bluuebunny/crossref_metadata_2025 huggingface dataset:
Mineralogical, geochronological, and geochemical characterization of Early Devonian aquamarine-bearing dykes of the Zealand Station beryl and molybdenite deposit, west central New Brunswick
Authors: Beal Kristy-Lee , Lentz David R. , Hall Douglas C. , Dunning Gregory
Published: July 2010

The Zealand Station beryl (aquamarine) and molybdenite deposit is located 25 km northwest of Fredericton, New Brunswick, along the northeastern cusp of the Hawkshaw Granite, previously dated at 411 ± 1 Ma (U–Pb titanite), of the multiphase Devonian Pokiok Batholith. A late-stage, southeast-trending, pegmatite–aplite dyke has abundant aquamarine associated with pegmatitic sections. An exposure of a pegmatitic dyke is predominantly quartz and K-feldspar that exhibits a border, intermediate, and core zone. The main pegmatite–aplite dyke has been dated at 400.5 ± 1.2 Ma using U–Pb thermal ionization mass spectrometry on magmatic zircon. This is consistent with the 404 ± 8 Ma age using the chemical U–Th – total Pb isochron method from the pegmatitic beryl-rich section. These ages link these pegmatitic to aplitic dykes to the Allandale Granite, which is the youngest (402 ± 1 Ma by U–Pb on monazite) and most evolved phase of the Pokiok Batholith. The granitic aplite and pegmatite dyke samples are predominantly magnesian with one pegmatite sample being ferroan (FeOt/(FeOt +MgO) = 0.64–0.94); the samples are slightly potassic and calc-alkaline with strong peraluminosity (A/CNK = 1.23–4.76). The various phases of dykes were derived from magma with crustal A-type source characteristics similar to the Allandale Granite. The Sm–Nd isotope values for the aplite dyke (εNd(400) = –2.15) and the Allandale Granite (εNd(400) = –1.6) reflect some assimilation of metasediments relative to other phases of the Pokiok Batholith. The pegmatite and aplite dykes are high-level, rare-earth element pegmatite phases (Nb–Y–F-type) with some Li–Cs–Ta-type characteristics.
Sensitivity of pH in a boreal stream network to a potential decrease in base cations caused by forest harvest
Authors: Ågren Anneli , Buffam Ishi , Bishop Kevin , Laudon Hjalmar
Published: July 2010

Increased forest harvest with more whole-tree utilization can decrease base cations (BC) in soils and stream runoff. This paper analyses how reducing stream BC changes the capacity of a boreal stream network to buffer pH changes. We estimated change in stream pH during spring snowmelt in 60 locations throughout a 68 km2 boreal catchment in northern Sweden with different scenarios of BC removal from stream water ranging from 10 to 50 µequiv.·L–1. The pH decreased in all scenarios, and if BC decreased by 50 µequiv.·L–1, stream length with pH above the acid threshold pH 5 during spring snowmelt decreased from 82% to 44% of the stream network, whereas the stream length with pH above 5.5 decreased from 60% to 10%. The pH sensitivity of different stream reaches to reductions in BC was positively related to the slope of the catchment, forest cover, and forested mires, whereas it was negatively related to the percentage of agricultural fields. Because the long-term effect of different forestry practices on stream BC is unclear, there is all the more reason to evaluate BC sensitivity before, rather than after, eventual problems arise.
An efficient approach for locating the critical slip surface in slope stability analyses using a real-coded genetic algorithm
Authors: Li Yu-Chao , Chen Yun-Min , Zhan Tony L.T. , Ling Dao-Sheng , Cleall Peter John
Published: July 2010

A real-coded genetic algorithm is employed to develop a search approach for locating the noncircular critical slip surface in slope stability analyses. Limit equilibrium methods and the finite-element-based method are incorporated with the proposed search approach to calculate the factor of safety. Geometrical and kinematical compatibility constraints are established based on the features of slope problems to prevent slip surfaces from being unreasonable. A dynamic bound technique is presented to improve the search performance with more effective exploration within the solution domain. A number of examples are investigated that demonstrate the proposed search approach to be efficient in yielding accurate solutions to practical slope stability problems. The proposed search approach is stable and highly correlated with the results of independent analyses. Furthermore, this paper demonstrates the successful application of a real-coded genetic algorithm to noncircular critical slip surface search problems.
Dimensional analysis of natural debris flows
Authors: Zhou Gordon G.D. , Ng Charles W.W.
Published: July 2010

Debris flow is generally composed of a wide range of solid particles and viscous pore fluid. It flows at a high velocity down a slope channel. Interactions between solid and fluid phases affected by multiple parameters govern the rheological properties of debris flows. A dimensional analysis for a systematic study of the governing parameters is presented. Multiple dimensionless numbers with clear physical meanings are critically reviewed. The applications of field data to the studying of natural debris flows are demonstrated. Specific values of dimensionless numbers for classifying flow regimes of large-scale natural debris flows are obtained. Compared with previous small-scale physical model tests, this study shows that the contact friction between particles dominates in natural debris flows. In addition, the solid inertial stress due to particle collisions and the pore-fluid viscous shearing stress play key roles in governing the dynamic properties of debris flows. The channel width as a confinement to the flows can affect the solids discharge per unit width significantly. A dimensionless number related to pore-fluid pressure dissipation is also found that can satisfactorily distinguish between surge flows and continuous flows in the field.
Cementation and bond degradation of rubber–sand mixtures
Authors: Lee Changho , Truong Q. Hung , Lee Jong-Sub
Published: July 2010

Cementation influences the mechanical behavior of soils. The effects of cementation and bond degradation are investigated for lightly cemented rigid sand and soft rubber particle mixtures subjected to vertical loading under the K0condition. Cemented and uncemented specimens were prepared with various sand volume fractions. The propagation velocity of small strain body waves was measured by piezo materials, incorporated within an oedometer. Cemented specimens exhibited a bilinear behavior in the semi-log plot (vertical strain versus log of vertical stress). Vertical strains of a cemented specimen normalized by an uncemented specimen show that the stress–strain behavior is controlled by several different mechanisms and forces: capillary force, cementation bonds, and interparticle contact stresses after bond degradation. The elastic wave velocities dramatically increase due to cementation hardening under fixed vertical stress, and are constant after curing even though vertical stress increases. Additional loading of the vertical effective stress decreases the elastic wave velocities due to bond degradation. The shear wave velocity presents three behavior regions as a function of the sand fraction for both uncemented and cemented specimens: rubber-like, sand-like, and transition behaviors. The vertical stress–strain response and the elastic wave velocities can serve as indicators of cementation and bond degradation.
Ortho-phenylene-bridged aryloxy phosphine ligands and their coordination chemistry with tantalum(V)
Authors: Carmichael Christopher D. , Fryzuk Michael D.
Published: July 2010

The lithium complexes RP(3,5-tBu2C6H2OLi)2(THF)4, where R = Ph or iPr, (R[OPO]Li2)2(THF)4, can be converted quantitatively into the protonated forms, R[OPO]H2, by reaction with Et3NHCl. Reaction of the protonated compounds with KH yields the potassium complexes (Ph[OPO]K2)2(THF)6 and (iPr[OPO]K2)3(THF)3. The reaction of R[OPO]H2 with TaCl5 yields the sparingly soluble tantalum trichloride complexes R[OPO]TaCl3 via elimination of HCl. Reaction of Ph[OPO]H2 with TaMe3Cl2 leads to the monomethyl complex Ph[OPO]TaMeCl2, or the dimethyl halide complex, Ph[OPO]TaMe2Cl, via protonolysis, and the potassium complex (Ph[OPO]K2)2(THF)6 yields the trimethyl complex, Ph[OPO]TaMe3 by a metathesis process.
Organocatalysis in the stereoselective bromohydrin reaction of alkenes
Authors: Bar Sukanta
Published: July 2010

An efficient regio- and stereo-selective (>99:1) trans-bromohydrination (bromohydroxylation and bromomethoxylation) of alkenes including α,β-unsaturated carbonyl compounds with N-bromosuccinimide (NBS) has been achieved by using 1.0 mol% of N,N′-diarylthiourea catalyst.
Radiolysis of supercritical water at 400 °C and liquid-like densities near 0.5 g/cm3 — A Monte Carlo calculation
Authors: Meesungnoen Jintana , Guzonas David , Jay-Gerin Jean-Paul
Published: July 2010

Monte Carlo simulations are used to calculate the primary radical yields [Formula: see text], g(•OH), the sum [[Formula: see text] + g(•OH) + g(H•)], and the ratio g(H•)/[Formula: see text] in the low linear energy transfer (LET) radiolysis of supercritical water (SCW) at 400 °C in the high-density, liquid-like region near ∼0.5 g/cm3. Using all the currently available information on the reactivities and diffusion coefficients of the radiation-induced species under these conditions, and assuming the aqueous medium to be a “continuum”, a good accord is found between our calculations and the available experimental data. In particular, our computed [Formula: see text] yields at 60 ps and 1 ns compare very well with recently reported direct time-dependent [Formula: see text] yield measurements in SCW (D2O) at 400 °C and 0.570 g/cm3 using picosecond pulse radiolysis experiments.
A new family of bent-core C2-symmetric liquid crystals
Authors: Hope-Ross Kyle A. , Heiney Paul A. , Kadla John F.
Published: July 2010

A series of C2-symmetric compounds with different core sizes and varying lengths and numbers of alkoxy side chains were prepared, and the factors influencing their liquid crystalline mesophase behaviour were investigated. The compounds studied were based on benzophenone, dibenzylidene-acetone, and 1,9-diphenyl-nona-1,3,6,8-tetraen-5-one cores with either 1 or 2 linear alkoxy side chains. The side chains were varied in length from C6H13 to C12H25. The liquid crystalline mesophase behaviour of the compounds was investigated using differential scanning calorimetry, polarizing optical microscopy, and small-angle X-ray scattering (SAXS). It was found that a number of the molecules were able to self-assemble into smectic and nematic liquid crystalline phases.
TiO2/biscyanine and CdS/biscyanine heterostructures — Influence of the structural composition on the photocatalytic activity
Authors: Kobasa I. , Kondratyeva I. , Odosiy L.
Published: July 2010

This paper deals with investigation of a character of the light reflection and absorption of some newly synthesized heterostructural materials based on TiO2 or CdS semiconductors and bisquinocyanine dyes (carbocyanine and styrile). Changes in spectral parameters of the heterostructures caused by adding the dye to the semiconducting material have also been investigated. The changes in the spectra can be caused by different chromophores disposition induced by influence of the semiconductor on the electron configuration in the dye molecules. A well-known test reaction of methylene blue reduction has been used to detect the photocatalytic activity of the materials, which was found directly depending on the efficiency of the mutual influence of the components of the heterostructures. The heterostructures containing a dye, which causes more significant spectral changes, ensure higher photocatalytic activity.
Dry-matter and Element Content of Roots of Several Natural Stands of Pinusbanksiana Lamb. in Northern Ontario
Authors: Morrison I. K.
Published: July 2010

The present paper is a companion to a previous report that described the content of dry matter and N, P, K, Ca, and Mg in 30- to 35-year-old stands of Pinusbanksiana Lamb. in northern Ontario. The root systems of eight trees were excavated, weighed, and analyzed for chemical content. Using the regression-stand table method, dry-matter and nutrient content per hectare were estimated. On an areal basis, root weight of P. banksiana was lower than for stands of comparable age of other species located elsewhere. Likewise a smaller proportion of the total plant was in root with P. banksiana.
Response of Selected Pinusstrobus L. Clones to Fumigations with Sulfur Dioxide and Ozone
Authors: Houston Daniel B.
Published: July 2010

Response of eastern white pine (Pinusstrobus L.) to ozone (O3) and sulfur dioxide (SO2) was studied utilizing controlled fumigation chambers in the greenhouse. Tolerant and sensitive clones were fumigated for 6 h at concentrations of 5, 10, 30, and 60 parts per hundred million (p.p.h.m.) O3, 2.5, 5, 15, and 45 p.p.h.m. SO2, and 2.5 p.p.h.m. SO2 plus 5 p.p.h.m. O3 in combination. Response was judged by needle elongation and two indices of direct needle damage.Ozone exposures did not produce a consistent response among tolerant and sensitive classes, while injury caused by SO2 and SO2 plus O3 correlated well with field observations of damage under ambient conditions. The most sensitive clone was injured by concentrations of SO2 as low as 2.5 ± 1 p.p.h.m. Sixty percent of the tolerant clones were injured by 5 and 15 p.p.h.m. SO2, and all tolerant material was injured at 45 p.p.h.m. SO2. The interaction of SO2 and O3 at low concentrations was established as more serious than that caused by either pollutant alone at similar levels.
Seedling Size and Age as Factors of Morphogenesis in White Spruce Piceaglauca (Moench) Voss Buds
Authors: Pollard D. F.W.
Published: July 2010

Terminal bud formation was induced in seedling white spruce of different sizes by transferring seedlings to a 10-week short day treatment at ages ranging from 6 to 16 weeks. Subsequent counts of needles initiated and measurements of height increment showed strong relationships with height and age of seedlings during bud formation. The implications of results for regeneration schemes are discussed.
Relative Influence of Moisture–Aeration and Nutrients on Vegetation and Black Spruce Growth in Northern Ontario
Authors: Jeglum J. K.
Published: July 2010

Results from a principal component analysis suggest that nutrient regime is more important to vegetational variation than the moisture–aeration regime. Correlations between site index and habitat measures suggest that the moisture–aeration regime influences tree growth more than the nutrient regime. For particular components of vegetational variation and for segments of the total data, the proportional influence of the two gradients varies. Moisture–aeration and nutrient regimes explain a large proportion of the variation in minor vegetation and tree growth on black spruce peatlands.
Rhizina Root Rot: Severity and Distribution in British Columbia
Authors: Ginns James H.
Published: July 2010

Rhizinaundulata Fr. occurred on about one-third of the 160 logging sites sampled 1 year after each area was burned. Three years after burning, apothecia were rarely found. The fungus causes mortality of seedlings planted on burned sites. Severity of attack within a seedling plantation was evaluated entirely on field observations which gave a satisfactory estimate of infection. Most rhizina root rot mortality occurred in the first year after planting and after 2 years the mortality on one study area was 24%.
Use of Logarithmic Regression in the Estimation of Plant Biomass: Reply
Authors: Baskerville G. L.
Published: July 2010

not available
LEARNING FUZZY USER PROFILES FOR RESOURCE RECOMMENDATION
Authors: CASTELLANO GIOVANNA , CASTIELLO CIRO , DELL'AGNELLO DANILO , FANELLI ANNA MARIA , MENCAR CORRADO , TORSELLO MARIA ALESSANDRA
Published: July 2010

Recommender systems are systems capable of assisting users by quickly providing them with relevant resources according to their interests or preferences. The efficacy of a recommender system is strictly connected with the possibility of creating meaningful user profiles, including information about user preferences, interests, goals, usage data and interactive behavior. In particular, analysis of user preferences is important to predict user behaviors and make appropriate recommendations. In this paper, we present a fuzzy framework to represent, learn and update user profiles. The representation of a user profile is based on a structured model of user cognitive states, including a competence profile, a preference profile and an acquaintance profile. The strategy for deriving and updating profiles is to record the sequence of accessed resources by each user, and to update preference profiles accordingly, so as to suggest similar resources at next user accesses. The adaption of the preference profile is performed continuously, but in earlier stages it is more sensitive to updates (plastic phase) while in later stages it is less sensitive (stable phase) to allow resource recommendation. Simulation results are reported to show the effectiveness of the proposed approach.
MILLING EFFECT AND ENHANCED LUMINESCENCE PROPERTY OF BAM NANOPHOSPHOR VIA SURFACE MODIFICATIONS
Authors: DULDA A. , JO D. S. , TAKAKI M. , YOON D. H.
Published: July 2010

Surface modification of luminescent nanomaterials has attracted considerable technological interest. With decreasing particle size, the passivation of surface defects is of vital importance. This paper reports the effect of an alkali (KOH) solution treatment and organic functional groups on the luminescence efficiency and particle dispersibility. Fourier transform infrared spectroscopy provided clear evidence of surface modification with organic functional groups from the C=O , C–H , and C–O stretching modes at 1740, 1365, and 1218 cm-1. The KOH-treated sample showed a 40% increase in luminescence intensity, whereas 87% increase in luminescence intensity was obtained from the dispersion-agent-containing sample. To the best of our knowledge, this is the highest efficiency improvement for sub-micrometer-sized BAM: Eu2+ phosphors reported thus far.
ASYMPTOTIC STABILITY OF DELAY-DIFFERENCE CONTROL SYSTEM VIA MATRIX INEQUALITIES AND APPLICATION
Authors: Ratchagit K.
Published: July 2010

In this paper, we obtain some criteria for determining the asymptotic stability of the zero solution of delay-difference control system in terms of certain matrix inequalities by using a discrete version of the Lyapunov second method. The result has been applied to obtain new stability conditions for some classes of delay-difference control system such as delay-difference control system with multiple delays in terms of certain matrix inequalities. Our results can be well suited for computational purposes.
PRIME IDEAL CHARACTERIZATION OF STONE ADLs
Authors: Swamy U. M. , Ramesh S. , Raj Ch. Shanthi Sundar
Published: July 2010

In this paper we obtain certain necessary and sufficient conditions for an almost distributive lattice to become a Stone almost distributive lattice in topological and algebraic terms.
Software Development with Code Maps
Authors: DeLine Robert , Venolia Gina , Rowan Kael
Published: July 2010

To better understand how professional software developers use visual representations of their code, we interviewed nine developers at Microsoft to identify common scenarios, and then surveyed more than 400 developers to understand the scenarios more deeply.
Multimodal Therapy for the Treatment of Severe Ischemic Stroke Combining Endovascular Embolectomy and Stenting of Long Intracranial Artery Occlusion
Authors: Bunc Matjaž , Kocijančič Igor J. , Pregelj Rado , Dolenc Vinko V.
Published: July 2010

Embolic occlusion of cerebral arteries is a major cause for stroke. Intravenous thrombolysis showed positive results in this condition, however even when strict criteria are used, the risk of hemorrhagic transformation is possible. Microsurgical embolectomy has been described earlier.Purpose. We performed multimodal therapy of cerebral artery occlusion.Case Report. We present a case of a 49-year-old female patient who—according to the National Institute of Health Stroke Scale (NIHSS)—was rated as 19 due to acute occlusion of the horizontal segment of the left middle cerebral artery (MCA). After failed i.v. thrombolysis, only a part of the clot could be evacuated by the endovascular approach—without restoration of blood flow. Normal patency of the left MCA was re-established after stenting. Within 72 hours, the patient had an NIHSS score of 14, with a small haematoma in the left hemisphere.Conclusion. In our case multimodal therapy combining i.v. thrombolysis, mechanical disruption of thrombus, MCA stenting and platelet function antagonists, resulted in successful recanalization of the acutely occluded left MCA.
Calculation of Effective Earth Radius and Point Refractivity Gradient in UAE
Authors: Abu-Almal Abdulhadi , Al-Ansari Kifah
Published: July 2010

A large set of 14 years of reliable local radiosonde meteorological data, from 1990 to 2003, has been used to calculate the effective Earth radius and point refractivity gradient in the United Arab Emirates. The obtained values are used to investigate their impact on the design of microwave links. The cumulative distribution of the refractivity gradient in the first 65 meters above the ground surface, the monthly distribution for the median value of thek-factor, as well as their comparison with the ITU-maps are provided. Both experimental and global standard values are applied to specific link budget calculations.
On the Controllability of a Differential Equation with Delayed and Advanced Arguments
Authors: Manzanilla Raúl , Mármol Luis Gerardo , Vanegas Carmen J.
Published: July 2010

A semigroup theory for a differential equation with delayed and advanced arguments is developed, with a detailed description of the infinitesimal generator. This in turn allows to study the exact controllability of the equation, by rewriting it as a classical Cauchy problem.
Laugier-Hunziker Syndrome: An Uncommon Cause of Oral Pigmentation and a Review of the Literature
Authors: Montebugnoli Lucio , Grelli Ivana , Cervellati Fabio , Misciali Cosimo , Raone Beatrice
Published: July 2010

Laugier-Hunziker syndrome is a rare benign condition characterized by diffuse oral hyperpigmentation associated with pigmentation of the nails. The syndrome must be included in the differential diagnosis of diffuse oral pigmentation to exclude other conditions with systemic implications. We describe a 43-year-old white woman with the clinical and histological features of Laugier-Hunziker syndrome associated with toenail pigmentation. The correct clinical identification avoids the need for detailed investigations and treatment. We also review the potential causes of oral pigmentation.
Approximate Endpoints for Set-Valued Contractions in Metric Spaces
Authors: Hussain N , Amini-Harandi A , Cho YJ
Published: July 2010

The existence of approximate fixed points and approximate endpoints of the multivalued almost "Equation missing"-contractions is established. We also develop quantitative estimates of the sets of approximate fixed points and approximate endpoints for multivalued almost "Equation missing"-contractions. The proved results unify and improve recent results of Amini-Harandi (2010), M. Berinde and V. Berinde (2007), Ćirić (2009), M. Păcurar and R. V. Păcurar (2007) and many others.
An Explicit Representation of the Extended Skorokhod Map with Two Time‐Dependent Boundaries
Authors: Slaby Marek
Published: July 2010

We consider the extended Skorokhod problem for real‐valued càdlàg functions with the constraining interval [α, β], where α and β change in time as values of two càdlàg functions. We find an explicit
form of the solution and discuss its continuity properties with respect to the uniform, J1 and M1, metrics on the space of càdlàg functions. We develop a useful technique of extending known results
for the Skorokhod maps onto the larger class of extended Skorokhod maps.
About Statistical Analysis of Qualitative Survey Data
Authors: Loehnert Stefan
Published: July 2010

Gathered data is frequently not in a numerical form allowing immediate appliance of the quantitative mathematical-statistical methods. In this paper are some basic aspects examining how quantitative-based statistical methodology can be utilized in the analysis of qualitative data sets. The transformation of qualitative data into numeric values is considered as the entrance point to quantitative analysis. Concurrently related publications and impacts of scale transformations are discussed. Subsequently, it is shown how correlation coefficients are usable in conjunction with data aggregation constrains to construct relationship modelling matrices. For illustration, a case study is referenced at which ordinal type ordered qualitative survey answers are allocated to process defining procedures as aggregation levels. Finally options about measuring the adherence of the gathered empirical data to such kind of derived aggregation models are introduced and a statistically based reliability check approach to evaluate the reliability of the chosen model specification is outlined.
Consistency Degrees of Theories in Łukasiewicz Fuzzy andn-Valued Propositional Logic Systems
Authors: Zhang Jiancheng
Published: July 2010

By means of theory of truth degrees of formulas, according to deduction theorems and completeness theorems, the new concepts of consistency degrees and polar index for general theories in Łukasewicz fuzzy andn-valued propositional logic systems are introduced. Moreover, sufficient and necessary conditions for a theoryΓto be consistent, inconsistent, and fully divergent are obtained. Finally, some important properties of truth degrees of formulas are proposed.
Identification of Differentially Methylated Genes in Normal Prostate Tissues from African American and Caucasian Men
Authors: Kwabi-Addo Bernard , Wang Songping , Chung Woonbok , Jelinek Jaroslav , Patierno Steven R. , Wang Bi-Dar , Andrawis Ramez , Lee Norman H. , Apprey Victor , Issa Jean-Pierre , Ittmann Michael
Published: July 2010

Purpose: Aberrant DNA methylation changes are common somatic alterations in prostate carcinogenesis. We examined the methylation status of six genes in prostate tissue specimens from African American (AA) and Caucasian (Cau) males.

Experimental Design: We used pyrosequencing to quantitatively measure the methylation status of GSTP1, AR, RARβ2, SPARC, TIMP3, and NKX2-5. Real-time PCR was used to determine gene expression, and gene reactivation was analyzed by 5-aza-2′-deoxycytidine and/or trichostatin A treatment.

Results: Statistical analysis showed significantly higher methylation in the prostate cancer tissue samples in comparison with matched normal samples for GSTP1 (P = 0.0001 for AA; P = 0.0008 for Cau), RARβ2 (P < 0.001 for AA and Cau), SPARC (P < 0.0001 for AA and Cau), TIMP3 (P < 0.0001 for AA and Cau), and NKX2-5 (P < 0.0001 for AA; P = 0.003 for Cau). Overall, we observed significant differences (P < 0.05) in the methylation level for all genes, except GSTP1, in the AA samples in comparison with the Cau samples. Furthermore, regression analysis revealed significantly higher methylation for NKX2-5 (P = 0.008) and TIMP3 (P = 0.039) in normal prostate tissue samples from AA in comparison with Cau, and a statistically significant association of methylation with age for NKX2-5 (P = 0.03) after adjusting for race.

Conclusion: Our findings show higher methylation of several genes in prostate tissue samples from AA in comparison with Cau and may potentially contribute to the racial differences that are observed in prostate cancer pathogenesis. Clin Cancer Res; 16(14); 3539–47. ©2010 AACR.
Metronomic Gemcitabine in Combination with Sunitinib Inhibits Multisite Metastasis and Increases Survival in an Orthotopic Model of Pancreatic Cancer
Authors: Tran Cao Hop S. , Bouvet Michael , Kaushal Sharmeela , Keleman Alex , Romney Eric , Kim Ginna , Fruehauf John , Imagawa David K. , Hoffman Robert M. , Katz Matthew H.G.
Published: July 2010

Metronomic chemotherapy suppresses growth of primary tumors and established metastases. However, its effect on metastatic progression is essentially unknown. We report the treatment of a metastatically competent model of pancreatic cancer with metronomic gemcitabine and sunitinib. Mice with orthotopic, red fluorescent protein-expressing, pancreatic cancer tumorgrafts were treated with gemcitabine on a metronomic (1 mg/kg daily, METG) or maximum tolerated dose (150 mg/kg twice weekly, MTDG) schedule with or without sunitinib (SU). Rates of primary tumor growth, metastasis, ascites, and survival were calculated. Gemcitabine at a daily dose of 2 mg or greater led to toxicity within 1 month in mice without tumors but METG at 1 mg/kg/d was well tolerated. Mice with pancreatic cancer tumorgrafts died with metastatic disease at a median of 25 days. METG/SU significantly prolonged median overall survival (44 days) compared with control or either regimen alone (P < 0.05). Primary tumor growth was inhibited by METG/SU (P = 0.03) but neither METG nor sunitinib alone. In contrast, treatment with METG suppressed metastasis at multiple sites, an effect enhanced by sunitinib. MTDG with or without sunitinib had the most favorable effect on primary tumor growth and survival, but its antimetastatic efficacy was similar to that of METG/SU. von Willebrand factor expression was inhibited by METG. Antimetastatic activity approaching that of MTDG is achieved with a total dose reduced 42 times using METG and is further enhanced by sunitinib. Our results suggest the potential of this therapeutic paradigm against pancreatic cancer in the adjuvant and maintenance settings. Mol Cancer Ther; 9(7); 2068–78. ©2010 AACR.
Exon-Level Microarray Analyses Identify Alternative Splicing Programs in Breast Cancer
Authors: Lapuk Anna , Marr Henry , Jakkula Lakshmi , Pedro Helder , Bhattacharya Sanchita , Purdom Elizabeth , Hu Zhi , Simpson Ken , Pachter Lior , Durinck Steffen , Wang Nicholas , Parvin Bahram , Fontenay Gerald , Speed Terence , Garbe James , Stampfer Martha , Bayandorian Hovig , Dorton Shannon , Clark Tyson A. , Schweitzer Anthony , Wyrobek Andrew , Feiler Heidi , Spellman Paul , Conboy John , Gray Joe W.
Published: July 2010

Protein isoforms produced by alternative splicing (AS) of many genes have been implicated in several aspects of cancer genesis and progression. These observations motivated a genome-wide assessment of AS in breast cancer. We accomplished this by measuring exon level expression in 31 breast cancer and nonmalignant immortalized cell lines representing luminal, basal, and claudin-low breast cancer subtypes using Affymetrix Human Junction Arrays. We analyzed these data using a computational pipeline specifically designed to detect AS with a low false-positive rate. This identified 181 splice events representing 156 genes as candidates for AS. Reverse transcription-PCR validation of a subset of predicted AS events confirmed 90%. Approximately half of the AS events were associated with basal, luminal, or claudin-low breast cancer subtypes. Exons involved in claudin-low subtype–specific AS were significantly associated with the presence of evolutionarily conserved binding motifs for the tissue-specific Fox2 splicing factor. Small interfering RNA knockdown of Fox2 confirmed the involvement of this splicing factor in subtype-specific AS. The subtype-specific AS detected in this study likely reflects the splicing pattern in the breast cancer progenitor cells in which the tumor arose and suggests the utility of assays for Fox-mediated AS in cancer subtype definition and early detection. These data also suggest the possibility of reducing the toxicity of protein-targeted breast cancer treatments by targeting protein isoforms that are not present in limiting normal tissues. Mol Cancer Res; 8(7); 961–74. ©2010 AACR.
New Role of (−)-Epicatechin in Enhancing the Induction of Growth Inhibition and Apoptosis in Human Lung Cancer Cells by Curcumin
Authors: Saha Achinto , Kuzuhara Takashi , Echigo Noriko , Suganuma Masami , Fujiki Hirota
Published: July 2010

Curcumin, a phenolic compound isolated from the plant Curcuma longa (Linn), is ingested every day in the Indian subcontinent and is well reported to possess cancer-preventive activity. To achieve effective cancer prevention with curcumin, we need to find a new method to enhance the effects of curcumin in the diet. Based on our evidence that (−)-epicatechin (EC), an inert catechin, enhances the cancer-preventive activity of green tea catechins, we studied the enhancing effects of EC on inductions of growth inhibition and apoptosis in human lung cancer cell lines PC-9 and A549 with curcumin. The combination of curcumin with EC significantly increased the inhibition of cell growth compared with curcumin or EC alone. The combination similarly increased both apoptosis and expression of GADD153 and GADD45 genes, associated with their enhanced protein production. Knockdown of GADD153 or GADD45 by small interfering RNA abrogated the apoptosis induction and growth inhibition induced by the combination, indicating the crucial role of their upregulation. Treatments of PC-9 cells with c-Jun-NH2-kinase inhibitor SP600125, with p38 mitogen-activated protein kinase inhibitor SB202190 and with PD98059 (extracellular signal-regulated kinase 1/2 inhibitor) all increased the upregulation of GADD153 and GADD45 genes by the combination. Because EC was previously shown to enhance the incorporation of EGCG into PC-9 cells, we think that EC has similar effects on curcumin. This report is the first report on the enhancing effects of EC on curcumin, and the data suggest that EC plays a significant role in the enhancement of the cancer-preventive activity of curcumin in the diet. Cancer Prev Res; 3(8); 953–62. ©2010 AACR.
Human GnRH Deficiency: A Unique Disease Model to Unravel the Ontogeny of GnRH Neurons
Authors: Balasubramanian Ravikumar , Dwyer Andrew , Seminara Stephanie B. , Pitteloud Nelly , Kaiser Ursula B. , Crowley, Jr. William F.
Published: July 2010

Evolutionary survival of a species is largely a function of its reproductive fitness. In mammals, a sparsely populated and widely dispersed network of hypothalamic neurons, the gonadotropin-releasing hormone (GnRH) neurons, serve as the pilot light of reproduction via coordinated secretion of GnRH. Since it first description, human GnRH deficiency has been recognized both clinically and genetically as a heterogeneous disease. A spectrum of different reproductive phenotypes comprised of congenital GnRH deficiency with anosmia (Kallmann syndrome), congenital GnRH deficiency with normal olfaction (normosmic idiopathic hypogonadotropic hypogonadism), and adult-onset hypogonadotropic hypogonadism has been described. In the last two decades, several genes and pathways which govern GnRH ontogeny have been discovered by studying humans with GnRH deficiency. More importantly, detailed study of these patients has highlighted the emerging theme of oligogenicity and genotypic synergism, and also expanded the phenotypic diversity with the documentation of reversal of GnRH deficiency later in adulthood in some patients. The underlying genetic defect has also helped understand the associated nonreproductive phenotypes seen in some of these patients. These insights now provide practicing clinicians with targeted genetic diagnostic strategies and also impact on clinical management.
The Caries-Preventive Effect of Chlorhexidine Varnish in Children and Adolescents: A Systematic Review
Authors: James P. , Parnell C. , Whelton H.
Published: July 2010

Aims: Our purpose was to systematically review the literature on the effectiveness of chlorhexidine varnish for preventing dental caries in children and adolescents and to determine its effectiveness compared to fluoride varnish. Methods: MEDLINE, EMBASE and the Cochrane Library were searched through December 2009 to identify relevant randomised trials with blind outcome assessment and a minimum duration of 1 year. The search was later updated in MEDLINE and the Cochrane Library to March 19th, 2010. Risk of bias of the included trials was assessed. The primary outcome was the caries increment. Results: Twelve trials met the inclusion criteria for the review. There was considerable variation between trials in the concentration and frequency of application of the chlorhexidine varnish, in baseline caries levels and in background exposure to fluoride. Six parallel-group trials reported no statistically significant difference in caries increment in permanent teeth with the application of chlorhexidine varnish compared to placebo or no treatment. The results of 4 split-mouth trials were conflicting: 2 trials found no significant difference in caries increment and 2 reported statistically significant results in favour of chlorhexidine varnish. One trial of the effect of chlorhexidine varnish in primary teeth demonstrated a statistically significant reduction in caries increment. The results of 1 trial comparing chlorhexidine varnish with fluoride varnish for preventing caries in adolescents were equivocal. Conclusion: Evidence regarding the effectiveness of chlorhexidine varnish for preventing caries is inconclusive. Further well-conducted randomised trials are required before chlorhexidine varnish can be recommended for caries prevention.
B-Type Natriuretic Peptide Signal Peptide Circulates in Human Blood
Authors: Siriwardena Maithri , Kleffmann Torsten , Ruygrok Peter , Cameron Vicky A. , Yandle Tim G. , Nicholls M. Gary , Richards A. Mark , Pemberton Chris J.
Published: July 2010

Background—

The diagnosis of cardiac necrosis such as myocardial infarction can be difficult and relies on the use of circulating protein markers like troponin. However, there is a clear need to identify circulating, specific biomarkers that can detect cardiac ischemia without necrosis.

Methods and Results—

Using specific immunoassay and tandem mass spectrometry, we show that a fragment derived from the signal peptide of B-type natriuretic peptide (BNPsp) not only is detectable in cytosolic extracts of explant human heart tissue but also is secreted from the heart into the circulation of healthy individuals. Furthermore, plasma levels of BNPsp in patients with documented acute ST-elevation myocardial infarction (n=25) rise to peak values (≈3 times higher than the 99th percentile of the normal range) significantly earlier than the currently used biomarkers myoglobin, creatine kinase-MB, and troponin. Preliminary receiver-operating characteristic curve analysis comparing BNPsp concentrations in ST-elevation myocardial infarction patients and other patient groups was positive (area under the curve=0.97;
P
<0.001), suggesting that further, more rigorous studies in heterogeneous chest pain patient cohorts are warranted.

Conclusion—

Our results demonstrate for the first time that BNPsp exists as a distinct entity in the human circulation and could serve as a new class of circulating biomarker with the potential to accelerate the clinical diagnosis of cardiac ischemia and myocardial infarction.

Clinical Trial Registration—

URL: http://www.anzctr.org.au. Unique identifier: ACTRN12609000040268.
Bystander-Initiated Rescue Breathing for Out-of-Hospital Cardiac Arrests of Noncardiac Origin
Authors: Kitamura Tetsuhisa , Iwami Taku , Kawamura Takashi , Nagao Ken , Tanaka Hideharu , Hiraide Atsushi
Published: July 2010

Background—

Although chest compression-only cardiopulmonary resuscitation (CPR) is effective for adult out-of-hospital cardiac arrest (OHCA) of cardiac origin, it remains uncertain whether bystander-initiated rescue breathing has an incremental benefit for OHCA of noncardiac origin.

Methods and Results—

A nationwide, prospective, population-based, observational study covering the whole population of Japan and involving consecutive OHCA patients with emergency responder resuscitation attempts was conducted from January 2005 through December 2007. The primary outcome was neurologically intact 1-month survival. Multiple logistic regression analysis was used to assess the contribution of bystander-initiated CPR to better neurological outcomes. Among a total of 43 246 bystander-witnessed OHCAs of noncardiac origin, 8878 (20.5%) received chest compression-only CPR, and 7474 (17.3%) received conventional CPR with rescue breathing. The conventional CPR group (1.8%) had a higher rate of better neurological outcome than both the no CPR group (1.4%; odds ratio, 1.58; 95% confidence interval, 1.28 to 1.96) and the compression-only CPR group (1.5%; odds ratio, 1.32; 95% confidence interval, 1.03 to 1.69). However, the compression-only CPR group did not produce better neurological outcome than the no CPR group (odds ratio, 1.19; 95% confidence interval, 0.96 to 1.47). The number of OHCAs needed to treat with conventional CPR versus compression-only CPR to save a life with favorable neurological outcome after OHCA was 290.

Conclusions—

This nationwide observational study indicates that rescue breathing has an incremental benefit for OHCAs of noncardiac origin, but the impact on the overall survival after OHCA was small.
Left Atrial Appendage
Authors: Di Biase Luigi , Burkhardt J. David , Mohanty Prasant , Sanchez Javier , Mohanty Sanghamitra , Horton Rodney , Gallinghouse G. Joseph , Bailey Shane M. , Zagrodzky Jason D. , Santangeli Pasquale , Hao Steven , Hongo Richard , Beheiry Salwa , Themistoclakis Sakis , Bonso Aldo , Rossillo Antonio , Corrado Andrea , Raviele Antonio , Al-Ahmad Amin , Wang Paul , Cummings Jennifer E. , Schweikert Robert A. , Pelargonio Gemma , Dello Russo Antonio , Casella Michela , Santarelli Pietro , Lewis William R. , Natale Andrea
Published: July 2010

Background—

Together with pulmonary veins, many extrapulmonary vein areas may be the source of initiation and maintenance of atrial fibrillation. The left atrial appendage (LAA) is an underestimated site of initiation of atrial fibrillation. Here, we report the prevalence of triggers from the LAA and the best strategy for successful ablation.

Methods and Results—

Nine hundred eighty-seven consecutive patients (29% paroxysmal, 71% nonparoxysmal) undergoing redo catheter ablation for atrial fibrillation were enrolled. Two hundred sixty-six patients (27%) showed firing from the LAA and became the study population. In 86 of 987 patients (8.7%; 5 paroxysmal, 81 nonparoxysmal), the LAA was found to be the only source of arrhythmia with no pulmonary veins or other extrapulmonary vein site reconnection. Ablation was performed either with focal lesion (n=56; group 2) or to achieve LAA isolation by placement of the circular catheter at the ostium of the LAA guided by intracardiac echocardiography (167 patients; group 3). In the remaining patients, LAA firing was not ablated (n=43; group 1). At the 12±3-month follow-up, 32 patients (74%) in group 1 had recurrence compared with 38 (68%) in group 2 and 25 (15%) in group 3 (
P
<0.001).

Conclusions—

The LAA appears to be responsible for arrhythmias in 27% of patients presenting for repeat procedures. Isolation of the LAA could achieve freedom from atrial fibrillation in patients presenting for a repeat procedure when arrhythmias initiating from this structure are demonstrated.
Role of Prolylcarboxypeptidase in Angiotensin II Type 2 Receptor–Mediated Bradykinin Release in Mouse Coronary Artery Endothelial Cells
Authors: Zhu Liping , Carretero Oscar A. , Liao Tang-Dong , Harding Pamela , Li Hongwei , Sumners Colin , Yang Xiao-Ping
Published: July 2010

Activation of angiotensin II type 2 receptors (AT2R) causes the release of kinins, which have beneficial effects on the cardiovascular system. However, it is not clear how AT2R interact with the kallikrein-kinin system to generate kinins. Prolylcarboxypeptidase is an endothelial membrane-bound plasma prekallikrein activator that converts plasma prekallikrein to kallikrein, leading to generation of bradykinin from high-molecular-weight kininogen. We hypothesized that AT2R-induced bradykinin release is at least in part mediated by activation of prolylcarboxypeptidase. Cultures of mouse coronary artery endothelial cells were transfected with an adenoviral vector containing the AT2R gene (Ad-AT2R) or green fluorescent protein only (Ad-GFP) as control. We found that overexpression of AT2R increased prolylcarboxypeptidase mRNA by 1.7-fold and protein 2.5-fold compared with Ad-GFP controls. AT2R overexpression had no effect on angiotensin II type 1 receptor mRNA. Bradykinin release was increased 2.2-fold in AT2R-transfected cells. Activation of AT2R by CGP42112A, a specific AT2R agonist, increased bradykinin further in AT2R-transfected cells. These effects were diminished or abolished by AT2R blockade or a plasma kallikrein inhibitor. Furthermore, blocking prolylcarboxypeptidase with a small interfering RNA partially but significantly reduced bradykinin release by transfected AT2R cells either at the basal condition or when stimulated by the AT2R agonist CGP42112A. These findings suggest that overexpression of AT2R in mouse coronary artery endothelial cells increases expression of prolylcarboxypeptidase, which may contribute to kinin release.
Longer Time Spent in Light Physical Activity Is Associated With Reduced Arterial Stiffness in Older Adults
Authors: Gando Yuko , Yamamoto Kenta , Murakami Haruka , Ohmori Yumi , Kawakami Ryoko , Sanada Kiyoshi , Higuchi Mitsuru , Tabata Izumi , Miyachi Motohiko
Published: July 2010

Habitual moderate-to-vigorous–intensity physical activity attenuates arterial stiffening. However, it is unclear whether light physical activity also attenuates arterial stiffening. It is also unclear whether light physical activity has the same effects in fit and unfit individuals. This cross-sectional study was performed to determine the relationships between amount of light physical activity determined with a triaxial accelerometer and arterial stiffness. A total of 538 healthy men and women participated in this study. Subjects in each age category were divided into either high-light or low-light physical activity groups based on daily time spent in light physical activity. Arterial stiffness was measured by carotid-femoral pulse wave velocity. Two-way ANOVA indicated a significant interaction between age and time spent in light physical activity in determining carotid-femoral pulse wave velocity (
P
<0.05). In the older group, carotid femoral pulse wave velocity was higher in the low-light physical activity level group than in the high-light physical activity level group (945±19 versus 882±16 cm/s;
P
<0.01). The difference remained significant after normalizing carotid-femoral pulse wave velocity for amounts of moderate and vigorous physical activity. The carotid-femoral pulse wave velocity (
r
=−0.47;
P
<0.01) was correlated with daily time spent in light physical activity in older unfit subjects. No relationship was observed in older fit subjects. These results suggested that longer time spent in light physical activity is associated with attenuation of arterial stiffening, especially in unfit older people.