bluuebunny/crossref_metadata_2025 huggingface dataset:
Tieftemperaturphysik: Kalt, kälter, ultrakalt: Die internationalen Temperaturskala wurde in den Milli‐Kelvin‐Bereich erweitert
Authors: Kühne Michael
Published: February 2013

Für das Verständnis der Materie ist es von großer Bedeutung, ihre Eigenschaften bei tiefen und ultratiefen Temperaturen zu untersuchen. Insbesondere quantenphysikalische Phänomene wie z. B. Supraleitung und Superfluidität treten erst bei tiefen Temperaturen weit unterhalb der Raumtemperatur auf. In den letzten Jahrzehnten wurden daher große Anstrengungen unternommen, um möglichst tiefe Temperaturen zu erzeugen, und heute werden Tieftemperaturexperimente in vielen Labors routinemäßig bei Temperaturen bis zu unterhalb von 1 mK durchgeführt. Wegen der Temperaturabhängigkeit physikalischer Vorgänge ist es dabei essenziell, die Temperatur möglichst genau zu kennen, zum einen, um die Vergleichbarkeit von Experimenten sicherzustellen, die an verschiedenen Orten durchgeführt werden, zum anderen, um quantitative theoretische Vorhersagen durch Experimente verifizieren zu können. Kürzlich hat sich das Internationale Komitee für Maße und Gewichte (CIPM) auf eine erweiterte Temperaturskala geeinigt, die die bestehende Skala um drei Größenordnungen bis zu 0,9 mK fortsetzt.
Energie: Gibt es den katastrophenfreien Kernreaktor?: Beim Hochtemperaturreaktor mit kugelförmigen graphitischen Brennelementen ist eine Kernschmelze ausgeschlossen
Authors: Kugeler Kurt
Published: February 2013

Die Bedeutung der Kernenergie wird weltweit wieder zunehmen, wenn die Frage der CO2‐Emissionen wirklich ernst genommen und die langfristig zu erwartende Verteuerung und Erschöpfung der fossilen Rohstoffe bedacht wird. Dies setzt allerdings voraus, dass höchste Sicherheitsstandards sowohl bei den Kraftwerken als auch bei der Entsorgung gewährleistet werden. Reaktoren, bei denen es nachweislich nicht zu katastrophalen Unfällen kommen kann, sind heute möglich.
Vom World Wide Web zum World Wide Grid: Eine neue Informations‐Infrastruktur für wissenschaftliche Anwendungen
Authors: Hoffmann Hans Falk , Putzer Alois , Reinefeld Alexander
Published: February 2013

In Analogie zu den Elektrizitätsnetzen (electricity grid), von denen die technische Revolution ausging, wurde der Begriff Computational Grid (kurz Grid) geprägt. Ein wichtiger Bestandteil dieses Systems liegt im benutzerfreundlichen Zugang und der koordinierten Nutzung der weltweit verteilten Speicherressourcen und Rechnerkapazitäten. Bei der Entwicklung dazu notwendiger Technologien und Software (Middleware) profitiert man von Kenntnissen und Erfahrungen bei der Entwicklung verteilter Algorithmen, dem Software‐Engineering und dem Supercomputing.
Utilizing nonlinear ELF generation in modulated ionospheric heating experiments for communications applications
Authors: Jin G. , Spasojevic M. , Cohen M. B. , Inan U. S.
Published: February 2013

Modulated high‐frequency heating of the D region ionosphere near the auroral electrojet can generate extremely low frequency (ELF; 3 Hz–3 kHz) radio waves. The modulated heating process is nonlinear and generates harmonics at integer multiples of the ELF modulation frequency. Quaternary phase shift keying, a digital modulation technique is applied to ELF waves to demonstrate transmission of digital data. Data were successfully decoded at a nearby receiver and the bit error rate computed. Square wave modulation of the high‐frequency heater results in stronger signals and hence a smaller bit error rate. Simulations of the communication system using ELF waveforms and noise signals derived from ELF observations are also conducted. These simulations show that using higher harmonics of the ELF signal to improve the signal‐to‐noise ratio can reduce the bit error rate, although only when these harmonics are below ~4.5 kHz because of radio atmospherics (sferics) generating strong impulsive noise at higher frequencies.
Circuital characteristics and radiation properties of an UWB electric‐magnetic planar antenna for Ku‐band applications
Authors: Haider N. , Caratelli D. , Yarovoy A. G.
Published: February 2013

A planar, directive antenna with large fractional bandwidth is introduced in this paper. A detailed discussion on the proposed antenna topology and its architecture is reported. The proposed element is a combination of a patch and a loop radiator. A proper combination of the electric field radiator (patch) with a magnetic field radiator (loop around the patch) is exploited for expanding the operational bandwidth. A parametric study is presented to investigate the effect of the antenna geometrical parameters on its performance. A general and computationally efficient procedure for extracting the antenna equivalent circuit is described and used to achieve a meaningful circuit theory‐based insight into the characteristics of the radiating structure. The theoretical and experimental results are compared, and it is demonstrated that the element features over 100% fractional bandwidth, good impedance matching, and unidirectional and stable radiation patterns.
Sectorized approach and measurement reduction for mutual coupling calibration of non‐omnidirectional antenna arrays
Authors: Aksoy Taylan , Engin Tuncer T.
Published: February 2013

Mutual coupling calibration is an important problem for antenna arrays. There are different methods proposed for omnidirectional antennas in the literature. However, many practical antennas have non‐omnidirectional (NOD) characteristics. Hence, the previous mutual coupling calibration methods cannot be applied directly since the mutual coupling matrix of an NOD antenna array has angular dependency. In this paper, a sectorized approach is proposed with a transformation matrix for mutual coupling calibration of NOD antenna arrays. In addition, the symmetry of the array radiation patterns for the symmetric array elements is used to reduce the number of calibration measurements. A novel antenna is used to show the accuracy and performance of the proposed approach in direction finding problem where numerical electromagnetic simulations are used to obtain the simulation data.
Optical diagnosis for lung cancer using multiphoton imaging
Authors: Chen Gang , Wang Linghua , Lu Jianping , Zhu Weifeng , Zhang Hui , Chen Jianxin , Zhuo Shuangmu , Yan Jun
Published: February 2013

Currently, hematoxylin–eosin (H–E) stained histopathology is the golden standard for diagnosing lung cancer. This time‐consuming procedure needs tissue biopsy, sample fixation, slicing, and labeling. Therefore, the availability of a noninvasive optical diagnosis that can obtain real‐time analysis comparable to golden standard H–E stained histopathology will be of extraordinary benefit to the medical community. In this study, we investigated whether multiphoton imaging can make real‐time optical diagnosis for normal and cancerous lung tissue, compared with H–E stained histopathology. In the normal lung tissue, we found that multiphoton imaging could display normal lung parenchyma composed of alveolar spaces separated by thin septa. In the cancerous lung tissue, multiphoton imaging clearly illustrated that cancer cells displayed marked cellular and nuclear pleomorphism. These cancer cells were characterized by irregular size and shape, enlarged nuclei, and increased nuclear‐cytoplasmic ratio. All of these histopathological features of tissue architecture and cell morphology identified by multiphoton images were readily correlated with H–E staining images. All together, multiphoton imaging can make real‐time optical diagnosis for lung cancer. This study provides the groundwork for further using multiphoton imaging to perform real‐time noninvasive “optical biopsy” for lung cancer in the near future. SCANNING 35:362–365, 2013. © Wiley Periodicals, Inc.
Development of Asymmetric Reactions Catalyzed by Chiral Organotin‐Alkoxide Reagents
Authors: Yanagisawa Akira , Yoshida Kazuhiro
Published: February 2013

Asymmetric catalysis under almost‐neutral reaction conditions is key for the efficient synthesis of optically active polar molecules. We have developed catalytic enantioselective reactions of acyclic or cyclic alkenyl esters by using an (S)‐BINOL‐derived chiral tin‐dibromide reagent that possesses a bulky aryl group at the 3 or 3′ position as the chiral pre‐catalyst in the presence of a sodium alkoxide and an alcohol, in which a chiral tin alkoxide bromide is generated in situ and recycled with the assistance of an alcohol. In this Personal Account, we describe three types of asymmetric transformation that proceed through a chiral tin enolate: 1) The asymmetric aldol reaction of alkenyl esters or unsaturated lactones with aldehydes or isatins; 2) the asymmetric three‐component Mannich‐type reaction of alkenyl esters and related cycloaddition reactions; and 3) the asymmetric N‐nitroso aldol reaction of unsaturated lactones with nitrosoarenes.
Parameter estimation and predictive uncertainty in stochastic inverse modeling of groundwater flow: Comparing null‐space Monte Carlo and multiple starting point methods
Authors: Yoon Hongkyu , Hart David B. , McKenna Sean A.
Published: February 2013

Key Points

Comparing null‐space Monte Carlo and multiple starting point methods

Inverse stochastic modeling of groundwater flow

Multiple calibration‐constrained NSMC
Synthesis, Crystal Structure, and Variable‐Temperature‐Luminescent Property of the Organically Templated Pentaborate [C10N2H9][B5O6(OH)4]·H3BO3·H2O
Authors: Yang Yang , Fu DongSheng , Li GuoFa , Zhang Yun
Published: February 2013

The organically templated pentaborate [C10N2H9][B5O6(OH)4]·H3BO3·H2O (1a) was synthesized by boric acid and 4, 4′‐bipyridine in aqueous solution and characterized by single‐crystal X‐ray diffraction, elemental analysis, FTIR spectroscopy, thermogravimetric analysis, powder X‐ray diffraction, and photoluminescence spectroscopy. The compound crystallizes in the triclinic system with space group P$\bar{1}$ (a = 9.196(3) Å, b = 9.822(3) Å, c = 12.113(3) Å, α = 66.243(3)°, β = 76.998(3)°, γ = 75.067(3)°, V = 958.4(5) Å3, and Z = 2). The polyanions form a novel 3D supramolecular network with three kinds of channels by extensive hydrogen bonds. The title compound shows a UV photoluminescence with an emission maximum at 372 nm upon excitation at 248 nm, and the photoluminescence can be modified from UV to blue by means of a simple heat‐treatment process. The pentaborate could be a promising blue component for possible application in the white LED.
Room-temperature single phase multiferroic magnetoelectrics: Pb(Fe, M)x(Zr,Ti)(1−x)O3 [M = Ta, Nb]
Authors: Sanchez Dilsom A. , Ortega Nora , Kumar Ashok , Sreenivasulu G. , Katiyar Ram S. , Scott J. F. , Evans Donald M. , Arredondo-Arechavala Miryam , Schilling A. , Gregg J. M.
Published: February 2013

We describe extensive studies on a family of perovskite oxides that are ferroelectric and ferromagnetic at ambient temperatures. The data include x-ray diffraction, Raman spectroscopy, measurements of ferroelectric and magnetic hysteresis, dielectric constants, Curie temperatures, electron microscopy (both scanning electron microscope and transmission electron microscopy (TEM)) studies, and both longitudinal and transverse magnetoelectric constants α33 and α31. The study extends earlier work to lower Fe, Ta, and Nb concentrations at the B-site (from 15%–20% down to 5%). The magnetoelectric constants increase supralinearly with Fe concentrations, supporting the earlier conclusions of a key role for Fe spin clustering. The room-temperature orthorhombic C2v point group symmetry inferred from earlier x-ray diffraction studies is confirmed via TEM, and the primitive unit cell size is found to be the basic perovskite Z = 1 structure of BaTiO3, also the sequence of phase transitions with increasing temperature from rhombohedral to orthorhombic to tetragonal to cubic mimics barium titanate.
Comparison of light scattering in solar cells modeled by rigorous and scalar approach
Authors: Ermes M. , Bittkau K. , Carius R.
Published: February 2013

We investigate and compare two very different approaches for obtaining light scattering properties at a rough interface with a focus on applications in silicon based thin-film solar cells. The scattering properties of a rigorous solving of Maxwell's equations and a recently developed model by Dominé et al. [J. Appl. Phys. 107, 044505 (2010)] based on a scalar approach are compared. The former yields extensive information and is very versatile, but needs much computation time. The latter is only applicable for single textures between two half-spaces and yields only scattering properties of said textures, but is extremely fast. The applicability and limitations of the scalar approach are examined. The results show that a combination of both can improve and accelerate simulation and development of new devices.
Comparison of finite difference based methods to obtain sensitivities of stochastic chemical kinetic models
Authors: Srivastava Rishi , Anderson David F. , Rawlings James B.
Published: February 2013

Sensitivity analysis is a powerful tool in determining parameters to which the system output is most responsive, in assessing robustness of the system to extreme circumstances or unusual environmental conditions, in identifying rate limiting pathways as a candidate for drug delivery, and in parameter estimation for calculating the Hessian of the objective function. Anderson [SIAM J. Numer. Anal. 50, 2237 (2012)]10.1137/110849079 shows the advantages of the newly developed coupled finite difference (CFD) estimator over the common reaction path (CRP) [M. Rathinam, P. W. Sheppard, and M. Khammash, J. Chem. Phys. 132, 034103 (2010)]10.1063/1.3280166 estimator. In this paper, we demonstrate the superiority of the CFD estimator over the common random number (CRN) estimator in a number of scenarios not considered previously in the literature, including the sensitivity of a negative log likelihood function for parameter estimation, the sensitivity of being in a rare state, and a sensitivity with fast fluctuating species. In all examples considered, the superiority of CFD over CRN is demonstrated. We also provide an example in which the CRN method is superior to the CRP method, something not previously observed in the literature. These examples, along with Anderson's results, lead to the conclusion that CFD is currently the best estimator in the class of finite difference estimators of stochastic chemical kinetic models.
The influence of laterally inhomogeneous corrosion on electrical and optical calcium moisture barrier characterization
Authors: Klumbies H. , Müller-Meskamp L. , Mönch T. , Schubert S. , Leo K.
Published: February 2013

The reaction of calcium thin films with water – monitored optically or electrically – is widely used for evaluating ultrahigh barrier foils for the encapsulation of organic electronic devices. We studied the common optical and the electrical method and compared them with in situ atomic force microscope topography scans. All three methods were applied at the same sample in parallel in a typical test design containing a gas volume for water distribution next to the calcium layer of 60 and 1000 nm thickness, respectively. The common assumption for the interpretation of such measurement data is laterally homogeneous calcium consumption of the layer from top to bottom. In contrast, we observed a significant ratio of laterally inhomogeneous corrosion of the calcium on the micro-scale for both thicknesses. Some areas were strongly or completely corroded through the whole layer while others exhibited less or no corrosion. Furthermore, those corroded spots grew in lateral direction. As a consequence of lateral inhomogeneous calcium corrosion the electrical calcium measurement method underestimates the amount of calcium left; according to our results this does not affect the water vapor transmission rate (WVTR). Optical data evaluated by Lambert-Beer law underestimate the amount of calcium left as well and also underestimate the WVTR. If the data are evaluated, using a linear relationship between transmission and amount of calcium left, the both values are more precise. The scope of this study is to call attention to the existence of lateral inhomogeneity in calcium corrosion and its impact on the calcium permeation measurements. While more investigations would be needed to quantify the effect of this inhomogeneity on the electrical and optical method in general, the discussion sheds light on the way, calcium test data are influenced by lateral inhomogeneous calcium corrosion. Our observations highlight the need for careful interpretation of calcium test results, but also demonstrate its capabilities for precise ultrahigh barrier measurements.
Current-controllable planar S-(S/F)-S Josephson junction
Authors: Vávra O. , Pfaff W. , Monaco R. , Aprili M. , Strunk C.
Published: February 2013

We report on the experimental realization of a current-controllable lateral S-(S/F)-S Josephson junction based on the inverse proximity effect in the superconductor-ferromagnet bilayer (S/F). The dependence of the critical current on the magnetic field Ic(B) shows a Fresenel-like pattern, which could qualitatively be understood with the theory of Josephson junctions in a magnetic field gradient. The amplitude and the period of the Ic(B) pattern can be controlled by spin-polarized quasiparticles injection into the weak link. The period change suggests controllability of effective area of the Josephson junction. Furthermore, a temperature-induced transition from a weak-link behavior to a strong coupling between the superconducting banks is also observed in these lateral Josephson junctions.
Tuning of refractive index of poly(vinyl alcohol): Effect of embedding Cu and Ag nanoparticles
Authors: Mahendia Suman , Kumar Tomar Anil , Goyal Parveen K. , Kumar Shyam
Published: February 2013

In this article, we have reported the results of our measurements, related to the tuning of the refractive index of the poly(vinyl alcohol) (PVA) polymer on embedding Cu and Ag nanoparticles at different concentrations. The size distribution and dispersion behaviour of embedded nanoparticles within PVA have been studied through transmission electron microscopy. A systematic increase in refractive index of PVA on increasing the concentration of embedded nanoparticles has been observed. These results have been tried to be explained using Bhar and Pinto model based on the Lorimar's theory for polymer composites. The values of refractive index of these nanocomposites have also been calculated using the Lorentz-Lorenz effective medium theory and found to be in close agreement with the experimental data. Nanoparticles embedded induced modifications in the structure of PVA have been revealed through FTIR spectroscopy.
Transition from paramagnetism to ferromagnetism in HfO2 nanorods
Authors: Liu Xiaoli , Chen Yuanzhi , Wang Laisen , Peng Dong-Liang
Published: February 2013

Whether or not nanoscale HfO2 has ferromagnetism is a debatable issue. In this study, monoclinic HfO2 nanorods with an average size of about 33.7 ± 3.1 nm in length and 8.9 ± 0.7 nm in width were synthesized via a chemical solution method. In comparison with many HfO2 nanoparticles/nanoclusters synthesized by physical methods, the as-prepared HfO2 nanorods were characterized by their better crystallinity and anisotropic shape. Interestingly, although the pristine HfO2 nanorods showed overall paramagnetic characteristics, when the nanorods were annealed in reducing environment, they exhibited clear room-temperature ferromagnetism (RTFM). The observed RTFM probably resulted from oxygen vacancies generated in the annealing process. In the mean time, it is suggested that factors such as the dimension, specific shape, and crystallinity of the HfO2 materials also should not be ignored when correlating the occurrence of ferromagnetism with defects.
Strain induced intermixing of Ge atoms in Si epitaxial layer on Ge(111)
Authors: Tosaka Aki , Mochizuki Izumi , Negishi Ryota , Shigeta Yukichi
Published: February 2013

The relationship between strain and effective mass of the √3 × √3-Ag structure surface metallic state, when formed on strained Si(111) layers on Ge(111), has been investigated by angle resolved photoelectron spectroscopy at various film thicknesses. Si layer lattice spacing expands and effective mass decreases at film thickness greater than 2 bilayers. This result is inconsistent with a previous study showing increasing effective mass with tensile strain for the √3 × √3-Ag structure. Ge-3d core level photoelectron spectra confirm that this disparity is caused by the intermixing of Ge atoms in the Si layer. The relationship between effective mass and strain is useful for gauging intermixing, and the effective mass of surface metallic states is useful for gauging nanoscale strain.
Active subnanometer spectral control of a random laser
Authors: Leonetti Marco , López Cefe
Published: February 2013

We demonstrate an experimental technique that allows to achieve a robust control on the emission spectrum of a micro random laser and to select individual modes with sub-nanometer resolution. The presented approach relies on an optimization protocol of the spatial profile of the pump beam. Here we demonstrate not only the possibility to increase the emission at a wavelength but also that we can “isolate” an individual peak suppressing unwanted contributions form other modes.
Molecular beam epitaxial growth and optical properties of red-emitting (λ = 650 nm) InGaN/GaN disks-in-nanowires on silicon
Authors: Jahangir S. , Mandl M. , Strassburg M. , Bhattacharya P.
Published: February 2013

We have investigated the radiative properties of InGaN disks in GaN nanowires grown by plasma enhanced molecular beam epitaxy on (001) silicon substrates. The growth of the nanowire heterostructures has been optimized to maximize the radiative efficiency, or internal quantum efficiency (IQE), for photoluminescence emission at λ = 650 nm. It is found that the IQE increases significantly (by ∼10%) to 52%, when post-growth passivation of nanowire surface with silicon nitride or parylene is applied. The increase in efficiency is supported by radiative- and nonradiative lifetimes derived from data obtained from temperature dependent- and time-resolved photoluminescence measurements. Light emitting diodes with p-i-n disk-in-nanowire heterostructures passivated with parylene have been fabricated and characterized.
Remyelination reporter reveals prolonged refinement of spontaneously regenerated myelin
Authors: Powers Berit E. , Sellers Drew L. , Lovelett Emilie A. , Cheung Willy , Aalami Sheida P. , Zapertov Nikolai , Maris Don O. , Horner Philip J.
Published: February 2013

Neurological diseases and trauma often cause demyelination, resulting in the disruption of axonal function and integrity. Endogenous remyelination promotes recovery, but the process is not well understood because no method exists to definitively distinguish regenerated from preexisting myelin. To date, remyelinated segments have been defined as anything abnormally short and thin, without empirical data to corroborate these morphological assumptions. To definitively identify regenerated myelin, we used a transgenic mouse with an inducible membrane-bound reporter and targeted Cre recombinase expression to a subset of glial progenitor cells after spinal cord injury, yielding remarkably clear visualization of spontaneously regenerated myelin in vivo. Early after injury, the mean length of sheaths regenerated by Schwann cells and oligodendrocytes (OLs) was significantly shorter than control, uninjured myelin, confirming past assumptions. However, OL-regenerated sheaths elongated progressively over 6 mo to approach control values. Moreover, OL-regenerated myelin thickness was not significantly different from control myelin at most time points after injury. Thus, many newly formed OL sheaths were neither thinner nor shorter than control myelin, vitiating accepted dogmas of what constitutes regenerated myelin. We conclude that remyelination, once thought to be static, is dynamic and elongates independently of axonal growth, in contrast to stretch-based mechanisms proposed in development. Further, without clear identification, past assessments have underestimated the extent and quality of regenerated myelin.
Development of a generic adenovirus delivery system based on structure-guided design of bispecific trimeric DARPin adapters
Authors: Dreier Birgit , Honegger Annemarie , Hess Christian , Nagy-Davidescu Gabriela , Mittl Peer R. E. , Grütter Markus G. , Belousova Natalya , Mikheeva Galina , Krasnykh Victor , Plückthun Andreas
Published: February 2013

Adenoviruses (Ads) have shown promise as vectors for gene delivery in clinical trials. Efficient viral targeting to a tissue of choice requires both ablation of the virus’ original tropism and engineering of an efficient receptor-mediated uptake by a specific cell population. We have developed a series of adapters binding to the virus with such high affinity that they remain fully bound for >10 d, block its natural receptor binding site and mediate interaction with a surface receptor of choice. The adapter contains two fused modules, both consisting of designed ankyrin repeat proteins (DARPins), one binding to the fiber knob of adenovirus serotype 5 and the other binding to various tumor markers. By solving the crystal structure of the complex of the trimeric knob with three bound DARPins at 1.95-Å resolution, we could use computer modeling to design a link to a trimeric protein of extraordinary kinetic stability, the capsid protein SHP from the lambdoid phage 21. We arrived at a module which binds the knob like a trimeric clamp. When this clamp was fused with DARPins of varying specificities, it enabled adenovirus serotype 5-mediated delivery of a transgene in a human epidermal growth factor receptor 2-, epidermal growth factor receptor-, or epithelial cell adhesion molecule-dependent manner with transduction efficiencies comparable to or even exceeding those of Ad itself. With these adapters, efficiently produced in
Escherichia coli
, Ad can be converted rapidly to new receptor specificities using any ligand as the receptor-binding moiety. Prefabricated Ads with different payloads thus can be retargeted readily to many cell types of choice.
Combined targeting of MEK and PI3K/mTOR effector pathways is necessary to effectively inhibit NRAS mutant melanoma in vitro and in vivo
Authors: Posch Christian , Moslehi Homayoun , Feeney Luzviminda , Green Gary A. , Ebaee Anoosheh , Feichtenschlager Valentin , Chong Kim , Peng Lily , Dimon Michelle T. , Phillips Thomas , Daud Adil I. , McCalmont Timothy H. , LeBoit Philip E. , Ortiz-Urda Susana
Published: February 2013

Activating mutations in the neuroblastoma rat sarcoma viral oncogene homolog (NRAS) gene are common genetic events in malignant melanoma being found in 15–25% of cases. NRAS is thought to activate both mitogen activated protein kinase (MAPK) and PI3K signaling in melanoma cells. We studied the influence of different components on the MAP/extracellular signal-regulated (ERK) kinase (MEK) and PI3K/mammalian target of rapamycin (mTOR)-signaling cascade in NRAS mutant melanoma cells. In general, these cells were more sensitive to MEK inhibition compared with inhibition in the PI3K/mTOR cascade. Combined targeting of MEK and PI3K was superior to MEK and mTOR
1,2
inhibition in all NRAS mutant melanoma cell lines tested, suggesting that PI3K signaling is more important for cell survival in NRAS mutant melanoma when MEK is inhibited. However, targeting of PI3K/mTOR
1,2
in combination with MEK inhibitors is necessary to effectively abolish growth of NRAS mutant melanoma cells in vitro and regress xenografted NRAS mutant melanoma. Furthermore, we showed that MEK and PI3K/mTOR
1,2
inhibition is synergistic. Expression analysis confirms that combined MEK and PI3K/mTOR
1,2
inhibition predominantly influences genes in the rat sarcoma (RAS) pathway and growth factor receptor pathways, which signal through MEK/ERK and PI3K/mTOR, respectively. Our results suggest that combined targeting of the MEK/ERK and PI3K/mTOR pathways has antitumor activity and might serve as a therapeutic option in the treatment of NRAS mutant melanoma, for which there are currently no effective therapies.
Layered pattern receptor signaling via ethylene and endogenous elicitor peptides during
Arabidopsis
immunity to bacterial infection
Authors: Tintor Nico , Ross Annegret , Kanehara Kazue , Yamada Kohji , Fan Li , Kemmerling Birgit , Nürnberger Thorsten , Tsuda Kenichi , Saijo Yusuke
Published: February 2013

Recognition of molecular patterns characteristic of microbes or altered-self leads to immune activation in multicellular eukaryotes. In
Arabidopsis thaliana
, the leucine-rich-repeat receptor kinases
FLAGELLIN-SENSING2
(
FLS2
) and
EF-TU RECEPTOR
(
EFR
) recognize bacterial flagellin and elongation factor EF-Tu (and their elicitor-active epitopes flg22 and elf18), respectively. Likewise,
PEP1 RECEPTOR1
(
PEPR1
) and PEPR2 recognize the elicitor-active Pep epitopes conserved in
Arabidopsis ELICITOR PEPTIDE PRECURSOR
s (
PROPEP
s). Here we reveal that loss of
ETHYLENE-INSENSITIVE2
(
EIN2
), a master signaling regulator of the phytohormone ethylene (ET), lowers sensitivity to both elf18 and flg22 in different defense-related outputs. Remarkably, in contrast to a large decrease in
FLS2
expression,
EFR
expression and receptor accumulation remain unaffected in
ein2
plants. Genome-wide transcriptome profiling has uncovered an inventory of EIN2-dependent and EFR-regulated genes. This dataset highlights important aspects of how ET modulates EFR-triggered immunity: the potentiation of salicylate-based immunity and the repression of a jasmonate-related branch. EFR requires ET signaling components for
PROPEP2
activation but not for
PROPEP3
activation, pointing to both ET-dependent and -independent engagement of the PEPR pathway during EFR-triggered immunity. Moreover, PEPR activation compensates the
ein2
defects for a subset of EFR-regulated genes. Accordingly,
ein2 pepr1 pepr2
plants exhibit additive defects in EFR-triggered antibacterial immunity, compared with
ein2
or
pepr1 pepr2
plants. Our findings suggest that the PEPR pathway not only mediates ET signaling but also compensates for its absence in enhancing plant immunity.
Variants at serotonin transporter and 2A receptor genes predict cooperative behavior differentially according to presence of punishment
Authors: Schroeder Kari B. , McElreath Richard , Nettle Daniel
Published: February 2013

Punishment of free-riding has been implicated in the evolution of cooperation in humans, and yet mechanisms for punishment avoidance remain largely uninvestigated. Individual variation in these mechanisms may stem from variation in the serotonergic system, which modulates processing of aversive stimuli. Functional serotonin gene variants have been associated with variation in the processing of aversive stimuli and widely studied as risk factors for psychiatric disorders. We show that variants at the serotonin transporter gene (
SLC6A4
) and serotonin 2A receptor gene (
HTR2A
) predict contributions to the public good in economic games, dependent upon whether contribution behavior can be punished. Participants with a variant at the serotonin transporter gene contribute more, leading to group-level differences in cooperation, but this effect dissipates in the presence of punishment. When contribution behavior can be punished, those with a variant at the serotonin 2A receptor gene contribute more than those without it. This variant also predicts a more stressful experience of the games. The diversity of institutions (including norms) that govern cooperation and punishment may create selective pressures for punishment avoidance that change rapidly across time and space. Variant-specific epigenetic regulation of these genes, as well as population-level variation in the frequencies of these variants, may facilitate adaptation to local norms of cooperation and punishment.
Design of a superior cytokine antagonist for topical ophthalmic use
Authors: Hou Jinzhao , Townson Sharon A. , Kovalchin Joseph T. , Masci Allyson , Kiner Olga , Shu Yanqun , King Bracken M. , Schirmer Emily , Golden Kathryn , Thomas Christoph , Garcia K. Christopher , Zarbis-Papastoitsis Gregory , Furfine Eric S. , Barnes Thomas M.
Published: February 2013

IL-1 is a key inflammatory and immune mediator in many diseases, including dry-eye disease, and its inhibition is clinically efficacious in rheumatoid arthritis and cryopyrin-associated periodic syndromes. To treat ocular surface disease with a topical biotherapeutic, the uniqueness of the site necessitates consideration of the agent’s size, target location, binding kinetics, and thermal stability. Here we chimerized two IL-1 receptor ligands, IL-1β and IL-1Ra, to create an optimized receptor antagonist, EBI-005, for topical ocular administration. EBI-005 binds its target, IL-1R1, 85-fold more tightly than IL-1Ra, and this increase translates to an ∼100-fold increase in potency in vivo. EBI-005 preserves the affinity bias of IL-1Ra for IL-1R1 over the decoy receptor (IL-1R2), and, surprisingly, is also more thermally stable than either parental molecule. This rationally designed antagonist represents a unique approach to therapeutic design that can potentially be exploited for other β-trefoil family proteins in the IL-1 and FGF families.
Worldwide data sets constrain the water vapor uptake coefficient in cloud formation
Authors: Raatikainen Tomi , Nenes Athanasios , Seinfeld John H. , Morales Ricardo , Moore Richard H. , Lathem Terry L. , Lance Sara , Padró Luz T. , Lin Jack J. , Cerully Kate M. , Bougiatioti Aikaterini , Cozic Julie , Ruehl Christopher R. , Chuang Patrick Y. , Anderson Bruce E. , Flagan Richard C. , Jonsson Haflidi , Mihalopoulos Nikos , Smith James N.
Published: February 2013

Cloud droplet formation depends on the condensation of water vapor on ambient aerosols, the rate of which is strongly affected by the kinetics of water uptake as expressed by the condensation (or mass accommodation) coefficient, αc. Estimates of αcfor droplet growth from activation of ambient particles vary considerably and represent a critical source of uncertainty in estimates of global cloud droplet distributions and the aerosol indirect forcing of climate. We present an analysis of 10 globally relevant data sets of cloud condensation nuclei to constrain the value of αcfor ambient aerosol. We find that rapid activation kinetics (αc> 0.1) is uniformly prevalent. This finding resolves a long-standing issue in cloud physics, as the uncertainty in water vapor accommodation on droplets is considerably less than previously thought.
Cotransplantation with specific populations of spina bifida bone marrow stem/progenitor cells enhances urinary bladder regeneration
Authors: Sharma Arun K. , Bury Matthew I. , Fuller Natalie J. , Marks Andrew J. , Kollhoff David M. , Rao Manoj V. , Hota Partha V. , Matoka Derek J. , Edassery Seby L. , Thaker Hatim , Sarwark John F. , Janicki Joseph A. , Ameer Guillermo A. , Cheng Earl Y.
Published: February 2013

Spina bifida (SB) patients afflicted with myelomeningocele typically possess a neurogenic urinary bladder and exhibit varying degrees of bladder dysfunction. Although surgical intervention in the form of enterocystoplasty is the current standard of care in which to remedy the neurogenic bladder, it is still a stop-gap measure and is associated with many complications due to the use of bowel as a source of replacement tissue. Contemporary bladder tissue engineering strategies lack the ability to reform bladder smooth muscle, vasculature, and promote peripheral nerve tissue growth when using autologous populations of cells. Within the context of this study, we demonstrate the role of two specific populations of bone marrow (BM) stem/progenitor cells used in combination with a synthetic elastomeric scaffold that provides a unique and alternative means to current bladder regeneration approaches. In vitro differentiation, gene expression, and proliferation are similar among donor mesenchymal stem cells (MSCs), whereas poly(1,8-octanediol-cocitrate) scaffolds seeded with SB BM MSCs perform analogously to control counterparts with regard to bladder smooth muscle wall formation in vivo. SB CD34
+
hematopoietic stem/progenitor cells cotransplanted with donor-matched MSCs cause a dramatic increase in tissue vascularization as well as an induction of peripheral nerve growth in grafted areas compared with samples not seeded with hematopoietic stem/progenitor cells. Finally, MSC/CD34
+
grafts provided the impetus for rapid urothelium regeneration. Data suggest that autologous BM stem/progenitor cells may be used as alternate, nonpathogenic cell sources for SB patient-specific bladder tissue regeneration in lieu of current enterocystoplasty procedures and have implications for other bladder regenerative therapies.
Phylogeographic structure of a protogynous hermaphrodite species, the ballan wrasse Labrus bergylta, in Ireland, Scotland, and Norway, using mitochondrial DNA sequence data
Authors: D'Arcy J. , Mirimin L. , FitzGerald R.
Published: February 2013

D'Arcy, J., Mirimin, L., and FitzGerald, R. Phylogeographic structure of a protogynous hermaphrodite species, the ballan wrasse Labrus bergylta, in Ireland, Scotland, and Norway, using mitochondrial DNA sequence data. – ICES Journal of Marine Science, 70: 685–693. The ballan wrasse, Labrus bergylta, is a protogynous hermaphrodite marine fish species that inhabits coastal waters of the eastern North Atlantic. Sequential hermaphrodite species tend to be characterized by a skewed sex ratio, which is thought to lead to marked population structuring due to a reduced effective number of breeders. Furthermore, due to its large body size (compared with other wrasse species) and its peculiar feeding behaviour, this species has been identified as a candidate cleaner fish to be used in parasite control of farmed finfish. In the present study, we used mitochondrial DNA (control region) sequence data to investigate the genetic diversity and population structuring of ballan wrasse in waters around the British Isles and southern Norway. Ballan wrasse in southern Norway showed lower levels of genetic diversity than around the British Isles, which appear to be the result of historical demographic events (population bottleneck followed by expansion). Analysis of mismatch distributions and the presence of two highly divergent clades unevenly represented in Atlantic and Scandinavian regions suggest distinct recolonization patterns in these two regions. These results provide a first insight on the status of wild populations of ballan wrasse in the eastern North Atlantic, with implications for conservation and management.
The active metabolic rate predicts a male spider's proximity to females and expected fitness
Authors: Kasumovic Michael M. , Seebacher Frank
Published: February 2013

Conspicuous traits, such as weaponry and body size, are often correlated with fitness. By contrast, we understand less about how inconspicuous physiological traits affect fitness. Not only is linking physiology directly to fitness a challenge, but in addition, behavioural studies most often focus on resting or basal metabolic rates, resulting in a poor understanding of how active metabolic rates affect fitness. Here we use the golden orb-web spider (
Nephila plumipes
), a species for which proximity to a female on the web predicts a male's paternity share, to examine the role of resting and active metabolic rates in fitness. Using a semi-natural experimental set-up, we show that males closer to a female have higher active metabolic rates than males further from females. This higher metabolic activity is paralleled by increased citrate synthase activity, suggesting greater mitochondrial densities. Our results link both higher active metabolic rates and increased citrate synthase activity with fitness. Coupled with the behaviour and life history of
N. plumipes
, these results provide insight into the evolution of physiological systems.
Chimpanzees' (
Pan troglodytes
) strategic helping in a collaborative task
Authors: Melis Alicia P. , Tomasello Michael
Published: February 2013

Many animal species cooperate, but the underlying proximate mechanisms are often unclear. We presented chimpanzees with a mutualistic collaborative food-retrieval task requiring complementary roles, and tested subjects' ability to help their partner perform her role. For each role, subjects required a different tool, and the tools were not interchangeable. We gave one individual in each dyad both tools, and measured subjects' willingness to transfer a tool to their partner as well as which tool (correct versus incorrect) they transferred. Most subjects helped their partner and transferred the tool the partner needed. Thus, chimpanzees not only coordinate different roles, but they also know which particular action the partner needs to perform. These results add to previous findings suggesting that many of chimpanzees' limitations in collaboration are, perhaps, more motivational than cognitive.
Efficient distributed quantum computing
Authors: Beals Robert , Brierley Stephen , Gray Oliver , Harrow Aram W. , Kutin Samuel , Linden Noah , Shepherd Dan , Stather Mark
Published: February 2013

We provide algorithms for efficiently moving and addressing quantum memory in parallel. These imply that the standard circuit model can be simulated with a low overhead by a more realistic model of a distributed quantum computer. As a result, the circuit model can be used by algorithm designers without worrying whether the underlying architecture supports the connectivity of the circuit. In addition, we apply our results to existing memory-intensive quantum algorithms. We present a parallel quantum search algorithm and improve the time–space trade-off for the element distinctness and collision finding problems.
Proteolysis, Texture, and Sensory Characteristics of Serrano Hams from Duroc and Large White Pigs during Dry‐Curing
Authors: del Olmo Ana , Calzada Javier , Gaya Pilar , Nuñez Manuel
Published: February 2013

Proteolysis, texture, physicochemical, and sensory characteristics of Serrano hams from Duroc and Large White pigs at 5, 7, 9, 12, and 15 m of curing (3 hams per breed per curing time) were investigated. Higher concentrations of some sarcoplasmic and myofibrillar proteins, peptides with molecular mass in the ranges 3700 to 12000 Da, 700 to 2000 Da, and below 450 Da, and total free amino acids were recorded for Large White hams, while hydrophobic peptides were at higher levels in Duroc hams. A 40 kDa peak in the low‐ionic‐strength soluble protein fraction and 2 peaks of 40 and 45 kDa in the high‐ionic‐strength soluble protein fraction found only in Duroc hams could be of use in discriminating products from different breeds. Physicochemical and textural characteristics of both types of hams evolved similarly during curing and differences in organoleptic traits between breeds were negligible. Flavor intensity and flavor quality of hams were strongly correlated to curing time, with r2 values over 0.95 for flavor intensity and over 0.90 for flavor quality, and to the concentration of total free amino acids, with r2 values over 0.90 for both flavor intensity and flavor quality. The sensory evaluation scores of Duroc hams, at least as high as those of Large White hams, make the production of high‐quality Serrano ham from pure breed Duroc pigs feasible.

Practical Application:  Duroc breed crosses are advantageous in the production of dry‐cured hams, resulting in higher marbling, enhanced flavor and lower processing losses, but the characteristics of pure breed Duroc hams have not been investigated. The similar evolution of the compositional, proteolytic, textural, and sensory characteristics of Serrano hams from Duroc and Large White pigs during dry‐curing recorded in the present work makes the production of high‐quality dry‐cured hams from pure breed Duroc pigs feasible. Three protein peaks found only in Duroc hams can be of use to discriminate products from different breeds.
Outcomes in smokers and alcohol users after fast‐track hip and knee arthroplasty
Authors: JØRGENSEN C. C , KEHLET H. ,   Lundbeck Foundation Centre for Fast‐track Hip and Knee Replacement collaborative group
Published: February 2013

Background

Smoking and alcohol use impair post‐operative outcomes. However, no studies include fast‐track surgery, which is a multimodal‐enhanced recovery programme demonstrated to improve outcome. We hypothesised that outcome is similar in smokers and alcohol users as in non‐users after fast‐track hip and knee arthroplasty.

Methods

Prospective questionnaires on co‐morbidity and smoking/alcohol use were cross‐referenced with the Danish National Health Registry to investigate relationship between smoking/alcohol use and length of stay of > 4 days and readmissions ≤ 90 days after fast‐track hip and knee arthroplasty.

Results

In 3041 consecutive patients, 458 reported smoking and 216 drinking > 2 drinks a day, of which 66 did both. Smokers/alcohol users were younger than non‐users (mean age: 64.3 vs. 68.0 years, P < 0.001). Multiple regression analysis showed no relation between length of stay of > 4 days and smoking (odds ratio [95% confidence interval], P) (1.34 [0.92–1.95], 0.127) or alcohol use (0.59 [0.30–1.16], 0.127). Thirty‐ and ninety‐day readmission rate was 6.6% (n = 201) and 9.4% (n = 285). Multiple logistic regression analysis showed an increased risk of readmissions in smokers at 30 (1.60 [1.05–2.44], 0.028) but not 90‐day follow‐up (1.17 [0.80–1.73], 0.419). No increased risk of readmissions was found in alcohol users at 30 (0.94 [0.50–1.76], 0.838) or 90‐day follow‐up (0.83 [0.47–1.49], 0.532). No increased risk of specific readmissions (i.e. wound infections or pneumonia) typically related to smoking/alcohol use was found in smokers (1.56 [0.93–2.62], 0.091) or alcohol users (1.00 [0.47–2.15], 0.999) at 90‐day follow‐up.

Conclusion

Influence of smoking or alcohol use may be less pronounced in fast‐track hip and knee arthroplasty compared with data with conventional care programmes.
‘I don't know if I should believe him’: Knowledge and believability in interviews with children
Authors: Iversen Clara
Published: February 2013

Social psychologists interested in social interaction have, in recent years, addressed the ways that people negotiate ‘who is entitled to know what’ across a variety of conversational settings. Using recordings of interviews conducted as a part of a Swedish national evaluation of interventions for abused children, the current article examines how children navigate knowledge and its moral implications. The analysis focuses on a particular question (‘What do you believe [the perpetrator] thinks about what he has done’), which draws on the psychological concept ofmentalization: the cognitive ability to picture others’ mental states based on their behaviour. The findings suggest that the concept of mentalization fails to account for the moral properties of knowing someone's thoughts: The perpetrator, most often the child's father, must bebelievable– recognized as both credible and knowable – for the children to claim access to his thoughts. The interviewees used contrastive constructions in claims of (no) access to their fathers’ thoughts as they simultaneously contested idiomatic knowledge that undermined their claims. The article contributes to recent developments in discursive social psychology concerning how subjectivity, in particular, epistemic stance, is managed in institutional interaction, and continues the discursive psychological project of respecifying concepts such as mentalization.