bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural stabilities and transformations in cationized asparagine at finite temperatures: An ab initio molecular dynamics study
Authors: Sun Shoutian , Liu Jianwen , Liu Zhi-Feng
Published: March 2014

The cationic complexes of Asparagine (Asn), M +( Asn ), with M + = Li +, Na +, K +, Cs +, and H +, are models for studying the interaction between cations and Asn. Ab initio molecular dynamics (AIMD) method is employed to simulate their behavior at finite temperatures. Structural transformation between conformers is observed, which becomes progressively easier as the cation varies from Li +, to Na +, K +, Cs +, and H +. The fluctuation of the M +– N and M +– O distances and rotation of torsional angles are significant even at room temperature for K +, Cs + and H +. Vibrational profiles based on AIMD trajectories provide insights into the broadening and shifts in relative intensities observed in the vibrational spectra measured by infrared multi-photon dissociation (IRMPD) experiments.
Folding simulation of Trp-cage utilizing a new AMBER compatible force field with coupled main chain torsions
Authors: Mou Lirong , Jia Xiangyu , Gao Ya , Li Yongxiu , Zhang John Z. H. , Mei Ye
Published: March 2014

A newly developed AMBER compatible force field with coupled backbone torsion potential terms (AMBER032D) is utilized in a folding simulation of a mini-protein Trp-cage. Through replica exchange and direct molecular dynamics (MD) simulations, a multi-step folding mechanism with a synergetic folding of the hydrophobic core (HPC) and the α-helix in the final stage is suggested. The native structure has the lowest free energy and the melting temperature predicted from the specific heat capacity Cvis only 12 K higher than the experimental measurement. This study, together with our previous study, shows that AMBER032Dis an accurate force field that can be used for protein folding simulations.
GAUGE CHOICE FOR THE YANG–MILLS EQUATIONS USING THE YANG–MILLS HEAT FLOW AND LOCAL WELL-POSEDNESS IN H1
Authors: OH SUNG-JIN
Published: March 2014

We introduce a novel approach to the problem of gauge choice for the Yang–Mills equations on the Minkowski space ℝ1+3, which uses the Yang–Mills heat flow in a crucial way. As this approach does not possess the drawbacks of the previous approaches, it is expected to be more robust and easily adaptable to other settings. As a first application, we give an alternative proof of the local well-posedness of the Yang–Mills equations for initial data [Formula: see text], which is a classical result of Klainerman and Machedon (1995) that had been proved using a different method (local Coulomb gauges). The new proof does not involve localization in space–time, which had been the key drawback of the previous method. Based on the results proved in this paper, a new proof of finite energy global well-posedness of the Yang–Mills equations, also using the Yang–Mills heat flow, is established in a companion article.
A STUDY OF ORGANISATIONAL DETERMINANTS AND INNOVATION PRACTICES IN DUBAI SMEs
Authors: AL-ANSARI YAHYA , XU JUN , PERVAN SIMON
Published: March 2014

This study explores the relevance of established organisational determinants of innovation practice in small and medium-sized enterprises (SMEs) in the emerging market of Dubai, United Arab Emirates. Drawing upon data from 200 SMEs, the findings suggest that management orientation, technology orientation, alliance and cooperation and market orientation are important antecedents to SMEs' innovative practices, but question the importance of organisational culture. This study is the first to examine the organisational determinants of innovation in both an SME and emerging market context. Implications and suggestions for future research are offered to both scholars and practitioners.
ARE COMPLEX INNOVATORS MORE PERSISTENT THAN SINGLE INNOVATORS? AN EMPIRICAL ANALYSIS OF INNOVATION PERSISTENCE DRIVERS
Authors: LE BAS CHRISTIAN , POUSSING NICOLAS
Published: March 2014

This paper examines the persistence of innovation behaviour at the firm level (in the manufacturing and services sectors). We attempt to answer the question of whether being successful in past innovation activities increase the probability of being successful in current innovation activities. We contribute to the literature by explicitly distinguishing between single and complex innovation strategies. Using two waves of the Community Innovation Survey (2002–2004, 2006–2008) conducted in Luxembourg, the regressions show that complex innovators are more inclined to remain persistent rather than single innovators. Within the group of single innovators, pure product innovators have an advantage over pure process innovators. The results support the idea that the differences in innovation strategies across firms are important for understanding the firm's innovation dynamics.
PERCEPTIONS OF INNOVATION CLIMATE AND THE INFLUENCE OF OTHERS: A MULTI-COUNTRY STUDY OF SMEs
Authors: MAZZAROL TIM , CLARK DELWYN , REBOUD SOPHIE , GOUGH NEWELL (SANDY) , OLSON PHILIP
Published: March 2014

This paper examines the perceptions of small firms from eight OECD countries towards their national climate for innovation, and the perceived importance of outsiders in assisting them with innovation projects. A total of 505 firms were surveyed, each had an innovation they were seeking to commercialise. Key issues examined were the firm's senior managers' perceptions of how supportive their country was to innovators in relation to government policy, the cost of doing business and the quality of communications infrastructure. Also examined was the ease of access to markets, skilled labour, research centres and external financing. The managers were also asked to indicate how much value they placed on outsiders such as accountants, venture financiers, customers, suppliers, lawyers and others in relation to their strategic decision making over commercialisation activities. Differences were found between the country sub-samples using discriminant analysis. However, the similarities between these firms suggest more commonality than differences.
IMAGE THRESHOLDING USING FUZZY CORRELATION CRITERION AND HARMONY SEARCH ALGORITHM
Authors: NIE FANGYAN , LI JIANQI , TU TIANYI , PAN MEISEN
Published: March 2014

This paper reports a novel image thresholding method based on fuzzy set theory and maximum correlation criterion using harmony search algorithm. In this study, the maximum fuzzy correlation criterion is defined using Z- and S- fuzzy member function on image gray level histogram. Then fuzzy correlation criterion image segmentation based on harmony search algorithm is implemented. The experimental studies were conducted on a variety of images by testing the proposed method and some classical thresholding methods. The experimental results demonstrate that the proposed method can select the threshold automatically and effectively. Compared with the exhaustive search method, the harmony search algorithm can give high degree of accuracy while needing less search time and has good search stability in the segmentation experiments.
TRAINING NEURAL NETWORKS TO PREDICT STUDENT ACADEMIC PERFORMANCE: A COMPARISON OF CUCKOO SEARCH AND GRAVITATIONAL SEARCH ALGORITHMS
Authors: CHEN JENG-FUNG , DO QUANG HUNG
Published: March 2014

The accurate prediction of students' academic performance is of importance to institutions as it provides valuable information for decision making in the admission process and enhances educational services by allocating customized assistance according to the predicted performance. The purpose of this study is to investigate the prediction ability of neural networks trained by two recent heuristic algorithms inspired by the behaviors of natural phenomena, namely, the cuckoo search and gravitational search algorithms. We used previous exam results and other factors, such as the location of the student's high school and the student's gender, as input variables, and predicted the student's expected performance. The cuckoo search and gravitational search algorithms were utilized to train the feed-forward neural network for prediction. These algorithms optimized the weights between layers and biases of the neuron network. The simulation results of the two algorithms were then discussed and analyzed. It was found that the neural network trained by the cuckoo search could be used in the prediction of students' academic performance. It is expected that this work may be used to support student admission procedures and strengthen the service system in educational institutions.
Cross-border labor mobility in information technology services: A quantitative approach to estimate protectionism in selected developed country markets
Authors: Gupta Pralok
Published: March 2014

This paper analyzes regulatory measures affecting cross-border labor movement (mode 4 of services trade) in Information Technology (IT) services for selected developed countries (Australia, Canada, UK and US). It contributes to the existing literature by developing a template for quantifying the qualitative nature of regulations affecting the mode 4 service trade. It constructs trade restrictiveness indices for assessing protectionism affecting the temporary movement of Indian IT professionals to these countries in the pre- and post-recession periods. It finds that developed country IT markets have become more protectionist after the recent financial crisis, mainly on account of stricter immigration measures in these countries.
PULSAR WIND NEBULAE MODELING
Authors: BUCCIANTINI NICCOLÒ
Published: March 2014

Pulsar Wind Nebulae (PWNe) are ideal astrophysical laboratories where high energy relativistic phenomena can be investigated. They are close, well resolved in our observations, and the knowledge derived in their study has a strong impact in many other fields, from AGNs to GRBs. Yet there are still unresolved issues, that prevent us from a full clear understanding of these objects. The lucky combination of high resolution X-ray imaging and numerical codes to handle the outflow and dynamical properties of relativistic MHD, has opened a new avenue of investigation that has lead to interesting progresses in the last years. Despite all of this, we do not understand yet how particles are accelerated, and the functioning of the pulsar wind and pulsar magnetosphere, that power PWNe. I will review what is now commonly known as the MHD paradigm, and in particular I will focus on various approaches that have been and are currently used to model these systems. For each I will highlight its advantages, limitations, and degree of applicability.
MULTIWAVELENGTH PROBES OF THE ENVIRONS OF RELATIVISTIC SHOCKS IN BLAZAR JETS
Authors: BARING MATTHEW G. , BÖTTCHER MARKUS , SUMMERLIN ERROL J.
Published: March 2014

Diffusive shock acceleration (DSA) at relativistic shocks is likely to be an important acceleration mechanism in various astrophysical jet sources, including radio-loud AGN. An important recent development for blazar science is the ability of Fermi-LAT data to pin down the power-law index of the high energy portion of emission in these sources, and therefore also the index of the underlying non-thermal particle population. This diagnostic potential was not possible prior to Fermi launch, when gamma-ray information was dominated by the highly-absorbed TeV band. This paper highlights how multiwavelength spectra including X-ray band and Fermi data can be used to probe diffusive acceleration in relativistic, oblique, MHD shocks in blazar jets. The spectral index of the non-thermal particle distributions resulting from Monte Carlo simulations of DSA, and the fraction of thermal particles accelerated to non-thermal energies, depend sensitively on the particles' mean free path scale, and also on the magnetic field obliquity to the shock normal. We investigate self-consistently the radiative synchrotron/Compton signatures of the resulting thermal and non-thermal particle distributions. Important constraints on the frequency of particle scattering and the level of field turbulence are identified for the blazar AO 0235+164. The possible interpretation that turbulence levels decline with remoteness from jet shocks, and a significant role for non-gyroresonant diffusion, are discussed.
SOLUTION TO THE SIGMA PROBLEM OF PULSAR WIND NEBULAE
Authors: PORTH OLIVER , KOMISSAROV SERGUEI S. , KEPPENS RONY
Published: March 2014

Pulsar wind nebulae (PWN) provide a unique test-bed for the study of highly relativistic processes right at our astronomical doorstep. In this contribution we will show results from the first 3D RMHD simulations of PWN. Of key interest to our study is the long standing "sigma-problem" that challenges MHD models of Pulsars and their nebulae now for 3 decades. Earlier 2D MHD models were very successful in reproducing the morphology of the inner Crab nebula showing a jet, torus, concentric wisps and a variable knot. However, these models are limited to a purely toroidal field geometry which leads to an exaggerated compression of the termination shock and polar jet — in contrast to the observations. In three dimensions, the toroidal field structure is susceptible to current driven instabilities; hence kink instability and magnetic dissipation govern the dynamics of the nebula flow. This leads to a resolution of the sigma-problem once also the pulsar's obliqueness (striped wind) is taken into account. In addition, we present polarized synchrotron maps constructed from the 3D simulations, showing the wealth of morphological features reproduced in 2D is preserved in the 3D case.
RADIO MONITORING OF THE GAMMA-RAY BINARY PSR B1259–63
Authors: MOLDÓN J. , RIBÓ M. , PAREDES J. M. , JOHNSTON S.
Published: March 2014

PSR B1259–63 is a 48 ms pulsar in a highly eccentric 3.4-year orbit around the young massive star LS 2883. During the periastron passage the system displays transient non-thermal unpulsed emission from radio to very high energy gamma rays. At radio wavelengths we can independently study the pulsations and the unpulsed transient emission, which was shown to be extended on AU scales and variable. The pulsed and unpulsed components provide valuable information on the binary system geometry, the physical properties of the pulsar, which is the main source of energy of the broadband emission, and the characteristics of the outflow of accelerated particles. We present a summary of the observational instruments and techniques at radio wavelengths used to observe PSR B1259–63 and we describe the observable and derived properties we can obtain. Finally, we summarize the main radio results of the last years and describe different observational radio campaigns currently ongoing for PSR B1259–63. We aim to provide a general insight on the observational approach to study this gamma-ray binary at radio wavelengths.
THE VERY BRIGHT AND NEARBY GRB130427A: THE EXTRA HARD SPECTRAL COMPONENT AND IMPLICATIONS FOR VERY HIGH-ENERGY GAMMA-RAY OBSERVATIONS OF GAMMA-RAY BURSTS
Authors: TAM PAK-HIN THOMAS
Published: March 2014

The extended high-energy gamma-ray (>100 MeV) emission occurring after the prompt gamma-ray bursts (GRBs) is usually characterized by a single power-law spectrum, which has been explained as the afterglow synchrotron radiation. We report on the Fermi Large Area Telescope (LAT) observations of the >100 MeV emission from the very bright and nearby GRB 130427A, up to ~100 GeV. By performing time-resolved spectral fits of GRB 130427A, we found a strong evidence of an extra hard spectral component above a few GeV that exists in the extended high-energy emission of this GRB. This extra spectral component may represent the first clear evidence of the long sought-after afterglow inverse Compton emission. Prospects for observations at the very high-energy gamma-rays, i.e., above 100 GeV, are described.
MICROVARIABILITY OF 0.3-10 keV FLUX IN HBL SOURCE PKS 2155-304
Authors: KAPANADZE BIDZINA , KAPANADZE SERGO , VARDOSANIDZE MANANA
Published: March 2014

The high energy peaked BL Lacertae object PKS 2155-304 has been observed 106-times by the X-ray Telescope onboard the Swift satellite through the 0.3-10 keV band since 2005 November 17. Among these observations, we have revealed 19 cases of the intraday flux variability at 99.9% confidence level with fractional rms amplitudes up to 30% and timescales ranging from 40 ks down to 0.4 ks. Flux changes were often accompanied by a spectral variability which showed a complex character in the presence of both clockwise and counter-clockwise evolution in a hardness ratio-flux plane. These events show rather curved spectra fitted well with the log-parabolic model. The curvature parameter ranged from 0.13 to 0.73 and showed different values for the spectra corresponding to the separate orbits of a single observation. The peak of spectral energy distribution ranged between 1.76 keV and 2.67 keV and generally was variable during the intraday flux changes. The soft and hard X-ray fluxes showed a strong correlation to each other. No correlation between the occurrence of intraday variations and source brightness state was seen — they are found as in flaring as well for intermediate and low states. The X-ray microvariability in PKS 2155-304 can be explained both with the shock-in-jet scenario and emergence of a "blob" of very energetic particles in the jet base.
THE NEED FOR HARD SPECTRA SOURCES OF NEARBY HEAVY COSMIC RAYS
Authors: TAYLOR ANDREW M.
Published: March 2014

Using recent Pierre Auger Observatory energy spectrum and composition analysis results, an investigation is carried out into the requirements placed on the UHECR sources. The spatial distribution of these sources is investigated along with the energy distribution of UHECR they output. These investigations reveal the need for local UHECR sources which output a hard spectrum of intermediate/heavy UHECR. These results demand that local (<80 Mpc) UHECR sources exist,placing exciting and difficult requirements on the local extragalactic candidate sources. From these results, a relation between the maximum energy (E max ) and the source spectral index α is also noted, which results directly from the nature of the photo-disintegration losses.
THE UNIFICATION OF RELATIVISTIC JETS
Authors: FOSCHINI LUIGI
Published: March 2014

I report about the unification of relativistic jets from compact objects. The mass range is between 1.4 and 10 billion solar masses (i.e. from neutron stars to supermassive black holes in galaxies).
NEUTRON PRODUCTION IN BLACK HOLE CORONAE AND PROTON LOADING OF JETS
Authors: VILA GABRIELA S. , VIEYRO FLORENCIA L. , ROMERO GUSTAVO E.
Published: March 2014

We study the production of neutrons in the corona of an accreting black hole through the interaction of locally accelerated protons with matter and radiation. A fraction of these neutrons may escape and penetrate into the base of the jet, later decaying into protons. This is a possible mechanism for loading Poynting-dominated outflows with baryons.

We characterize the spatial and energy distribution of neutrons in the corona and that of the protons injected in the jet by neutron decay. We assess the contribution of these protons to the radiative spectrum of the jet. We also investigate the fate of the neutrons that escape the corona into the external medium.
ASYMMETRIES OF AGN JETS IN INHOMOGENEOUS MEDIA
Authors: GAIBLER VOLKER
Published: March 2014

Considerable asymmetries in jets from active galactic nuclei (AGN) and associated double radio sources can be caused by an inhomogeneous interstellar medium of the host galaxy. These asymmetries can easily be estimated by 1D propagation models, but hydrodynamical simulations have shown that the actual asymmetries can be considerably larger. With a set of smaller-scale hydrodynamical simulations we examine these asymmetries, and find they are typically a factor of ~ 3 larger than in 1D models. We conclude that, at high redshift, large asymmetries in radio sources are expected in gas-rich galaxies with a clumpy interstellar medium.
INVESTIGATION OF DENSE GAS TOWARDS RELATIVISTIC OUTFLOW SOURCES
Authors: HAWKES J. , ROWELL G. , DAWSON B. , AHARONIAN F. , BURTON M. , FUKUI Y. , FURUKAWA N. , HAYAKAWA T. , KAWAMURA A. , MAXTED N. , de OÑA-WILHELMI E. , de WILT P. , WALSH A.
Published: March 2014

We probe the interstellar medium towards the objects Circinus X-1, a low-mass X-ray binary with relativistic jets; and the highly energetic Westerlund 2 stellar cluster, which is located towards TeV gamma-ray emission and interesting arc- and jet-like features seen in Nanten 12CO data. We have mapped both regions with the Mopra radio telescope, in 7 mm and 12 mm wavebands, looking for evidence of disrupted/dense gas caused by the interaction between high energy outflows and the ISM. Towards Westerlund 2, peaks in CS(J=1-0) emission indicate high density gas towards the middle of the arc and the endpoint of the jet; and radio recombination line emission is seen overlapping the coincident HII region RCW49. Towards Circinus X-1, 12CO(J = 1-0) Nanten data reveals three molecular clouds that lie in the region of Cir X-1. Gas parameters for each cloud are presented here.
MOPRA AND NANTEN STUDIES OF HESS J1825-137 NORTHERN CLOUD
Authors: VOISIN F. , ROWELL G. , FUKUI Y. , BURTON M. , WALSH A. , AHARONIAN F.
Published: March 2014

The Pulsar Wind Nebula (PWN) HESS J1825-137 is one of the most extended TeV PWN and its morphology is influenced by the molecular gas located north of the TeV sources. In order to refine the composition and dynamics of the cloud, we have used the telescope Mopra in the 7 and 12 mm bands. Our results highlight dense regions and also perturbations in the southern part of the dense cloud.
SOLUTIONS OF THE WIND EQUATION IN RELATIVISTIC MAGNETIZED JETS
Authors: MILLAS D. , KATSOULAKOS G. , LINGRI D. , KARAMPELAS K. , VLAHAKIS N.
Published: March 2014

We study the bulk acceleration in relativistic axisymmetric magnetized outflows, by solving the momentum equation along the flow, the so-called wind equation. The solutions for the bulk Lorentz factor depend on the geometry of the field/streamlines through the "bunching function" S. We investigate the general characteristics of the S function and how its choice affects the acceleration. In our study, various fast rise and slow decay examples are selected for S, with a global maximum near the fast magnetosonic critical point, as required from the regularity condition. For each case we determine the terminal Lorentz factor γ∞ and the acceleration efficiency γ∞/μ, where μ is the total energy-to-mass flux ratio (which equals the maximum possible Lorentz factor of the outflow). With proper choices of S we can achieve efficiencies greater than 50%. Last, we examine the shape of the field/streamlines with respect to the choice of the S function. The results of this work, depending on the choices of μ, can be applied to relativistic GRB or AGN jets.
ON THE PRODUCTION OF HIGH-ENERGY NEUTRINOS IN GAMMA-RAY BURSTS
Authors: REYNOSO MATIAS M.
Published: March 2014

We present preliminary results of a model with two zones in order to study the production of high energy neutrinos at the prompt phase of gamma-ray bursts (GRB). We consider an acceleration zone, where protons and electrons are injected and accelerated, being subject to synchrotron, proton-proton, and proton-gamma cooling. We also assume that they can escape from this zone at a certain rate. The produced pions and the decaying muons are also subject to energy loss and gain processes within the acceleration zone, and the escaping ones are re-injected in a second zone where acceleration no longer operates. We compute the neutrino output expected from both of these zones using typical GRB parameters, and integrate in the redshift to obtain a diffuse neutrino flux which can be different from the expected within one-zone models.
THE INFLUENCE OF PLASMA EFFECTS OF PAIR BEAMS ON THE INTERGALACTIC CASCADE EMISSION OF BLAZARS
Authors: MENZLER ULF , SCHLICKEISER REINHARD
Published: March 2014

The attenuation of TeV γ-rays from distant blazars by the extragalactic background light (EBL) produces relativistic electron-positron pair beams. It has been shown by Broderick et. al. (2012) and Schlickeiser et. al (2012) that a pair beam traversing the intergalactic medium is unstable to linear two-stream instabilities of both electrostatic and electromagnetic nature. While for strong blazars all free pair energy is dissipated in heating the intergalactic medium and a potential electromagnetic cascade via inverse-Compton scattering with the cosmic microwave background is suppressed, we investigate the case of weak blazars where the back reaction of generated electrostatic turbulence leads to a plateauing of the electron energy spectrum. In the ultra-relativistic Thomson limit we analytically calculate the inverse-Compton spectral energy distribution for both an unplateaued and a plateaued beam scenario, showing a peak reduction factor of Rpeak ≈ 0.345. This is consistent with the FERMI non-measurements of a GeV excess in the spectrum of EBL attenuated TeV blazars. Claims on the lower bound of the intergalactic magnetic field strengths, made by several authors neglecting plasma effects, are thus put into question.
Bridges and random truncations of random matrices
Authors: Beffara Vincent , Donati-Martin Catherine , Rouault Alain
Published: March 2014

Let U be a Haar distributed matrix in 𝕌(n) or 𝕆(n). In a previous paper, we proved that after centering, the two-parameter process [Formula: see text] converges in distribution to the bivariate tied-down Brownian bridge. In the present paper, we replace the deterministic truncation of U by a random one, in which each row (respectively, column) is chosen with probability s (respectively, t) independently. We prove that the corresponding two-parameter process, after centering and normalization by n-1/2 converges to a Gaussian process. On the way we meet other interesting convergences.
The 2013 Marche offshore earthquakes: new insights into the active tectonic setting of the outer northern Apennines
Authors: Mazzoli S. , Macchiavelli C. , Ascione A.
Published: March 2014

A seismic sequence offshore the Marche region sheds new light on the active tectonic setting of the outer northern Apennines, revealing the existence of a previously unknown transcurrent seismogenic structure. In contrast to the Po Plain area, where vigorous seismicity testifies to active frontal thrusting, the seismotectonic setting of the Adriatic domain is characterized by the occurrence of active crustal strike-slip faults dissecting the thrust belt. As recent studies suggest that thrust faults represent the unique seismogenic sources characterizing the Adriatic sector of the outer northern Apennines, our results pose new challenges to the identification of seismogenic structures in the region.
Erosion rates in the source region of an ancient sediment routing system: comparison of depositional volumes with thermochronometric estimates
Authors: Michael Nikolaos A. , Carter Andrew , Whittaker Alexander C. , Allen Philip A.
Published: March 2014

Calculation of the total depositional volume of an ancient source-to-sink system, combined with estimates of the area of catchments acting as source regions using provenance methods, is used to evaluate average catchment erosion rates on a million year time scale. These rates are compared with values derived from thermochronological methods. Using the mid- to late Eocene (33.9–41.6 Ma) Escanilla palaeo-sediment routing system from the south–central Pyrenean orogenic wedge-top zone as an example,
c
. 3500 ± 300 km
3
of solid particulate sediment was derived from two catchments in the south–central Pyrenees over a 7.7 myr period, equivalent to a mean erosion rate of
c
. 0.15–0.18 mm a
−1
. Average exhumation rates in contributing catchments over the same time interval are estimated at 0.2–0.3 mm a
−1
based on apatite fission-track analysis of pebbles in proximal conglomerates, and 0.23–0.34 mm a
−1
from fission-track analysis of detrital apatites sampling a wider range of grain size. Sediment supply progressively increased during the mid- to late Eocene time period, at least in part driven by catchment expansion deep into the Pyrenean Axial Zone at
c
. 39 Ma. The consistency of the rates of catchment-averaged erosion calculated from different methods builds confidence that source areas have been connected to depositional sinks correctly.

Supplementary materials:

A description of the provenance methods used to link sources and sinks of the Escanilla palaeo-sediment routing system, including the analysis of clast lithologies, palaeocurrents, heavy minerals and geochronology of detrital zircons, are available at
http://www.geolsoc.org.uk/SUP18727
.
Eocene to Miocene igneous activity in NE Greenland: northward younging of magmatism along the East Greenland margin
Authors: Larsen Lotte M. , Pedersen Asger K. , Tegner Christian , Duncan Robert A.
Published: March 2014

Radiometric dating by the
40
Ar–
39
Ar incremental heating method was carried out on lavas, sills, dykes, and a central intrusion from NE Greenland. Eighteen samples gave acceptable crystallization ages. Lavas of both Lower and Upper Plateau Lava Series gave ages in the range 55.5–53.5 Ma and cannot be constrained to better than 56–53 Ma. Sills and dykes from Traill Ø to Shannon, with compositions fairly similar to those of the lavas, gave ages of 55.1–51.3 Ma, contemporaneous with and slightly younger than the lavas. Alkaline lavas on inland nunataks have ages of 53–50 Ma, and the Kap Broer Ruys intrusive centre has an age of 48.7 ± 0.5 Ma. An alkaline sill on Hvalrosø is much younger at 20.3 ± 0.1 Ma. There are no pre-breakup lavas onshore NE Greenland. We surmise that the hot mantle of the Iceland plume arrived and melted extensively beneath the northern basins only at the time of breakup around 55 Ma. Post-breakup intrusive events in NE Greenland coincided with plate-tectonic events such as reorganization, uplift and opening in the north. The Hvalrosø sill represents a local small melting event that may be related to coeval opening of the Lena Trough.

Supplementary materials:

Details of the source data, results, and the compositions and locations of the dated samples, are available at
www.geolsoc.org.uk/SUP18738
.
Lunar mare volcanism: lateral heterogeneities in volcanic activity and relationship with crustal structure
Authors: Morota Tomokatsu , Ishihara Yoshiaki , Sasaki Sho , Goossens Sander , Matsumoto Koji , Noda Hirotomo , Araki Hiroshi , Hanada Hideo , Tazawa Seiichi , Kikuchi Fuyuhiko , Ishikawa Toshiaki , Tsuruta Seiitsu , Kamata Shunichi , Otake Hisashi , Haruyama Junichi , Ohtake Makiko
Published: March 2014

Lunar mare basalts are spatially unevenly distributed, and their abundances differ between the nearside and farside of the Moon. Although mare asymmetry has been attributed to thickness variations in the low-density anorthositic crust, the eruptive mechanism of lunar magma remains unknown. In this study, we investigate the relationship between mare distribution and crustal thickness using geological and geophysical data obtained by the SELENE (Kaguya) and the Gravity Recovery and Interior Laboratory spacecraft, and quantitatively re-evaluate the influence of the anorthositic crust on magma eruption. We identify a lateral heterogeneity in the upper limit of crustal thickness that allows magma extrusion to the surface. In the Procellarum KREEP Terrane, where the surface abundances of heat-producing elements are extremely high, magmas can erupt in regions of crustal thickness below about 30 km. In contrast, magma eruptions are limited to regions of crustal thickness below about 20 km in other nearside regions, around 10 km in the South Pole–Aitken Basin and approximately 5 km in the farside Felspathic Highland Terrane. Such heterogeneity may result from lateral variations in magma production in the lunar mantle and/or crustal density.
Modelling of structural and lithological controls on mobility of fluids and gold in orogenic belts, New Zealand
Authors: Upton Phaedra , Craw Dave
Published: March 2014

Numerical models have been run to evaluate the key parameters that affect fluid flow and gold mineralization at a range of scales, from the full thickness of the crust to the mineral grain scale. These models are constrained with real examples of orogenic gold in southern New Zealand. Large scale modelling shows that differences in crustal strength and thickness affect the locus, scale, and rate of crustal fluid flow and hence influence gold deposition. The most vigorous hydrothermal activity and gold mineralization occurs in narrow zones with maximum uplift close to a major crustal boundary. Relatively strong middle crust develops deformation-driven permeability and fluid flow in a broad diffuse zone. Deformation of randomly inhomogeneous rocks under mid-crustal conditions results in horizontal fabric and horizontal shear zones, and these can control fluid flow locally. The addition of graphite to flat shear zones causes an increase in deformation-induced permeability, and this can encourage further graphite deposition in a feedback effect. Fluid flow in these flat shears is very slow (mm/year) compared to fluid flow in fracture-controlled permeability at shallow crustal levels. Rock strength inhomogeneities in mid-crustal shear zones can result in localized decrease in differential stress, facilitating the switching of orientations of principal stress axes and the formation of steeply-dipping quartz veins.
Chemokines and Chemokine Receptors: Positioning Cells for Host Defense and Immunity
Authors: Griffith Jason W. , Sokol Caroline L. , Luster Andrew D.
Published: March 2014

Chemokines are chemotactic cytokines that control the migratory patterns and positioning of all immune cells. Although chemokines were initially appreciated as important mediators of acute inflammation, we now know that this complex system of approximately 50 endogenous chemokine ligands and 20 G protein–coupled seven-transmembrane signaling receptors is also critical for the generation of primary and secondary adaptive cellular and humoral immune responses. Recent studies demonstrate important roles for the chemokine system in the priming of naive T cells, in cell fate decisions such as effector and memory cell differentiation, and in regulatory T cell function. In this review, we focus on recent advances in understanding how the chemokine system orchestrates immune cell migration and positioning at the organismic level in homeostasis, in acute inflammation, and during the generation and regulation of adoptive primary and secondary immune responses in the lymphoid system and peripheral nonlymphoid tissue.
The Aryl Hydrocarbon Receptor: Multitasking in the Immune System
Authors: Stockinger Brigitta , Meglio Paola Di , Gialitakis Manolis , Duarte João H.
Published: March 2014

The aryl hydrocarbon receptor (AhR), for many years almost exclusively studied by the pharmacology/toxicology field for its role in mediating the toxicity of xenobiotics such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), has more recently attracted the attention of immunologists. The evolutionary conservation of this transcription factor and its widespread expression in the immune system point to important physiological functions that are slowly being unraveled. In particular, the emphasis is now shifting from the role of AhR in the xenobiotic pathway toward its mode of action in response to physiological ligands. In this article, we review the current understanding of the molecular interactions and functions of AhR in the immune system in steady state and in the presence of infection and inflammation, with a focus on barrier organs such as the skin, the gut, and the lung.
Young Investigator Perspectives. Teaching and the postdoctoral experience: impact on transition to faculty positions
Authors: Uno Jennifer , Walton Kristen L. W.
Published: March 2014

This editorial continues with our Young Investigator Perspectives series. Drs. Uno and Walton are young investigators who hold faculty positions. They completed a K12 postdoctoral program through the IRACDA (Institutional Research and Career Development Award) program sponsored through the NIGMS institute at NIH. IRACDA programs exist at multiple institutions in the USA to combine postdoctoral training with formal training in academic skills and teaching at partner institutions. I thank Drs. Walton and Uno for a thoughtful perspective on how this experience shaped their career goals to combine teaching and research and inspire undergraduates to science careers. Given the current national dialog on broadening career paths and outcomes for PhD scientists, this is a timely perspective.

— P. Kay Lund
Embelin Reduces Colitis-Associated Tumorigenesis through Limiting IL-6/STAT3 Signaling
Authors: Dai Yun , Jiao Hongmei , Teng Guigen , Wang Weihong , Zhang Rongxin , Wang Yunhong , Hebbard Lionel , George Jacob , Qiao Liang
Published: March 2014

The interleukin-6 (IL-6)/STAT3 signaling regulates survival and proliferation of intestinal epithelial cells and plays an important role in the pathogenesis of inflammatory bowel disease and colorectal cancer. Embelin is a small molecule inhibitor of X-linked inhibitor of apoptosis protein (XIAP), with antioxidant, anti-inflammatory, and antitumor activities. We previously showed that embelin inhibits the growth of colon cancer cells in vitro, and effectively suppresses 1,2-dimethylhydrazine dihydrochloride-induced colon carcinogenesis in mice. Here, we explored the antitumor effects and mechanisms of embelin on colitis-associated cancer (CAC) using the azoxymethane/dextran sulfate sodium (AOM/DSS) model, with a particular focus on whether embelin exerts its effect through the IL-6/STAT3 pathway. We found that embelin significantly reduced incidence and tumor size in CAC-bearing mice. In addition to inhibiting proliferation of tumor epithelial cells, embelin suppressed colonic IL-6 expression and secretion, and subsequently STAT3 activation in vivo. Importantly, in vitro studies have revealed that in colon cancer cells, embelin diminished both the constitutive and IL-6–induced STAT3 activation by stimulating Src homology domain 2-containing protein tyrosine phosphatase (SHP2) activity. Moreover, embelin protected mice from AOM/DSS-induced colitis before tumor development. Embelin decreased IL-1β, IL-17a, and IL-23a expression as well as the number of CD4+ T cells and macrophages infiltrating the colonic tissues. Thus, our findings demonstrated that embelin suppresses CAC tumorigenesis, and its antitumor effect is partly mediated by limiting IL-6/STAT3 activation and Th17 immune response. Embelin may be a potential agent in the prevention and treatment of CAC. Mol Cancer Ther; 13(5); 1206–16. ©2014 AACR.
MAPK Pathway Inhibition Enhances the Efficacy of an Anti-Endothelin B Receptor Drug Conjugate by Inducing Target Expression in Melanoma
Authors: Asundi Jyoti , Lacap Jennifer A. , Clark Suzanna , Nannini Michelle , Roth Leslie , Polakis Paul
Published: March 2014

Therapies targeting the mitogen-activated protein (MAP) kinase pathway in melanoma have produced significant clinical responses; however, duration of response is limited by acquisition of drug resistance. Rational drug combinations may improve outcomes in this setting. We assessed the therapeutic combination of an antibody–drug conjugate (ADC) targeting the endothelin B receptor (EDNRB) with small-molecule inhibitors of the MAP kinase signaling pathway in melanoma. Cell lines and tumor models containing either mutant BRAF or NRAS, or wild-type for both, were exposed to small-molecule inhibitors of BRAF and MEK. Expression of EDNRB was analyzed and the therapeutic impact of combining the anti-EDNRB ADC with the BRAF and MEK inhibitors was assessed. Increased expression of EDNRB in response to inhibition of BRAF and/or MEK was observed and augmented the antitumor activity of the ADC. Enhanced target expression and ADC antitumor activity were realized irrespective of the response of the tumor model to the BRAF or MEK inhibitors alone and could be achieved in melanoma with mutant NRAS, BRAF, or neither mutation. Cells that acquired resistance to BRAF inhibition through long-term culture retained drug-induced elevated levels of EDNRB expression. Expression of EDNRB was not enhanced in normal human melanocytes by inhibition of BRAF and the combination of the ADC with MAPK inhibitors was well-tolerated in mice. The anti-EDNRB ADC combines well with BRAF and MEK inhibitors and could have therapeutic use in the majority of human melanoma cases. Mol Cancer Ther; 13(6); 1599–610. ©2014 AACR.
Slow Overmethylation of Housekeeping Genes in the Body Mucosa Is Associated with the Risk for Gastric Cancer
Authors: Oh Jung-Hwan , Rhyu Mun-Gan , Jung Sung-Hoon , Choi Sang-Wook , Kim Suk-Il , Hong Seung-Jin
Published: March 2014

Helicobacter pylori infection increases age-related diverse overmethylation in gene-control regions, which increases the risk of gastric cancer. The H. pylori-associated overmethylation changes subsequently disappear when gastric atrophy and cancer develop. To identify cancer-risk epigenotypes, we traced dynamic methylation changes in the background mucosa of the stomach depending on the extent of gastric atrophy. Paired biopsy specimens were obtained from the noncancerous antrum and body mucosa of 102 patients with cancer and 114 H. pylori–positive and 112 H. pylori–negative controls. The grade of gastric atrophy was evaluated using the endoscopic atrophic border score. The methylation-variable sites at the CpG-island margins and near the transcriptional start sites lacking CpG islands were semiquantitatively analyzed by radioisotope-labeling methylation-specific PCR. We selected eight housekeeping genes adjacent to Alu (CDH1, ARRDC4, PPARG, and TRAPPC2L) or LTR retroelements (MMP2, CDKN2A, RUNX2, and RUNX3) and eight stomach-specific genes (TFF2, PGC, ATP4B, TFF1, TFF3, GHRL, PGA, and ATP4A). Analysis of age-related methylation in the H. pylori–positive controls revealed slow overmethylation in the body and in the LTR-adjacent genes. A high-frequency overmethylation defined based on the slowly overmethylated genes was frequently observed in the body of patients with gastric cancer with open-type atrophy (OR, 12.7; 95% confidence interval, 3.2–49.8). The rapidly changing methylation of Alu-adjacent genes was barely increased in the antrum of patients with gastric cancer. Among diverse methylation changes associated with H. pylori infection, an increase in slowly changing methylation could serve as a cancer-risk marker. Cancer Prev Res; 7(6); 585–95. ©2014 AACR.
Predicted for Greatness: 1994 Molecule of the Year—The DNA Repair Enzyme
Authors: Berwick Marianne
Published: March 2014

Lung cancer mortality is the highest of any cancer. Primary prevention has stalled, however, new lung cancer screening trials of low-dose computerized tomography (LDCT) have shown that the mortality from lung cancer can be reduced by up to 20% among current and former smokers. There are potential harms that must be taken into account when evaluating any screening program. With LDCT, there is a 90% rate of false positives and the potential for high doses of radiation from subsequent workup of benign lesions. The development of biomarkers that might refine the ability of screening to identify individuals at high risk for developing and dying from lung cancer is a ripe area for investigation. Sevilya and colleagues have developed a highly promising set of biomarkers of DNA repair capacity that may satisfy that goal. The large estimate of risk, the thoughtful combination of functional assays of DNA repair capacity, and the population-based design of the study make it reasonable to test these biomarkers in a larger study. Cancer Prev Res; 7(4); 375–7. ©2014 AACR.
Effects of Various Extracellular Matrix Proteins on the Growth of HL-1 Cardiomyocytes
Authors: Choi Seongkyun , Hong Yoonmi , Lee Insu , Huh Dongeun , Jeon Tae-Joon , Kim Sun Min
Published: March 2014

We present the physical and biochemical effects of extracellular matrixes (ECMs) on HL-1 cardiomyocytes. ECMs play major roles in cell growth, adhesion and the maintenance of native cell functions. We investigated the effects of 6 different cell culture systems: 5 different ECM-treated surfaces (fibronectin, laminin, collagen I, gelatin and a gelatin/fibronectin mixture) and 1 nontreated surface. Surface morphology was scanned and analyzed using atomic force microscopy in order to investigate the physical effects of ECMs. The attachment, growth, viability, proliferation and phenotype of the cells were analyzed using phase-contrast microscopy and immunocytochemistry to elucidate the biochemical effects of ECMs. Our study provides basic information for understanding cell-ECM interactions and should be utilized in future cardiac cell research and tissue engineering.
2013 Statement on Human Papillomavirus DNA Test Utilization
Authors: Davis Davey Diane , Goulart Robert , Nayar Ritu ,   on behalf of the Cytopathology Education and Technology Consortium (CETC)
Published: March 2014

This statement from the Cytopathology Education and Technology Consortium summarizes appropriate and inappropriate uses of human papillomavirus testing in cervical cancer screening based on guidelines from the American Society for Colposcopy and Cervical Pathology and the American Cancer Society.
Integrating Circulating Tumor Cell Data with Imaging and Serum Prostate-Specific Antigen Measurement for Metastatic Prostate Cancer Therapy Management
Authors: Goodman Oscar , Schuur Eric R.
Published: March 2014

Optimal management of therapy can improve quality of life, and potentially survival, of patients with metastatic prostate cancer. Circulating tumor cell (CTC) enumeration in the peripheral blood holds promise for facilitating optimal therapy management based on high cancer specificity and prompt response to changes in disease status. We present the case of a 54-year-old male diagnosed with metastatic prostate cancer. The patient's disease status was monitored radiographically and by serial determinations of serum prostate-specific antigen concentration, performance status, and CTC enumeration. At multiple visits, the disease status was not clear due to discordance between standard assessments. The additional information provided by CTC enumeration helped clarify disease status and provided support for treatment decisions.
Pegylated Liposomal Doxorubicin-Induced Acute Transient Encephalopathy in a Patient with Breast Cancer: A Case Report
Authors: Baker Michelle , Markman Maurie , Niu Jiaxin
Published: March 2014

Background: Pegylated liposomal doxorubicin (PLD) has a unique pharmacokinetic profile and is widely used to treat a variety of malignancies, alone or in combination with other agents. Case Report: A 57-year-old female patient with metastatic breast cancer developed dural metastases to the brain and underwent craniotomy and whole-brain radiation. She continued to receive chemotherapy with carboplatin without any serious complications. Four months later, there was evidence of progression leading to the institution of PLD. During the first course of PLD, there was evidence of acute encephalopathy which resolved after 18 h with discontinuation of this agent. Interestingly, she did well when she was rechallenged with conventional doxorubicin in the following cycles. Conclusion: We hereby report, to the best of our knowledge, the first case of acute transient encephalopathy induced by PLD. We postulate that partial disruption of the blood-brain barrier may have been responsible for PLD-induced encephalopathy.