bluuebunny/crossref_metadata_2025 huggingface dataset:
Mixing of a dye tracer in the Delaware plume: Comparison of observations and simulations
Authors: Tilburg C. E. , Houghton R. W. , Garvine R. W.
Published: December 2007

In April 2003 we injected Rhodamine‐WT fluorescent dye into the halocline at the base of the Delaware River plume during an upwelling event. The dye immediately bifurcated: One third of the dye moved offshore with a portion of the plume, while the other 2/3 remained within the halocline, near the coastline. This behavior has not been previously observed, and it presents a strong challenge to contemporary coastal ocean models. Here we employ a numerical model of Delaware Bay and the adjacent coastal region that incorporates the Mellor‐Yamada Level 2.5 turbulence closure scheme to simulate the observed dye injection event. Comparison between the simulation and observations reveals that the model is able to successfully reproduce the flow field, simulating the separation and subsequent advection of the dye. Consequently, the simulation is used to examine the relative effects of wind‐ and buoyancy‐driven transport on mixing and advection of the dye. Comparison of simulated and observed plumes reveals that the model accurately reproduces the observed mixing and accompanying vertical salt flux within the offshore plume. Examination of the simulation reveals a unique combination of wind‐ and buoyancy‐driven flow that results in the dye remaining in the halocline of the onshore plume despite significant vertical mixing due to winds. The strong stratification within the inshore plume causes the closure scheme to shut off the vertical diffusivities, leaving the circulation model with arbitrarily chosen constant background values. Varying these values reveals only a weak dependence of the salt flux within the highly stratified regions due to the highly localized nature of the salt flux.
Hydrologic and aeolian controls on vegetation patterns in arid landscapes
Authors: Ravi Sujith , D'Odorico Paolo , Okin Gregory S.
Published: December 2007

Hydrological and aeolian processes redistribute sediments and nutrients within arid landscapes with important effects on the composition and structure of vegetation. Despite the relevance of wind and water erosion to the dynamics of arid and semiarid ecosystems, the interactions between these two processes remain poorly understood. In this paper we present the results of an intensive set of infiltration experiments from the Chihuahuan Desert, showing that in this system the infiltration capacity under the shrub canopy is lower than that at the outer edges of the vegetated patches. Hence, runoff is more likely to occur from the middle of these shrub‐dominated areas to the edges. These experimental results show that the differential rates of soil deposition and removal by aeolian processes result in differential rates of hydrological processes such as infiltration and runoff with important implications for the formation and expansion of mesquite dunes in arid landscapes.
Flexural stresses beneath Hawaii: Implications for the October 15, 2006, earthquakes and magma ascent
Authors: McGovern Patrick J.
Published: December 2007

On October 15, 2006, two large earthquakes rocked the northwest coast of the island of Hawaii six minutes apart: the Kiholo Bay and Mahukona events, with magnitudes Mw = 6.7 and 6.0, respectively. Their close proximity in space and time suggests a common origin, but sharp contrasts in mechanism and depth present an unusual fault‐aftershock relationship. Here I account for the October 15th earthquakes as the divergent outcomes of a single process: downward flexing of the lithosphere in response to loading by Hawaiian volcanoes. Viscoelastic finite element models of lithospheric flexure reveal that a strong stiffness contrast between crustal and mantle materials produces peak upper lithosphere stresses at the top of the stiffer mantle. High compression at the mantle top explains the tendency to trap magmas near the base of the crust: the underplating observed seismically at older Hawaiian volcanoes. These phenomena produce peak stress regions at depths consistent with that of the unexpectedly deep Mahukona event.
Vibrational and thermodynamic properties of wadsleyite: A density functional study
Authors: Wu Zhongqing , Wentzcovitch Renata M.
Published: December 2007

The vibrational properties of Mg2SiO4 wadsleyite have been calculated over a wide pressure range using density functional perturbation theory (DFPT). Both the normal mode frequencies and their volume dependences are consistent with the available Raman and infrared data. We provide detailed information about vibrational properties that are still not experimentally available. The vibrational density of states (vDOS) is used to calculate the Helmholtz free energy within the quasi‐harmonic approximation (QHA) and other thermodynamic quantities without further approximations. The extensive and successful comparisons with experiments demonstrate once more that the QHA combined with first principles vDOSs can provide accurate thermodynamic properties of minerals over the large pressure‐temperature regime relevant for the Earth.
Ku recruits XLF to DNA double‐strand breaks
Authors: Yano Ken‐ichi , Morotomi‐Yano Keiko , Wang Shih‐Ya , Uematsu Naoya , Lee Kyung‐Jong , Asaithamby Aroumougame , Weterings Eric , Chen David J
Published: December 2007

XRCC4‐like factor (XLF)—also known as Cernunnos—has recently been shown to be involved in non‐homologous end‐joining (NHEJ), which is the main pathway for the repair of DNA double‐strand breaks (DSBs) in mammalian cells. XLF is likely to enhance NHEJ by stimulating XRCC4–ligase IV‐mediated joining of DSBs. Here, we report mechanistic details of XLF recruitment to DSBs. Live cell imaging combined with laser micro‐irradiation showed that XLF is an early responder to DSBs and that Ku is essential for XLF recruitment to DSBs. Biochemical analysis showed that Ku–XLF interaction occurs on DNA and that Ku stimulates XLF binding to DNA. Unexpectedly, XRCC4 is dispensable for XLF recruitment to DSBs, although photobleaching analysis showed that XRCC4 stabilizes the binding of XLF to DSBs. Our observations showed the direct involvement of XLF in the dynamic assembly of the NHEJ machinery and provide mechanistic insights into DSB recognition.
Fluorescence-detected two-dimensional electronic coherence spectroscopy by acousto-optic phase modulation
Authors: Tekavec Patrick F. , Lott Geoffrey A. , Marcus Andrew H.
Published: December 2007

Two-dimensional electronic coherence spectroscopy (ECS) is an important method to study the coupling between distinct optical modes of a material system. Such studies often involve excitation using a sequence of phased ultrashort laser pulses. In conventional approaches, the delays between pulse temporal envelopes must be precisely monitored or maintained. Here, we introduce a new experimental scheme for phase-selective nonlinear ECS, which combines acousto-optic phase modulation with ultrashort laser excitation to produce intensity modulated nonlinear fluorescence signals. We isolate specific nonlinear signal contributions by synchronous detection, with respect to appropriately constructed references. Our method effectively decouples the relative temporal phases from the pulse envelopes of a collinear train of four sequential pulses. We thus achieve a robust and high signal-to-noise scheme for phase-selective ECS to investigate the resonant nonlinear optical response of photoluminescent systems. We demonstrate the validity of our method using a model quantum three-level system—atomic Rb vapor. Moreover, we show how our measurements determine the resonant complex-valued third-order susceptibility.
Generalized eigenfunctions for Dirac operators near criticality
Authors: Pickl Peter
Published: December 2007

Critical Dirac operators are those which have eigenfunctions and∕or resonances for E=m. We estimate the behavior of the generalized eigenfunctions of critical Dirac operators under small perturbations of the potential. The estimates are done in the L∞-norm. We show that for small k, the generalized eigenfunctions are in leading order multiples of the respective eigenfunctions and∕or resonances. We also estimate the k-derivatives which are important for estimating decay. The method also applies for other differential operators (for example, Schrödinger operators).
Nanopatterning by dual-ion-beam sputtering
Authors: Joe M. , Choi C. , Kahng B. , Kim J.-S.
Published: December 2007

We studied the development of ordered nanopatterns during dual-ion-beam sputtering (DIBS) of Au(001) in which two ion beams that cross perpendicular to each other at their azimuth are incident on the surface at a grazing angle. In the erosion (diffusion) regime, a square-symmetric two-dimensional (2D) pattern of nanodots (holes) is formed. The 2D pattern is achieved only when the two beams are balanced in the erosion regime. In the diffusion regime, no such condition is required. The observations cannot be explained by the Kuramoto-Sivashinsky (KS) equation derived from Sigmund theory with two ion beams.
High temperature ferromagnetism in Mn-doped SnO2 nanocrystalline thin films
Authors: Gopinadhan K. , Kashyap Subhash C. , Pandya Dinesh K. , Chaudhary Sujeet
Published: December 2007

It has been possible to induce room temperature ferromagnetism, exhibiting high transition temperature, in tin oxide thin films by introducing manganese in a SnO2 lattice. The observed temperature dependence of the magnetization predicts a Curie temperature exceeding 550 K. A maximum saturation magnetic moment of 0.18±0.04 μB per Mn ion has been estimated for spray pyrolized Sn1−xMnxO2−δ thin films, with x=0.10. For Mn concentration (x) higher than 0.10, the films show linear behavior. The magnetization-versus-field studies indicate that the origin of ferromagnetism lies neither in ferromagnetic metal clusters nor in the presence of metastable phases. The structure factor calculations reveal that Mn has been incorporated in the SnO2 lattice. Also, the electron transport investigation indicates that there is a change of Mn occupancy from substitutional to interstitial sites of the SnO2 lattice when the Mn concentration exceeds 7.5 at. %. These films do not exhibit anomalous Hall effects at room temperature. The optical absorption study indicates that the Sn1−xMnxO2−δ system behaves like a random alloy. The generation of additional free electrons by F doping in Sn0.90Mn0.10O2−δ thin films does not cause any increase in the magnetic moment per Mn ion, suggesting no significant role of electrons in bringing about the magnetic ordering.
Design and simulation of deep-well GaAs-based quantum cascade lasers for 6.7μm room-temperature operation
Authors: Gao X. , D’Souza M. , Botez D. , Knezevic I.
Published: December 2007

We present the design and simulation of a GaAs-based quantum cascade laser (QCL) emitting at 6.7 μm, the shortest room-temperature lasing wavelength projected to date for GaAs-based QCLs. This is achieved by introducing compressive strain only in the active quantum wells, where the optical transition occurs. A Monte Carlo simulation including both Γ- and X-valley transport demonstrates that the proposed QCL achieves room-temperature lasing at a threshold-current density of 14 kA/cm2, lower than that of the conventional 9.4 μm QCL (16.7 kA/cm2). Furthermore, the electron temperature at 300 K lattice temperature is similar to that of the 9.4 μm device.
The reconstruction of the effective interaction potential on the base of pair correlation function measurements in dusty plasma
Authors: Apfelbaum E. M.
Published: December 2007

The effective interaction potentials between dusty particles were reconstructed by the Shommers technique (W. Schommers, Phys. Rev. A 28, 3599 (1983)) on the basis of recent measurements in dusty plasma. The potentials have both repulsive and attractive parts. The form of the potentials varies with density and also depends on the dimensions of the dusty particle structure. The Yukawa potential can fit the repulsive part of the potentials at relatively high densities.
Silicon nanowire solar cells
Authors: Tsakalakos L. , Balch J. , Fronheiser J. , Korevaar B. A. , Sulima O. , Rand J.
Published: December 2007

Silicon nanowire-based solar cells on metal foil are described. The key benefits of such devices are discussed, followed by optical reflectance, current-voltage, and external quantum efficiency data for a cell design employing a thin amorphous silicon layer deposited on the nanowire array to form the p-n junction. A promising current density of ∼1.6mA∕cm2 for 1.8cm2 cells was obtained, and a broad external quantum efficiency was measured with a maximum value of ∼12% at 690nm. The optical reflectance of the silicon nanowire solar cells is reduced by one to two orders of magnitude compared to planar cells.
Highly tunable SrTiO3∕DyScO3 heterostructures for applications in the terahertz range
Authors: Kužel P. , Kadlec F. , Petzelt J. , Schubert J. , Panaitov G.
Published: December 2007

Several types of multilayer structures based on SrTiO3 and DyScO3 thin films were prepared by laser ablation. The dielectric properties of these samples without and under applied static or low-frequency electric field at room temperature were determined in the terahertz spectral range by time-domain terahertz spectroscopy. We demonstrate up to 65% variation of the permittivity of SrTiO3 films and up to 33% modulation of the power transmission of terahertz waves at 500GHz and 100V (67kV∕cm) bias.
Ultrafast switching by controlling Rabi splitting
Authors: Manzacca Gianluca , Cincotti Gabriella , Hingerl Kurt
Published: December 2007

We analyze the behavior of a quantum dot embedded in an add-drop filter for optical signal processing applications. The joint effects of dipole induced transparency and electromagnetic induced transparency, which shift the transparency peak induced by a dipole in an add-drop filter due to vacuum Rabi splitting, have been considered. The mathematical model and some different conditions for tuning the transparency peak are derived for application to all optical switching and wavelength tunable devices.
Single molecule diffusion analysis on cellular nanotubules: Implications on plasma membrane structure below the diffraction limit
Authors: Wieser Stefan , Schütz Gerhard J. , Cooper Michael E. , Stockinger Hannes
Published: December 2007

Cells are frequently interconnected by tunneling nanotubules, recently discovered cylindrical structures which facilitate material exchange. We employed here single molecule fluorescence microscopy to study the diffusion of the glycosylphosphatidylinositol-protein CD59 in the plasma membrane of tunneling nanotubules in living cells at subwavelength resolution. Our study provides the nanotubule radius in vivo, yielding a surprisingly narrow size distribution (7nm standard deviation) around a mean value of 65nm. Moreover, by separating longitudinal and transverse mobilities, we find isotropic diffusion behavior.
Effect of anodic TiO2 powder as additive on electron transport properties in nanocrystalline TiO2 dye-sensitized solar cells
Authors: Lin Chin-Jung , Yu Wen-Yueh , Chien Shu-Hua
Published: December 2007

Highly crystalline anodic TiO2 (AO-TiO2) powder was obtained by grinding of annealed TiO2 nanotube arrays grown using anodization of Ti foil. The influence of AO-TiO2 as additive in nanocrystalline TiO2 film on electron transport properties affecting the performance of these dye-sensitized solar cell was investigated using electrochemical impedance spectroscopy and the open-circuit voltage decay technique under AM 1.5 illumination. As a result of the enhanced charge-collection and light harvesting efficiencies, an increase of above 20% in photocurrent density was observed after the addition of AO-TiO2.
Use of bentonite to control the release of copper from contaminated soils
Authors: Ling Wanting , Shen Qing , Gao Yanzheng , Gu Xiaohong , Yang Zhipeng
Published: December 2007

A decrease in release and availability of heavy metals in soil has been of worldwide interest in recent years. Bentonite is a type of expandable montmorillonite clay, and has strong sorption for heavy metals. In this work, the control of amended bentonite on the release of copper (Cu2+) from spiked soils was investigated using a batch equilibrium technique. Sorption of Cu by bentonite was pH-dependent, and could be well described using the Langmiur model. Maximum sorption capacity of the bentonite used in this study was 5.4 mg/g, which was much greater than soils reported in the literature. The extent of Cu2+ release from spiked soils was correlated with slurry concentrations, pH, and soil ageing process. In all cases, the amendment of bentonite was observed to effectively decrease the release of Cu2+ from soils. The apparent aqueous concentrations of Cu2+ released from soils devoid of bentonite treatment were 113–1160% higher than those from the soils amended with bentonite. Moreover, the magnitude of Cu2+ release decreased with increasing amount of bentonite added to soils. The bentonite added was more effective in retaining Cu2+ in sorbents for aged contaminated soils. Such enhanced retention resulting from the presence of bentonite was observed within a wide pH range from 2.5 to 7.0. Bentonite, as one of the most abundant minerals in soils, is regarded to improve the soil overall quality. The results obtained from this work provide useful information on utilisation of bentonite to control the release of heavy metals from contaminated soils.
Global food security under climate change
Authors: Schmidhuber Josef , Tubiello Francesco N.
Published: December 2007

This article reviews the potential impacts of climate change on food security. It is found that of the four main elements of food security, i.e., availability, stability, utilization, and access, only the first is routinely addressed in simulation studies. To this end, published results indicate that the impacts of climate change are significant, however, with a wide projected range (between 5 million and 170 million additional people at risk of hunger by 2080) strongly depending on assumed socio-economic development. The likely impacts of climate change on the other important dimensions of food security are discussed qualitatively, indicating the potential for further negative impacts beyond those currently assessed with models. Finally, strengths and weaknesses of current assessment studies are discussed, suggesting improvements and proposing avenues for new analyses.
Mast cells are an essential hematopoietic component for polyp development
Authors: Gounaris Elias , Erdman Susan E. , Restaino Clifford , Gurish Michael F. , Friend Daniel S. , Gounari Fotini , Lee David M. , Zhang Guoying , Glickman Jonathan N. , Shin Kichul , Rao Varada P. , Poutahidis Theofilos , Weissleder Ralph , McNagny Kelly M. , Khazaie Khashayarsha
Published: December 2007

It is generally agreed that most colon cancers develop from adenomatous polyps, and it is this fact on which screening strategies are based. Although there is overwhelming evidence to link intrinsic genetic lesions with the formation of these preneoplastic lesions, recent data suggest that the tumor stromal environment also plays an essential role in this disease. In particular, it has been suggested that CD34+immature myeloid precursor cells are required for tumor development and invasion. Here we have used mice conditional for the stabilization of β-catenin or defective for the adenomatous polyposis coli (APC) gene to reinvestigated the identity and importance of tumor-infiltrating hematopoietic cells in polyposis. We show that, from the onset, polyps are infiltrated with proinflammatory mast cells (MC) and their precursors. Depletion of MC either pharmacologically or through the generation of chimeric mice with genetic lesions in MC development leads to a profound remission of existing polyps. Our data suggest that MC are an essential hematopoietic component for preneoplastic polyp development and are a novel target for therapeutic intervention.
Nucleomorph genome of
Hemiselmis andersenii
reveals complete intron loss and compaction as a driver of protein structure and function
Authors: Lane Christopher E. , van den Heuvel Krystal , Kozera Catherine , Curtis Bruce A. , Parsons Byron J. , Bowman Sharen , Archibald John M.
Published: December 2007

Nucleomorphs are the remnant nuclei of algal endosymbionts that took up residence inside a nonphotosynthetic eukaryotic host. The nucleomorphs of cryptophytes and chlorarachniophytes are derived from red and green algal endosymbionts, respectively, and represent a stunning example of convergent evolution: their genomes have independently been reduced and compacted to <1 megabase pairs (Mbp) in size (the smallest nuclear genomes known) and to a similar three-chromosome architecture. The molecular processes underlying genome reduction and compaction in eukaryotes are largely unknown, as is the impact of reduction/compaction on protein structure and function. Here, we present the complete 0.572-Mbp nucleomorph genome of the cryptophyte
Hemiselmis andersenii
and show that it is completely devoid of spliceosomal introns and genes for splicing RNAs—a case of complete intron loss in a nuclear genome. Comparison of
H. andersenii
proteins to those encoded in the slightly smaller (0.551-Mbp) nucleomorph genome of another cryptophyte,
Guillardia theta
, and to their homologs in the unicellular red alga
Cyanidioschyzon merolae
reveal that (
i
) cryptophyte nucleomorph genomes encode proteins that are significantly smaller than those in their free-living algal ancestors, and (
ii
) the smaller, more compact
G. theta
nucleomorph genome encodes significantly smaller proteins than that of
H. andersenii
. These results indicate that genome compaction can eliminate both coding and noncoding DNA and, consequently, drive the evolution of protein structure and function. Nucleomorph proteins have the potential to reveal the minimal functional units required for basic eukaryotic cellular processes.
Identification of genotype-correlated sensitivity to selective kinase inhibitors by using high-throughput tumor cell line profiling
Authors: McDermott Ultan , Sharma Sreenath V. , Dowell Lori , Greninger Patricia , Montagut Clara , Lamb Jennifer , Archibald Heidi , Raudales Raul , Tam Angela , Lee Diana , Rothenberg S. Michael , Supko Jeffrey G. , Sordella Raffaella , Ulkus Lindsey E. , Iafrate A. John , Maheswaran Shyamala , Njauw Ching Ni , Tsao Hensin , Drew Lisa , Hanke Jeff H. , Ma Xiao-Jun , Erlander Mark G. , Gray Nathanael S. , Haber Daniel A. , Settleman Jeffrey
Published: December 2007

Kinase inhibitors constitute an important new class of cancer drugs, whose selective efficacy is largely determined by underlying tumor cell genetics. We established a high-throughput platform to profile 500 cell lines derived from diverse epithelial cancers for sensitivity to 14 kinase inhibitors. Most inhibitors were ineffective against unselected cell lines but exhibited dramatic cell killing of small nonoverlapping subsets. Cells with exquisite sensitivity to EGFR, HER2, MET, or BRAF kinase inhibitors were marked by activating mutations or amplification of the drug target. Although most cell lines recapitulated known tumor-associated genotypes, the screen revealed low-frequency drug-sensitizing genotypes in tumor types not previously associated with drug susceptibility. Furthermore, comparing drugs thought to target the same kinase revealed striking differences, predictive of clinical efficacy. Genetically defined cancer subsets, irrespective of tissue type, predict response to kinase inhibitors, and provide an important preclinical model to guide early clinical applications of novel targeted inhibitors.
Profiling of UV-induced ATM/ATR signaling pathways
Authors: Stokes Matthew P. , Rush John , MacNeill Joan , Ren Jian Min , Sprott Kam , Nardone Julie , Yang Vicky , Beausoleil Sean A. , Gygi Steven P. , Livingstone Mark , Zhang Hui , Polakiewicz Roberto D. , Comb Michael J.
Published: December 2007

To ensure survival in the face of genomic insult, cells have evolved complex mechanisms to respond to DNA damage, termed the DNA damage checkpoint. The serine/threonine kinases ataxia telangiectasia-mutated (ATM) and ATM and Rad3-related (ATR) activate checkpoint signaling by phosphorylating substrate proteins at SQ/TQ motifs. Although some ATM/ATR substrates (Chk1, p53) have been identified, the lack of a more complete list of substrates limits current understanding of checkpoint pathways. Here, we use immunoaffinity phosphopeptide isolation coupled with mass spectrometry to identify 570 sites phosphorylated in UV-damaged cells, 498 of which are previously undescribed. Semiquantitative analysis yielded 24 known and 192 previously uncharacterized sites differentially phosphorylated upon UV damage, some of which were confirmed by SILAC, Western blotting, and immunoprecipitation/Western blotting. ATR-specific phosphorylation was investigated by using a Seckel syndrome (ATR mutant) cell line. Together, these results provide a rich resource for further deciphering ATM/ATR signaling and the pathways mediating the DNA damage response.
Skeletal muscle resists stretch by rapid binding of the second motor domain of myosin to actin
Authors: Brunello Elisabetta , Reconditi Massimo , Elangovan Ravikrishnan , Linari Marco , Sun Yin-Biao , Narayanan Theyencheri , Panine Pierre , Piazzesi Gabriella , Irving Malcolm , Lombardi Vincenzo
Published: December 2007

A shortening muscle is a machine that converts metabolic energy into mechanical work, but, when a muscle is stretched, it acts as a brake, generating a high resistive force at low metabolic cost. The braking action of muscle can be activated with remarkable speed, as when the leg extensor muscles rapidly decelerate the body at the end of a jump. Here we used time-resolved x-ray and mechanical measurements on isolated muscle cells to elucidate the molecular basis of muscle braking and its rapid control. We show that a stretch of only 5 nm between each overlapping set of myosin and actin filaments in a muscle sarcomere is sufficient to double the number of myosin motors attached to actin within a few milliseconds. Each myosin molecule has two motor domains, only one of which is attached to actin during shortening or activation at constant length. A stretch strains the attached motor domain, and we propose that combined steric and mechanical coupling between the two domains promotes attachment of the second motor domain. This mechanism allows skeletal muscle to resist external stretch without increasing the force per motor and provides an answer to the longstanding question of the functional role of the dimeric structure of muscle myosin.
Assessing the significance of chromosomal aberrations in cancer: Methodology and application to glioma
Authors: Beroukhim Rameen , Getz Gad , Nghiemphu Leia , Barretina Jordi , Hsueh Teli , Linhart David , Vivanco Igor , Lee Jeffrey C. , Huang Julie H. , Alexander Sethu , Du Jinyan , Kau Tweeny , Thomas Roman K. , Shah Kinjal , Soto Horacio , Perner Sven , Prensner John , Debiasi Ralph M. , Demichelis Francesca , Hatton Charlie , Rubin Mark A. , Garraway Levi A. , Nelson Stan F. , Liau Linda , Mischel Paul S. , Cloughesy Tim F. , Meyerson Matthew , Golub Todd A. , Lander Eric S. , Mellinghoff Ingo K. , Sellers William R.
Published: December 2007

Comprehensive knowledge of the genomic alterations that underlie cancer is a critical foundation for diagnostics, prognostics, and targeted therapeutics. Systematic efforts to analyze cancer genomes are underway, but the analysis is hampered by the lack of a statistical framework to distinguish meaningful events from random background aberrations. Here we describe a systematic method, called Genomic Identification of Significant Targets in Cancer (GISTIC), designed for analyzing chromosomal aberrations in cancer. We use it to study chromosomal aberrations in 141 gliomas and compare the results with two prior studies. Traditional methods highlight hundreds of altered regions with little concordance between studies. The new approach reveals a highly concordant picture involving ≈35 significant events, including 16–18 broad events near chromosome-arm size and 16–21 focal events. Approximately half of these events correspond to known cancer-related genes, only some of which have been previously tied to glioma. We also show that superimposed broad and focal events may have different biological consequences. Specifically, gliomas with broad amplification of chromosome 7 have properties different from those with overlapping focalEGFRamplification: the broad events act in part through effects onMETand its ligandHGFand correlate with MET dependencein vitro. Our results support the feasibility and utility of systematic characterization of the cancer genome.
Homer1a
is a core brain molecular correlate of sleep loss
Authors: Maret Stéphanie , Dorsaz Stéphane , Gurcel Laure , Pradervand Sylvain , Petit Brice , Pfister Corinne , Hagenbuchle Otto , O'Hara Bruce F. , Franken Paul , Tafti Mehdi
Published: December 2007

Sleep is regulated by a homeostatic process that determines its need and by a circadian process that determines its timing. By using sleep deprivation and transcriptome profiling in inbred mouse strains, we show that genetic background affects susceptibility to sleep loss at the transcriptional level in a tissue-dependent manner. In the brain,
Homer1a
expression best reflects the response to sleep loss. Time-course gene expression analysis suggests that 2,032 brain transcripts are under circadian control. However, only 391 remain rhythmic when mice are sleep-deprived at four time points around the clock, suggesting that most diurnal changes in gene transcription are, in fact, sleep–wake-dependent. By generating a transgenic mouse line, we show that in
Homer1
-expressing cells specifically, apart from
Homer1a
, three other activity-induced genes (
Ptgs2
,
Jph3
, and
Nptx2
) are overexpressed after sleep loss. All four genes play a role in recovery from glutamate-induced neuronal hyperactivity. The consistent activation of
Homer1a
suggests a role for sleep in intracellular calcium homeostasis for protecting and recovering from the neuronal activation imposed by wakefulness.
Jealous Monopolists? British Banks and Responses to the Macmillan Gap during the 1930s
Authors: Scott Peter , Newton Newton
Published: December 2007

By the end of World War I successive merger waves had produced an oligopolistic, tightly cartelized, English banking system, which was widely viewed as having restricted lending to small-medium-sized firms—the famous 'Macmillan Gap' in industrial finance. We explore the reasons behind the failure of market entry to bridge this gap. The clearing banks are shown to have acted as 'jealous monopolists', obstructing the activities of the Credit for Industry Ltd (CFI), the only significant firm established to breach the gap (rather than narrow its upper limit). By poaching many clients it had vetted and approved, the banks blocked CFI's growth, deterring further market entry, and thus, preserving their monopoly position.
Neonatal outcome following pregnancy exposure to antidepressants: a prospective controlled cohort study
Authors: Maschi S , Clavenna A , Campi R , Schiavetti B , Bernat M , Bonati M
Published: December 2007

Objective  To determine the incidence of early adverse effects associated with antidepressant drug use during pregnancy.

Design  Prospective, controlled cohort study.

Setting  A Drug and Health Information Centre in Milan, Italy.

Population  A total of 200 neonates exposed to antidepressants in utero and 1200 controls.

Methods  Women who took antidepressants during pregnancy and delivered liveborn children between 1995 and 2003 were selected. Each case was matched for maternal age and gravidity to six randomly selected controls (not exposed to teratogenic drugs or drugs known to cause neonatal side effects). Odds ratio was estimated for attributable risks.

Main outcome measures  Neonatal adverse events and Special Care Unit admission rate, assessed through an interview with the mothers.

Results  Of the 200 neonates exposed to antidepressants in utero, 14 had adverse events and 3 required Special Care Unit admission. Jaundice (n = 5), agitation (n = 3) and respiratory distress (n = 2) were the most common symptoms. In the control group, 50 newboms had side effects and no statistically significant differences in the prevalence rate compared to the exposed group were found, even after stratification for drugs and pregnancy period of exposure. Only the prematurity rate was significantly higher in exposed compared to non‐exposed newborns (OR = 2.31; 95% CI 1.14–4.63).

Conclusions  These results do not support an association between antidepressant exposure and unsafe fetal and neonatal outcomes in newborns. However, a collaborative international multicentre epidemiological monitoring of the use of psychotropic drugs during pregnancy is needed in order to guarantee pregnant women and their children safe and effective treatments, both at brief and long time from exposure.
Is adiposity across life associated with subsequent hysterectomy risk? Findings from the 1946 British birth cohort study
Authors: Cooper R , Hardy R , Kuh D
Published: December 2007

Objective  To examine the associations between adiposity at time points from early life onwards and subsequent hysterectomy risk.

Design  Prospective birth cohort study.

Setting  England, Scotland and Wales.

Population  Women from the Medical Research Council National Survey of Health and Development study, with complete data on hysterectomy status (n= 1790).

Methods  Survival analysis methods were used to examine the associations between body mass index at time points across life and subsequent hysterectomy rates.

Main outcome measure  Self‐reported hysterectomy with or without oophorectomy.

Results  From 20 years onwards, those women who were classified as underweight had lower hysterectomy rates, and from 36 years onwards, those women who were overweight had higher hysterectomy rates than those who were normal weight. Women who were obese in adolescence and early adulthood had lower rates of hysterectomy than those who were normal weight, although numbers categorised as obese at these ages were small. Women who were obese in later adulthood had higher subsequent rates of hysterectomy. Greater increases in weight between ages 36 and 53 years were associated with higher rates of hysterectomy in later adulthood. These results were not explained by parity, age at menarche or socio‐economic position.

Conclusions  These results suggest that variation in hysterectomy rates may be partially explained by variation in adiposity, and so with the recent changes in levels of overweight and obesity in populations, there may be increasing demand for gynaecological treatments in the future.
Review article: Developmental mismatch: consequences for later cardiorespiratory health
Authors: Pike KC , Hanson MA , Godfrey KM
Published: December 2007

Clinical and epidemiological studies have established that people who were small at birth and had poor infant growth have an increased risk of adult cardiovascular and respiratory disease, particularly if their restricted early growth is followed by accelerated childhood weight gain. This relationship extends across the normal range of infant size in a graded manner. The ‘mismatch hypothesis’ proposes that ill health in later life originates through developmental plastic responses made by the fetus and infant; these responses increase the risk of adult disease if the environment in childhood and adult life differs from that predicted during early development.
Muscle [phosphocreatine] dynamics following the onset of exercise in humans: the influence of baseline work‐rate
Authors: Jones Andrew M. , Wilkerson Daryl P. , Fulford Jonathan
Published: December 2007

The kinetics of pulmonary O2 uptake is known to be substantially slower when exercise is initiated from a baseline of lower‐intensity exercise rather than from rest. However, it is not known whether putative intracellular regulators of mitochondrial respiration (and in particular the phosphocreatine concentration, [PCr]) show similar non‐linearities in their response dynamics. The purpose of this study was therefore to investigate the influence of baseline metabolic rate on muscle [PCr] kinetics (as assessed using 31P‐magnetic resonance spectroscopy) following the onset of exercise. Seven male subjects completed ‘step’ tests to heavy‐intensity exercise (80% of peak work‐rate) from a resting baseline and also from a baseline of moderate‐intensity exercise (40% of peak work‐rate) using a single‐leg knee‐extensor ergometer situated inside the bore of a 1.5 T super‐conducting magnet. The time constant describing the kinetics of the initial exponential‐like fall in [PCr] was significantly different between rest‐to‐moderate (25 ± 14 s), rest‐to‐heavy (48 ± 11 s) and moderate‐to‐heavy exercise (95 ± 40 s) (P < 0.05 for all comparisons). A delayed‐onset ‘slow component’ in the [PCr] response was observed in all subjects during rest‐to‐heavy exercise, but was attenuated in the moderate‐to‐heavy exercise condition. These data indicate that muscle [PCr] kinetics does not conform to ‘linear, first‐order’ behaviour during dynamic exercise, and thus have implications for understanding the regulation of muscle oxidative metabolism.
The kinetics of competitive antagonism of nicotinic acetylcholine receptors at physiological temperature
Authors: Demazumder Deeptankar , Dilger James P.
Published: December 2007

Detailed information about the ligand‐binding site of nicotinic acetylcholine receptors has emerged from structural and mutagenesis experiments. However, these approaches provide only static images of ligand–receptor interactions. Kinetic measurements of changes in protein function are needed to develop a more dynamic picture. Previously, we measured association and dissociation rate constants for competitive inhibition of current through embryonic muscle acetylcholine receptor channels at 25°C. Little is known about competitive antagonism at physiological temperatures. Here, we performed measurements at 37°C and used thermodynamics to estimate the energetics of antagonism. We used rapid solution exchange protocols to determine equilibrium and kinetics of inhibition of acetylcholine‐activated currents in outside‐out patches by (+)‐tubocurarine, pancuronium and cisatracurium. Kinetic rates as high as 600 s−1were resolved by this technique. Binding was primarily enthalpy driven. The 12°C increase in temperature decreased equilibrium antagonist binding by 1.7‐ to 1.9‐fold. In contrast, association and dissociation rate constants increased 1.9‐ to 6.0‐fold. Activation energies for dissociation were 90 ± 6, 106 ± 8 and 116 ± 10 kJ mol−1for cisatracurium, (+)‐tubocurarine and pancuronium, respectively. The corresponding apparent activation energies for association were 38 ± 6, 85 ± 6 and 107 ± 13 kJ mol−1. The higher activation energy for association of (+)‐tubocurarine and pancuronium compared with cisatracurium is notable. This may arise from either a more superficial binding site for the large antagonist cisatracurium compared to the other ligands, or from a change in receptor conformation upon binding of (+)‐tubocurarine and pancuronium but not cisatracurium. Differences in ligand desolvation and ligand conformation are not likely to be important.
Developmental maturation of synaptic and extrasynaptic GABAAreceptors in mouse thalamic ventrobasal neurones
Authors: Peden Dianne R. , Petitjean Caroline M. , Herd Murray B. , Durakoglugil Murat S. , Rosahl Thomas W. , Wafford Keith , Homanics Gregg E. , Belelli Delia , Fritschy Jean‐Marc , Lambert Jeremy J.
Published: December 2007

Thalamic ventrobasal (VB) relay neurones express multiple GABAAreceptor subtypes mediating phasic and tonic inhibition. During postnatal development, marked changes in subunit expression occur, presumably reflecting changes in functional properties of neuronal networks. The aims of this study were to characterize the properties of synaptic and extrasynaptic GABAAreceptors of developing VB neurones and investigate the role of the α1subunit during maturation of GABA‐ergic transmission, using electrophysiology and immunohistochemistry in wild type (WT) and α10/0mice and mice engineered to express diazepam‐insensitive receptors (α1H101R, α2H101R). In immature brain, rapid (P8/9–P10/11) developmental change to mIPSC kinetics and increased expression of extrasynaptic receptors (P8–27) formed by the α4and δ subunit occurred independently of the α1subunit. Subsequently (≥ P15), synaptic α2subunit/gephyrin clusters of WT VB neurones were replaced by those containing the α1subunit. Surprisingly, in α10/0VB neurones the frequency of mIPSCs decreased between P12 and P27, because the α2subunit also disappeared from these cells. The loss of synaptic GABAAreceptors led to a delayed disruption of gephyrin clusters. Despite these alterations, GABA‐ergic terminals were preserved, perhaps maintaining tonic inhibition. These results demonstrate that maturation of synaptic and extrasynaptic GABAAreceptors in VB follows a developmental programme independent of the α1subunit. Changes to synaptic GABAAreceptor function and the increased expression of extrasynaptic GABAAreceptors represent two distinct mechanisms for fine‐tuning GABA‐ergic control of thalamic relay neurone activity during development.
KIR channels function as electrical amplifiers in rat vascular smooth muscle
Authors: Smith Pamela D. , Brett Suzanne E. , Luykenaar Kevin D. , Sandow Shaun L. , Marrelli Sean P. , Vigmond Edward J. , Welsh Donald G.
Published: December 2007

Strong inward rectifying K+ (KIR) channels have been observed in vascular smooth muscle and can display negative slope conductance. In principle, this biophysical characteristic could enable KIR channels to ‘amplify’ responses initiated by other K+ conductances. To test this, we have characterized the diversity of smooth muscle KIR properties in resistance arteries, confirmed the presence of negative slope conductance and then determined whether KIR inhibition alters the responsiveness of middle cerebral, coronary septal and third‐order mesenteric arteries to K+ channel activators. Our initial characterization revealed that smooth muscle KIR channels were highly expressed in cerebral and coronary, but not mesenteric arteries. These channels comprised KIR2.1 and 2.2 subunits and electrophysiological recordings demonstrated that they display negative slope conductance. Computational modelling predicted that a KIR‐like current could amplify the hyperpolarization and dilatation initiated by a vascular K+ conductance. This prediction was consistent with experimental observations which showed that 30 μm Ba2+ attenuated the ability of K+ channel activators to dilate cerebral and coronary arteries. This attenuation was absent in mesenteric arteries where smooth muscle KIR channels were poorly expressed. In summary, smooth muscle KIR expression varies among resistance arteries and when channel are expressed, their negative slope conductance amplifies responses initiated by smooth muscle and endothelial K+ conductances. These findings highlight the fact that the subtle biophysical properties of KIR have a substantive, albeit indirect, role in enabling agonists to alter the electrical state of a multilayered artery.
An Apparatus and Protocol to Measure Shoulder Girdle Strength
Authors: Garner Brian A. , Shim Jaeho , Wilson Scott
Published: December 2007

Muscles actuating the shoulder girdle are important for stabilizing the scapula and coordinating phased kinematics of the shoulder complex. If these muscles become weak or imbalanced, joint instability and injury may result. Reliable measurement of shoulder strength is thus important for prevention, diagnosis, and rehabilitation of shoulder problems. To date, studies quantifying the strength of the shoulder girdle are limited. The purpose of this work was to design and evaluate a custom apparatus and corresponding protocol for measuring maximal, voluntary, isometric strength of the shoulder girdle during various forms of shrugging exercise. A custom apparatus was constructed as a rigid frame with a vertical post supporting a seat, seat back, and horizontal beam. The beam extends laterally on either side beyond and around the shoulders of a seated subject. A pair of arm extension members pivots on the beam about an axis aligned with the shoulder flexion-extension axis. These members can be locked in place at any angle. Between them is mounted a force-sensing grip assembly, which can be adjusted proximally or distally to accommodate varying shoulder girdle positions. Subjects grasp the grip assembly handles with extended elbows and push or pull as forcefully as possible. Nine female and ten male subjects participated in a protocol using the apparatus to measure maximum isometric force generated at three positions each for elevation, depression, protraction, and retraction of the shoulder girdle (3positions×4modes=12tests). A video motion capture system was used to measure shoulder girdle angles. The reliability of the approach was evaluated based on the repeatability of measured shoulder elevation angle, protraction angle, and total force over three days of testing. The apparatus performed well during the tests, providing a stable, rigid, yet adjustable platform for measuring shoulder girdle strength. Repeatability of force measurements was interpreted as very good to excellent, with intraclass correlation coefficient (ICC) (2,1) values ranging from 0.83 to 0.95 for all tests except one (ICC=0.79). Repeatability of angle measurements was interpreted as good to excellent. For tests measuring elevation and depression strength, the ICC of elevation angle ranged from 0.85 to 0.89. For tests measuring protraction and retraction strength, the ICC of protraction angle ranged from 0.68 to 0.88. This type of apparatus could be an effective clinical tool for measuring strength in the shoulder girdle muscles. Use of the video motion capture system is optional.