bluuebunny/crossref_metadata_2025 huggingface dataset:
Xenon computed tomography shows hemodynamic change during the progression of chronic hepatitis C
Authors: Ikeda Hiroki , Suzuki Michihiro , Kobayashi Minoru , Takahashi Hideaki , Matsumoto Nobuyuki , Maeyama Shiro , Iino Shiro , Sase Shigeru , Itoh Fumio
Published: September 2010

Aim:  Xenon computed tomography (Xe‐CT) is a non‐invasive method of quantifying and visualizing tissue blood flow (TBF). Xe‐CT allows separate measurement of hepatic arterial and portal venous flow. The aim of this study was to investigate correlations between the progression of fibrosis and hemodynamic changes in chronic hepatitis C (CHC) patients using Xe‐CT.

Methods:  Separate measurements of portal venous TBF (PVTBF) and hepatic arterial TBF (HATBF) were performed using Xe‐CT, and total hepatic TBF (THTBF) was calculated as the sum of PVTBF and HATBF. A total of 50 patients with CHC underwent Xe‐CT. Liver biopsy was performed on 42 of the 50 patients, and hepatic fibrosis was classified as mild (F1), moderate (F2), severe (F3) or Child–Pugh class A cirrhosis (F4a). In addition, eight patients with Child–Pugh class B cirrhosis (F4b) were evaluated.

Results:  Significant negative correlations were identified between PVTBF and progression of stage (rs = –0.622, P < 0.0001) and between THTBF and progression of stage (rs = –0.458, P = 0.0041).

Conclusion:  Separate measurement of PVTBF and HATBF using non‐invasive Xe‐CT provided quantitative and visual information regarding hemodynamics of the entire liver in CHC patients. PVTBF decreases with the progression of fibrosis, even in CHC patients.
Protection of hepatic cells from apoptosis induced by ischemia/reperfusion injury by protein therapeutics
Authors: Nagai Shinya , Asoh Sadamitsu , Kobayashi Yasuhiro , Shidara Yujiro , Mori Takashi , Suzuki Misao , Moriyama Yukichi , Ohta Shigeo
Published: September 2010

Aim:  Apoptosis is involved in hepatic ischemia/reperfusion injury. The protein FNK, constructed from an anti‐apoptotic protein Bcl‐xL, exhibits the stronger anticell death activity. We evaluated the effect of FNK on apoptosis after hepatic ischemia and reperfusion, using FNK‐overexpressing transgenic mice and the HIV/Tat protein‐transduction‐domain (PTD) that mediates the introduction of FNK into cells when fused with FNK (PTD‐FNK).

Methods:  Mice were given hepatic ischemic insult for 90 min followed by reperfusion for 3 h. FNK overexpression was determined by immunohistochemistry and Western blot. PTD‐FNK was intraperitoneally injected into wild mice 3 h before the insult. Liver injury was determined by the caspase activation, DNA fragmentation, and hematoxylin–eosin and terminal deoxynucleotidyl transferase‐mediated dUTP‐ digoxigenin nick‐end labelling (TUNEL) stainings.

Results:  In FNK‐transgenic mice, FNK overexpression inhibited the activation of caspase 3/caspase 3‐like activity and DNA fragmentation caused by the injury. In wild mice preinjected with PTD‐FNK, PTD‐FNK significantly inhibited the caspase activation and DNA fragmentation, reduced the area of liver vacuolization, and protected hepatic cells surrounding blood vessels, irrespective of central or portal veins, from the ischemia/reperfusion damage.

Conclusions:  FNK inhibits apoptotic death due to the ischemia/reperfusion injury. Our results provide the reasonable expectation of therapeutic protein PTD‐FNK for clinical applications, such as transplantation, to protect against ischemia/reperfusion injury.
Complex aromatic hydrocarbons in Stardust samples collected from comet 81P/Wild 2
Authors: CLEMETT Simon J. , SANDFORD Scott A. , NAKAMURA‐MESSENGER Keiko , HÖRZ Friedrich , McKAY David S.
Published: September 2010

Abstract–  The successful return of the Stardust spacecraft provides a unique opportunity to investigate the nature and distribution of organic matter in cometary dust particles collected from comet 81P/Wild 2. Analysis of individual cometary impact tracks in silica aerogel using the technique of two‐step laser mass spectrometry demonstrates the presence of complex aromatic organic matter. While concerns remain as to the organic purity of the aerogel collection medium and the thermal effects associated with hypervelocity capture, the majority of the observed organic species appear indigenous to the impacting particles and are hence of cometary origin. While the aromatic fraction of the total organic matter present is believed to be small, it is notable in that it appears to be N rich. Spectral analysis in combination with instrumental detection sensitivies suggest that N is incorporated predominantly in the form of aromatic nitriles (R–C≡N). While organic species in the Stardust samples do share some similarities with those present in the matrices of carbonaceous chondrites, the closest match is found with stratospherically collected interplanetary dust particles. These findings are consistent with the notion that a fraction of interplanetary dust is of cometary origin. The presence of complex organic N containing species in comets has astrobiological implications as comets are likely to have contributed to the prebiotic chemical inventory of both the Earth and Mars.
GIP: No Longer the Neglected Incretin Twin?
Authors: Kulkarni Rohit N.
Published: September 2010

A pair of complementary studies suggest that scientists consider the incretin hormone gastric inhibitory polypeptide as a new therapeutic target for Type 2 diabetes.
Molecular Snapshot
Authors: Cheng Elaine
Published: September 2010

A new microfluidic device allows for easy isolation of neutrophils for genomic and proteomic analyses.
Real-Time Quantitative PCR Detection of Four Human Bocaviruses
Authors: Kantola Kalle , Sadeghi Mohammadreza , Antikainen Jenni , Kirveskari Juha , Delwart Eric , Hedman Klaus , Söderlund-Venermo Maria
Published: September 2010

Human bocavirus (HBoV) was discovered in 2005 and is associated with respiratory tract symptoms in young children. Three additional members of the genus
B
ocavirus
, HBoV2, -3, and -4, were discovered recently from fecal specimens, and early results indicate an association between HBoV2 and gastrointestinal disease. In this study, we present an undifferentiating multiplex real-time quantitative PCR assay for the detection of these novel viruses. Differentiation of the individual bocavirus species can be subsequently achieved with corresponding singleplex PCRs or by sequencing. Both multiplex and singleplex assays were consistently able to detect ≤10 copies of HBoV1 to -4 plasmid templates/reaction, with dynamic quantification ranges of 8 logs and 97% to 102% average reaction efficiencies. These new assays were used to screen stool samples from 250 Finnish patients (median age, 40 years) that had been sent for diagnosis of gastrointestinal infection. Four patients (1.6%; median age, 1.1 years) were reproducibly positive for HBoV2, and one patient (0.4%; 18 years of age) was reproducibly positive for HBoV3. The viral DNA loads varied from <10
3
to 10
9
copies/ml of stool extract. None of the stool samples harbored HBoV1 or HBoV4. The highly conserved sequence of the hydrolysis probe used in this assay may provide a flexible future platform for the quantification of additional, hitherto-unknown human bocaviruses that might later be discovered. Our results support earlier findings that HBoV2 is a relatively common pathogen in the stools of diarrheic young children, yet does not often occur in the stools of adults.
AUTONOMOUS GROUP TESTING BASED FAULT TOLERANCE IN RECONFIGURABLE LOGIC DEVICES
Authors: SABABEH JAVAD , MOHAMMADI KARIM
Published: September 2010

It has been found by the office of the Compliance & University RIO at the University of Central Florida (UCF) on behalf of Robert DeMara and Carthik Sharma that the concerned paper contains original text, tables, and figures from the sources authored or co-authored by the complainant. The respondent (Javad Sababeh) rebutted with two emails and stated that he had used the complainant's ideas and some text in the source papers. After carefully examining the materials provided by both sides, and considering the weight of evidence available and the request of the office of the Compliance & University RIO at the UCF, we retract this article.
TERRAIN ROUGHNESS ASSESSMENT FOR HIGH SPEED UGV NAVIGATION IN UNKNOWN HETEROGENEOUS TERRAINS
Authors: EL-KABBANY AHMED , RAMIREZ-SERRANO A.
Published: September 2010

This paper addresses the problem of determining the maximum allowable speed (V) of a vehicle traversing unknown off-road terrains. The calculated maximum speed achieves the fastest navigation without exceeding an allowable range of transmitted force (Fall) to the vehicle's frame. The proposed system enables the vehicle to transit between different terrains safely. The system's input are: (i) a 3D range image of the terrain and (ii) the vehicle's dimensions and characteristics (e.g., suspension parameters). First the terrain roughness is assessed; then the corresponding maximum allowable speed is calculated. In this paper a novel Roughness Index (RI) is used to represent the terrain roughness. This index is calculated based on the standard deviation of the terrain points' elevations (3D range image). A closed form expression of the maximum allowable vehicle speed is developed (as function of the vehicle's properties, Fall, RI, and probability of not exceeding Fall). The proposed system can be used as a driver assistant system to enhance the vehicle performance, increase its life time, and reduce the maintenance cost. In addition, it is a key module in Unmanned Ground Vehicles (UGVs) navigation systems; as it provides the navigation system with necessary information for path and speed planning.
Assessing the durability of mudrocks using the modified jar slake index test
Authors: Czerewko M. A. , Cripps J. C.
Published: September 2010

As exposure to weathering processes or other changes in moisture content can be the cause of troublesome breakdown of many mudrocks, it is essential to have reliable means of predicting this behaviour. Although the ISRM slake durability test is the standard test used to distinguish between durable and non-durable mudrocks, the test does not always identify problematic materials. The dynamic nature of the test and the use of an arbitrary 2 mm drum mesh size are particular short falls. The test is too aggressive to characterize properly the behaviour of low durability mudrocks and slaking of samples to a fragment size greater than 2 mm is not measured.

This paper reviews the various tests that have been used for predicting slaking potential. Comparative durability testing of 49 selected UK mudrocks ranging in age from Cambrian slates to Carboniferous Coal Measures is described. An evaluation of the performance of these materials in the one- and three-cycle ISRM slake durability test confirms the greater value of the latter. The modified jar slake test was found to be a suitably simple and accurate means of determining the durability of these mudrocks. Comparisons with the results of natural slaking trials confirm that the modified jar slake test presents a more detailed evaluation of the slaking potential of samples. In practice it is anticipated that the described test procedure will be used to provide data that would augment sample evaluation based on the ISRM slake durability test.
A methodology for the assessment of risk of
Cryptosporidium
contamination of groundwater
Authors: Boak R. A. , Packman M. J.
Published: September 2010

Water companies are now required by the Drinking Water Inspectorate to install continuous monitoring for
Cryptosporidium
at all sources (surface water and groundwater) where there is deemed to be a significant risk of
Cryptosporidium
oocysts being present in the final water. This has substantial cost implications, not only for the one-off installation of monitoring equipment, but also for the daily collection and analysis of samples.

This paper describes a methodology that has been used by Southern Water to screen all their groundwater sources, in order to identify those which are at significant risk of
Cryptosporidium
contamination, and which therefore need continuous monitoring. The methodology is a semi-quantitative scoring technique, developed by the authors, which produces a ranked list of sources and enables action to be prioritized. The methodology is designed to operate with a level of information and data easily available to a water company, overcoming the problems of significant data requirements associated with probabilistic methodologies.
Tectonic and mining induced fault reactivation around Barlaston on the Midlands Microcraton, North Staffordshire, UK
Authors: Donnelly L. J. , Rees J. G.
Published: September 2010

The North Staffordshire Coalfield occupies the northern apex of a triangular area of late Proterozoic continental crust, the Midlands Microcraton. Most faults identified at surface in the late Carboniferous rocks originated either as a result of reactivation of structure during the Variscan orogen in the late Carboniferous, or its collapse in the early Permian. The coalfield has been extensively undermined and many examples of mining-induced fault movement have been recorded in the Barlaston area between 1960–2000. The style of ground deformation observed in the area is described. Most movements have resulted in a series of distinct, extensive, fault scarps and fissures on the ground surface, causing widespread damage to structures, property, underground utilities and land. Several phases of fault movement have occurred, separated by periods of relative stability. Fault scarps may occasionally reach 2 m high, being indicative of multi-seam (3+) mining operations. These are restricted to a few metres in width but reach several hundreds of metres in length. The reasons why so many faults have been reactivated around Barlaston, why the surface expression of the faults are different in Carboniferous and Triassic outcrops, and why some faults appear to have reactivated since the cessation of mining are discussed.
Coast erosion at a nuclear waste shaft, Dounreay, Scotland
Authors: Hutchinson J. N. , Millar D. L. , Trewin N. H.
Published: September 2010

The risk from coast erosion to a shaft containing nuclear waste at Dounreay, Caithness is assessed. The physical setting of the shaft, data on the rates of erosion in the Devonian Flagstones and the drift capping of the local cliffs and future influences on erosion rates and flooding are summarized.

A two-layer model of superficials and flagstones is used to address the immediate concern of lateral erosion towards the shaft. Superficials’ erosion is assessed from a comparison of successive cliff surveys. Flagstones’ erosion proceeds chiefly by the deepening of slots in the weaker interbeds, with associated cantilever failures and block removal through wave action. The rate of slot development is estimated from the growth rate of tafoni within them. Whether erosion proceeds by superficials’ or flagstones’ erosion alone or in combination depends on the level of rockhead in the cliffs in relation to tide and wave levels. These threshold rockhead levels vary with the morphology and degree of exposure of the cliffs. They will also rise with time relative to Ordnance Datum in response to the general rise in sea level.

Estimates of the periods remaining before the shaft is exposed by coast erosion are made through the above model, both planimetrically and sectionally. They range from about 160 to over 240 years. Flooding by the sea is likely to commence about 400 years hence. The UKAEA plans to remove the nuclear waste from the shaft within the next two decades, well before the above factors would have an impact.
Converging flow tracer tests in fissured limestone
Authors: Riley M. S. , Ward R. S. , Greswell R. B.
Published: September 2010

As part of an investigation into the dual porosity behaviour of fractured limestone aquifers, a sequence of converging flow tracer tests was devised and conducted at an extensively investigated experimental site in a major aquifer in the UK. The tests were designed specifically to produce detailed, high-resolution information about the tails of the breakthrough curves typically observed in this kind of aquifer and test. A set of mutually compatible, low detection limit tracers was identified through laboratory investigations. Two tests were carried out over distances of 20 m and 40 m along each of the two radii towards an abstraction borehole where tracer concentration was monitored. Simple dual porosity models were calibrated using the data from one test on each radius. Blind validations of these models were undertaken by attempting to predict the outcome of the second test on each radius, producing one success and one significant failure.
An early warning system for active landslides
Authors: Husaini Omar , Ratnasamy M.
Published: September 2010

Slope failures are commonplace in tropical countries like Malaysia. Where they affect infrastructure, an efficient and safe method for monitoring of such collapsed slopes provides an indispensable safeguard. This paper describes an early warning system that was assembled and trialed during the reconstruction of a collapsed slope at Gunung Tempurung on the North South Expressway. The magnitude of the landslide and the risk involved in the reconstruction of the active slope posed a direct challenge to researchers, academicians, consulting engineers and contractors alike. The paper explains the procedures followed for safe installation of the instrumentation over the failed slope. It also outlines the techniques used for remote management of the instrumentation and the associated early warning alarm system.
Mine water rebound in South Nottinghamshire: risk evaluation using 3-D visualization and predictive modelling
Authors: Dumpleton S. , Robins N. S. , Walker J. A. , Merrin P. D.
Published: September 2010

Progressive abandonment of the South Nottinghamshire Coalfield raises concerns over the security of the Permo–Triassic Sherwood Sandstone aquifer which overlies the concealed part of the coalfield. A 3-D digital visualization package has been used to assemble and display the complex and diverse data-sets of relevance. Predictive scenarios have been run from these data using the University of Newcastle program GRAM (Groundwater Rebound in Abandoned Mineworkings). The work comprised three phases: (i) confirmation of the geological framework for the so-called ‘Pond 3’ area (southernmost part of the coalfield) and establishment of a water balance along with an outline groundwater flow path system for the Coal Measures and adjacent strata; (ii) the collation of detailed geometric information on the spatial distribution of discrete geological layers that are considered to have hydrogeological significance, the distribution of mineworkings within key horizons, and the locations of boreholes, shafts and pumping stations (both in the Coal Measures and within overlying strata). Possible flooding configurations have been assessed geometrically to identify ‘hot spots’ where mine water discharge to surface may occur, and areas where the piezometric level of the rising mine water might promote upward fluxes into the Permo–Triassic Sherwood Sandstone aquifer. In addition, critical areas where coal has been worked close to the base of the Permian and where hydraulic continuity may occur between the Sherwood Sandstone and Coal Measures have been identified; (iii) the GRAM model used data held in the 3-D visualization package VULCAN to define discrete ‘ponds’ within the coalfield. Recharge to the system allows each pond to fill until overflow pathways are reached, when the adjacent pond may start to fill. A variety of such scenarios have been completed and predictive data generated, which suggest that possible discharge to surface and into the Sherwood Sandstone might occur about 20 years after the end of dewatering.
Reducing the impact of acid sulphate soils at a site in Shoalhaven Floodplain of New South Wales, Australia
Authors: Indraratna Buddhima , Tularam Gurudeo Anand , Blunden Bruce
Published: September 2010

Oxidation of sulphide minerals in acid sulphate soils has acidified a substantial part of the low-lying coastal land in Australia. Such sulphides, including pyrite (FeS
2
) formed thousands of years ago during saline inundation of soils rich in iron. They do not pose a serious concern when submerged by the water table, because this prevents atmospheric oxygen reacting with the pyritic layer. However, flood protection of low-lying coastal land through the installation of deep surface drains has caused a general lowering of the water table elevation, that in turn has exposed the pyritic layers to atmospheric oxygen. High rainfall following droughts causes acid pollution of the surrounding flood mitigation drains, creeks and river systems. Large ground areas are affected by the transport of acid constituents during seepage. One way of controlling new acid production is through the installation of weirs in the flood mitigation drains in order to raise the water table elevation. In this paper, the acid pollution in New South Wales is reviewed, and the effect of groundwater elevation is examined. Relationship between acid production and groundwater table is examined. Mathematical models are developed to simulate acid production and transport, and two groundwater management regimes are examined. Weir based control of the groundwater table is shown to be successful in controlling acid production.
Classification and stability assessment for chalk cuttings: the Metropolitan Line case study
Authors: Phipps P. J. , McGinnity B. T.
Published: September 2010

This paper describes the findings of an assessment related to the nature and impact of slope instability for 20 km of chalk cuttings on the Metropolitan Line, and which forms an integral element of London Underground Ltd’s Earth Structures Management Strategy. A desk study and detailed geomorphological field mapping were utilized in order to develop a comprehensive classification scheme for the chalk cuttings. The classification depends primarily on cut-slope geometry and proportion of superficial deposits found in the slope. Restrictive thresholds were identified between classes that controlled the type of instability hazards present. The relative risk to the track was assessed which enabled targeting of future remedial measures to the most appropriate locations and the development of a cost-effective maintenance strategy.
Optical Recording of Neuronal Spiking Activity From Unbiased Populations of Neurons With High Spike Detection Efficiency and High Temporal Precision
Authors: Ranganathan Gayathri N. , Koester Helmut J.
Published: September 2010

Activity in populations of neurons is essential for cortical function including signaling of information and signal transport. Previous methods have made advances in recording activity from many neurons but have both technical and analytical limitations. Here we present an optical method, dithered random-access functional calcium imaging, to record somatic calcium signals from up to 100 neurons, in vitro and in vivo. We further developed a maximum-likelihood deconvolution algorithm to detect spikes and precise spike timings from the recorded calcium fluorescence signals. Spike detection efficiency and spike timing detection was determined in acute slices of juvenile mice. The results indicate that the combination of the two methods detected precise spiking activity from unbiased and spatially distributed populations of neurons in acute slices with high efficiency of spike detection (>97%), low rate of false positives (0.0023 spikes/s), and high temporal precision. The results further indicate that there is only a small window of excitation intensities where high spike detection can be achieved consistently.
Modulation of Neuronal Activity in the Monkey Putamen Associated With Changes in the Habitual Order of Sequential Movements
Authors: Deffains Marc , Legallet Eric , Apicella Paul
Published: September 2010

The striatum, especially its dorsolateral part, plays a major role in motor skill learning and habit formation, but it is still unclear how this contribution might be mediated at the neuronal level. We recorded single neurons in the posterior putamen of two monkeys performing an overlearned sequence of arm reaching movements to examine whether task-related activities are sensitive to manipulations of the serial order of stimulus-target locations. The monkeys' capacity to learn sequential regularities was assessed by comparing arm movement latencies and saccadic ocular reactions when a fixed repeating sequence was replaced with a random sequence. We examined neurons classified as phasically active projection neurons (PANs) and tonically active presumed cholinergic interneurons (TANs). About one-third of the PANs (35/106, 33%) activated during specific parts of a trial displayed modulations of their level of activation when the sequential structure was changed. This differential activity consisted of either decreases or increases in activity without altering the time period during which task-related activations occurred. In addition, half of the TANs (41/80, 51%) changed their responses to task stimuli with the sequence switch, indicating that the response selectivity of TANs reflects the detection of the context that requires adaptation to changes in the serial order of stimulus presentations. Our findings suggest that task-related changes in activity of projection neurons may be an important factor contributing to the production and adjustment of sequential behavior executed in an automatic fashion, whereas putative interneurons may provide a signal for performance monitoring in specific contexts.
Automatic Identification of Fluorescently Labeled Brain Cells for Rapid Functional Imaging
Authors: Valmianski Ilya , Shih Andy Y. , Driscoll Jonathan D. , Matthews David W. , Freund Yoav , Kleinfeld David
Published: September 2010

The on-line identification of labeled cells and vessels is a rate-limiting step in scanning microscopy. We use supervised learning to formulate an algorithm that rapidly and automatically tags fluorescently labeled somata in full-field images of cortex and constructs an optimized scan path through these cells. A single classifier works across multiple subjects, regions of the cortex of similar depth, and different magnification and contrast levels without the need to retrain the algorithm. Retraining only has to be performed when the morphological properties of the cells change significantly. In conjunction with two-photon laser scanning microscopy and bulk-labeling of cells in layers 2/3 of rat parietal cortex with a calcium indicator, we can automatically identify ∼50 cells within 1 min and sample them at ∼100 Hz with a signal-to-noise ratio of ∼10.
Plastic Changes in Hand Proprioception Following Force-Field Motor Learning
Authors: Goble Daniel J. , Anguera Joaquin A.
Published: September 2010

Motor neurophysiologists are placing greater emphasis on sensory feedback processing than ever before. In line with this shift, a recent article by Ostry and colleagues provided timely new evidence that force-field motor learning influences not only motor output, but also proprioceptive sense. In this Neuro Forum, the merits and limitations of Ostry and colleagues are explored in the context of recent work on proprioceptive function, including several recent studies from this journal.
Depolarization-Induced Ca2+ Entry Preferentially Evokes Release of Large Quanta in the Developing Xenopus Neuromuscular Junction
Authors: Sun Xiao-Ping , Chen Bo-Ming , Sand Olav , Kidokoro Yoshi , Grinnell Alan D.
Published: September 2010

The amplitude histogram of spontaneously occurring miniature synaptic currents (mSCs) is skewed positively at developing Xenopus neuromuscular synapses formed in culture. To test whether the quantal size of nerve-evoked quanta (eSCs) distributes similarly, we compared the amplitude histogram of single quantum eSCs in low external Ca2+ with that of mSCs and found that nerve stimulation preferentially released large quanta. Depolarization of presynaptic terminals by elevating [K+] in the external solution or by direct injection of current through a patch pipette increased the mSC frequency and preferentially, but not exclusively, evoked the release of large quanta, resulting in a second broad peak in the amplitude histogram. Formation of the second peak under these conditions was blocked by the N-type Ca2+ channel blocker, ω-conotoxin GVIA. In contrast, when the mSC frequency was elevated by thapsigargin- or caffeine-induced mobilization of internal Ca2+, formation of the second peak did not occur. We conclude that the second peak in the amplitude histogram is generated by Ca2+ influx through N-type Ca2+ channels, causing a local elevation of internal Ca2+. The mSC amplitude in the positively skewed portion of the histogram varied over a wide range. A competitive blocker of acetylcholine (ACh) receptors, d-tubocurarine, reduced the amplitude of smaller mSCs in this range relatively more than that of larger mSCs, suggesting that this variation in the mSC amplitude is due to variable amounts of ACh released from synaptic vesicles. We suggest that Ca2+ influx through N-type Ca2+ channels preferentially induces release of vesicles with large ACh content.
Ab initiostructure determination of bethanechol chloride
Authors: Le Bail A.
Published: September 2010

The structure of bethanechol chloride C7H17ClN2O2is solved from conventional X-ray powder diffraction data in direct space [monoclinic unit cell witha=8.8749(3) Å,b=16.4118(7) Å,c=7.1373(3) Å,β=93.803(1)°,V=1037.29(7) Å3,Z=4, and space groupP21/n]. The existence of a second orthorhombic closely related form is discussed.
Crystallographic study of ternary ordered skutterudite IrGe1.5Se1.5
Authors: Laufek F. , Návrátil J.
Published: September 2010

The crystal structure of skutterudite-related phase IrGe1.5Se1.5has been refined by the Rietveld method from laboratory X-ray powder diffraction data. Refined crystallographic data for IrGe1.5Se1.5area=12.0890(2) Å,c=14.8796(3) Å,V=1883.23(6) Å3, space groupR3(No. 148),Z=24, andDc=8.87 g/cm3. Its crystal structure can be derived from the ideal skutterudite structure (CoAs3), where Se and Ge atoms are ordered in layers perpendicular to the [111] direction of the original skutterudite cell. Weak distortions of the anion and cation sublattices were also observed.
On the crystal structures and hydrogen bond patterns in proline pseudopolymorphs
Authors: Seijas Luis E. , Delgado Gerzon E. , Mora Asiloé J. , Fitch Andrew N. , Brunelli Michela
Published: September 2010

Amino acids often cocrystallize with water molecules, which make them pseudopolymorphs of their anhydrous forms. In this work, we discuss in detail the hydrogen bond patterns in anhydrous L-proline and DL-proline and its pseudopolymorphic forms: L-proline monohydrate and DL-proline monohydrate. For this propose, the crystal structure of L-proline anhydrous was determined from synchrotron X-ray powder diffraction data and refined using the Rietveld method. Special emphasis is given to the role played by the water molecule in the hydrogen bond network observed in the crystalline structures.
In situ X-ray diffraction analysis of Pb(Zr0.52Ti0.48)O3 phase transition in CoFe2O4/Pb(Zr0.52Ti0.48)O3 2-2-type bilayer films
Authors: Wang Ji-Ning , Li Wei-Li , Li Xiao-Liang , Fei W. D.
Published: September 2010

A 2-2-type nanostructure bilayer film of CoFe2O4/Pb(Zr0.52Ti0.48)O3 was successfully prepared on the (111)Pt/Ti/SiO2/Si substrate. The Pb(Zr0.52Ti0.48)O3 layer in the bilayer film is (111) oriented and is a mixture of tetragonal and monoclinic phases. The results from an in situ X-ray diffraction analysis of the multiferroic bilayer film under statistic magnetic field indicate that the monoclinic-tetragonal phase transition was induced by magnetostriction of the CoFe2O4 layer. A large magnetoelectric effect was obtained probably because of the different polarization directions of the tetragonal and monoclinic phases.
Neutron diffraction study of the magnetic refrigerant Mn1.1Fe0.9P0.76Ge0.24
Authors: Liu L. J. , Liu D. M. , Huang Q. Z. , Zhang T. L. , Zhang L. , Yue M. , Lynn J. W. , Zhang J. X.
Published: September 2010

Polycrystalline Mn1.1Fe0.9P0.76Ge0.24 was prepared by mechanical alloying and spark plasma sintering. Neutron diffraction was used to determine the structure of the title compound, and its nuclear and magnetic structures were refined using the Rietveld method. It is found that temperature and magnetic field can induce phase transition between the paramagnetic and the ferromagnetic phases in the material, and the paramagnetic and ferromagnetic phases have very distinct crystal structures and different Ge contents.
MIMO Self‐Encoded Spread Spectrum with Iterative Detection over Rayleigh Fading Channels
Authors: Ma Shichuan , Nguyen Lim , Jang Won Mee , Yang Yaoqing (Lamar)
Published: September 2010

Self‐encoded spread spectrum (SESS) is a novel communication technique that derives its spreading code from the randomness of the source stream rather than using conventional pseudorandom noise (PN) code. In this paper, we propose to incorporate SESS in multiple‐input multiple‐output (MIMO) systems as a means to combat against fading effects in wireless channels. Orthogonal space‐time block‐coded MIMO technique is employed to achieve spatial diversity, and the inherent temporal diversity in SESS modulation is exploited with iterative detection. Simulation results demonstrate that MIMO‐SESS can effectively mitigate the channel fading effect such that the system can achieve a bit error rate of 10−4with very low signal‐to‐noise ratio, from 3.3 dB for a 2 × 2 antenna configuration to just less than 0 dB for a 4 × 2 configuration under Rayleigh fading. The performance improvement for the 2 × 2 case is as much as 6.7 dB when compared to an MIMO PN‐coded spread spectrum system.
Global Stability of Polytopic Linear Time‐Varying Dynamic Systems under Time‐Varying Point Delays and Impulsive Controls
Authors: de la Sen M.
Published: September 2010

This paper investigates the stability properties of a class of dynamic linear systems possessing several linear time‐invariant parameterizations (or configurations) which conform a linear time‐varying polytopic dynamic system with a finite number of time‐varying time‐differentiable point delays. The parameterizations may be timevarying and with bounded discontinuities and they can be subject to mixed regular plus impulsive controls within a sequence of time instants of zero measure. The polytopic parameterization for the dynamics associated with each delay is specific, so that (q+ 1) polytopic parameterizations are considered for a system withqdelays being also subject to delay‐free dynamics. The considered general dynamic system includes, as particular cases, a wide class of switched linear systems whose individual parameterizations are timeinvariant which are governed by a switching rule. However, the dynamic system under consideration is viewed as much more general since it is time‐varying with timevarying delays and the bounded discontinuous changes of active parameterizations are generated by impulsive controls in the dynamics and, at the same time, there is not a prescribed set of candidate potential parameterizations.
Transcriptional Modulation of Heat-Shock Protein Gene Expression
Authors: Stephanou Anastasis , Latchman David S.
Published: September 2010

Heat-shock proteins (Hsps) are molecular chaperones that are ubiquitously expressed but are also induced in cells exposed to stressful stimuli. Hsps have been implicated in the induction and propagation of several diseases. This paper focuses on regulatory factors that control the transcription of the genes encoding Hsps. We also highlight how distinct transcription factors are able to interact and modulate Hsps in different pathological states. Thus, a better understanding of the complex signaling pathways regulating Hsp expression may lead to novel therapeutic targets.
Zoledronic Acid as a New Adjuvant Therapeutic Strategy for Ewing's Sarcoma Patients
Authors: Odri Guillaume A. , Dumoucel Sophie , Picarda Gaëlle , Battaglia Séverine , Lamoureux François , Corradini Nadège , Rousseau Julie , Tirode Franck , Laud Karine , Delattre Olivier , Gouin François , Heymann Dominique , Redini Françoise
Published: September 2010

Ewing's sarcoma (ES) is the second most frequent pediatric bone tumor also arising in soft tissues (15% of cases). The prognosis of patients with clinically detectable metastases at diagnosis, not responding to therapy or with disease relapse, is still very poor. Among new therapeutic approaches, bisphosphonates represent promising adjuvant molecules to chemotherapy to limit the osteolytic component of bone tumors and to protect from bone metastases. The combined effects of zoledronic acid and mafosfamide were investigated on cell proliferation, viability, apoptosis, and cell cycle distribution of human ES cell lines differing in their p53 and p16/ink4 status. ES models were developed to reproduce both soft tissue and intraosseous tumor development. Mice were treated with 100 μg/kg zoledronic acid (two or four times per week) and/or ifosfamide (30 mg/kg, one to three cycles of three injections). ES cell lines showed different sensitivities to zoledronic acid and mafosfamide at the cell proliferation level, with no correlation with their molecular status. Both drugs induced cell cycle arrest, but in the S or G2M phase, respectively. In vivo, zoledronic acid had no effect on soft tissue tumor progression, although it dramatically inhibited ES development in bone. When combined with ifosfamide, zoledronic acid exerted synergistic effects in the soft tissue model: Its combination with one cycle of ifosfamide resulted in an inhibitory effect similar to three cycles of ifosfamide alone. This very promising result could allow clinicians to diminish the doses of chemotherapy. Cancer Res; 70(19); 7610–9. ©2010 AACR.
Functional MicroRNA Is Transferred between Glioma Cells
Authors: Katakowski Mark , Buller Benjamin , Wang Xinli , Rogers Thomas , Chopp Michael
Published: September 2010

MicroRNAs (miRNA) are single-stranded 17- to 27-nucleotide RNA molecules that regulate gene expression by posttranscriptional silencing of target mRNAs. Here, we transformed rat 9L gliosarcoma cells to express cel-miR-67, a miRNA that lacks homology in rat. Coculture of these cells with cells that expressed a luciferase reporter that contained a complementary sequence to cel-miR-67 resulted in significant suppression of luciferase expression. This effect was also observed in the U87-MG human glioma cell line. Moreover, luciferase suppression was inhibited by the addition of carbenoxolone to cocultures, suggesting that gap junction communication regulates intercellular transfer of miRNA. Finally, in situ hybridization revealed the presence of cel-miR-67 in cel-miR-67–null 9L cells after coculture with cel-miR-67–expressing cells. Our data show that miRNA transcribed in glioma cells can be transferred to adjacent cells and induces targeted inhibition of protein expression in the acceptor cells. These findings reveal a novel mechanism of targeted intercellular protein regulation between brain tumor cells. Cancer Res; 70(21); 8259–63. ©2010 AACR.
Macrophage Expression of Hypoxia-Inducible Factor-1α Suppresses T-Cell Function and Promotes Tumor Progression
Authors: Doedens Andrew L. , Stockmann Christian , Rubinstein Mark P. , Liao Debbie , Zhang Na , DeNardo David G. , Coussens Lisa M. , Karin Michael , Goldrath Ananda W. , Johnson Randall S.
Published: September 2010

T cells can inhibit tumor growth, but their function in the tumor microenvironment is often suppressed. Many solid tumors exhibit abundant macrophage infiltration and low oxygen tension, yet how hypoxic conditions may affect innate immune cells and their role in tumor progression is poorly understood. Targeted deletion of the hypoxia-responsive transcription factor hypoxia-inducible factor-1α (HIF-1α) in macrophages in a progressive murine model of breast cancer resulted in reduced tumor growth, although vascular endothelial growth factor-A levels and vascularization were unchanged. Tumor-associated macrophages can suppress tumor-infiltrating T cells by several mechanisms, and we found that hypoxia powerfully augmented macrophage-mediated T-cell suppression in vitro in a manner dependent on macrophage expression of HIF-1α. Our findings link the innate immune hypoxic response to tumor progression through induction of T-cell suppression in the tumor microenvironment. Cancer Res; 70(19); 7465–75. ©2010 AACR.
Aggressive Fibromatosis (Desmoid Tumor) Is Derived from Mesenchymal Progenitor Cells
Authors: Wu Colleen , Nik-Amini Saied , Nadesan Puviindran , Stanford William L. , Alman Benjamin A.
Published: September 2010

The cellular origins from which most tumors arise are poorly defined, especially in mesenchymal neoplasms. Aggressive fibromatosis, also known as desmoid tumor, is a locally invasive soft tissue tumor that has mesenchymal characteristics. We found that aggressive fibromatosis tumors express genes and cell surface markers characteristic of mesenchymal stem cells (MSC). In mice that are genetically predisposed to develop aggressive fibromatosis tumors (Apcwt/1638N), we found that the number of tumors formed was proportional to the number of MSCs present. Sca-1−/− mice, which develop fewer MSCs, were crossed with Apcwt/1638N mice. Doubly mutant mice deficient in Sca-1 developed substantially fewer aggressive fibromatosis tumors than wild-type (WT) littermates, but Sca-1 deficiency had no effect on the formation of epithelial-derived intestinal polyps. MSCs isolated from Apcwt/1638N mice (or mice expressing a stabilized form of β-catenin) induced aberrant cellular growth reminiscent of aggressive fibromatosis tumors after engraftment to immunocompromised mice, but WT cells and mature fibroblasts from the same animals did not. Taken together, our findings indicate that aggressive fibromatosis is derived from MSCs, and that β-catenin supports tumorigenesis by maintaining mesenchymal progenitor cells in a less differentiated state. Protecting this progenitor cell population might prevent tumor formation in patients harboring a germline APC mutation, where fibromatosis is currently the leading cause of mortality. Cancer Res; 70(19); 7690–8. ©2010 AACR.
Clinical Pharmacology of Resveratrol and Its Metabolites in Colorectal Cancer Patients
Authors: Patel Ketan R. , Brown Victoria A. , Jones Donald J.L. , Britton Robert G. , Hemingway David , Miller Andrew S. , West Kevin P. , Booth Tristan D. , Perloff Marjorie , Crowell James A. , Brenner Dean E. , Steward William P. , Gescher Andreas J. , Brown Karen
Published: September 2010

Resveratrol is a phytochemical with chemopreventive activity in preclinical rodent models of colorectal carcinogenesis. Antiproliferation is one of the many chemopreventive modes of action it has been shown to engage in. Concentrations of resveratrol, which can be achieved in human tissues after p.o. administration, have not yet been defined. The purpose of this study was to measure concentrations of resveratrol and its metabolites in the colorectal tissue of humans who ingested resveratrol. Twenty patients with histologically confirmed colorectal cancer consumed eight daily doses of resveratrol at 0.5 or 1.0 g before surgical resection. Resveratrol was found to be well tolerated. Normal and malignant biopsy tissue samples were obtained before dosing. Parent compound plus its metabolites resveratrol-3-O-glucuronide, resveratrol-4′-O-glucuronide, resveratrol-3-O-sulfate, resveratrol-4′-O-sulfate, resveratrol sulfate glucuronide, and resveratrol disulfate were identified by high-performance liquid chromatography (HPLC) with UV or mass spectrometric detection in colorectal resection tissue. Quantitation was achieved by HPLC/UV. Cell proliferation, as reflected by Ki-67 staining, was compared in preintervention and postintervention tissue samples. Resveratrol and resveratrol-3-O-glucuronide were recovered from tissues at maximal mean concentrations of 674 and 86.0 nmol/g, respectively. Levels of resveratrol and its metabolites were consistently higher in tissues originating in the right side of the colon compared with the left. Consumption of resveratrol reduced tumor cell proliferation by 5% (P = 0.05). The results suggest that daily p.o. doses of resveratrol at 0.5 or 1.0 g produce levels in the human gastrointestinal tract of an order of magnitude sufficient to elicit anticarcinogenic effects. Resveratrol merits further clinical evaluation as a potential colorectal cancer chemopreventive agent. Cancer Res; 70(19); 7392–9. ©2010 AACR.
Overexpression of the Protein Tyrosine Phosphatase PRL-2 Correlates with Breast Tumor Formation and Progression
Authors: Hardy Serge , Wong Nau Nau , Muller William J. , Park Morag , Tremblay Michel L.
Published: September 2010

The PRL-1, PRL-2, and PRL-3 phosphatases are prenylated protein tyrosine phosphatases with oncogenic activity that are proposed to drive tumor metastasis. We found that PRL-2 mRNA is elevated in primary breast tumors relative to matched normal tissue, and also dramatically elevated in metastatic lymph nodes compared with primary tumors. PRL-2 knockdown in metastatic MDA-MB-231 breast cancer cells decreased anchorage-independent growth and cell migration, suggesting that the malignant phenotype of these cells is mediated at least in part through PRL-2 signaling. In different mouse mammary tumor–derived cell lines overexpressing PRL-2, we confirmed its role in anchorage-independent growth and cell migration. Furthermore, injection of PRL-2–overexpressing cells into the mouse mammary fat pad promoted extracellular signal-regulated kinase 1/2 activation and tumor formation. MMTV–PRL-2 transgenic mice engineered to overexpress the enzyme in mammary tissue did not exhibit spontaneous tumorigenesis, but they exhibited an accelerated development of mammary tumors initiated by introduction of an MMTV-ErbB2 transgene. Together, our results argue that PRL-2 plays a role in breast cancer progression. Cancer Res; 70(21); 8959–67. ©2010 AACR.
Knockdown of Inwardly Rectifying Potassium Channel Kir2.2 Suppresses Tumorigenesis by Inducing Reactive Oxygen Species–Mediated Cellular Senescence
Authors: Lee Inkyoung , Park Chaehwa , Kang Won Ki
Published: September 2010

Senescence is an important determinant of treatment outcome in cancer therapy. In the present study, we show that knockdown of the inwardly rectifying K+ channel Kir2.2 induced growth arrest without additional cellular stress in cancer cells lacking functional p53, p16, and/or Rb. Kir2.2 knockdown also induced senescence-associated β-galactosidase activity and upregulated senescence marker proteins in multiple cancer cell lines derived from different tissues, including prostate, stomach, and breast. Interestingly, knockdown of Kir2.2 induced a significant increase in reactive oxygen species (ROS) that was accompanied by cell cycle arrest, characterized by significant upregulation of p27, with concomitant downregulation of cyclinA, cdc2, and E2F1. Kir2.2 knockdown cells displayed increased levels of PML bodies, DNA damage (γH2AX) foci, senescence-associated heterochromatin foci, mitochondrial dysfunction, secretory phenotype, and phosphatase inactivation. Conversely, overexpression of Kir2.2 decreased doxorubicin-induced ROS accumulation and cell growth inhibition. Kir2.2 knockdown-induced cellular senescence was blocked by N-acetylcysteine, indicating that ROS is a critical mediator of this pathway. In vivo tumorigenesis analyses revealed that tumors derived from Kir2.2 knockdown cells were significantly smaller than those derived from control cells (P < 0.0001) and showed a remarkable increase in senescence-associated proteins, including senescence-associated β-galactosidase, p27, and plasminogen activator inhibitor-1. Moreover, the preestablished tumors are reduced in size after the injection of siKir2.2 (P = 0.0095). Therefore, we propose for the first time that Kir2.2 knockdown induces senescence of cancer cells by a mechanism involving ROS accumulation that requires p27, but not Rb, p53, or p16. Mol Cancer Ther; 9(11); 2951–9. ©2010 AACR.