bluuebunny/crossref_metadata_2025 huggingface dataset:
Parametric stability and dynamic buckling of an encapsulated microbubble subject to acoustic disturbances
Authors: Tsiglifis Kostas , Pelekasis Nikos A.
Published: January 2011

Stability analysis of the radial pulsations of a gas microbubble that is encapsulated by a thin viscoelastic shell and surrounded by an ideal incompressible liquid is carried out. Small axisymmetric disturbances in the microbubble shape are imposed and their long and short term stability is examined depending on the initial bubble radius, the shell properties, and the parameters, i.e., frequency and amplitude, of the external acoustic excitation. Owing to the anisotropy of the membrane that is forming the encapsulating shell, two different types of elastic energy are accounted for, namely, the membrane and bending energy per unit of initial area. They are used to describe the tensions that develop on the shell due to shell stretching and bending, respectively. In addition, two different constitutive laws are used in order to relate the tensions that develop on the membrane as a result of stretching, i.e., the Mooney–Rivlin law describing materials that soften as deformation increases and the Skalak law describing materials that harden as deformation increases. The limit for static buckling is obtained when the external overpressure exerted upon the membrane surpasses a critical value that depends on the membrane bending resistance. The stability equations describing the evolution of axisymmetric disturbances, in the presence of an external acoustic field, reveal that static buckling becomes relevant when the forcing frequency is much smaller than the resonance frequency of the microbubble, corresponding to the case of slow compression. The resonance frequencies for shape oscillations of the microbubble are also obtained as a function of the shell parameters. Floquet analysis shows that parametric instability, similar to the case of an oscillating free bubble, is possible for the case of a pulsating encapsulated microbubble leading to shape oscillations as a result of subharmonic or harmonic resonance. These effects take place for acoustic amplitude values that lie above a certain threshold but below those required for static buckling to occur. They are quite useful in providing estimates for the shell elasticity and bending resistance based on a frequency/amplitude sweep that monitors the onset of shape oscillations when the forcing frequency resonates with the radial pulsation, ωf=ω0, or with a certain shape mode, ωf=2ωn. An acceleration based instability, identified herein as dynamic buckling, is observed during the compression phase of the pulsation, evolving over a small number of periods of the forcing, when the amplitude of the acoustic excitation is further increased. It corresponds to the Rayleigh–Taylor instability observed for free bubbles, and has been observed with contrast agents as well, e.g., BR-14. Finally, phase diagrams for contrast agent BR-14 are constructed and juxtaposed with available experimental data, illustrating the relevance and range of the above instabilities.
Thicker, more efficient superconducting strip-line detectors for high throughput macromolecules analysis
Authors: Casaburi A. , Ejrnaes M. , Zen N. , Ohkubo M. , Pagano S. , Cristiano R.
Published: January 2011

Fast detectors with large area are required in time-of-flight mass spectrometers for high throughput analysis of biological molecules. We fabricated and characterized subnanosecond 1×1 mm2 NbN superconducting strip-line detectors. The influence of the strip-line thickness on the temporal characteristics and efficiency of the detector for the impacts of keV accelerated molecules is investigated. We find that the increase of thickness improves both efficiency and response time. In the thicker sample we achieved a rise time of 380 ps, a fall time of 1.38 ns, and a higher count rate. The physics involved in this behavior is investigated.
Low aspect-ratio hemispherical nanopit surface texturing for enhancing light absorption in crystalline Si thin film-based solar cells
Authors: Li Junshuai , Yu HongYu , Li Yali , Wang Fei , Yang Mingfei , Wong She Mein
Published: January 2011

In this letter, we report light absorption enhancement in crystalline Si thin film-based solar cells through introducing low aspect-ratio hemispherical nanopit surface textures. Optical characteristics of the system are systematically investigated in terms of the structural parameters including nanopit diameter (D) and array periodicity (P) via simulation. An ultimate efficiency of ∼35.7% is predicted when both D and P are ∼700 nm, which is more than double of that (∼15.9%) of the flat Si film with the same thickness of 2 μm. An understanding on the light absorption enhancement is provided based on the optical processes in the subwavelength structures.
Excitation of inertial modes in a closed grid turbulence experiment under rotation
Authors: Lamriben Cyril , Cortet Pierre-Philippe , Moisy Frédéric , Maas Leo R. M.
Published: January 2011

We report an experimental study of the decay of grid-generated turbulence in a confined geometry submitted to a global rotation. Turbulence is generated by rapidly towing a grid in a parallelepipedic water tank. The velocity fields of a large number of independent decays are measured in a vertical plane parallel to the rotation axis using a corotating particle image velocimetry system. We first show that, when a “simple” grid is used, a significant amount of the kinetic energy (typically 50%) is stored in a reproducible flow composed of resonant inertial modes. The spatial structure of those inertial modes, extracted by band-pass filtering, is found compatible with the numerical results of L. R. M. Maas [Fluid Dyn. Res. 33, 373 (2003)]. The possible coupling between these modes and turbulence suggests that turbulence cannot be considered as freely decaying in this configuration. We demonstrate however that these inertial modes may be significantly reduced (down to 15% of the total energy) by adding a set of inner tanks attached to the grid. These results suggest that it is possible to produce an effectively freely decaying rotating turbulence in a confined geometry.
Linear feedback control of transient energy growth and control performance limitations in subcritical plane Poiseuille flow
Authors: Martinelli F. , Quadrio M. , McKernan J. , Whidborne J. F.
Published: January 2011

Suppression of the transient energy growth in subcritical plane Poiseuille flow via feedback control is addressed. It is assumed that the time derivative of any of the velocity components can be imposed at the walls as control input and that full-state information is available. We show that it is impossible to design a linear state-feedback controller that leads to a closed-loop flow system without transient energy growth. In a subsequent step, state-feedback controllers—directly targeting the transient growth mechanism—are designed using a procedure based on a linear matrix inequalities approach. The performance of such controllers is analyzed first in the linear case, where comparison to previously proposed linear-quadratic optimal controllers is made; further, transition thresholds are evaluated via direct numerical simulations of the controlled three-dimensional Poiseuille flow against different initial conditions of physical interest, employing different velocity components as wall actuation. The present controllers are effective in increasing the transition thresholds in closed loop, with varying degree of performance depending on the initial condition and the actuation component employed.
Optical racetrack ring-resonator based on two U-bent microfibers
Authors: Jung Yongmin , Brambilla Gilberto , Murugan Ganapathy Senthil , Richardson David J.
Published: January 2011

We experimentally demonstrate an optical racetrack ring-resonator with four optical ports constructed using two U-shaped bent microfibers placed into direct physical contact. Localized light is clearly observed along the closed loop path as a result of the resulting strong optical resonance. The resonator was embedded in a low-index polymer matrix to improve the long term mechanical and optical stability allowing a detailed study of its polarization characteristics.
Driving vertical phase separation in a bulk-heterojunction by inserting a poly(3-hexylthiophene) layer for highly efficient organic solar cells
Authors: Oh Jin Young , Jang Woo Soon , Lee Tae Il , Myoung Jae-Min , Baik Hong Koo
Published: January 2011

A desirable vertical phase separation of a bulk-heterojunction was achieved by inserting a P3HT layer between the blend layer and the poly(3,4-ethylenedioxythiophene) poly(styrenesulfonate) (PEDOT:PSS) layer. According to the high (PEDOT:PSS) and low (P3HT) surface energies of substrate, it might be possible to modulate the vertical phase separation in the bulk-heterojunction. The result of vertical phase separation was determined using time-of-flight secondary-ion mass spectroscopy analysis. A controlled thickness of 50 nm for the inserted P3HT layer prevented undesirable light absorption and the power conversion efficiency of this condition was increased by 44% compared to that of a reference device.
Droplet charging regimes for ultrasonic atomization of a liquid electrolyte in an external electric field
Authors: Forbes Thomas P. , Degertekin F. Levent , Fedorov Andrei G.
Published: January 2011

Distinct regimes of droplet charging, determined by the dominant charge transport process, are identified for an ultrasonic droplet ejector using electrohydrodynamic computational simulations, a fundamental scale analysis, and experimental measurements. The regimes of droplet charging are determined by the relative magnitudes of the dimensionless Strouhal and electric Reynolds numbers, which are a function of the process (pressure forcing), advection, and charge relaxation time scales for charge transport. Optimal (net maximum) droplet charging has been identified to exist for conditions in which the electric Reynolds number is of the order of the inverse Strouhal number, i.e., the charge relaxation time is on the order of the pressure forcing (droplet formation) time scale. The conditions necessary for optimal droplet charging have been identified as a function of the dimensionless Debye number (i.e., liquid conductivity), external electric field (magnitude and duration), and atomization drive signal (frequency and amplitude). The specific regime of droplet charging also determines the functional relationship between droplet charge and charging electric field strength. The commonly expected linear relationship between droplet charge and external electric field strength is only found when either the inverse of the Strouhal number is less than the electric Reynolds number, i.e., the charge relaxation is slower than both the advection and external pressure forcing, or in the electrostatic limit, i.e., when charge relaxation is much faster than all other processes. The analysis provides a basic understanding of the dominant physics of droplet charging with implications to many important applications, such as electrospray mass spectrometry, ink jet printing, and drop-on-demand manufacturing.
Density functional theory in surface chemistry and catalysis
Authors: Nørskov Jens K. , Abild-Pedersen Frank , Studt Felix , Bligaard Thomas
Published: January 2011

Recent advances in the understanding of reactivity trends for chemistry at transition-metal surfaces have enabled in silico design of heterogeneous catalysts in a few cases. The current status of the field is discussed with an emphasis on the role of coupling theory and experiment and future challenges.
Atomic structure of a nanobody-trapped domain-swapped dimer of an amyloidogenic β2-microglobulin variant
Authors: Domanska Katarzyna , Vanderhaegen Saskia , Srinivasan Vasundara , Pardon Els , Dupeux Florine , Marquez Jose A. , Giorgetti Sofia , Stoppini Monica , Wyns Lode , Bellotti Vittorio , Steyaert Jan
Published: January 2011

Atomic-level structural investigation of the key conformational intermediates of amyloidogenesis remains a challenge. Here we demonstrate the utility of nanobodies to trap and characterize intermediates of β2-microglobulin (β2m) amyloidogenesis by X-ray crystallography. For this purpose, we selected five single domain antibodies that block the fibrillogenesis of a proteolytic amyloidogenic fragment of β2m (ΔN6β2m). The crystal structure of ΔN6β2m in complex with one of these nanobodies (Nb24) identifies domain swapping as a plausible mechanism of self-association of this amyloidogenic protein. In the swapped dimer, two extended hinge loops—corresponding to the heptapetide NHVTLSQ that forms amyloid in isolation—are unmasked and fold into a new two-stranded antiparallel β-sheet. The β-strands of this sheet are prone to self-associate and stack perpendicular to the direction of the strands to build large intermolecular β-sheets that run parallel to the axis of growing oligomers, providing an elongation mechanism by self-templated growth.
Using mechanobiological mimicry of red blood cells to extend circulation times of hydrogel microparticles
Authors: Merkel Timothy J. , Jones Stephen W. , Herlihy Kevin P. , Kersey Farrell R. , Shields Adam R. , Napier Mary , Luft J. Christopher , Wu Huali , Zamboni William C. , Wang Andrew Z. , Bear James E. , DeSimone Joseph M.
Published: January 2011

It has long been hypothesized that elastic modulus governs the biodistribution and circulation times of particles and cells in blood; however, this notion has never been rigorously tested. We synthesized hydrogel microparticles with tunable elasticity in the physiological range, which resemble red blood cells in size and shape, and tested their behavior in vivo. Decreasing the modulus of these particles altered their biodistribution properties, allowing them to bypass several organs, such as the lung, that entrapped their more rigid counterparts, resulting in increasingly longer circulation times well past those of conventional microparticles. An 8-fold decrease in hydrogel modulus correlated to a greater than 30-fold increase in the elimination phase half-life for these particles. These results demonstrate a critical design parameter for hydrogel microparticles.
TNF activates calcium–nuclear factor of activated T cells (NFAT)c1 signaling pathways in human macrophages
Authors: Yarilina Anna , Xu Kai , Chen Janice , Ivashkiv Lionel B.
Published: January 2011

Acute activation of cells by tumor necrosis factor (TNF) has been well characterized, but little is known about later phases of TNF responses that are relevant for cells exposed to TNF for several days during inflammation. We found that prolonged exposure of human macrophages to TNF resulted in a wave of delayed but sustained activation of c-Jun and nuclear factor κB (NF-κB) proteins and of calcium oscillations that became apparent 1–3 d after TNF stimulation. These signaling events culminated in the induction and activation of the calcium-dependent transcription factor, nuclear factor of activated T cells (NFAT)c1, which mediated a gene expression program leading to cell fusion and osteoclast differentiation. TNF-induced NFATc1 activity primed macrophages for enhanced osteoclastogenesis in response to RANKL. High NFATc1 expression was apparent in synovial macrophages in a subset of patients with TNF-driven inflammatory arthritis. Thus, long-term exposure to TNF activates calcium-dependent signaling and an NFATc1-mediated gene activation program important for cell fusion and osteoclastogenesis. These findings identify a signaling pathway activated by TNF that is important for myeloid cell differentiation and suggest a role for TNF-induced calcium and NFAT signaling in chronic inflammation and associated bone resorption.
Deep bradycardia and heart block caused by inducible cardiac-specific knockout of the pacemaker channel gene
Hcn4
Authors: Baruscotti Mirko , Bucchi Annalisa , Viscomi Carlo , Mandelli Giacomo , Consalez Giacomo , Gnecchi-Rusconi Tomaso , Montano Nicola , Casali Karina Rabello , Micheloni Stefano , Barbuti Andrea , DiFrancesco Dario
Published: January 2011

Cardiac pacemaking generation and modulation rely on the coordinated activity of several processes. Although a wealth of evidence indicates a relevant role of the I
f
(“funny,” or pacemaker) current, whose molecular constituents are the hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels and particularly HCN4, work with mice where
Hcn
genes were knocked out, or functionally modified, has challenged this view. However, no previous studies used a cardiac-specific promoter to induce HCN4 ablation in adult mice. We report here that, in an inducible and cardiac-specific HCN4 knockout (ciHCN4-KO) mouse model, ablation of HCN4 consistently leads to progressive development of severe bradycardia (∼50% reduction of original rate) and AV block, eventually leading to heart arrest and death in about 5 d. In vitro analysis of sinoatrial node (SAN) myocytes isolated from ciHCN4-KO mice at the mean time of death revealed a strong reduction of both the I
f
current (by ∼70%) and of the spontaneous rate (by ∼60%). In agreement with functional results, immunofluorescence and Western blot analysis showed reduced expression of HCN4 protein in SAN tissue and cells. In ciHCN4-KO animals, the residual I
f
was normally sensitive to β-adrenergic receptor (β-AR) modulation, and the permanence of rate response to β-AR stimulation was observed both in vivo and in vitro. Our data show that cardiac HCN4 channels are essential for normal heart impulse generation and conduction in adult mice and support the notion that dysfunctional HCN4 channels can be a direct cause of rhythm disorders. This work contributes to identifying the molecular mechanism responsible for cardiac pacemaking.
Loss-of-function mutation in
GATA4
causes anomalies of human testicular development
Authors: Lourenço Diana , Brauner Raja , Rybczyńska Magda , Nihoul-Fékété Claire , McElreavey Ken , Bashamboo Anu
Published: January 2011

Approximately 1 of every 250 newborns has some abnormality of genital and/or gonadal development. However, a specific molecular cause is identified in only 20% of these cases of disorder of sex development (DSD). We identified a family of French origin presenting with 46,XY DSD and congenital heart disease. Sequencing of the ORF of
GATA4
identified a heterozygous missense mutation (p.Gly221Arg) in the conserved N-terminal zinc finger of GATA4. This mutation was not observed in 450 ancestry-matched control individuals. The mutation compromised the ability of the protein to bind to and transactivate the anti-Müllerian hormone (
AMH
) promoter. The mutation does not interfere with the direct protein–protein interaction, but it disrupts synergistic activation of the
AMH
promoter by GATA4 and NR5A1. The p.Gly221Arg mutant protein also failed to bind to a known protein partner FOG2 that is essential for gonad formation. Our data demonstrate the key role of GATA4 in human testicular development.
Molecular imaging of active mutant L858R EGF receptor (EGFR) kinase-expressing nonsmall cell lung carcinomas using PET/CT
Authors: Yeh Hsin Hsien , Ogawa Kazuma , Balatoni Julius , Mukhapadhyay Uday , Pal Asutosh , Gonzalez-Lepera Carlos , Shavrin Aleksandr , Soghomonyan Suren , Flores Leo , Young Daniel , Volgin Andrei Y. , Najjar Amer M. , Krasnykh Victor , Tong William , Alauddin Mian M. , Gelovani Juri G.
Published: January 2011

The importance of the EGF receptor (EGFR) signaling pathway in the development and progression of nonsmall cell lung carcinomas (NSCLC) is widely recognized. Gene sequencing studies revealed that a majority of tumors responding to EGFR kinase inhibitors harbor activating mutations in the EGFR kinase domain. This underscores the need for novel biomarkers and diagnostic imaging approaches to identify patients who may benefit from particular therapeutic agents and approaches with improved efficacy and safety profiles. To this goal, we developed 4-[(3-iodophenyl)amino]-7-{2-[2-{2-(2-[2-{2-([
18
F]fluoroethoxy)-ethoxy}-ethoxy]-ethoxy)-ethoxy}-ethoxy]-quinazoline-6-yl-acrylamide ([
18
F]F-PEG6-IPQA), a radiotracer with increased selectivity and irreversible binding to the active mutant L858R EGFR kinase. We show that PET with [
18
F]F-PEG6-IPQA in tumor-bearing mice discriminates H3255 NSCLC xenografts expressing L858R mutant EGFR from H441 and PC14 xenografts expressing EGFR or H1975 xenografts with L858R/T790M dual mutation in EGFR kinase domain, which confers resistance to EGFR inhibitors (i.e., gefitinib). The T790M mutation precludes the [
18
F]F-PEG6-IPQA from irreversible binding to EGFR. These results suggest that PET with [
18
F]F-PEG6-IPQA could be used for the selection of NSCLC patients for individualized therapy with small molecular inhibitors of EGFR kinase that are currently used in the clinic and have a similar structure (i.e., iressa, gefitinib, and erlotinib).
Phosphorylation of glutamyl-prolyl tRNA synthetase by cyclin-dependent kinase 5 dictates transcript-selective translational control
Authors: Arif Abul , Jia Jie , Moodt Robyn A. , DiCorleto Paul E. , Fox Paul L.
Published: January 2011

Cyclin-dependent kinase 5 (Cdk5) is an atypical but essential member of the Cdk kinase family, and its dysregulation or deletion has been implicated in inflammation-related disorders by an undefined mechanism. Here we show that Cdk5 is an indispensable activator of the GAIT (IFN-γ–activated inhibitor of translation) pathway, which suppresses expression of a posttranscriptional regulon of proinflammatory genes in myeloid cells. Through induction of its regulatory protein, Cdk5R1 (p35), IFN-γ activates Cdk5 to phosphorylate Ser
886
in the linker domain of glutamyl-prolyl tRNA synthetase (EPRS), the initial event in assembly of the GAIT complex. Cdk5/p35 also induces, albeit indirectly via a distinct kinase, phosphorylation of Ser
999
, the second essential event in GAIT pathway activation. Diphosphorylated EPRS is released from its residence in the tRNA multisynthetase complex for immediate binding to NS1-associated protein and subsequent binding to ribosomal protein L13a and GAPDH. The mature heterotetrameric GAIT complex binds the 3′ UTR GAIT element of VEGF-A and other target mRNAs and suppresses their translation in myeloid cells. Inhibition of Cdk5/p35 inhibits both EPRS phosphorylation events, prevents EPRS release from the tRNA multisynthetase complex, and blocks translational suppression of GAIT element–bearing mRNAs, resulting in increased expression of inflammatory proteins. Our study reveals a unique role of Cdk5/p35 in activation of the major noncanonical function of EPRS, namely translational control of macrophage inflammatory gene expression.
Holocephalan embryos provide evidence for gill arch appendage reduction and opercular evolution in cartilaginous fishes
Authors: Gillis J. Andrew , Rawlinson Kate A. , Bell Justin , Lyon Warrick S. , Baker Clare V. H. , Shubin Neil H.
Published: January 2011

Chondrichthyans possess endoskeletal appendages called branchial rays that extend laterally from their hyoid and gill-bearing (branchial) arches. Branchial ray outgrowth, like tetrapod limb outgrowth, is maintained by Sonic hedgehog (Shh) signaling. In limbs, distal endoskeletal elements fail to form in the absence of normalShhsignaling, whereas shortened duration ofShhexpression correlates with distal endoskeletal reduction in naturally variable populations. Chondrichthyans also exhibit natural variation with respect to branchial ray distribution—elasmobranchs (sharks and batoids) possess a series of ray-supported septa on their hyoid and gill arches, whereas holocephalans (chimaeras) possess a single hyoid arch ray-supported operculum. Here we show that the elongate hyoid rays of the holocephalanCallorhinchus miliigrow in association with sustainedShhexpression within an opercular epithelial fold, whereasShhis only transiently expressed in the gill arches. Coincident with this transientShhexpression, branchial ray outgrowth is initiated inC. miliibut is not maintained, yielding previously unrecognized vestigial gill arch branchial rays. This is in contrast to the condition seen in sharks, where sustainedShhexpression corresponds to the presence of fully formed branchial rays on the hyoid and gill arches. Considered in light of current hypotheses of chondrichthyan phylogeny, our data suggest that the holocephalan operculum evolved in concert with gill arch appendage reduction by attenuation of Shh-mediated branchial ray outgrowth, and that chondrichthyan branchial rays and tetrapod limbs exhibit parallel developmental mechanisms of evolutionary reduction.
Selective early-acquired fear memories undergo temporary suppression during adolescence
Authors: Pattwell Siobhan S. , Bath Kevin G. , Casey B. J. , Ninan Ipe , Lee Francis S.
Published: January 2011

Highly conserved neural circuitry between rodents and humans has allowed for in-depth characterization of behavioral and molecular processes associated with emotional learning and memory. Despite increased prevalence of affective disorders in adolescent humans, few studies have characterized how associative-emotional learning changes during the transition through adolescence or identified mechanisms underlying such changes. By examining fear conditioning in mice, as they transitioned into and out of adolescence, we found that a suppression of contextual fear occurs during adolescence. Although contextual fear memories were not expressed during early adolescence, they could be retrieved and expressed as the mice transitioned out of adolescence. This temporary suppression of contextual fear was associated with blunted synaptic activity in the basal amygdala and decreased PI3K and MAPK signaling in the hippocampus. These findings reveal a unique form of brain plasticity in fear learning during early adolescence and may prove informative for understanding endogenous mechanisms to suppress unwanted fear memories.
Nrf2-mediated induction of p62 controls Toll-like receptor-4–driven aggresome-like induced structure formation and autophagic degradation
Authors: Fujita Ken-ichi , Maeda Daisuke , Xiao Qi , Srinivasula Srinivasa M.
Published: January 2011

Toll-like receptors (TLRs) play a crucial role in several innate immune responses by regulating autophagy, but little is known about how TLR signaling controls autophagy. Here we demonstrate that p62/SQSTM1 is required for TLR4-mediated autophagy, which we show as selective autophagy of aggresome-like induced structures (ALIS). Treatment with LPS or
Escherichia coli
induced LC3
+
dot-like structures, and their assembly, but not lysosomal degradation, occurred independently of classic autophagic machinery. Microscopic and ultrastructural analyses showed that p62 is a component of the induced LC3
+
dots and these TLR4-induced p62
+
structures resemble ALIS. The levels of p62 mRNA and protein were increased in TLR4-activated cells and knockdown of p62 suppressed the ALIS formation and LC3-II conversion. The accumulation of p62 and ALIS required activation of Nrf2 by reactive oxygen species-p38 axis-dependent TLR4/MyD88 signaling, suggesting a link between innate immune and oxidative-stress responses. These findings indicate that TLR4-driven induction of p62 plays an essential role in the formation and the autophagic degradation of ALIS, which might be critical for regulating host defense.
Spring temperature change and its implication in the change of vegetation growth in North America from 1982 to 2006
Authors: Wang Xuhui , Piao Shilong , Ciais Philippe , Li Junsheng , Friedlingstein Pierre , Koven Charlie , Chen Anping
Published: January 2011

Understanding how vegetation growth responds to climate change is a critical requirement for projecting future ecosystem dynamics. Parts of North America (NA) have experienced a spring cooling trend over the last three decades, but little is known about the response of vegetation growth to this change. Using observed climate data and satellite-derived Normalized Difference Vegetation Index (NDVI) data from 1982 to 2006, we investigated changes in spring (April–May) temperature trends and their impact on vegetation growth in NA. A piecewise linear regression approach shows that the trend in spring temperature is not continuous through the 25-year period. In the northwestern region of NA, spring temperature increased until the late 1980s or early 1990s, and stalled or decreased afterwards. In response, a spring vegetation greening trend, which was evident in this region during the 1980s, stalled or reversed recently. Conversely, an opposite phenomenon occurred in the northeastern region of NA due to different spring temperature trends. Additionally, the trends of summer vegetation growth vary between the periods before and after the turning point (TP) of spring temperature trends. This change cannot be fully explained by summer drought stress change alone and is partly explained by changes in the trends of spring temperature as well as those of summer temperature. As reported in previous studies, summer vegetation browning trends have occurred in the northwestern region of NA since the early 1990s, which is consistent with the spring and summer cooling trends in this region during this period.
Morphological change in machines accelerates the evolution of robust behavior
Authors: Bongard Josh
Published: January 2011

Most animals exhibit significant neurological and morphological change throughout their lifetime. No robots to date, however, grow new morphological structure while behaving. This is due to technological limitations but also because it is unclear that morphological change provides a benefit to the acquisition of robust behavior in machines. Here I show that in evolving populations of simulated robots, if robots grow from anguilliform into legged robots during their lifetime in the early stages of evolution, and the anguilliform body plan is gradually lost during later stages of evolution, gaits are evolved for the final, legged form of the robot more rapidly—and the evolved gaits are more robust—compared to evolving populations of legged robots that do not transition through the anguilliform body plan. This suggests that morphological change, as well as the evolution of development, are two important processes that improve the automatic generation of robust behaviors for machines. It also provides an experimental platform for investigating the relationship between the evolution of development and robust behavior in biological organisms.
CUB-domain–containing protein 1 (CDCP1) activates Src to promote melanoma metastasis
Authors: Liu Hui , Ong Shao-En , Badu-Nkansah Kwabena , Schindler Jeffrey , White Forest M. , Hynes Richard O.
Published: January 2011

We report the application of quantitative mass spectrometry to identify plasma membrane proteins differentially expressed in melanoma cells with high vs. low metastatic abilities. Using stable isotope labeling with amino acids in culture (SILAC) coupled with nanospray tandem mass spectrometry, we identified CUB-domain–containing protein 1 (CDCP1) as one such differentially expressed transmembrane protein. CDCP1 is not only a surface marker for cells with higher metastatic potential, but also functionally involved in enhancing tumor metastasis. Overexpression of CDCP1 also correlates with activation of Src. Pharmacological reagents, PP2 and Dasatinib, which block Src family kinase activation, blocked scattered growth of CDCP1-overexpressing cells in 3D Matrigel culture, suggesting that CDCP1 might function through the activation of Src-family kinases (SFKs). This hypothesis was further supported by mutational studies of CDCP1. Whereas wild-type CDCP1 enhances Src activation, point mutation Y734F abolishes in vitro dispersive growth in 3D culture and in vivo metastasis-enhancing activities of CDCP1. In addition, the Y734F mutation also eliminated enhanced Src activation. Thus, this work provides molecular mechanisms for the metastasis-enhancing functions of CDCP1.
Imaging electrical resonance in hair cells
Authors: Fisher Jonathan A. N. , Kowalik Lukasz , Hudspeth A. J.
Published: January 2011

The mechanosensory hair cells of many auditory receptor organs are tuned by an electrical resonance that increases their responses to stimulation over a narrow band of frequencies. The small oscillations of membrane potential characteristic of this phenomenon have previously been detectable only through intracellular electrode measurements, which are laborious and preclude analysis at the level of an entire sensory organ. We used a voltage-sensitive dye to image hair-cell electrical resonance in an intact preparation of the bullfrog's sacculus, a receptor organ sensitive to low-frequency seismic and auditory stimuli. Imaging revealed distinct populations of hair cells whose resonant response varied with the frequency of transepithelial electrical stimulation. Most of the hair cells in the saccular epithelium in vitro were electrically tuned to stimulation at 25–50 Hz. The frequency dependence of the fluorescence signal was sensitive to pharmacological blockade of large-conductance Ca
2+
-sensitive K
+
channels and to enzymatic digestion. At an elevated concentration of Ca
2+
, we observed transient fluorescence signals that probably represented action potentials. The stroboscopic imaging and analysis techniques described here present a general approach for studying subthreshold oscillations in electrically excitable cells.
Extranuclear protection of chromosomal DNA from oxidative stress
Authors: Vanderauwera Sandy , Suzuki Nobuhiro , Miller Gad , van de Cotte Brigitte , Morsa Stijn , Ravanat Jean-Luc , Hegie Alicia , Triantaphylidès Christian , Shulaev Vladimir , Van Montagu Marc C. E. , Van Breusegem Frank , Mittler Ron
Published: January 2011

Eukaryotic organisms evolved under aerobic conditions subjecting nuclear DNA to damage provoked by reactive oxygen species (ROS). Although ROS are thought to be a major cause of DNA damage, little is known about the molecular mechanisms protecting nuclear DNA from oxidative stress. Here we show that protection of nuclear DNA in plants requires a coordinated function of ROS-scavenging pathways residing in the cytosol and peroxisomes, demonstrating that nuclear ROS scavengers such as peroxiredoxin and glutathione are insufficient to safeguard DNA integrity. Both catalase (CAT2) and cytosolic ascorbate peroxidase (APX1) play a key role in protecting the plant genome against photorespiratory-dependent H
2
O
2
-induced DNA damage. In
apx1/cat2
double-mutant plants, a DNA damage response is activated, suppressing growth via a WEE1 kinase-dependent cell-cycle checkpoint. This response is correlated with enhanced tolerance to oxidative stress, DNA stress-causing agents, and inhibited programmed cell death.
Bile acid stimulates hepatocyte polarization through a cAMP-Epac-MEK-LKB1-AMPK pathway
Authors: Fu Dong , Wakabayashi Yoshiyuki , Lippincott-Schwartz Jennifer , Arias Irwin M.
Published: January 2011

This study describes a unique function of taurocholate in bile canalicular formation involving signaling through a cAMP-Epac-MEK-Rap1-LKB1-AMPK pathway. In rat hepatocyte sandwich cultures, polarization was manifested by sequential progression of bile canaliculi from small structures to a fully branched network. Taurocholate accelerated canalicular network formation and concomitantly increased cAMP, which were prevented by adenyl cyclase inhibitor. The cAMP-dependent PKA inhibitor did not prevent the taurocholate effect. In contrast, activation of Epac, another cAMP downstream kinase, accelerated canalicular network formation similar to the effect of taurocholate. Inhibition of Epac downstream targets, Rap1 and MEK, blocked the taurocholate effect. Taurocholate rapidly activated MEK, LKB1, and AMPK, which were prevented by inhibition of adenyl cyclase or MEK. Our previous study showed that activated-LKB1 and AMPK participate in canalicular network formation. Linkage between bile acid synthesis, hepatocyte polarization, and regulation of energy metabolism is likely important in normal hepatocyte development and disease.
Inducible formation of breast cancer stem cells and their dynamic equilibrium with non-stem cancer cells via IL6 secretion
Authors: Iliopoulos Dimitrios , Hirsch Heather A. , Wang Guannan , Struhl Kevin
Published: January 2011

Tumors are often heterogeneous, being composed of multiple cell types with different phenotypic and molecular properties. Cancer stem-like cells (CSCs) are a highly tumorigenic cell type found in developmentally diverse tumors or cancer cell lines, and they are often resistant to standard chemotherapeutic drugs. The origins of CSCs and their relationships to nonstem cancer cells (NSCCs) are poorly understood. In an inducible breast oncogenesis model, CSCs are generated from nontransformed cells at a specific time during the transformation process, but CSC formation is not required for transformation. MicroRNA profiles indicate that CSCs and NSCCs are related, but different cell types arising from a common nontransformed population. Interestingly, medium from the transformed population stimulates NSCCs to become CSCs, and conversion of NSCCs to CSCs occurs in mouse xenografts. Furthermore, IL6 is sufficient to convert NSCCs to CSCs in genetically different breast cell lines, human breast tumors, and a prostate cell line. Thus, breast and prostate CSCs and NSCCs do not represent distinct epigenetic states, and these CSCs do not behave as or arise from classic stem cells. Instead, tumor heterogeneity involves a dynamic equilibrium between CSCs and NSCCs mediated by IL6 and activation of the inflammatory feedback loop required for oncogenesis. This dynamic equilibrium provides an additional rationale for combining conventional chemotherapy with metformin, which selectively inhibits CSCs.
CD83 increases MHC II and CD86 on dendritic cells by opposing IL-10–driven MARCH1-mediated ubiquitination and degradation
Authors: Tze Lina E. , Horikawa Keisuke , Domaschenz Heather , Howard Debbie R. , Roots Carla M. , Rigby Robert J. , Way David A. , Ohmura-Hoshino Mari , Ishido Satoshi , Andoniou Christopher E. , Degli-Esposti Mariapia A. , Goodnow Christopher C.
Published: January 2011

Effective vaccine adjuvants must induce expression of major histocompatability (MHC) class II proteins and the costimulatory molecule CD86 on dendritic cells (DCs). However, some adjuvants elicit production of cytokines resulting in adverse inflammatory consequences. Development of agents that selectively increase MHC class II and CD86 expression without triggering unwanted cytokine production requires a better understanding of the molecular mechanisms influencing the production and degradation of MHC class II and CD86 in DCs. Here, we investigate how CD83, an immunoglobulin protein expressed on the surface of mature DCs, promotes MHC class II and CD86 expression. Using mice with an N-ethyl-N-nitrosourea–induced mutation eliminating the transmembrane (TM) region of CD83, we found that the TM domain of CD83 enhances MHC class II and CD86 expression by blocking MHC class II association with the ubiquitin ligase MARCH1. The TM region of CD83 blocks interleukin 10–driven, MARCH1-dependent ubiquitination and degradation of MHC class II and CD86 in DCs. Exploiting this posttranslational pathway for boosting MHC class II and CD86 expression on DCs may provide an opportunity to enhance the immunogenicity of vaccines.
Neuroprotection and progenitor cell renewal in the injured adult murine retina requires healing monocyte-derived macrophages
Authors: London Anat , Itskovich Elena , Benhar Inbal , Kalchenko Vyacheslav , Mack Matthias , Jung Steffen , Schwartz Michal
Published: January 2011

The death of retinal ganglion cells (RGCs) is a hallmark of many retinal neuropathies. Neuroprotection, axonal regeneration, and cell renewal are vital for the integrity of the visual system after insult but are scarce in the adult mammalian retina. We hypothesized that monocyte-derived macrophages, known to promote healing in peripheral tissues, are required after an insult to the visual system, where their role has been largely overlooked. We found that after glutamate eye intoxication, monocyte-derived macrophages infiltrated the damaged retina of mice. Inhibition of this infiltration resulted in reduced survival of RGCs and diminished numbers of proliferating retinal progenitor cells (RPCs) in the ciliary body. Enhancement of the circulating monocyte pool led to increased RGC survival and RPC renewal. The infiltrating monocyte-derived macrophages skewed the milieu of the injured retina toward an antiinflammatory and neuroprotective one and down-regulated accumulation of other immune cells, thereby resolving local inflammation. The beneficial effect on RGC survival depended on expression of interleukin 10 and major histocompatibility complex class II molecules by monocyte-derived macrophages. Thus, we attribute to infiltrating monocyte-derived macrophages a novel role in neuroprotection and progenitor cell renewal in the injured retina, with far-reaching potential implications to retinal neuropathies and other neurodegenerative disorders.
Counting dihedral and quaternionic extensions
Authors: Fouvry Étienne , Luca Florian , Pappalardi Francesco , Shparlinski Igor
Published: January 2011

We give asymptotic formulas for the number of biquadratic extensions of

Q

\mathbb {Q}

that admit a quadratic extension which is a Galois extension of

Q

\mathbb {Q}

with a prescribed Galois group, for example, with a Galois group isomorphic to the quaternionic group. Our approach is based on a combination of the theory of quadratic equations with some analytic tools such as the Siegel–Walfisz theorem and the double oscillations theorem.
The application of satellite remote sensing for assessing productivity in relation to fisheries yields of the world's large marine ecosystems
Authors: Sherman Kenneth , O'Reilly John , Belkin Igor M. , Melrose Christopher , Friedland Kevin D.
Published: January 2011

Sherman, K., O'Reilly, J., Belkin, I. M., Melrose, C., and Friedland, K. D. 2011. The application of satellite remote sensing for assessing productivity in relation to fisheries yields of the world's large marine ecosystems. – ICES Journal of Marine Science, 68: 667–676. In 1992, world leaders at the historical UN Conference on Environment and Development (UNCED) recognized that the exploitation of resources in coastal oceans was becoming increasingly unsustainable, resulting in an international effort to assess, recover, and manage goods and services of large marine ecosystems (LMEs). More than $3 billion in support to 110 economically developing nations have been dedicated to operationalizing a five-module approach supporting LME assessment and management practices. An important component of this effort focuses on the effects of climate change on fisheries biomass yields of LMEs, using satellite remote sensing and in situ sampling of key indicators of changing ecological conditions. Warming appears to be reducing primary productivity in the lower latitudes, where stratification of the water column has intensified. Fishery biomass yields in the Subpolar LMEs of the Northeast Atlantic are also increasing as zooplankton levels increase with warming. During the current period of climate warming, it is especially important for space agency programmes in Asia, Europe, and the United States to continue to provide satellite-borne radiometry data to the global networks of LME assessment scientists.
Correlation Between Hump Dimensions and Curve Severity in Idiopathic Scoliosis Before and After Conservative Treatment
Authors: Aulisa Angelo Gabriele , Guzzanti Vincenzo , Perisano Carlo , Marzetti Emanuele , Menghi Amerigo , Giordano Marco , Aulisa Lorenzo
Published: January 2011

Study Design.

Prospective study in 150 consecutive outpatients affected by adolescent idiopathic scoliosis (AIS).

Objectives.

The purposes were to (1) identify a correlation between hump dimensions and the severity of scoliotic curve, and (2) evaluate how the treatment influenced the main parameters of scoliosis.

Summary of Background Data.

The existence of a relationship between clinical deformities and curve severity in AIS is still debated. Furthemore, only a few studies have investigated the effectiveness of conservative treatment for idiopathic scoliosis taking into account both clinical and radiologic factors.

Methods.

150 consecutive outpatients (mean age 12.8 ± 1.9 years) affected by AIS were subjected to conservative brace-based treatment. 134 participants completed the treatment protocol. Two parameters were considered to evaluate the treatment progress: the hump and the Cobb angle. Measurements were determined at the beginning and the end of treatment. Statistical analyses were performed in the whole sample and after dividing the study participants into 4 subgroups: patients with lumbar (n = 66) or thoracic curves (n = 68), patients ranging in age between 6 and 13 years (n = 89) and patients ≥ 14 years of age (n = 45).

Results.

A positive correlation was detected between the hump dimension and curve severity at the beginning and the end of treatment, except for lumbar curves at baseline. The deformity was effectively corrected by the orthotic treatment (Cobb angle: 29.4 ± 8.5° at baseline and 19.3 ± 9.8° at the end of treatment; hump severity: 11.6 ± 5.6 mm at baseline and 6.2 ± 4.6 mm at the end). In addition, our data indicate that the hump correction is more evident than that of the curve registered in Cobb degrees.

Conclusion.

A significant correlation exists between the hump dimension and curve severity both at the beginning and the end of treatment, except for lumbar curves at baseline. The brace treatment confirmed its effectiveness in arresting the deformity progression and inducing a remodeling both of the scoliotic curve and the hump.
Cloning and Characterization of Purple Acid Phosphatase Phytases from Wheat, Barley, Maize, and Rice
Authors: Dionisio Giuseppe , Madsen Claus K. , Holm Preben B. , Welinder Karen G. , Jørgensen Malene , Stoger Eva , Arcalis Elsa , Brinch-Pedersen Henrik
Published: January 2011

Barley (Hordeum vulgare) and wheat (Triticum aestivum) possess significant phytase activity in the mature grains. Maize (Zea mays) and rice (Oryza sativa) possess little or virtually no preformed phytase activity in the mature grain and depend fully on de novo synthesis during germination. Here, it is demonstrated that wheat, barley, maize, and rice all possess purple acid phosphatase (PAP) genes that, expressed in Pichia pastoris, give fully functional phytases (PAPhys) with very similar enzyme kinetics. Preformed wheat PAPhy was localized to the protein crystalloid of the aleurone vacuole. Phylogenetic analyses indicated that PAPhys possess four conserved domains unique to the PAPhys. In barley and wheat, the PAPhy genes can be grouped as PAPhy_a or PAPhy_b isogenes (barley, HvPAPhy_a, HvPAPhy_b1, and HvPAPhy_b2; wheat, TaPAPhy_a1, TaPAPhy_a2, TaPAPhy_b1, and TaPAPhy_b2). In rice and maize, only the b type (OsPAPhy_b and ZmPAPhy_b, respectively) were identified. HvPAPhy_a and HvPAPhy_b1/b2 share 86% and TaPAPhya1/a2 and TaPAPhyb1/b2 share up to 90% (TaPAPhy_a2 and TaPAPhy_b2) identical amino acid sequences. despite of this, PAPhy_a and PAPhy_b isogenes are differentially expressed during grain development and germination. In wheat, it was demonstrated that a and b isogene expression is driven by different promoters (approximately 31% identity). TaPAPhy_a/b promoter reporter gene expression in transgenic grains and peptide mapping of TaPAPhy purified from wheat bran and germinating grains confirmed that the PAPhy_a isogene set present in wheat/barley but not in rice/maize is the origin of high phytase activity in mature grains.