced areal coverage of clouds (−14.4% K−1).
A global perspective on Langmuir turbulence in the ocean surface boundary layer
Authors: Belcher Stephen E. , Grant Alan L. M. , Hanley Kirsty E. , Fox‐Kemper Baylor , Van Roekel Luke , Sullivan Peter P. , Large William G. , Brown Andy , Hines Adrian , Calvert Daley , Rutgersson Anna , Pettersson Heidi , Bidlot Jean‐Raymond , Janssen Peter A. E. M. , Polton Jeff A.
Published: August 2012

The turbulent mixing in thin ocean surface boundary layers (OSBL), which occupy the upper 100 m or so of the ocean, control the exchange of heat and trace gases between the atmosphere and ocean. Here we show that current parameterizations of this turbulent mixing lead to systematic and substantial errors in the depth of the OSBL in global climate models, which then leads to biases in sea surface temperature. One reason, we argue, is that current parameterizations are missing key surface‐wave processes that force Langmuir turbulence that deepens the OSBL more rapidly than steady wind forcing. Scaling arguments are presented to identify two dimensionless parameters that measure the importance of wave forcing against wind forcing, and against buoyancy forcing. A global perspective on the occurrence of wave‐forced turbulence is developed using re‐analysis data to compute these parameters globally. The diagnostic study developed here suggests that turbulent energy available for mixing the OSBL is under‐estimated without forcing by surface waves. Wave‐forcing and hence Langmuir turbulence could be important over wide areas of the ocean and in all seasons in the Southern Ocean. We conclude that surface‐wave‐forced Langmuir turbulence is an important process in the OSBL that requires parameterization.
Understanding Atlantic multi‐decadal variability prediction skill
Authors: García‐Serrano J. , Doblas‐Reyes F. J. , Coelho C. A. S.
Published: August 2012

Initialized and uninitialized decadal retrospective forecasts (re‐forecasts) are used to assess the key regions providing multi‐year prediction skill of the Atlantic multi‐decadal sea surface temperature variability (AMV) and to address the relative roles of the initial conditions and external forcing on this skill. The results show that there is a decay in the AMV skill with forecast time, which is likely to be driven by skill degradation in predicting the AMV subpolar branch due to the lack of skill in predicting the subtropical branch. An important role of the varying radiative forcing in the AMV‐related prediction skill is found over the Labrador and Irminger deep convection regions. Initialized predictions show the largest impact on the improvement in the AMV‐related skill over the area where the Atlantic subpolar gyre operates. Initialization appears also to correct an unrealistic anticorrelation between the AMV phase and the Gulf Stream found in the uninitialized re‐forecasts.
Historical tsunamis and present tsunami hazard in eastern Indonesia and the southern Philippines
Authors: Løvholt Finn , Kühn Daniela , Bungum Hilmar , Harbitz Carl B. , Glimsdal Sylfest
Published: August 2012

Eastern Indonesia and the southern Philippines comprise a huge and seismically highly active region that has received less than the deserved attention in tsunami research compared with the surrounding areas exposed to the major subduction zones. In an effort to redress the balance the tsunami hazard in this region is studied by establishing a tsunami event database which, in combination with seismological and tectonic information from the region, has allowed us to define and justify a number of ‘credible worst‐case’ tsunami scenarios. These scenarios have been used in numerical simulations of tsunami generation and propagation to study maximum water level along potentially affected shorelines. The scenarios have in turn been combined to provide regional tsunami hazard maps. In many cases the simulations indicate that the maximum water level may exceed 10 m locally and even reach above 20 m in the vicinity of the source, which is of the same order as what is forecasted along the Sumatra and Java trenches for comparable return periods. For sections of coastlines close to a source, a tsunami may strike only a few minutes after it is generated, providing little time for warning. Moreover, several of the affected areas are highly populated and are therefore also high risk areas. The combination of high maximum water levels, short warning times, dense populations, and relatively short return periods suggests strongly that the tsunami hazard and risk in these regions are alarmingly high.
Stratosphere‐to‐troposphere transport revealed by ground‐based lidar and ozonesonde at a midlatitude site
Authors: Kuang Shi , Newchurch M. J. , Burris John , Wang Lihua , Knupp Kevin , Huang Guanyu
Published: August 2012

This paper presents ozone structures measured by a ground‐based ozone lidar and ozonesonde at Huntsville, Alabama, on 27–29 April 2010 originating from a stratosphere‐to‐troposphere transport event associated with a cutoff cyclone and tropopause fold. In this case, the tropopause reached 6 km and the stratospheric intrusion resulted in a 2‐km thick elevated ozone layer with values between 70 and 85 ppbv descending from the ∼306‐K to 298‐K isentropic surface at a rate of ∼5 km day−1. The potential temperature was provided by a collocated microwave profiling radiometer. We examine the corresponding meteorological fields and potential vorticity (PV) structures derived from the analysis data from the North American Mesoscale model. The 2‐PVU (PV unit) surface, defined as the dynamic tropopause, is able to capture the variations of the ozone tropopause estimated from the ozonesonde and lidar measurements. The estimated ozone/PV ratio, from the measured ozone and model derived PV, for the mixing layer between the troposphere and stratosphere is ∼41 ppbv/PVU with an uncertainty of ∼33%. Within two days, the estimated mass of ozone irreversibly transported from the stratospheric into the troposphere is between 0.07 Tg (0.9 × 1033 molecules) and 0.11 Tg (1.3 × 1033molecules) with an estimated uncertainty of 59%. Tropospheric ozone exhibited enormous variability due to the complicated mixing processes. Low ozone and large variability were observed in the mid‐troposphere after the stratospheric intrusion due to the westerly advection including the transition from a cyclonic system to an anticyclonic system. This study using high temporal and vertical‐resolution measurements suggests that, in this case, stratospheric air quickly lost its stratospheric characteristics once it is irreversibly mixed down into the troposphere.
Nutrients and particulate organic matter discharged by the Changjiang (Yangtze River): Seasonal variations and temporal trends
Authors: Gao Lei , Li Daoji , Zhang Yanwei
Published: August 2012

From September 2009 to August 2010, intensive monthly sampling of nutrients was conducted at two stations at the mouth of the Changjiang (Yangtze River). Particulate organic carbon (POC), particulate nitrogen (PN), and their stable isotope values (δ13C and δ15N) were also measured in selected samples of all months. Most nutrients (nitrate, phosphate, ammonia, and nitrite) as well as POC, PN, and δ13C displayed peak values when the highest or lowest Changjiang monthly discharges occurred, suggesting the Changjiang discharges strongly influence the seasonal variations of these chemicals. The sharply increases in concentrations of ammonia and nitrite in winter probably suggest nitrification was greatly depressed during this cold period. Using five interpolation methods, the annual discharge fluxes of nutrients, POC, and PN from the Changjiang to the East China Sea shelf were calculated. Combining this nutrient data with data from previous studies, the seasonal Mann‐Kendall test, in which the influence of seasonal variation was considered, suggests concentrations of nitrate and phosphate in the Changjiang have significantly increased during recent decades at rates of 2.2μM yr−1 and 0.03 μM yr−1, respectively; no significant trend for silicate was noted. Decreased POC annual fluxes along with sharply decreased suspended particulate matter yields were also seen in recent years (1993–2010). However, no distinct changes of δ13C, δ15N, and the POC/PN ratio, which describe the particulate organic matter properties, were observed during this period.
Dynamics of decadally cycling carbon in subsurface soils
Authors: Koarashi Jun , Hockaday William C. , Masiello Caroline A. , Trumbore Susan E.
Published: August 2012

Subsurface horizons contain more than half of the global soil carbon (C), yet the dynamics of this C remains poorly understood. We estimated the amount of decadally cycling subsurface C (∼20 to 60 cm depth) from the incorporation of ‘bomb’ radiocarbon (14C) using samples taken over 50 years from grassland and forest soils in the Sierra Nevada Mountains, California. The radiocarbon content of all organic matter fractions (roots, low‐density (LF), high‐density (HF), and non‐oxidizable HF) increased from the pre‐ to post‐bomb samples, indicating ∼1–6 kgC m−2, or about half of the subsoil C, consists of C fixed since 1963. Low‐density (LF‐C) represented <24% (grassland) to 40–55% (forest) of the subsurface C and represented a mixture of post‐bomb C and varying amounts of pre‐1950 charcoal, identified using13C‐NMR spectroscopy. The14C content of HF‐C increased rapidly from 1992 to 2009, indicating a significant time lag (>20 years) for the arrival of ‘bomb’14C to this fraction. A two‐pool (fast‐cycling and passive) model including >20 year time lag showed that 28–73% of the subsoil mineral‐associated C had turnover times of 10–95 years. Microbially respired C was enriched in bomb14C compared to both LF and HF fractions in 2009. Overall, we estimate that C fluxes through decadally cycling pools in the subsurface are equivalent to 1–9% (grassland) to 10–54% (forest) of the surface litterfall at these sites. Our results demonstrate the importance of decadally cycling C for ecosystem C balance, and that a lagged response of the large subsurface C stores to changes in environmental conditions is possible.
Multipartite quantum entanglement evolution in photosynthetic complexes
Authors: Zhu Jing , Kais Sabre , Aspuru-Guzik Alán , Rodriques Sam , Brock Ben , Love Peter J.
Published: August 2012

We investigate the evolution of entanglement in the Fenna-Matthew-Olson (FMO) complex based on simulations using the scaled hierarchical equations of motion approach. We examine the role of entanglement in the FMO complex by direct computation of the convex roof. We use monogamy to give a lower bound for entanglement and obtain an upper bound from the evaluation of the convex roof. Examination of bipartite measures for all possible bipartitions provides a complete picture of the multipartite entanglement. Our results support the hypothesis that entanglement is maximum primary along the two distinct electronic energy transfer pathways. In addition, we note that the structure of multipartite entanglement is quite simple, suggesting that there are constraints on the mixed state entanglement beyond those due to monogamy.
Dynamical quantum-electrodynamics embedding: Combining time-dependent density functional theory and the near-field method
Authors: Gao Yi , Neuhauser Daniel
Published: August 2012

We develop an approach for dynamical (ω > 0) embedding of mixed quantum mechanical (QM)/classical (or more precisely QM/electrodynamics) systems with a quantum sub-region, described by time-dependent density functional theory (TDDFT), within a classical sub-region, modeled here by the recently proposed near-field (NF) method. Both sub-systems are propagated simultaneously and are coupled through a common Coulomb potential. As a first step we implement the method to study the plasmonic response of a metal film which is half jellium-like QM and half classical. The resulting response is in good agreement with both full-scale TDDFT and the purely classical NF method. The embedding method is able to describe the optical response of the whole system while capturing quantum mechanical effects, so it is a promising approach for studying electrodynamics in hybrid molecules-metals nanostructures.
Scattering of N2O on electron impact over an extensive energy range (0.1 eV–2000 eV)
Authors: Vinodkumar Minaxi , Barot Mayuri
Published: August 2012

We report electron impact total cross sections, QT, for e-N2O scattering over an extensive range of impact energies approximately from 0.1 eV to 2000 eV. We employ an ab initio calculation using R-matrix formalism below the ionization threshold of the target and above it we use the well established spherical complex optical potential to compute the cross sections. Total cross section is obtained as a sum of total elastic and total electronic excitation cross sections below the ionization threshold and above the ionization threshold as a sum of total elastic and total inelastic cross sections. Ample cross section data for e-N2O scattering are available at low impact energies and hence meaningful comparisons are made. Good agreement is observed with the available theoretical as well as experimental results over the entire energy range studied here.
A critical evaluation of the 0–3 approach for magnetoelectric nanocomposites with metallic nanoparticles
Authors: Gojdka B. , Hrkac V. , Xiong J. , Gerken M. , Kienle L. , Strunskus T. , Zaporojtchenko V. , Faupel F.
Published: August 2012

Granular nanocomposite films with embedded metallic particles have been suggested as a promising material class for magnetoelectric (ME) applications. We present a thorough case study of nanogranular aluminum nitride (AlN)/cobalt (Co) composites accompanied by finite element simulations. The present study shows that the use of metallic nanoparticles in 0–3 nanocomposites has fundamental limitations for the development of ME materials. AlN/Co films are deposited by magnetron co-sputtering with a gas aggregation cluster source, allowing the direct investigation of the cluster influence on the structural properties of the matrix under otherwise identical deposition conditions. While commonly leakage currents are perceived as the major challenge of the granular approach, our findings indicate further inherent hindrances. Apart from an increase of dielectric losses tanδ with increasing cobalt content, we find a drastic degradation of matrix crystallinity already at very low filling factors and a pronounced increase in dielectric permittivity εr. In addition, finite element simulations indicate a local short circuiting of the matrix, reducing the electric polarization. In the face of our results, existing literature on ME 0–3 nanocomposites with metallic particles is critically discussed.
Incorporation of quantum effects for selected degrees of freedom into the trajectory-based dynamics using spatial domains
Authors: Garashchuk Sophya , Volkov Mikhail V.
Published: August 2012

The approach of defining quantum corrections on nuclear dynamics of molecular systems incorporated approximately into selected degrees of freedom, is described. The approach is based on the Madelung-de-Broglie-Bohm formulation of time-dependent quantum mechanics which represents a wavefunction in terms of an ensemble of trajectories. The trajectories follow classical laws of motion except that the quantum potential, dependent on the wavefunction amplitude and its derivatives, is added to the external, classical potential. In this framework the quantum potential, determined approximately for practical reasons, is included only into the “quantum” degrees of freedom describing light particles such as protons, while neglecting with the quantum force for the heavy, nearly classical nuclei. The entire system comprised of light and heavy particles is described by a single wavefunction of full dimensionality. The coordinate space of heavy particles is divided into spatial domains or subspaces. The quantum force acting on the light particles is determined for each domain of similar configurations of the heavy nuclei. This approach effectively introduces parametric dependence of the reduced dimensionality quantum force, on classical degrees of freedom. This strategy improves accuracy of the quantum force and does not restrict interaction between the domains. The concept is illustrated for two-dimensional scattering systems, where the quantum force is required to reproduce vibrational energy of the quantum degree of freedom.
Effect of strong electron correlation on the efficiency of photosynthetic light harvesting
Authors: Mazziotti David A.
Published: August 2012

Research into the efficiency of photosynthetic light harvesting has focused on two factors: (1) entanglement of chromophores, and (2) environmental noise. While chromophores are conjugated π-bonding molecules with strongly correlated electrons, previous models have treated this correlation implicitly without a mathematical variable to gauge correlation-enhanced efficiency. Here we generalize the single-electron/exciton models to a multi-electron/exciton model that explicitly shows the effects of enhanced electron correlation within chromophores on the efficiency of energy transfer. The model provides more detailed insight into the interplay of electron correlation within chromophores and electron entanglement between chromophores. Exploiting this interplay is assisting in the design of new energy-efficient materials, which are just beginning to emerge.
Integral equation for electrostatic waves generated by a point source in a spatially homogeneous magnetized plasma
Authors: Podesta John J.
Published: August 2012

The electric field generated by a time varying point charge in a three-dimensional, unbounded, spatially homogeneous plasma with a uniform background magnetic field and a uniform (static) flow velocity is studied in the electrostatic approximation which is often valid in the near field. For plasmas characterized by Maxwell distribution functions with isotropic temperatures, the linearized Vlasov-Poisson equations may be formulated in terms of an equivalent integral equation in the time domain. The kernel of the integral equation has a relatively simple mathematical form consisting of elementary functions such as exponential and trigonometric functions (sines and cosines), and contains no infinite sums of Bessel functions. Consequently, the integral equation is amenable to numerical solutions and may be useful for the study of the impulse response of magnetized plasmas and, more generally, the response to arbitrary waveforms.
The complete set of Casimirs in Hall-magnetohydrodynamics
Authors: Kawazura Yohei , Hameiri Eliezer
Published: August 2012

A procedure for determining all the Casimir constants of motion in magnetohydrodynamics (MHD) [E. Hameiri, Phys. Plasmas 11, 3423 (2004)] is extended to Hall-MHD. We obtain and solve differential equations for the variational derivatives of all the Casimirs, which must be satisfied for any dynamically accessible motion in Hall-MHD. In an extension of the more commonly considered Hall-MHD model, we also include the electron fluid entropy. The most interesting case for plasma confinement, which is usually true for axisymmetric configurations but desirable in general, is when both the magnetic field and the ion velocity field form the two separate families of nested toroidal surfaces. The Casimirs are then three functionals for each surface, involving the fluxes of certain vector fields and the number of particles contained in each. We also determine a family of independent Casimirs in a general configuration.
Photocatalytic CO
2
reduction with high turnover frequency and selectivity of formic acid formation using Ru(II) multinuclear complexes
Authors: Tamaki Yusuke , Morimoto Tatsuki , Koike Kazuhide , Ishitani Osamu
Published: August 2012

Previously undescribed supramolecules constructed with various ratios of two kinds of Ru(II) complexes—a photosensitizer and a catalyst—were synthesized. These complexes can photocatalyze the reduction of CO
2
to formic acid with high selectivity and durability using a wide range of wavelengths of visible light and NADH model compounds as electron donors in a mixed solution of dimethylformamide–triethanolamine. Using a higher ratio of the photosensitizer unit to the catalyst unit led to a higher yield of formic acid. In particular, of the reported photocatalysts, a trinuclear complex with two photosensitizer units and one catalyst unit photocatalyzed CO
2
reduction (Φ
HCOOH
 = 0.061, TON
HCOOH
 = 671) with the fastest reaction rate (TOF
HCOOH
 = 11.6 min
-1
). On the other hand, photocatalyses of a mixed system containing two kinds of model mononuclear Ru(II) complexes, and supramolecules with a higher ratio of the catalyst unit were much less efficient, and black oligomers and polymers were produced from the Ru complexes during photocatalytic reactions, which reduced the yield of formic acid. The photocatalytic formation of formic acid using the supramolecules described herein proceeds via two sequential processes: the photochemical reduction of the photosensitizer unit by NADH model compounds and intramolecular electron transfer to the catalyst unit.
Top-down attention switches coupling between low-level and high-level areas of human visual cortex
Authors: Al-Aidroos Naseem , Said Christopher P. , Turk-Browne Nicholas B.
Published: August 2012

Top-down attention is an essential cognitive ability, allowing our finite brains to process complex natural environments by prioritizing information relevant to our goals. Previous evidence suggests that top-down attention operates by modulating stimulus-evoked neural activity within visual areas specialized for processing goal-relevant information. We show that top-down attention also has a separate influence on the background coupling between visual areas: adopting different attentional goals resulted in specific patterns of noise correlations in the visual system, whereby intrinsic activity in the same set of low-level areas was shared with only those high-level areas relevant to the current goal. These changes occurred independently of evoked activity, persisted without visual stimulation, and predicted behavioral success in deploying attention better than the modulation of evoked activity. This attentional switching of background connectivity suggests that attention may help synchronize different levels of the visual processing hierarchy, forming state-dependent functional pathways in human visual cortex to prioritize goal-relevant information.
Functional analysis of receptor tyrosine kinase mutations in lung cancer identifies oncogenic extracellular domain mutations of
ERBB2
Authors: Greulich Heidi , Kaplan Bethany , Mertins Philipp , Chen Tzu-Hsiu , Tanaka Kumiko E. , Yun Cai-Hong , Zhang Xiaohong , Lee Se-Hoon , Cho Jeonghee , Ambrogio Lauren , Liao Rachel , Imielinski Marcin , Banerji Shantanu , Berger Alice H. , Lawrence Michael S. , Zhang Jinghui , Pho Nam H. , Walker Sarah R. , Winckler Wendy , Getz Gad , Frank David , Hahn William C. , Eck Michael J. , Mani D. R. , Jaffe Jacob D. , Carr Steven A. , Wong Kwok-Kin , Meyerson Matthew
Published: August 2012

We assessed somatic alleles of six receptor tyrosine kinase genes mutated in lung adenocarcinoma for oncogenic activity. Five of these genes failed to score in transformation assays; however, novel recurring extracellular domain mutations of the receptor tyrosine kinase gene
ERBB2
were potently oncogenic. These ERBB2 extracellular domain mutants were activated by two distinct mechanisms, characterized by elevated C-terminal tail phosphorylation or by covalent dimerization mediated by intermolecular disulfide bond formation. These distinct mechanisms of receptor activation converged upon tyrosine phosphorylation of cellular proteins, impacting cell motility. Survival of Ba/F3 cells transformed to IL-3 independence by the
ERBB2
extracellular domain mutants was abrogated by treatment with small-molecule inhibitors of ERBB2, raising the possibility that patients harboring such mutations could benefit from ERBB2-directed therapy.
Ammonia clathrate hydrates as new solid phases for Titan, Enceladus, and other planetary systems
Authors: Shin Kyuchul , Kumar Rajnish , Udachin Konstantin A. , Alavi Saman , Ripmeester John A.
Published: August 2012

There is interest in the role of ammonia on Saturn’s moons Titan and Enceladus as the presence of water, methane, and ammonia under temperature and pressure conditions of the surface and interior make these moons rich environments for the study of phases formed by these materials. Ammonia is known to form solid hemi-, mono-, and dihydrate crystal phases under conditions consistent with the surface of Titan and Enceladus, but has also been assigned a role as water-ice antifreeze and methane hydrate inhibitor which is thought to contribute to the outgassing of methane clathrate hydrates into these moons’ atmospheres. Here we show, through direct synthesis from solution and vapor deposition experiments under conditions consistent with extraterrestrial planetary atmospheres, that ammonia forms clathrate hydrates and participates synergistically in clathrate hydrate formation in the presence of methane gas at low temperatures. The binary structure II tetrahydrofuran + ammonia, structure I ammonia, and binary structure I ammonia + methane clathrate hydrate phases synthesized have been characterized by X-ray diffraction, molecular dynamics simulation, and Raman spectroscopy methods.
Oral advanced glycation endproducts (AGEs) promote insulin resistance and diabetes by depleting the antioxidant defenses AGE receptor-1 and sirtuin 1
Authors: Cai Weijing , Ramdas Maya , Zhu Li , Chen Xue , Striker Gary E. , Vlassara Helen
Published: August 2012

The epidemics of insulin resistance (IR) and type 2 diabetes (T2D) affect the first world as well as less-developed countries, and now affect children as well. Persistently elevated oxidative stress and inflammation (OS/Infl) precede these polygenic conditions. A hallmark of contemporary lifestyle is a preference for thermally processed nutrients, replete with pro-OS/Infl advanced glycation endproducts (AGEs), which enhance appetite and cause overnutrition. We propose that chronic ingestion of oral AGEs promotes IR and T2D. The mechanism(s) involved in these findings were assessed in four generations of C57BL6 mice fed isocaloric diets with or without AGEs [synthetic methyl-glyoxal-derivatives (MG
+
)]. F3/MG
+
mice manifested increased adiposity and premature IR, marked by severe deficiency of anti-AGE advanced glycation receptor 1 (AGER1) and of survival factor sirtuin 1 (SIRT1) in white adipose tissue (WAT), skeletal muscle, and liver. Impaired 2-deoxy-glucose uptake was associated with marked changes in insulin receptor (InsR), IRS-1, IRS-2, Akt activation, and a macrophage and adipocyte shift to a pro-OS/inflammatory (M1) phenotype. These features were absent in F3/MG
−
mice. MG stimulation of 3T3-L1 adipocytes led to suppressed AGER1 and SIRT1, and altered InsR, IRS-1, IRS-2 phosphorylation, and nuclear factor kappa-light chain enhancer of activated B cells (Nf-κB) p65 acetylation. Gene modulation revealed these effects to be coregulated by AGER1 and SIRT1. Thus, prolonged oral exposure to MG-AGEs can deplete host-defenses AGER1 and SIRT1, raise basal OS/Infl, and increase susceptibility to dysmetabolic IR. Because exposure to AGEs can be decreased, these insights provide an important framework for alleviating a major lifestyle-linked disease epidemic.
Lesion mapping of cognitive control and value-based decision making in the prefrontal cortex
Authors: Gläscher Jan , Adolphs Ralph , Damasio Hanna , Bechara Antoine , Rudrauf David , Calamia Matthew , Paul Lynn K. , Tranel Daniel
Published: August 2012

A considerable body of previous research on the prefrontal cortex (PFC) has helped characterize the regional specificity of various cognitive functions, such as cognitive control and decision making. Here we provide definitive findings on this topic, using a neuropsychological approach that takes advantage of a unique dataset accrued over several decades. We applied voxel-based lesion-symptom mapping in 344 individuals with focal lesions (165 involving the PFC) who had been tested on a comprehensive battery of neuropsychological tasks. Two distinct functional-anatomical networks were revealed within the PFC: one associated with cognitive control (response inhibition, conflict monitoring, and switching), which included the dorsolateral prefrontal cortex and anterior cingulate cortex and a second associated with value-based decision-making, which included the orbitofrontal, ventromedial, and frontopolar cortex. Furthermore, cognitive control tasks shared a common performance factor related to set shifting that was linked to the rostral anterior cingulate cortex. By contrast, regions in the ventral PFC were required for decision-making. These findings provide detailed causal evidence for a remarkable functional-anatomical specificity in the human PFC.
Receptor interacting protein kinase mediates necrotic cone but not rod cell death in a mouse model of inherited degeneration
Authors: Murakami Yusuke , Matsumoto Hidetaka , Roh Miin , Suzuki Jun , Hisatomi Toshio , Ikeda Yasuhiro , Miller Joan W. , Vavvas Demetrios G.
Published: August 2012

Retinitis pigmentosa comprises a group of inherited retinal photoreceptor degenerations that lead to progressive loss of vision. Although in most cases rods, but not cones, harbor the deleterious gene mutations, cones do die in this disease, usually after the main phase of rod cell loss. Rod photoreceptor death is characterized by apoptotic features. In contrast, the mechanisms and features of subsequent nonautonomous cone cell death remain largely unknown. In this study, we show that receptor-interacting protein (RIP) kinase mediates necrotic cone cell death inrd10mice, a mouse model of retinitis pigmentosa caused by a mutation in a rod-specific gene. The expression of RIP3, a key regulator of programmed necrosis, was elevated inrd10mouse retinas in the phase of cone but not rod degeneration. Althoughrd10mice lackingRip3developed comparable rod degeneration to controlrd10mice, they displayed a significant preservation of cone cells. Ultrastructural analysis ofrd10mouse retinas revealed that a substantial fraction of dying cones exhibited necrotic morphology, which was rescued byRip3deficiency. Additionally, pharmacologic treatment with a RIP kinase inhibitor attenuated histological and functional deficits of cones inrd10mice. Thus, necrotic mechanisms involving RIP kinase are crucial in cone cell death in inherited retinal degeneration, suggesting the RIP kinase pathway as a potential target to protect cone-mediated central and peripheral vision loss in patients with retinitis pigementosa.
Distinguishing crystal-like amyloid fibrils and glass-like amorphous aggregates from their kinetics of formation
Authors: Yoshimura Yuichi , Lin Yuxi , Yagi Hisashi , Lee Young-Ho , Kitayama Hiroki , Sakurai Kazumasa , So Masatomo , Ogi Hirotsugu , Naiki Hironobu , Goto Yuji
Published: August 2012

Amyloid fibrils and amorphous aggregates are two types of aberrant aggregates associated with protein misfolding diseases. Although they differ in morphology, the two forms are often treated indiscriminately. β
2
-microglobulin (β2m), a protein responsible for dialysis-related amyloidosis, forms amyloid fibrils or amorphous aggregates depending on the NaCl concentration at pH 2.5. We compared the kinetics of their formation, which was monitored by measuring thioflavin T fluorescence, light scattering, and 8-anilino-1-naphthalenesulfonate fluorescence. Thioflavin T fluorescence specifically monitors amyloid fibrillation, whereas light scattering and 8-anilino-1-naphthalenesulfonate fluorescence monitor both amyloid fibrillation and amorphous aggregation. The amyloid fibrils formed via a nucleation-dependent mechanism in a supersaturated solution, analogous to crystallization. The lag phase of fibrillation was reduced upon agitation with stirring or ultrasonic irradiation, and disappeared by seeding with preformed fibrils. In contrast, the glass-like amorphous aggregates formed rapidly without a lag phase. Neither agitation nor seeding accelerated the amorphous aggregation. Thus, by monitoring the kinetics, we can distinguish between crystal-like amyloid fibrils and glass-like amorphous aggregates. Solubility and supersaturation will be key factors for further understanding the aberrant aggregation of proteins.
Nonviral delivery of self-amplifying RNA vaccines
Authors: Geall Andrew J. , Verma Ayush , Otten Gillis R. , Shaw Christine A. , Hekele Armin , Banerjee Kaustuv , Cu Yen , Beard Clayton W. , Brito Luis A. , Krucker Thomas , O’Hagan Derek T. , Singh Manmohan , Mason Peter W. , Valiante Nicholas M. , Dormitzer Philip R. , Barnett Susan W. , Rappuoli Rino , Ulmer Jeffrey B. , Mandl Christian W.
Published: August 2012

Despite more than two decades of research and development on nucleic acid vaccines, there is still no commercial product for human use. Taking advantage of the recent innovations in systemic delivery of short interfering RNA (siRNA) using lipid nanoparticles (LNPs), we developed a self-amplifying RNA vaccine. Here we show that nonviral delivery of a 9-kb self-amplifying RNA encapsulated within an LNP substantially increased immunogenicity compared with delivery of unformulated RNA. This unique vaccine technology was found to elicit broad, potent, and protective immune responses, that were comparable to a viral delivery technology, but without the inherent limitations of viral vectors. Given the many positive attributes of nucleic acid vaccines, our results suggest that a comprehensive evaluation of nonviral technologies to deliver self-amplifying RNA vaccines is warranted.
Short-term plasticity constrains spatial organization of a hippocampal presynaptic terminal
Authors: Nadkarni Suhita , Bartol Thomas M. , Stevens Charles F. , Sejnowski Terrence J. , Levine Herbert
Published: August 2012

Although the CA3–CA1 synapse is critically important for learning and memory, experimental limitations have to date prevented direct determination of the structural features that determine the response plasticity. Specifically, the local calcium influx responsible for vesicular release and short-term synaptic facilitation strongly depends on the distance between the voltage-dependent calcium channels (VDCCs) and the presynaptic active zone. Estimates for this distance range over two orders of magnitude. Here, we use a biophysically detailed computational model of the presynaptic bouton and demonstrate that available experimental data provide sufficient constraints to uniquely reconstruct the presynaptic architecture. We predict that for a typical CA3–CA1 synapse, there are ∼70 VDCCs located 300 nm from the active zone. This result is surprising, because structural studies on other synapses in the hippocampus report much tighter spatial coupling. We demonstrate that the unusual structure of this synapse reflects its functional role in short-term plasticity (STP).
Dengue reporter viruses reveal viral dynamics in interferon receptor-deficient mice and sensitivity to interferon effectors in vitro
Authors: Schoggins John W. , Dorner Marcus , Feulner Michael , Imanaka Naoko , Murphy Mary Y. , Ploss Alexander , Rice Charles M.
Published: August 2012

Dengue virus (DENV) is a global disease threat for which there are no approved antivirals or vaccines. Establishing state-of-the-art screening systems that rely on fluorescent or luminescent reporters may accelerate the development of anti-DENV therapeutics. However, relatively few reporter DENV platforms exist. Here, we show that DENV can be genetically engineered to express a green fluorescent protein or firefly luciferase. Reporter viruses are infectious in vitro and in vivo and are sensitive to antiviral compounds, neutralizing antibodies, and interferons. Bioluminescence imaging was used to follow the dynamics of DENV infection in mice and revealed that the virus localized predominantly to lymphoid and gut-associated tissues. The high-throughput potential of reporter DENV was demonstrated by screening a library of more than 350 IFN-stimulated genes for antiviral activity. Several antiviral effectors were identified, and they targeted DENV at two distinct life cycle steps. These viruses provide a powerful platform for applications ranging from validation of vaccine candidates to antiviral discovery.
FERONIA receptor kinase pathway suppresses abscisic acid signaling in
Arabidopsis
by activating ABI2 phosphatase
Authors: Yu Feng , Qian Lichao , Nibau Candida , Duan Qiaohong , Kita Daniel , Levasseur Kathryn , Li Xiaoqian , Lu Changqing , Li Hui , Hou Congcong , Li Legong , Buchanan Bob B. , Chen Liangbi , Cheung Alice Y. , Li Dongping , Luan Sheng
Published: August 2012

Plant growth and development are controlled by a delicate balance of hormonal cues. Growth-promoting hormones and growth-inhibiting counterparts often antagonize each other in their action, but the molecular mechanisms underlying these events remain largely unknown. Here, we report a cross-talk mechanism that enables a receptor-like kinase,
FERONIA
(
FER
), a positive regulator of auxin-promoted growth, to suppress the abscisic acid (ABA) response through activation of
ABI2
, a negative regulator of ABA signaling. The FER pathway consists of a FER kinase interacting with guanine exchange factors GEF1, GEF4, and GEF10 that, in turn, activate GTPase ROP11/ARAC10.
Arabidopsis
mutants disrupted in any step of the FER pathway, including
fer, gef1gef4gef10
, or
rop11/arac10
, all displayed an ABA-hypersensitive response, implicating the FER pathway in the suppression mechanism. In search of the target for the FER pathway, we found that the ROP11/ARAC10 protein physically interacted with the ABI2 phosphatase and enhanced its activity, thereby linking the FER pathway with the inhibition of ABA signaling.
Induction of apoptosis accelerates reactivation of latent HSV-1 in ganglionic organ cultures and replication in cell cultures
Authors: Du Te , Zhou Guoying , Roizman Bernard
Published: August 2012

Herpes simplex viruses replicate at the portal of entry into the body and are transported retrograde to sensory neurons in which they can establish a silent, latent infection characterized by the expression of a noncoding latency-associated transcript and a set of microRNAs. At the portal of entry into the body and in cell culture a viral protein, VP16, recruits cellular proteins that initiate a sequential derepression of several kinetic classes of viral genes. Earlier studies have shown that upon reactivation of latent virus in ganglionic organ cultures all genes are derepressed at once, thus obviating the need for VP16 to initiate sequential derepression of viral genes. One hypothesis that could explain the data is that the massive reactivation of all classes of viral genes is the consequence of activation of an apoptotic pathway. Here we show that two proapoptotic drugs, dexamethasone and 2[[3-(2,3-dichlorophenoxy)propyl]amino]-ethanol, each accelerates viral gene expression in ganglionic organ cultures. We also show that in cultured cells apoptosis induced by dexamethasone accelerates viral gene expression and accumulation of infectious virus. The results are surprising in light of the relatively large number of viral proteins that independently block apoptosis induced by viral gene products or exogenous agents. The results suggest that the virus may rely on apoptosis to exit from latency but that apoptosis may be detrimental for virus replication or spread at the portal of entry into the body.
π-Frontier molecular orbitals in
S
= 2 ferryl species and elucidation of their contributions to reactivity
Authors: Srnec Martin , Wong Shaun D. , England Jason , Que Lawrence , Solomon Edward I.
Published: August 2012

S
 = 2 Fe
IV
═O species are key intermediates in the catalysis of most nonheme iron enzymes. This article presents detailed spectroscopic and high-level computational studies on a structurally-defined
S
 = 2 Fe
IV
═O species that define its frontier molecular orbitals, which allow its high reactivity. Importantly, there are both π- and σ-channels for reaction, and both are highly reactive because they develop dominant oxyl character at the transition state. These π- and σ-channels have different orientation dependences defining how the same substrate can undergo different reactions (H-atom abstraction vs. electrophilic aromatic attack) with Fe
IV
═O sites in different enzymes, and how different substrates can undergo different reactions (hydroxylation vs. halogenation) with an Fe
IV
═O species in the same enzyme.
Breathing fluctuations in position-specific DNA base pairs are involved in regulating helicase movement into the replication fork
Authors: Jose Davis , Weitzel Steven E. , von Hippel Peter H.
Published: August 2012

We previously used changes in the near-UV circular dichroism and fluorescence spectra of DNA base analogue probes placed site specifically to show that the first three base pairs at the fork junction in model replication fork constructs are significantly opened by “breathing” fluctuations under physiological conditions. Here, we use these probes to provide mechanistic snapshots of the initial interactions of the DNA fork with a tight-binding replication helicase in solution. The primosome helicase of bacteriophage T4 was assembled from six (gp41) helicase subunits, one (gp61) primase subunit, and nonhydrolyzable GTPγS. When bound to a DNA replication fork construct this complex advances one base pair into the duplex portion of the fork and forms a stably bound helicase “initiation complex.” Replacement of GTPγS with GTP permits the completion of the helicase-driven unwinding process. Our spectroscopic probes show that the primosome in this stable helicase initiation complex binds the DNA of the fork primarily via backbone contacts and holds the first complementary base pair of the fork in an open conformation, whereas the second, third, and fourth base pairs of the duplex show essentially the breathing behavior that previously characterized the first three base pairs of the free fork. These spectral changes, together with dynamic fluorescence quenching results, are consistent with a primosome-binding model in which the lagging DNA strand passes through the central hole of the hexagonal helicase, the leading strand binds to the “outside” surfaces of subunits of the helicase hexamer, and the single primase subunit interacts with both strands.
Intercultural dimensions in the (new) curriculum of Cyprus: the way forward
Authors: Hajisoteriou Christina , Neophytou Lefkios , Angelides Panayiotis
Published: August 2012

In 2010, the Ministry of Education and Culture (MEC) in Cyprus introduced a ‘new’ national curriculum for all public schools of the Cypriot republic. The overarching purpose of this study is to examine how the ongoing educational reform in Cyprus could set a different ideological framework, within which intercultural education may be developed and implemented. To this end, it provides a number of important insights into the intercultural dimension of the ‘new’ national curriculum by exploring the formal and the ideological levels of the curriculum. More specifically, it indicates the ways in which the ideological curriculum has been formed by the complex and often counteractive discourses of monoculturalism, multiculturalism and interculturalism due to the socio‐historical context of Cyprus. The conclusions of this study assert that further research should be conducted to examine the implications pertaining to teachers’ practice and student learning with regard to intercultural education.