bluuebunny/crossref_metadata_2025 huggingface dataset:
Seasonal to interannual variations of the western boundary current of the subarctic North Pacific by a combination of the altimeter and tide gauge sea levels
Authors: Isoguchi Osamu , Kawamura Hiroshi
Published: April 2006

Seasonal to interannual variations of the East Kamchatka Current (EKC) and the Oyashio are examined by focusing on their barotropic response to wind forcing by a combined use of altimeter‐derived and tide gauge sea levels. An empirical orthogonal function (EOF) analysis is performed on the 9‐year altimeter sea level maps with thermosteric signals removed. A second EOF (EOF2) shows a spin‐up and spin‐down of the subarctic gyres, and its temporal variation is almost accounted for by the time‐dependent Sverdrup balance. Tide gauge sea levels at Petropavlovsk‐Kamchatsky (PK) agree with EOF2 and the Sverdrup transports in terms of not only the seasonal variation but also its year‐to‐year variability in winter when the subarctic gyre is spun up most. We also detect two types of EKC/Oyashio variations from the altimeter data: drifting velocities of sea level disturbances and geostrophic velocity anomalies. These two EKC/Oyashio temporal variations are also accounted for by the Sverdrup balance and agree with the PK sea levels and EOF2. The results imply that the PK sea levels can be a good representative of the subarctic gyre and EKC/Oyashio variations. On the basis of this relation, interannual variations during winter are discussed. The 44‐year wintertime sea levels at PK correlate with the wintertime Sverdrup transport and springtime sea surface temperature off the northeastern coast of Japan with decadal‐scale variability. This demonstrates that EKC/Oyashio is primarily explained by a barotropic response to large‐scale atmospheric forcing and fluctuates on a decadal timescale almost in phase with atmospheric changes and influences the oceanic condition east of Japan.
Determination of three‐dimensional cloud structures from high‐resolution radiance data
Authors: Zinner T. , Mayer B. , Schröder M.
Published: April 2006

The three‐dimensional structure and the inhomogeneity of clouds pose a field of challenges. The characterization of their spatial structure, their microphysical properties, and their variability is difficult. This kind of knowledge is crucial to any investigation on the impact of clouds on the radiation budget or on the reliability of cloud remote sensing data. In this article the characteristics of radiation transport in inhomogeneous clouds are studied using three‐dimensional (3‐D) simulations of radiative transport and the independent pixel approximation (IPA). The opposing effects of radiative smoothing and sharpening due to horizontal photon transport are examined in terms of the Green's function, which describes the interrelation of the radiance fields calculated using IPA and 3‐D radiative transport. On the basis of these considerations a novel method was developed for the retrieval of realistic 3‐D stratocumulus structures from high‐spatial‐resolution radiance fields observed by a compact airborne spectrographic imager (CASI, 15 m resolution). An initial distribution of liquid water content and effective droplet size retrieved using the IPA assumption and an adiabatic microphysical model is iteratively adjusted with the objective of matching the observation by the 3‐D forward radiative transfer simulation for the derived cloud. For the iterative adjustment an approximate Green's function is utilized to remove 3‐D effects from the observation. The performance of the method is characterized by application to a known cloud structure and by comparison of the derived cloud properties to in situ data from various field campaigns. The method provides the ideal basis for our studies on the remote sensing of inhomogeneous clouds.
Biases in total precipitable water vapor climatologies from Atmospheric Infrared Sounder and Advanced Microwave Scanning Radiometer
Authors: Fetzer Eric J. , Lambrigtsen Bjorn H. , Eldering Annmarie , Aumann Hartmut H. , Chahine Moustafa T.
Published: April 2006

We examine differences in total precipitable water vapor (PWV) from the Atmospheric Infrared Sounder (AIRS) and the Advanced Microwave Scanning Radiometer (AMSR‐E) experiments sharing the Aqua spacecraft platform. Both systems provide estimates of PWV over water surfaces. We compare AIRS and AMSR‐E PWV to constrain AIRS retrieval uncertainties as functions of AIRS retrieved infrared cloud fraction. PWV differences between the two instruments vary only weakly with infrared cloud fraction up to about 70%. Maps of AIRS‐AMSR‐E PWV differences vary with location and season. Observational biases, when both instruments observe identical scenes, are generally less than 5%. Exceptions are in cold air outbreaks where AIRS is biased moist by 10–20% or 10–60% (depending on retrieval processing) and at high latitudes in winter where AIRS is dry by 5–10%. Sampling biases, from different sampling characteristics of AIRS and AMSR‐E, vary in sign and magnitude. AIRS sampling is dry by up to 30% in most high‐latitude regions but moist by 5–15% in subtropical stratus cloud belts. Over the northwest Pacific, AIRS samples conditions more moist than AMSR‐E by a much as 60%. We hypothesize that both wet and dry sampling biases are due to the effects of clouds on the AIRS retrieval methodology. The sign and magnitude of these biases depend upon the types of cloud present and on the relationship between clouds and PWV. These results for PWV imply that climatologies of height‐resolved water vapor from AIRS must take into consideration local meteorological processes affecting AIRS sampling.
A study of P‐band synthetic aperture radar applicability and performance for Mars exploration: Imaging subsurface geology and detecting shallow moisture
Authors: Paillou Philippe , Lasne Yannick , Heggy Essam , Malézieux Jean‐Marie , Ruffié Gilles
Published: April 2006

Over the past decade, orbital images of the Martian surface revealed key evidence about the history of the planet environment (craters, faults, paleo‐lakes, and rivers), partially hidden under a widespread layer of aeolian deposits. Furthermore, several recent observations and studies support the hypothesis that water could be found in the shallow subsurface of Mars. Low‐frequency synthetic aperture radar (SAR) has demonstrated its subsurface imaging capabilities on Earth, especially in arid regions. While SAR potentials for Mars exploration have already been widely discussed, we present here results of a theoretical and parametric study, based on the experience we gained from terrestrial surveys on Mars analog test sites, which evaluates the capabilities of a P‐band (430 MHz) SAR for Mars exploration for both shallow subsurface geology mapping and moisture detection. We suggest that a P‐band polarimetric SAR can probe the first meters of the Martian subsurface to reveal the dust‐covered geology and to monitor moisture changes over large scales.
Topographic constraints on impact crater morphology on Venus from high‐resolution stereo synthetic aperture radar digital elevation models
Authors: Cochrane Christopher G. , Ghail Richard C.
Published: April 2006

High‐resolution digital elevation models (DEMs) derived from Magellan Left‐Left Stereo synthetic aperture radar data of Venus for a set of impact craters ranging in rim diameter from 5 to 300 km exhibit depths broadly as expected from theory but with significant departures for both large and small craters. In craters larger than 38 km diameter, rim‐floor depth becomes independent of diameter with a mean of about 900 m. Most craters smaller than 18 km diameter are also found to be unexpectedly shallow. We discuss the accuracy and principal sources of error in our DEMs and conclude that this shallowness is real. This shallowness of small craters shows that midsize bolides (200–1000 m diameter) fragment in Venus' atmosphere and disperse over an area 10 to 20 times the original bolide diameter. We identify these craters as a new class of impact feature, the Compound Crater, which may correspond to the Knobby Base morphological class defined by others.
North‐south roughness anisotropy on Venus from the Magellan Radar Altimeter: Correlation with geology
Authors: Bondarenko N. V. , Kreslavsky M. A. , Head J. W.
Published: April 2006

Analysis of the Doppler spectrum of Magellan Radar Altimeter echoes has revealed the spatially coherent deflection of the echo center from the nadir point (Tyler et al., 1992). We present and analyze a global map of the Doppler centroid of the radar altimeter echo, which, for the plains of Venus, characterizes the degree of anisotropy of the surface roughness in the north–south direction at scales from decimeters to kilometers. We found a global hemispherical trend of roughness anisotropy: on average, equator‐facing slopes are steeper than pole‐facing slopes. We searched globally for correlations between contrasts in roughness anisotropy and surface geology. We found that sharp contrasts in anisotropy often coincide with boundaries of geological units, although not consistently. We found a number of examples where radar‐bright (rough) lava flows have higher asymmetry than their surroundings. Diffuse radar‐dark crater‐related parabolic features and halos often have a symmetric roughness signature, while typical regional plains away from these diffuse features often have an anisotropic roughness. There is not, however, any direct and uniform correlation between the roughness anisotropy signature and geomorphologic terrain type or appearance in the radar images. We believe that asymmetric topography of deposits of windblown material, e.g., microdunes or small‐scale wind streaks in the wind shadow of obstacles, is the main contributor to the observed roughness anisotropy.
Topography, relief, and TRMM‐derived rainfall variations along the Himalaya
Authors: Bookhagen Bodo , Burbank Douglas W.
Published: April 2006

Along the southern Himalayan topographic front, the Indian summer monsoon modulates erosive processes and rates. To investigate the influence of topography and relief on rainfall generation and resultant erosion, we processed satellite rainfall amounts for the last 8 years (1998–2005) from the Tropical Rainfall Measurement Mission (TRMM). Based upon a spatial resolution of ∼5 × 5 km for the Himalaya, we identify (1) the spatial distribution of rainfall and (2) the large‐scale relationships between topography, relief, and rainfall locations. Our results show two distinct rainfall maxima along strike in the Himalaya. The first, outer rainfall peak occurs along the southern margin of the Lesser Himalaya within a narrow band of mean elevation (0.9 ± 0.4 km) and mean relief (1.2 ± 0.2 km). The second, discontinuous, inner band typically occurs along the southern flank of the Greater Himalaya (elevation and relief: both 2.1 ± 0.3 km).
Histone modification patterns associated with the human X chromosome
Authors: Brinkman Arie B , Roelofsen Thijs , Pennings Sebastiaan W C , Martens Joost H A , Jenuwein Thomas , Stunnenberg Hendrik G
Published: April 2006

X inactivation is associated with chromosome‐wide establishment of inactive chromatin. Although this is classically regarded as facultative heterochromatin that is uniform in nature, the exact distribution of associated epigenetic marks is not well defined. Here we have analysed histone modifications in human somatic cells within two selected regions of the X chromosome. Intergenic, coding and promoter regions are segregated into differentially marked chromatin. H3K27me3 is most prominent in intergenic and silenced coding regions, but is associated with some active coding regions as well. Histone H3/H4 acetylation and H3K4me3 are locally enriched at promoter regions but do not necessarily mark continuing transcription. Remarkably, H3K9me3 is predominant in coding regions of active genes, a phenomenon that is not restricted to the X chromosome. These results argue against the exclusiveness of individual marks to heterochromatin or euchromatin, but rather suggest that composite patterns of interdependent or mutually exclusive modifications together signal the gene expression status.
Cellular cholesterol controls TRPC3 function: evidence from a novel dominant-negative knockdown strategy
Authors: Graziani Annarita , Rosker Christian , Kohlwein Sepp D. , Zhu Michael X. , Romanin Christoph , Sattler Wolfgang , Groschner Klaus , Poteser Michael
Published: April 2006

TRPC3 (canonical transient receptor potential protein 3) has been suggested to be a component of cation channel complexes that are targeted to cholesterol-rich lipid membrane microdomains. In the present study, we investigated the potential role of membrane cholesterol as a regulator of cellular TRPC3 conductances. Functional experiments demonstrated that cholesterol loading activates a non-selective cation conductance and a Ca2+ entry pathway in TRPC3-overexpressing cells but not in wild-type HEK-293 (human embryonic kidney 293) cells. The cholesterol-induced membrane conductance exhibited a current-to-voltage relationship similar to that observed upon PLC (phospholipase C)-dependent activation of TRPC3 channels. Nonetheless, the cholesterol-activated conductance lacked negative modulation by extracellular Ca2+, a typical feature of agonist-activated TRPC3 currents. Involvement of TRPC3 in the cholesterol-dependent membrane conductance was further corroborated by a novel dominant-negative strategy for selective blockade of TRPC3 channel activity. Expression of a TRPC3 mutant, which contained a haemagglutinin epitope tag in the second extracellular loop, conferred antibody sensitivity to both the classical PLC-activated as well as the cholesterol-activated conductance in TRPC3-expressing cells. Moreover, cholesterol loading as well as PLC stimulation was found to increase surface expression of TRPC3. Promotion of TRPC3 membrane expression by cholesterol was persistent over 30 min, while PLC-mediated enhancement of plasma membrane expression of TRPC3 was transient in nature. We suggest the cholesterol content of the plasma membrane as a determinant of cellular TRPC3 activity and provide evidence for cholesterol dependence of TRPC3 surface expression.
Identification of mouse orthologue of endogenous secretory receptor for advanced glycation end-products: structure, function and expression
Authors: Harashima Ai , Yamamoto Yasuhiko , Cheng Chunmei , Tsuneyama Koichi , Myint Khin Mar , Takeuchi Akihiko , Yoshimura Kazunobu , Li Hui , Watanabe Takuo , Takasawa Shin , Okamoto Hiroshi , Yonekura Hideto , Yamamoto Hiroshi
Published: April 2006

The cell-surface RAGE [receptor for AGE (advanced glycation end-products)] is associated with the development of diabetic vascular complications, neurodegenerative disorders and inflammation. Recently, we isolated a human RAGE splice variant, which can work as a decoy receptor for RAGE ligands, and named it esRAGE (endogenous secretory RAGE). In the present study, we have isolated the murine equivalent of esRAGE from brain polysomal poly(A)+ (polyadenylated) RNA by RT (reverse transcription)–PCR cloning. The mRNA was generated by alternative splicing, and it encoded a 334-amino-acid protein with a signal sequence, but lacking the transmembrane domain. A transfection experiment revealed that the mRNA was actually translated as deduced to yield the secretory protein working as a decoy in AGE-induced NF-κB (nuclear factor κB) activation. RT–PCR and immunoblotting detected esRAGE mRNA and protein in the brain, lung, kidney and small intestine of wild-type mice, but not of RAGE-null mice. The esRAGE expression was increased in the kidney of diabetic wild-type mice. The present study has thus provided an animal orthologue of esRAGE for clarification of its roles in health and disease.
Characterization of yeast pyruvate kinase 1 as a protein kinase A substrate, and specificity of the phosphorylation site sequence in the whole protein
Authors: Portela Paula , Moreno Silvia , Rossi Silvia
Published: April 2006

Pyk1 (pyruvate kinase 1) from Saccharomyces cerevisiae was characterized as a substrate for PKA (protein kinase A) from bovine heart and yeast. By designing Pyk1 synthetic peptides containing potential PKA sequence targets (Ser22, Thr94 and Thr478) we determined that the peptide S22 was a substrate for PKA in vitro, with a Ksp* (specificity constant) 10-fold and 3-fold higher than Kemptide for bovine heart and yeast PKA respectively. In vitro phosphorylation of the Pyk1 S22A mutant protein was decreased by as much as 90% when compared with wild-type Pyk1 and the Pyk1 T94A mutant. The Ksp* values for Pyk1 and Pyk1 T94A were the same, indicating that both proteins are phosphorylated at the same site by PKA. Two-dimensional PAGE of Pyk1 and Pyk1 S22A indicates that in vivo the S22A mutation prevented the formation of one of the Pyk1 isoforms. We conclude that in yeast the major PKA phosphorylation site of Pyk1 is Ser22.

Phosphorylation of Ser22 leads to a Pyk1 enzyme that is more active in the absence of FBP (fructose 1,6-bisphosphate). The specificity of yeast and mammalian PKA towards the S22 peptide and towards whole Pyk1 protein was measured and compared. The Ksp* for the S22 peptide is higher than that for Pyk1, indicating that the peptide modelled on Pyk1 is a much better substrate than Pyk1, regardless of which tissue was used as the source of PKA. However, the Km of Pyk1 protein is lower than that of the better substrate, the S22 peptide, indicating that ground-state substrate binding is not the major determinant of substrate specificity for PKA.
Friction and tribochemical reactions occurring at shearing interfaces of nanothin silver films on various substrates
Authors: Akbulut Mustafa , Godfrey Alig Anna R. , Israelachvili Jacob
Published: April 2006

The tribological and tribochemical properties of 5–10nm thick Ag films sliding on various metal and inorganic substrates were measured using a surface forces apparatus coupled with ex situ x-ray photoelectron spectroscopy. We observed enhanced chemical reactivity in the sheared regions compared to the unsheared regions, which we attribute to significant frictional heating in agreement with two recent simulations. It is also found that the initial topography (roughness) of the films plays a significant role in determining the friction, wear, and tribochemical reactions. The larger the surface roughness, the larger are the friction coefficients. Initially smooth surfaces, forming large continuous junctions, create large wear debris particles; whereas initially rough surfaces, forming many small junctions, create many small particles. Even though initially smooth surfaces are chemically less reactive than initially rough surfaces, they are tribochemically more reactive, forming two to three times more oxides of silver during shearing than under static conditions and organometals of silver that under normal (static) conditions do not form. The chemical reactions observed cannot be explained without including the tribological processes, such as the local stresses, temperature rises, and type of wear produced by the shearing surfaces.
Optimized parallel tempering simulations of proteins
Authors: Trebst Simon , Troyer Matthias , Hansmann Ulrich H. E.
Published: April 2006

We apply a recently developed adaptive algorithm that systematically improves the efficiency of parallel tempering or replica exchange methods in the numerical simulation of small proteins. Feedback iterations allow us to identify an optimal set of temperatures/replicas which are found to concentrate at the bottlenecks of the simulations. A measure of convergence for the equilibration of the parallel tempering algorithm is discussed. We test our algorithm by simulating the 36-residue villin headpiece subdomain HP-36 where we find a lowest-energy configuration with a root-mean-square deviation of less than 4Å to the experimentally determined structure.
Ab initio study of structural and electronic properties of SrTiO3 (001) oxygen-vacancy surfaces
Authors: Cai Meng-Qiu , Zhang Yong-Jun , Yang Guo-Wei , Yin Zhen , Zhang Ming-Sheng , Hu Wang-Yu , Wang Yan-Guo
Published: April 2006

First-principles calculations are employed to study the surface relaxation and electronic structure of the fully relaxed SrTiO3 (001) oxygen-vacancy surfaces with both Sr and Ti terminations. In contrast to the perfect surface, the larger surface rumples and smaller interlayer distances have been found. Some in-gap Ti 3d states at about −1.13eV below the Fermi level were observed in the Ti-terminated surface caused by oxygen vacancies. For the Sr-terminated oxygen-vacancy surface, some in-gap Ti 3d states move into the bulk midgap region to become partially occupied. These theoretical results are in agreement with the experimental data.
Light emission from silicon-rich nitride nanostructures
Authors: Dal Negro L. , Yi J. H. , Kimerling L. C. , Hamel S. , Williamson A. , Galli G.
Published: April 2006

Light-emitting Si-rich silicon nitride (SRN) films were fabricated by plasma enhanced chemical vapor deposition followed by low temperature (500–900°C) annealing. The optical properties of SRN films were studied by micro-Raman and photoluminescence spectroscopy and indicate the presence of small Si clusters characterized by broad near-infrared emission, large absorption/emission Stokes shift, and nanosecond recombination. Our results are supported by first-principles simulations indicating that N atoms bonded to the surface of nanometer Si clusters play a crucial role in the emission mechanism of SRN films. Light emission from SRN systems can provide alternative routes towards the fabrication of optically active Si devices.
Current-to-current converter from a dc polarized generalized impedance converter circuit with input reference current
Authors: Ramírez Muñoz Diego , Sánchez Moreno J. , Casans Berga Silvia , Reig Escrivà Càndid , Navarro Antón Edith
Published: April 2006

An enhanced dc generalized impedance converter (GIC) is presented. The circuit is driven by a constant current input source. Connecting a load resistance at the output port the GIC circuit works as a current-to-current converter and is capable to drive at a constant current source a grounded resistance sensor series loop. The experimental results are shown with a temperature and pressure sensors loop.
Noncontact surface tension and viscosity measurements of molten oxides with a pressurized hybrid electrostatic-aerodynamic levitator
Authors: Ishikawa Takehiko , Yu Jianding , Paradis Paul-François
Published: April 2006

In order to measure the surface tension and the viscosity of molten oxides, the oscillation drop technique has been applied on a pressurized hybrid electrostatic-aerodynamic levitator. To suppress the electrical discharge between the top and bottom electrodes, the drop excitation method which has been used with high vacuum electrostatic levitators has been modified. As a demonstration, the surface tension and viscosity of liquid BaTiO3 were measured using this new method. Over the 1500–2000K interval, the surface tension was measured as γ(T)=349−0.03 (T−Tm) (10−3N∕m), where Tm=1893K is the melting temperature. Similarly, the viscosity was determined as η(T)=0.53exp[5.35×104∕(RT)](10−3Pas) over the same temperature interval.
Nanoscale n-channel and ambipolar organic field-effect transistors
Authors: Jung Taeho , Yoo Byungwook , Wang Liang , Dodabalapur Ananth , Jones Brooks A. , Facchetti Antonio , Wasielewski Michael R. , Marks Tobin J.
Published: April 2006

N -channel and ambipolar organic field-effect transistors (OFETs) with a few tens of nanometer channel length were fabricated and characterized. N,N′-bis(n-octyl)-dicyanoperylene-3,4:9,10-bis(dicarboximide) (PDI-8CN2) was employed as the active semiconductor and yielded a linear regime electron mobility of 2.3×10−3cm2∕Vs at 5×105V∕cm in an OFET with channel length of 15nm. An ambipolar heterostructure transistor consisting of thin layers of PDI-8CN2 and pentacene was fabricated with channel length of about 23nm. Field-effect hole and electron mobilities of 9.2×10−3 and 4.0×10−3cm2∕Vs, respectively, are obtained at 5×105V∕cm. These results represent the shortest channel length n-channel and ambipolar organic transistors that have been fabricated.
Multivortex micromixing
Authors: Sudarsan Arjun P. , Ugaz Victor M.
Published: April 2006

The ability to mix liquids in microchannel networks is fundamentally important in the design of nearly every miniaturized chemical and biochemical analysis system. Here, we show that enhanced micromixing can be achieved in topologically simple and easily fabricated planar 2D microchannels by simply introducing curvature and changes in width in a prescribed manner. This goal is accomplished by harnessing a synergistic combination of (i) Dean vortices that arise in the vertical plane of curved channels as a consequence of an interplay between inertial, centrifugal, and viscous effects, and (ii) expansion vortices that arise in the horizontal plane due to an abrupt increase in a conduit's cross-sectional area. We characterize these effects by using confocal microscopy of aqueous fluorescent dye streams and by observing binding interactions between an intercalating dye and double-stranded DNA. These mixing approaches are versatile and scalable and can be straightforwardly integrated as generic components in a variety of lab-on-a-chip systems.
GABA controls the level of quorum-sensing signal in
Agrobacterium tumefaciens
Authors: Chevrot Romain , Rosen Ran , Haudecoeur Elise , Cirou Amélie , Shelp Barry J. , Ron Eliora , Faure Denis
Published: April 2006

The concentration of GABA increases rapidly in wounded plant tissues, but the implication of this GABA pulse for plant–bacteria interactions is not known. Here we reveal that GABA stimulated the inactivation of the
N
-(3-oxooctanoyl)homoserine lactone (OC8-HSL) quorum-sensing signal (or “quormone”) by the
Agrobacterium
lactonase AttM. GABA induced the expression of the
attKLM
operon, which was correlated to a decrease in OC8-HSL concentration in
Agrobacterium tumefaciens
cultures. The
Agrobacterium
GABA transporter Bra was required for this GABA-signaling pathway. Furthermore, transgenic tobacco plants with elevated GABA levels were less sensitive to
A. tumefaciens
C58 infection than were wild-type plants. These findings indicate that plant GABA may modulate quorum sensing in
A. tumefaciens
, thereby affecting its virulence on plants. Whereas GABA is an essential cell-to-cell signal in eukaryotes, here we provide evidence of GABA acting as a signal between eukaryotes and pathogenic bacteria. The GABA signal represents a potential target for the development of a strategy to control the virulence of bacterial pathogens.
Evolutionary trace report_maker: a new type of service for comparative analysis of proteins
Authors: Mihalek I. , Reš I. , Lichtarge O.
Published: April 2006

Summary: Evolutionary trace report_maker offers a new type of service for researchers investigating the function of novel proteins. It pools, from different sources, information about protein sequence, structure and elementary annotation, and to that background superimposes inference about the evolutionary behavior of individual residues, using real-valued evolutionary trace method. As its only input it takes a Protein Data Bank identifier or UniProt accession number, and returns a human-readable document in PDF format, supplemented by the original data needed to reproduce the results quoted in the report.

Availability: Evolutionary trace reports are freely available for academic users at

Contact: {imihalek,ires,lichtarge}@bcm.tmc.edu
Genome‐Wide Profiling of Oral Squamous Cell Carcinoma by Array‐Based Comparative Genomic Hybridization
Authors: Sparano Anthony , Quesnelle Kelly M. , Kumar Madhu S. , Wang Yan , Sylvester Albert J. , Feldman Michael , Sewell Duane A. , Weinstein Gregory S. , Brose Marcia S.
Published: April 2006

Objectives: Array‐based comparative genomic hybridization (aCGH) was used to develop a genome‐wide molecular profile of oral squamous cell carcinoma (OSCC). Copy number alterations (CNAs) were identified by chromosomal region, mapped to specific genes, and compared with several previously documented CNAs associated with head and neck squamous cell carcinoma (HNSCC). The status of 512 commonly altered cancer genes was assessed and evaluated as potential correlates of tumor behavior.

Methods: Tumor tissue DNA was isolated for aCGH from 21 prospectively collected fresh–frozen OSCC specimens. aCGH was performed at 0.9‐Mb resolution to identify distinct regions of genomic alteration and their associated genes. Cancer genes commonly altered were then correlated with clinicopathologic tumor data.

Results: Genomic regions most frequently amplified (>35%) were located on 3q, 5p, 8q, 9q, and 20q, although regions most frequently deleted (>40%) involved chromosomes 3p, 8p, 13q, and 18q. Minimal regions of CNA identified, by aCGH narrowed larger, previously documented CNAs associated with HNSCC to significantly smaller regions, yielding shorter lists of candidate genes. Cancer‐related genes altered in greater than 25% OSCC samples were identified (22 amplified, 17 deleted). Several genes associated with the Fanconi anemia DNA‐damage response pathway were frequently altered, including BRCA1, BRCA2, FANCD2, and FANCG. Other cancer‐related genes linked to hereditary cancer syndromes include VHL, MLH1, XPC, and RB1.

Conclusions: Genome‐wide aCGH can be used to detect and map CNAs in OSCC tissue specimens with high resolution. These data implicate several candidate genes and gene pathways in the tumorigenesis of sporadic OSCC.
Direct Measurement of Subglottic Air Pressure While Swallowing
Authors: Gross Roxann Diez , Steinhauer Kimberly M. , Zajac David J. , Weissler Mark C.
Published: April 2006

Objective: The subglottic pressure theory for swallowing asserts that laryngeal mechanoreceptors have a role in the regulation of swallowing function. The primary purpose of this study was to determine if subglottic air pressure is generated during swallowing in a healthy, nontracheostomized person.

Methods: This pilot investigation used a prospective, repeated‐measures design in a single subject. Direct measurement of subglottic air pressure was obtained through percutaneous puncture of the cricothyroid membrane. Swallows were timed with four randomly assigned lung volumes: total lung capacity, tidal volume, functional residual capacity (FRC), and residual volume.

Results: Lung volumes above FRC generated positive subglottic pressure during the swallow, whereas lung volumes below FRC generated consistently negative subglottic pressures. The degree and polarity of the pressure was directly related to lung volume at the time of the swallow.

Conclusion: These findings illustrate that during normal swallowing, positive subglottic air pressure is likely present. Previously, subglottic air pressure during swallowing had been measured in tracheostomy patients only.
Molecular Basis of Posttransplant Squamous Cell Carcinoma: The Potential Role of Cyclosporine A in Carcinogenesis
Authors: Tiu Jeremy , Li Hongli , Rassekh Christopher , van der Sloot Paul , Kovach Rodney , Zhang Peilin
Published: April 2006

Cyclosporine (CSA) is a widely used immunosuppressive agent, predominantly for transplant patients. It is well recognized that transplant patients are prone to develop squamous carcinoma of the skin and mucosa, and this high incidence of squamous carcinoma in the transplant population cannot be explained by immunosuppression alone. We hypothesize that CSA may play a significant role in the transformation of normal epidermal squamous cells to carcinoma. CSA is a specific ligand for calcineurin, a ubiquitously expressed cellular serine/threonine phosphatase, that plays important roles in the immune system and cardiac muscles. Using global gene‐profiling methods, we studied the short‐time CSA effect on the squamous cell line (SCC‐015) using Affymetrix human gene chips (Human U133, 2.0 plus chip). Multiple groups of genes were identified to be responsive to CSA treatment, including many genes of unknown functions. We then used reverse transcriptase–polymerase chain reaction and immunoblot analyses to selectively confirm the results from the chips analyses with emphasis on the regulatory molecules important for cellular functions of apoptosis, DNA damage repair, and cellular transformation. This global gene‐profiling study indicated that CSA not only functions as an immunosuppressant on the immune system, but also activates/inhibits a wide array of genes important for cell‐cycle regulation, apoptosis, and oncogene/tumor‐suppressor activation. These functions of CSA on skin and mucosa systems at the molecular level are likely important in the pathogenesis of squamous carcinoma in transplant patients.
Squamous Cell Carcinoma of the Sinonasal Cavity Arising as a Second Primary in Individuals with Head and Neck Cancer
Authors: Wolpoe Matthew E. , Goldenberg David , Koch Wayne M.
Published: April 2006

Objectives/Hypothesis: Second primary tumors occur frequently in patients with head and neck carcinoma. This may be caused by generalized exposure to carcinogens resulting in “field cancerization” or to the individuals' generalized susceptibility to cancer. The paranasal sinuses are not commonly included in the sites considered at risk for this process. We therefore sought to assess the overall risk of contracting a primary cancer in this region after having a tumor elsewhere in the upper aerodigestive tract.

Study Design: Retrospective.

Methods: Two thousand four hundred seventy‐five patients with squamous cell carcinoma of the upper aerodigestive tract were analyzed using a tumor registry at a tertiary care institution.

Results: Five (0.2%) patients were identified as having a second primary in the sinonasal tract. The average interval between the index and second primary tumors was 28.4 (range 8–60) months. All five patients presented with symptoms typical of sinus inflammatory disease and had advanced sinus lesions at the time of diagnosis. These findings are typical of those with sinonasal carcinoma in that they present with nonspecific signs and symptoms and were diagnosed with locally advanced disease despite being in a surveillance program for their index cancer.

Conclusions: Although uncommon, the data reported here support inclusion of the sinonasal tract in these surveillance programs. This could result in earlier detection and greater opportunity for curative intervention.
SIX1 Mutation Associated With Enlargement of the Vestibular Aqueduct in a Patient With Branchio‐Oto Syndrome
Authors: Ito Taku , Noguchi Yoshihiro , Yashima Takatoshi , Kitamura Ken
Published: April 2006

Objectives: The objectives of this study were to identify SIX1 gene mutations in a patient with branchio‐oto syndrome (BO) and to clarify the relationship between SIX1 mutation and enlargement of the vestibular aqueduct (EVA).

Methods: A genetic study and retrospective chart review for a patient in whom EYA1 mutation had already been excluded was conducted. We studied a Japanese patient who had autosomal‐dominant mixed hearing loss, a unilateral ear pit and unilateral EVA, and who was previously diagnosed as having BO. We searched for SIX1 and SLC26A4 mutations using polymerase chain reaction and direct gene sequencing.

Results: The patient carried a heterozygous A→G mutation at nucleotide 386 within exon 1 of SIX1 that resulted in substitution of a cysteine for a tyrosine at codon 129 (Y129C) of the gene product. Y129C is a previously identified SIX1 mutation and was not detected in any of our 164 control chromosomes. No SLC26A4 mutations were identified.

Conclusion: Y129C mutation in SIX1 may cause EVA as well as BO.
Human Cochleae With Three Turns: An Unreported Malformation
Authors: Tian Qing , Linthicum Fred H. , Fayad Jose N.
Published: April 2006

Objective: The objective of this histologic study of archival temporal bone sections was to describe the morphology of human cochleae found with three turns, a previously unreported anomaly, found in three pairs of temporal bones.

Methods: The authors conducted histopathologic processing and measurement of basilar membrane length. Basilar membrane length was compared with that found in six normal control bones.

Results: Cochleae with three complete turns, rather than the usual two and a half turns, are described for the first time. All had longer than normal basilar membranes, with a mean length of 40.6 mm compared with a mean of 33.8 mm in the normal bones.

Conclusions: Human cochleae with three turns exist as an unreported anomaly. This is a new category of anomaly, not likely based on interruption of development.
Everolimus (RAD) Inhibits In Vivo Growth of Murine Squamous Cell Carcinoma (SCC VII)
Authors: Khariwala Samir S. , Kjaergaard Jorgen , Lorenz Robert , Van Lente Frederick , Shu Suyu , Strome Marshall
Published: April 2006

Objective: Everolimus (RAD) is an mTOR inhibitor closely related to rapamycin. A potent immunosuppressive agent, it has also shown evidence of antineoplastic properties. SCC VII is a spontaneously arising murine squamous cell carcinoma line. This study examines the effect of everolimus on SCC VII proliferation. The data may provide support for the use of everolimus in transplant recipients with a history of malignancy.

Methods: A dose efficacy study was conducted that used a murine model of intradermal tumor growth and pulmonary metastases. The development of intradermal tumors and pulmonary metastases were studied. Of 80 total mice, 40 received intradermal injection of 1 × 105 SCC VII cells and 40 received intravenous injection of 1 × 105 cells to establish pulmonary metastases. Within each group, animals were subdivided into four subgroups that received 1) 1 mg/kg everolimus twice a day, 2) 0.5 mg/kg everolimus twice a day, 3) 7.5 mg/kg cyclosporine per day, and 4) no treatment. Intradermal tumors were measured three times per week. Animals receiving an intravenous tumor injection were killed after 17 days and pulmonary metastases were quantified. Medication trough levels were measured in all treated animals.

Results: Everolimus showed statistically significant tumor inhibition at 1.0 mg/kg twice a day and 0.5 mg/kg twice a day when compared with animals treated with cyclosporine and with untreated animals (P < .0001). Tumor inhibition was evident in both models studied (intradermal tumors and pulmonary metastasis generation).

Conclusions: Everolimus provides potent tumor inhibition in animals inoculated with SCC VII cells. Inhibition of both local and distant spread of disease is evident. Although most immunosuppressives are known to potentiate neoplastic disease, this study supports the use of everolimus immunosuppression in the face of prior malignancy. This data has significant implication for laryngeal transplantation after laryngectomy.
Patient‐Controlled Comparison of Flexible Endoscopic Evaluation of Swallowing With Sensory Testing (FEESST) and Videofluoroscopy
Authors: Tabaee Abtin , Johnson Paul E. , Gartner Carolyn J. , Kalwerisky Kevin , Desloge Rosemary B. , Stewart Michael G.
Published: April 2006

Objective: The objective of this study was to compare the results of videofluoroscopy (VFS) with flexible endoscopic evaluation of swallowing with sensory testing (FEESST) in dysphagia testing.

Methods: The authors conducted a retrospective review of data collected over a 4‐year period at a tertiary care medical center. The FEESST and VFS results for patients receiving both examinations within a 2‐week period were compared with respect to swallowing function. Comparisons were categorized as full agreement, minor disagreement that would not result in a significant difference in diet recommendations, and major disagreement that would result in a significant difference in diet recommendations. Kappa with quadratic weighting was calculated to evaluate the inter‐test agreement.

Results: Fifty‐four patients met inclusion criteria and were reviewed. Forty‐one percent of patients were not eating by mouth at the time of FEESST and the mean interval between the two examinations was 5 days. Laryngeal examination revealed edema/erythema in 93%, impaired pharyngeal squeeze in 66%, decreased laryngopharyngeal sensation in 82%, and absent laryngeal adductor reflex in 30%. FEESST with all consistencies revealed pooling in 89%, penetration in 83%, and aspiration in 65% of patients. VFS revealed pooling in 65%, penetration in 67%, and aspiration in 54% of patients. Comparison of FEESST and VFS revealed full agreement in 52%, minor disagreement in 13%, and major disagreement in 35% of patients. A weighted kappa value of 0.324 signified only “fair” agreement between the two tests.

Conclusions: FEESST and VFS may not represent comparable tests of dysphagia. Further comparative studies of tests of swallowing function are required to determine the ideal approach to dysphagia testing.
Treatment with botulinum toxin of octo‐nonagerians with oesophageal achalasia: a two‐year follow‐up study
Authors: BASSOTTI G. , D'ONOFRIO V. , BATTAGLIA E. , FIORELLA S. , DUGHERA L. , IAQUINTO G. , MAZZOCCHI A. , MORELLI A. , ANNESE V.
Published: April 2006

Background

Treatment of oesophageal achalasia with intrasphincteric injections of botulinum toxin has proved to be a successful alternative treatment modality. However, little is known about its long‐term effects in very old patients.

Aim

To evaluate the effects of such treatment in octo‐nonagerians during a 2‐year follow‐up period.

Patients and methods

Thirty‐three patients with idiopathic oesophageal achalasia (range 81–94 years) entered the study. After basal evaluation and screening procedures, 100 U of botulinum toxin was injected at the lower oesophageal sphincter, and the procedure was repeated 1 month later. Data were collected at baseline and were compared after 1 and 2 years following the procedure.

Results

Seventy‐eight per cent of patients were considered responders at 1 year and 54% were considered responders at 2 years. The weight gain at the end of the follow‐up period was 2 (0–3) kg. No significant relationship was found between baseline lower oesophageal sphincter pressure and symptoms score after 1 and 2 years of follow‐up; moreover, no major complications of botulinum toxin therapy were reported.

Conclusion

Treatment of very old achalasic patients with botulinum toxin is safe, effective and yields good quality of life in a substantial proportion of these subjects.
Patients’ knowledge of adverse reactions to current medications
Authors: Cullen Garret , Kelly Emer , Murray Frank E.
Published: April 2006

Aims  Adverse drug reactions (ADRs) account for 3.2–7% of acute hospital admissions. The aim of this study was to assess prospectively knowledge of ADRs in patients admitted through the emergency department of a teaching hospital.

Methods  Three hundred and ninety‐nine patients were admitted on acute medical call during study periods in September 2002 and May 2003. One hundred gave their perception of the risk of ADRs using visual analogue scales, where 0 indicates minimum and 10 maximum risk. The medications studied were warfarin, proton pump inhibitors (PPIs), corticosteroids, nonsteroidal anti‐inflammatory drugs (NSAIDs) and aspirin. Responses are compared against a medical control group.

Results  Corticosteroids were ranked most dangerous by patients (median score, 25th–75th centiles: 5.4, 2.9–8.7). Medical staff ranked NSAIDs as highest risk (6.2, 4.0–7.5). Patients identified NSAIDs as low risk (2.1, 0.7–4.9), perceiving the risk of cardiac arrhythmias and disturbance in liver biochemistry to be equivalent to risk of upper gastrointestinal ulceration and bleeding. Risk of haemorrhage was ranked as the most common ADR for warfarin by patients (8.6, 3.3–9.5) and medical staff (8.8, 7.6–9.3).

Conclusions  Patients underrate the risk of ADRs of their medications. While there is a good level of knowledge of ADRs amongst warfarin and aspirin users, there is a clear lack of knowledge regarding the risk of upper GI bleeding in NSAID users. Increased education may reduce the incidence of ADRs but it is more likely that it will serve to meet increasing patient expectations.
Effects of the direct thrombin inhibitor dabigatran on ex vivo coagulation time in orthopaedic surgery patients: a population model analysis
Authors: Liesenfeld Karl‐Heinz , Schäfer Hans G. , Trocóniz Iñaki F. , Tillmann Christiane , Eriksson Bengt I. , Stangier Joachim
Published: April 2006

Aims

To describe the pharmacokinetic–pharmacodynamic (PK–PD) characteristics of the direct thrombin inhibitor dabigatran in hip replacement patients by assessing coagulation parameters activated partial thromboplastin time (aPTT) and ecarin clotting time (ECT), interindividual variability and factors affecting PD responses.

Methods

BISTRO I patients received oral dabigatran etexilate postsurgery for 6–10 days. Dabigatran plasma concentrations and aPTT/ECT were measured on the day of surgery, on subsequent days and at steady state. PK–PD characteristics of the dabigatran–aPTT/ECT relationships were evaluated using NONMEM V.

Results

The dabigatran concentration–aPTT relationship was described combining a linear and an Emax model. Mean baseline aPTT was 33.4 s and Emax (maximum increase in aPTT contributed by the Emax model) was 26.9 s. The dabigatran concentration needed to attain 50% of maximum effect (EC50) was 94.7 ng ml−1 and the mean slope of the linear concentration–response relationship (SLOP) was 0.0509 s ng−1 ml−1. Baseline aPTT and Emax were highest following surgery and declined with time. The dabigatran concentration–ECT relationship fitted a linear model. Mean baseline ECT was 28 s and decreased with time; 50% of the maximum effect was observed after 2.9 days. SLOP decreased from 0.38 to 0.27 s ng−1 ml−1 with a half‐life of 1.1 day, indicating greater PD effects on the day of surgery. Interindividual and residual variability was low. Covariates could not explain variability of this model.

Conclusions

aPTT and ECT prolongation were directly correlated with dabigatran concentrations. Blood coagulation prolongation was most pronounced following surgery. Data suggest that ECT provides a more precise description of the anticoagulant effect than aPTT.
CHILDREN'S HOUSING AND THEIR HEALTH AND PHYSICAL DEVELOPMENT
Authors: ESSEN JULIET , FOGELMAN KEN , HEAD JENNY
Published: April 2006

Summary The housing conditions of children in the National Child Development Study were related to their health and their height at the age of 16. Although children in crowded homes missed more school for medical reasons, the only illness they reported more often than children in better conditions was bronchitis. Those with inadequate amenities did not miss more school, although they also reported more bronchitis, as well as bilious attacks. Children in council houses were shorter than those in owner‐occupied homes, but the only difference in height related to the conditions of the home was that crowded boys were slightly shorter than those who were not crowded. There was therefore little evidence of an association between poor housing and either ill‐health or retarded growth among Britain's 16‐year‐olds in the 1970s, and this was still the case for children who had spent longer periods of their childhood in unsatisfactory housing.