bluuebunny/crossref_metadata_2025 huggingface dataset:
Radiocarbon dates from Anthony Island, Queen Charlotte Islands, and their geological and archaeological significance
Authors: Hebda Richard J. , Mathewes Rolf W.
Published: January 2011

Seven samples of peat or wood were collected from four small sedimentary basins on Anthony Island. Elevations of these sites range between 31.1 and 2.5 m above mean sea level. Radiocarbon dates from these indicate that sea level has not exceeded 31.1 m since 12 300 years ago. Furthermore, sea level has been less than 12.7 m above mean sea level since about 4000 BP and has declined at about 2.5 m/1000 years. A well-defined scarp with relict surge channels and sea caves may define the postglacial mean sea-level maximum at about 12–15 m. A date of 1750 ± 120 BP at the base of a pond is particularly significant, since it places a maximum possible age on the Skung-gwai village site (UNESCO World Heritage Site) and other known archaeological sites near present sea level.
Iron phosphate precipitation by epilithic microbial biofilms in Arctic Canada
Authors: Konhauser K. O. , Fyfe W. S. , Schultze-Lam S. , Ferris F. G. , Beveridge T. J.
Published: January 2011

On Ellesmere Island, in the Canadian Arctic, dark-colored biofilms proliferate on moist surfaces, including exposed granodiorite outcrops. Transmission electron microscopy of these biofilms indicates that complex epilithic microbial communities developed, consisting of cyanobacteria and fungi symbiotically associated in a lichen, along with a consortium of free-living algae and gram-negative bacteria. The epilithic cyanobacteria and bacteria were shown to extensively precipitate phosphatic minerals, ranging from relatively large polyphosphate granules (approximately 250 nm in diameter) within their cytoplasmic membranes to smaller iron phosphate grains (generally less than 50 nm in diameter) associated with the periplasmic space and encompassing capsule. Complete encrustation of some bacterial cells by the iron phosphates was observed. Energy-dispersive X-ray spectroscopy suggested that these grains are compositionally similar to the mineral strengite (FePO4∙2H2O). This study clearly indicates that the Arctic supports a thriving microbial community that influences the biogeochemical cycling of PO4 in an environment of low nutrient availability. Nutritional requirements by the microorganisms were actively maintained through a relatively closed recycling mechanism, which restricted the immediate loss of phosphorus from the biofilm.
Petrology of the ultramafic lamprophyre and associated rocks at Coral Rapids, Abitibi River, Ontario
Authors: Edgar A. D. , Pizzolato L. A. , Butler G. M.
Published: January 2011

An ultramafic lamprophyre sill and dikes, and an olivine–melilite-rich dike rock intrude Lower to Middle Devonian sediments and low- to high-grade Archean metamorphic rocks on the west bank of the Abitibi River, Coral Rapids, Ontario. Although previously considered to be kimberlitic, all these rocks contain olivine + clinopyroxene + phlogopite ± melilite, and hence are ultramafic alkaline rocks. The ultramafic lamprophyre can be distinguished from the dike by its lower SiO2, Na2O, Al2O3, and higher MgO and FeO. In contrast the olivine–melilite dike rock has a more uniform composition, characteristically contains melilite, and has higher Cr and Ni contents. Enriched light rare earth element (LREE) chondrite-normalized patterns are similar for all rocks.Olivine, clinopyroxene, and phlogopite have Mg# (Mg# = 100 Mg/(Mg + Fe) mol) typical of minerals in primitive alkaline rocks. Melilite composition is similar to that of igneous melilites. Phlogopites in all rock types are enriched in Ba and F and the degree of enrichment is distinct for each rock type. Accessory minerals include apatite, carbonates, chlorite, sericite, and sodalite (only in the olivine–melilite-bearing rock).The mineralogy and chemistry of the Coral Rapids rocks suggest that they are derived from a primitive olivine melilitite magma that may have evolved by fractionation of small amounts of olivine and clinopyroxene to form these alkaline ultramafic magmas.Xenoliths in the ultramafic lamprophyre sill and in lesser abundance in the olivine–melilite dike rock include olivine, phlogopite, and clinopyroxene-rich mantle-derived assemblages. The similarity between these xenoliths and their host rocks at Coral Rapids and those from southwest Uganda and West Eifel, Germany, suggests that the Coral Rapids rocks may be derived from magmas that originated from metasomatized mantle sources.
Toward a determination of the fine structure constant at LNE by means of a new Thompson–Lampard calculable capacitorThis paper was presented at the International Conference on Precision Physics of Simple Atomic Systems, held at École de Physique, les Houches, France, 30 May – 4 June, 2010.
Authors: Gournay P. , Thévenot O. , Dupont L. , David J. M. , Piquemal F.
Published: January 2011

This paper reports on the current development of a new Thompson–Lampard calculable capacitor at LNE. The goal is to determine the von Klitzing constant RK at a significant level of uncertainty of about one part in 108. The comparison with other accurate measurements of h/e2 serves as a relevant test of validity of the theory predicting RK = h/e2, a decisive issue within the context of the new SI. Conversely, assuming that this relation is exact, the measurement of RK and thus that of the fine structure constant α can be used for testing quantum electrodynamics theory. The mechanical structure of the new LNE calculable cross capacitor has been designed and a new set of electrodes has been fabricated. The assembling of the calculable capacitor is in progress.
Towards a direct measurement of the g-factor of a single isolated protonThis paper was presented at the International Conference on Precision Physics of Simple Atomic Systems, held at École de Physique, les Houches, France, 30 May–4 June, 2010.
Authors: Mooser Andreas , Blaum Klaus , Kracke Holger , Kreim Susanne , Quint Wolfgang , Rodeghéri Cricia , Ulmer Stefan , Walz Jochen
Published: January 2011

Our Penning trap experiment aims at a direct high-precision measurement of the proton g-factor. We present the experimental setup and the measurement technique using the continuous Stern-Gerlach effect. Recent test measurements with a single proton stored in a Penning trap with a strong magnetic bottle and a new toroidal detection system are discussed. For a stringent test of the CPT symmetry the described technique can also be applied to the antiproton.
Can CP-violation be observed in heavy-ion collisions?This paper was presented at the International Conference on Precision Physics of Simple Atomic Systems, held at École de Physique, les Houches, France, 30 May – 4 June, 2010.
Authors: Khriplovich I. B. , Rudenko A. S.
Published: January 2011

We demonstrate that, at least at present, there is no convincing way to detect CP-violation in heavy-ion collisions.
ARE ASIAN MIGRANTS DISCRIMINATED AGAINST IN THE LABOR MARKET? A CASE STUDY OF AUSTRALIA
Authors: JUNANKAR P. N. , PAUL SATYA , YASMEEN WAHIDA
Published: January 2011

This paper explores the issue of discrimination against Asian migrants relative to their non-Asian counterparts in the Australian labour market. A unique and consistent data set from three waves of the Longitudinal Survey of Immigrants to Australia (LSIA, 1993–95) is used to estimate probit models of the probability of being unemployed separately for males and females of Asian and non-Asian origins. The unemployment probability gap between the two migrant groups is decomposed into two components, the first associated with differences in their human capital and other demographic characteristics, and the second with differences in their impacts (called discrimination). The results provide an evidence of discrimination against Asian male migrants in all three waves. Discrimination against Asian females is detected only in the first wave. The Asian females who are professionals and can speak English 'well' are rather favoured relative to their non-Asian counterparts. Thus, the empirical evidence on discrimination against migrants of Asian origin is mixed.
AN INSTITUTIONAL PERSPECTIVE OF NATIONAL COMPETITIVENESS
Authors: LEE CASSEY
Published: January 2011

The literature on the role of institutions in economic growth and development is well-established. In contrast, the relationship between institutional quality and competitiveness, while important, received much less attention until recently, when there has been a growing interest in incorporating variables representing institutional quality into country competitiveness indices. Such attempts take cognizance of the results from cross-country empirical findings. However, any attempt to construct a satisfactory mapping of institutions to competitiveness is fraught with difficulties, including data consistencies, omission of causal factors and the lack of theoretical foundations. Some of these difficulties stem from differences in the overall objectives of the research literature and the development of competitiveness indices. The research literature can explain why, whether and what type of institutions are important, but such findings do not lend themselves to the construction of appropriate policy variables.
RECONSTRUCTION OF NEW HOLOGRAPHIC SCALAR FIELD MODELS OF DARK ENERGY IN BRANS–DICKE UNIVERSE
Authors: YANG WEI-QIANG , WU YA-BO , SONG LI-MIN , SU YANG-YANG , LI JIAN , ZHANG DAN-DAN , WANG XIAO-GANG
Published: January 2011

Motivated by the work: K. Karami and J. Fehri, Phys. Lett. B684, 61 (2010) and A. Sheykhi, Phys. Lett. B681, 205 (2009), we generalize their work to the new holographic dark energy model with [Formula: see text] in the framework of Brans–Dicke cosmology. Concretely, we study the correspondence between the quintessence, tachyon, K-essence, dilaton scalar field and Chaplygin gas model with the new holographic dark energy model in the non-flat Brans–Dicke universe. Furthermore, we reconstruct the potentials and dynamics for these models. By analysis we can show that for new holographic quintessence and Chaplygin gas models, if the related parameters to the potentials satisfy some constraints, the accelerated expansion can be achieved in Brans–Dicke cosmology. In particular, the counterparts of fields and potentials in general relativity can describe accelerated expansion of the universe. It is worth stressing that not only can we give some new results in the framework of Brans–Dicke cosmology, but also the previous results of the new holographic dark energy in Einstein gravity can be included as special cases given by us.
A LOGICAL FORMULATION OF ROUGH SET DEFINABILITY
Authors: FAN TUAN-FANG , LIAU CHURN-JUNG , LIU DUEN-REN
Published: January 2011

In data mining problems, data is usually provided in the form of data tables. To represent knowledge discovered from data tables, a decision logic (DL) is proposed in rough set theory. DL is an instance of propositional logic, but we can use other logical formalisms to describe data tables. In this paper, we propose two descriptions of data tables based on first-order data logic (FODL) and attribute value-sorted logic (AVSL) respectively. In the context of FODL, we show that explicit definability and implicit definability in classical logic implies the notion of definability in rough set theory. We also show that AVSL is particularly useful for the representation of properties of many-valued data tables.
RANKING DECISION MAKING UNITS BY MEANS OF SOFT COMPUTING DEA MODELS
Authors: BOSCÁ JOSÉ E. , LIERN VICENTE , SALA RAMÓN , MARTÍNEZ AURELIO
Published: January 2011

This paper presents a method for ranking a set of decision making units according to their level of efficiency and which takes into account uncertainty in the data. Efficiency is analysed using fuzzy DEA techniques and the ranking is based on the statistical analysis of cases that include representative situations. The method enables the removal of the sometimes unrealistic hypothesis of a perfect trade-off between increased inputs and outputs. This model is compared with other DEA models that work with imprecise or fuzzy data. As an illustration, we apply our ranking method to the evaluation of a group of Spanish seaports, as well as teams playing in the Spanish football league. We compare the results with other methods and we show that our method enables a total ranking of the seaports, and that the ranking of football teams is found to be more consistent with final league positions.
MULTIPLE POSITIVE SOLUTIONS FOR SEMIPOSITONE (n, p)-TYPE BOUNDARY VALUE PROBLEMS OF NONLINEAR FRACTIONAL DIFFERENTIAL EQUATIONS
Authors: YUAN CHENGJUN
Published: January 2011

In this paper, we consider the (n, p)-type boundary value problem of nonlinear fractional differential equation [Formula: see text] where λ is a parameter, α ∈ (n - 1, n] is a real number and n ≥ 3, 1 ≤ p ≤ α - 1 is fixed and integer, [Formula: see text] is the Riemann–Liouville's fractional derivative, and f is continuous and semipositone. We derive an interval of λ such that any λ lying in this interval, the semipositone boundary value problem has multiple positive solutions.
SOLUTION TO SYSTEM OF PARTIAL FRACTIONAL DIFFERENTIAL EQUATIONS USING THE $\mathcal{L}_2$-TRANSFORM
Authors: AGHILI A. , ANSARI A.
Published: January 2011

In this paper, the authors apply complex inversion formula for the [Formula: see text]-transform and also show some applications of the [Formula: see text]-transform for solving of singular integral equation with trigonometric kernel and system of partial fractional differential equations.
Pancreatic islet-specific overexpression of Reg3β protein induced the expression of pro-islet genes and protected the mice against streptozotocin-induced diabetes mellitus
Authors: Xiong Xiaoquan , Wang Xiao , Li Bing , Chowdhury Subrata , Lu Yarong , Srikant Coimbatore B. , Ning Guang , Liu Jun-Li
Published: January 2011

Reg family proteins have been implicated in islet β-cell proliferation, survival, and regeneration. The expression of Reg3β (pancreatitis-associated protein) is highly induced in experimental diabetes and acute pancreatitis, but its precise role has not been established. Through knockout studies, this protein was shown to be mitogenic, antiapoptotic, and anti-inflammatory in the liver and pancreatic acinars. To test whether it can promote islet cell growth or survival against experimental damage, we developed β-cell-specific overexpression using rat insulin I promoter, evaluated the changes in normal islet function, gene expression profile, and the response to streptozotocin-induced diabetes. Significant and specific overexpression of Reg3β was achieved in the pancreatic islets of RIP-I/Reg3β mice, which exhibited normal islet histology, β-cell mass, and in vivo and in vitro insulin secretion in response to high glucose yet were slightly hyperglycemic and low in islet GLUT2 level. Upon streptozotocin treatment, in contrast to wild-type littermates that became hyperglycemic in 3 days and lost 15% of their weight, RIP-I/Reg3β mice were significantly protected from hyperglycemia and weight loss. To identify specific targets affected by Reg3β overexpression, a whole genome DNA microarray on islet RNA isolated from the transgenic mice revealed more than 45 genes significantly either up- or downregulated. Among them, islet-protective osteopontin/SPP1 and acute responsive nuclear protein p8/NUPR1 were significantly induced, a result further confirmed by real-time PCR, Western blots, and immunohistochemistry. Our results suggest that Reg3β is unlikely an islet growth factor but a putative protector that prevents streptozotocin-induced damage by inducing the expression of specific genes.
Endothelium-derived microparticles inhibit angiogenesis in the heart and enhance the inhibitory effects of hypercholesterolemia on angiogenesis
Authors: Ou Zhi-Jun , Chang Feng-Jun , Luo Dan , Liao Xiao-Long , Wang Zhi-Ping , Zhang Xi , Xu Ying-Qi , Ou Jing-Song
Published: January 2011

Therapeutic angiogenesis remains unsuccessful in coronary artery disease. It is known that plasma endothelium-derived microparticles (EMPs) are increased in coronary artery disease and that hypercholesterolemia can inhibit angiogenesis. We evaluated the relationship between EMPs and hypercholesterolemia in the impairment of angiogenesis. EMPs isolated from human umbilical vein endothelial cells were injected into low-density lipoprotein receptor-null (LDLr−/−) mice fed a Western diet for 2 wk and C57BL6 mice for 6 h or were directly added to the tissue culture media. Hearts isolated from mice were sectioned and cultured, and endothelial tube formation was measured. The expression and phosphorylation of endothelial NO synthase (eNOS) and the generation of NO in the hearts were determined. Angiogenesis was inhibited by pathophysiological concentrations of EMPs but not physiological concentrations of EMPs in hearts from C57BL6 mice. However, angiogenesis was inhibited by EMPs at both physiological and pathophysiological concentrations of EMPs in hearts from hypercholesterolemic LDLr−/−mice. Pathophysiological concentrations of EMPs decreased eNOS phosphorylation at Ser1177and NO generation without altering eNOS expression in hearts from C57BL6 mice. Both physiological and pathophysiological concentrations of EMPs decreased not only eNOS phosphorylation at Ser1177and NO generation, but eNOS expression in hypercholesterolemic hearts from LDLr−/−mice. These data demonstrated that pathophysiological concentrations of EMPs could inhibit angiogenesis in hearts by decreasing eNOS activity. EMPs and hypercholesterolemia mutually enhanced their inhibitory effect of angiogenesis by inducing eNOS dysfunction. Our findings suggest a novel mechanism by which hypercholesterolemia impairs angiogenesis.
MicroRNA expression profile during adipogenic differentiation in mouse embryonic stem cells
Authors: Knelangen Julia M. , van der Hoek Mark B. , Kong Wee-Ching , Owens Julie A. , Fischer Bernd , Santos Anne Navarrete
Published: January 2011

Pluripotent embryonic stem cells (ESC) have the potential to differentiate into any cell type of the three germ layers. Differentiation processes depend on genetic and epigenetic factors. The guidance of cell fate determination by microRNAs (miRs) seems important for embryonic development and cell lineage decisions. MiRs are short, single-stranded, noncoding RNA molecules that regulate through posttranscriptional modulation, a subset of target genes involved in cell differentiation and specific cell function. We have used microarray profiling of miRs in the mouse embryonic stem cell line CGR8. Comparison of the miR profiles of undifferentiated stem cells with mesodermal progenitors cells ( day 5), preadipocytes ( day 10), and adipocytes ( day 21) showed that the expression level of 129 miRs changed (twofold) during adipogenic differentiation. We identified 10 clusters of differentially expressed miRs, which contain putative markers and regulators of mesodermal differentiation and cell fate determination into adipocytes. Notably, the adipocyte-specific miRs 143 and 103 were upregulated from day 10 onward. We have therefore demonstrated and characterized the dynamic profile of miR expression during murine adipogenic differentiation in vitro, including the initial differentiation from ESC via mesenchymal progenitors up to adipocytes. Our findings and experimental approach provide a suitable system to directly interrogate the role of miRs during adipogenic differentiation of embryonic stem cells.
Rumen epithelial adaptation to high-grain diets involves the coordinated regulation of genes involved in cholesterol homeostasis
Authors: Steele Michael A. , Vandervoort Gordon , AlZahal Ousama , Hook Sarah E. , Matthews James C. , McBride Brian W.
Published: January 2011

The molecular mechanisms underlying rumen epithelial adaption to high-grain (HG) diets are unknown. To gain insight into the metabolic mechanisms governing epithelial adaptation, mature nonlactating dairy cattle ( n = 4) were transitioned from a high-forage diet (HF, 0% grain) to an HG diet (65% grain). After the cattle were fed the HG diet for 3 wk, they returned to the original HF diet, which they were fed for an additional 3 wk. Continuous ruminal pH, ruminal short chain fatty acids, and plasma β-hydroxybutyrate were measured on a weekly basis, and rumen papillae were biopsied from the ventral sac to assess alterations in mRNA expression profiles. The subacute form of ruminal acidosis was diagnosed during the first week of the HG period (4.6 ± 1.6 h/day <pH 5.6), but not during weeks 2 and 3, thereby indicating ruminal adaption to the HG diet. Changes in the mRNA expression profile of rumen papillae were initially examined using Bovine Affymetrix microarrays; a total of 521 differentially expressed genes (false discovery rate P < 0.08) were uncovered from the first to third week of the HG period. Ingenuity Pathway Analysis of microarray results revealed that enzymes involved in cholesterol synthesis were coordinately downregulated from the first to third week of the HG period. In addition, the LXR/RXR activation pathway was significant and included several genes involved in intracellular cholesterol homeostasis. The differential expression signature of eight genes representing the key regulatory points of cholesterol homeostasis was confirmed by quantitative real-time PCR. Based upon our pathway and network results we propose a model to explain cellular events during rumen epithelial adaptation to HG diets and thus provide molecular targets that may be useful in the treatment and prevention of ruminal acidosis.
Type 1 Diabetes: Etiology, Immunology, and Therapeutic Strategies
Authors: Van Belle Tom L. , Coppieters Ken T. , Von Herrath Matthias G.
Published: January 2011

Type 1 diabetes (T1D) is a chronic autoimmune disease in which destruction or damaging of the beta-cells in the islets of Langerhans results in insulin deficiency and hyperglycemia. We only know for sure that autoimmunity is the predominant effector mechanism of T1D, but may not be its primary cause. T1D precipitates in genetically susceptible individuals, very likely as a result of an environmental trigger. Current genetic data point towards the following genes as susceptibility genes: HLA, insulin, PTPN22, IL2Ra, and CTLA4. Epidemiological and other studies suggest a triggering role for enteroviruses, while other microorganisms might provide protection. Efficacious prevention of T1D will require detection of the earliest events in the process. So far, autoantibodies are most widely used as serum biomarker, but T-cell readouts and metabolome studies might strengthen and bring forward diagnosis. Current preventive clinical trials mostly focus on environmental triggers. Therapeutic trials test the efficacy of antigen-specific and antigen-nonspecific immune interventions, but also include restoration of the affected beta-cell mass by islet transplantation, neogenesis and regeneration, and combinations thereof. In this comprehensive review, we explain the genetic, environmental, and immunological data underlying the prevention and intervention strategies to constrain T1D.
Effects of Disturbed Flow on Vascular Endothelium: Pathophysiological Basis and Clinical Perspectives
Authors: Chiu Jeng-Jiann , Chien Shu
Published: January 2011

Vascular endothelial cells (ECs) are exposed to hemodynamic forces, which modulate EC functions and vascular biology/pathobiology in health and disease. The flow patterns and hemodynamic forces are not uniform in the vascular system. In straight parts of the arterial tree, blood flow is generally laminar and wall shear stress is high and directed; in branches and curvatures, blood flow is disturbed with nonuniform and irregular distribution of low wall shear stress. Sustained laminar flow with high shear stress upregulates expressions of EC genes and proteins that are protective against atherosclerosis, whereas disturbed flow with associated reciprocating, low shear stress generally upregulates the EC genes and proteins that promote atherogenesis. These findings have led to the concept that the disturbed flow pattern in branch points and curvatures causes the preferential localization of atherosclerotic lesions. Disturbed flow also results in postsurgical neointimal hyperplasia and contributes to pathophysiology of clinical conditions such as in-stent restenosis, vein bypass graft failure, and transplant vasculopathy, as well as aortic valve calcification. In the venous system, disturbed flow resulting from reflux, outflow obstruction, and/or stasis leads to venous inflammation and thrombosis, and hence the development of chronic venous diseases. Understanding of the effects of disturbed flow on ECs can provide mechanistic insights into the role of complex flow patterns in pathogenesis of vascular diseases and can help to elucidate the phenotypic and functional differences between quiescent (nonatherogenic/nonthrombogenic) and activated (atherogenic/thrombogenic) ECs. This review summarizes the current knowledge on the role of disturbed flow in EC physiology and pathophysiology, as well as its clinical implications. Such information can contribute to our understanding of the etiology of lesion development in vascular niches with disturbed flow and help to generate new approaches for therapeutic interventions.
Reduction of Mutual Coupling and Return Loss in Microstrip Array Antennas Using Concave Rectangular Patches
Authors: Mohanna Shahram , Farahbakhsh Ali , Tavakoli Saeed , Ghassemi Nasser
Published: January 2011

An effective solution to reduce both the mutual coupling and return loss of a microstrip array antenna consisting of rectangular patches is proposed. The patch is made concave in both horizontal and vertical sides. Applying the proposed structure to a microstrip array antenna having two elements, the effects of patch concavity on the mutual coupling and return loss are simulated and studied. To obtain a concave rectangular patch array antenna having low amounts of mutual coupling and return loss, the patch length and width as well as the amounts of concavities are optimized using an enhanced genetic algorithm. To verify the simulation results, then, the optimal array antenna is fabricated. The simulation and experimental results confirm that the optimal concave rectangular array antenna has low amounts of mutual coupling and return loss.
Effect of Water Velocity on the Timing of Skeletogenesis in the Arctic Charr,Salvelinus alpinus(Salmoniformes: Teleostei): An Empirical Case of Developmental Plasticity
Authors: Cloutier Richard , Caron Alain , Grünbaum Thomas , Le François Nathalie R.
Published: January 2011

Phenotypic plasticity has been demonstrated in fishes but rarely addressed with respect to skeletogenesis. The influence of water velocity on the sequence of chondrification and ossification is studied for the median fins of Arctic charr,Salvelinus alpinus, during a period of 90 days post hatching. Time of appearance, relative position within sequences, and direction of development among serially repeated elements are compared between two velocity treatments. Water velocity has induced changes in the timing of events and to a lesser extent on the relative sequence events in the locomotor system. Ossification is more responsive to water velocity than chondrification, and early-forming elements are less responding than late-forming elements. Directions of development are fairly conservative. It is suggested that a faster sustained swimming (behavioural adaptation to a higher water velocity) could induce differential mechanical stresses on developing skeletal elements involved in locomotion and therefore induce changes primarily in the timing of the ossification.
Accuracy Improvement of the Method of Multiple Scales for Nonlinear Vibration Analyses of Continuous Systems with Quadratic and Cubic Nonlinearities
Authors: Abe Akira
Published: January 2011

This paper proposes an accuracy improvement of the method of multiple scales (MMSs) for nonlinear vibration analyses of continuous systems with quadratic and cubic nonlinearities. As an example, we treat a shallow suspended cable subjected to a harmonic excitation, and investigate the primary resonance of the mth in‐plane mode (Ω ≈ ωm) in which Ω
and ωm are the driving and natural frequencies, respectively. The application of Galerkin′s procedure to the equation of motion yields nonlinear ordinary differential equations with quadratic and cubic nonlinear terms. The steady‐state responses are obtained by using the discretization approach of the MMS in which the definition of the detuning parameter, expressing the relationship between the natural frequency and the driving frequency, is changed in an attempt to improve the accuracy of the solutions. The validity of the solutions is discussed by comparing them with solutions of the direct approach of the MMS and the finite difference method.
Associations between HIV Antiretroviral Therapy and the Prevalence and Incidence of Pregnancy in Rakai, Uganda
Authors: Makumbi Fredrick. E. , Nakigozi Gertrude , Reynolds Steven. J. , Ndyanabo Anthony , Lutalo Tom , Serwada David , Nalugoda Fred , Wawer Maria , Gray Ron
Published: January 2011

Background. Use of antiretroviral therapy (ART) may be associated with higher pregnancy rates.Methods. The prevalence and incidence of pregnancy was assessed in 712 HIV+ pre-ART women of reproductive age (WRA) (15–45) and 244 HIV+ WRA initiating ART. Prevalence rate ratios (PRR), incidence rate ratios (IRR), and 95% confidence interval (CI) were assessed.Results. The incidence of pregnancy was 13.1/100 py among women in pre-ART care compared to 24.6/100 py among women on ART (IRR = 0.54; 95% CI 0.37, 0.81,p<0.0017). The prevalence of pregnancy at ART initiation was 12.0% with CD4 counts 100–250 compared with 3.2% with CD4 <100 (PRR = 3.24, CI 1.51–6.93), and the incidence of pregnancy while on ART was highest in women with a good immunologic response. Desire for more children was a very important factor in fertility.Conclusion. ART was associated with increased pregnancy rates in HIV+ women, particularly those with higher CD4 counts and good immunologic response to therapy, suggesting a need to strengthen reproductive health services for both women and their partners that could address their fertility decisions/intentions particularly after ART initiation.
Oscillation of Second‐Order Neutral Functional DifferentialEquations with Mixed Nonlinearities
Authors: Sun Shurong , Li Tongxing , Han Zhenlai , Sun Yibing
Published: January 2011

We study the following second‐order neutral functional differential equation with mixed nonlinearities +q0(t) | u(τ0(t))|α−1u(τ0(t))+q1(t) | u(τ1(t))|β−1u(τ1(t))+q2(t) | u(τ2(t))|γ−1u(τ2(t)) = 0, where γ > α > β > 0, . Oscillation results for the equation are established which improve the results obtained by Sun and Meng (2006), Xu and Meng (2006), Sun and Meng (2009), and Han et al. (2010).
Smad4 Inactivation Promotes Malignancy and Drug Resistance of Colon Cancer
Authors: Papageorgis Panagiotis , Cheng Kuanghung , Ozturk Sait , Gong Yi , Lambert Arthur W. , Abdolmaleky Hamid M. , Zhou Jin-Rong , Thiagalingam Sam
Published: January 2011

SMAD4 is localized to chromosome 18q21, a frequent site for loss of heterozygosity in advanced stage colon cancers. Although Smad4 is regarded as a signaling mediator of the TGFβ signaling pathway, its role as a major suppressor of colorectal cancer progression and the molecular events underlying this phenomenon remain elusive. Here, we describe the establishment and use of colon cancer cell line model systems to dissect the functional roles of TGFβ and Smad4 inactivation in the manifestation of a malignant phenotype. We found that loss of function of Smad4 and retention of intact TGFβ receptors could synergistically increase the levels of VEGF, a major proangiogenic factor. Pharmacologic inhibition studies suggest that overactivation of the TGFβ-induced MEK-Erk and p38-MAPK (mitogen-activated protein kinase) auxiliary pathways are involved in the induction of VEGF expression in SMAD4 null cells. Overall, SMAD4 deficiency was responsible for the enhanced migration of colon cancer cells with a corresponding increase in matrix metalloprotease 9 enhanced hypoxia-induced GLUT1 expression, increased aerobic glycolysis, and resistance to 5′-fluoruracil–mediated apoptosis. Interestingly, Smad4 specifically interacts with hypoxia-inducible factor (HIF) 1α under hypoxic conditions providing a molecular basis for the differential regulation of target genes to suppress a malignant phenotype. In summary, our results define a molecular mechanism that explains how loss of the tumor suppressor Smad4 promotes colorectal cancer progression. These findings are also consistent with targeting TGFβ-induced auxiliary pathways, such as MEK-ERK, and p38-MAPK and the glycolytic cascade, in SMAD4-deficient tumors as attractive strategies for therapeutic intervention. Cancer Res; 71(3); 998–1008. ©2011 AACR.
Tumor Cell Invasion Is Promoted by Interstitial Flow-Induced Matrix Priming by Stromal Fibroblasts
Authors: Shieh Adrian C. , Rozansky Hallie A. , Hinz Boris , Swartz Melody A.
Published: January 2011

Interstitial flow emanates from tumors into the microenvironment where it promotes tumor cell invasion. Fibroblasts are key constituents of the tumor stroma that modulate the mechanical environment by matrix remodeling and contraction. Here, we explore how interstitial fluid flow affects fibroblast–tumor cell interactions. Using a 3-dimensional invasion assay and MDA-MB-435S cells cocultured with dermal fibroblasts in a collagen matrix, we showed a synergistic enhancement of tumor cell invasion by fibroblasts in the presence of interstitial flow. Interstitial flow also drove transforming growth factor (TGF)-β1 and collagenase-dependent fibroblast migration, consistent with previously described mechanisms in which flow promotes invasion through autologous chemotaxis and increased motility. Concurrently, migrating fibroblasts enhanced tumor cell invasion by matrix priming via Rho-mediated contraction. We propose a model in which interstitial flow promotes fibroblast migration through increased TGF-β1 activation and collagen degradation, positioning fibroblasts to locally reorganize collagen fibers via Rho-dependent contractility, in turn enhancing tumor cell invasion via mechanotactic cues. This represents a novel mechanism in which interstitial flow causes fibroblast-mediated stromal remodeling that facilitates tumor invasion. Cancer Res; 71(3); 790–800. ©2011 AACR.
Hippo/Mst1 Stimulates Transcription of the Proapoptotic Mediator NOXA in a FoxO1-Dependent Manner
Authors: Valis Karel , Prochazka Lubomir , Boura Evzen , Chladova Jaromira , Obsil Tomas , Rohlena Jakub , Truksa Jaroslav , Dong Lan-Feng , Ralph Stephen J. , Neuzil Jiri
Published: January 2011

The proapoptotic protein Noxa, a member of the BH3-only Bcl-2 protein family, can effectively induce apoptosis in cancer cells, although the relevant regulatory pathways have been obscure. Previous studies of the cytotoxic effects of α-tocopheryl succinate (α-TOS) on cancer cells identified a mechanism whereby α-TOS caused apoptosis requiring the Noxa-Bak axis. In the present study, ab initio analysis revealed a conserved FoxO-binding site (DBE; DAF-16 binding element) in the NOXA promoter, and specific affinity of FoxO proteins to this DBE was confirmed by fluorescence anisotropy. FoxO1 and FoxO3a proteins accumulated in the nucleus of α-TOS–treated cells, and the drug-induced specific FoxO1 association with the NOXA promoter and its activation were validated by chromatin immunoprecipitation. Using siRNA knockdown, a specific role for the FoxO1 protein in activating NOXA transcription in cancer cells was identified. Furthermore, the proapoptotic kinase Hippo/Mst1 was found to be strongly activated by α-TOS, and inhibiting Hippo/Mst1 by specific siRNA prevented phosphorylation of FoxO1 and its nuclear translocation, thereby reducing levels of NOXA transcription and apoptosis in cancer cells exposed to α-TOS. Thus, we have demonstrated that anticancer drugs, exemplified by α-TOS, induce apoptosis by a mechanism involving the Hippo/Mst1-FoxO1-Noxa pathway. We propose that activation of this pathway provides a new paradigm for developing targeted cancer treatments. Cancer Res; 71(3); 946–54. ©2011 AACR.
Imaging Colon Cancer Response Following Treatment with AZD1152: A Preclinical Analysis of [18F]Fluoro-2-deoxyglucose and 3′-deoxy-3′-[18F]Fluorothymidine Imaging
Authors: Moroz Maxim A. , Kochetkov Tatiana , Cai Shangde , Wu Jiyuan , Shamis Mikhail , Nair Jayasree , de Stanchina Elisa , Serganova Inna , Schwartz Gary K. , Banerjee Debabrata , Bertino Joseph R. , Blasberg Ronald G.
Published: January 2011

Purpose: To determine whether treatment response to the Aurora B kinase inhibitor, AZD1152, could be monitored early in the course of therapy by noninvasive [18F]-labeled fluoro-2-deoxyglucose, [18F]FDG, and/or 3′-deoxy-3′-[18F]fluorothymidine, [18F]FLT, PET imaging.

Experimental design: AZD1152-treated and control HCT116 and SW620 xenograft-bearing animals were monitored for tumor size and by [18F]FDG, and [18F]FLT PET imaging. Additional studies assessed the endogenous and exogenous contributions of thymidine synthesis in the two cell lines.

Results: Both xenografts showed a significant volume-reduction to AZD1152. In contrast, [18F]FDG uptake did not demonstrate a treatment response. [18F]FLT uptake decreased to less than 20% of control values in AZD1152-treated HCT116 xenografts, whereas [18F]FLT uptake was near background levels in both treated and untreated SW620 xenografts. The EC50 for AZD1152-HQPA was approximately 10 nmol/L in both SW620 and HCT116 cells; in contrast, SW620 cells were much more sensitive to methotrexate (MTX) and 5-Fluorouracil (5FU) than HCT116 cells. Immunoblot analysis demonstrated marginally lower expression of thymidine kinase in SW620 compared with HCT116 cells. The aforementioned results suggest that SW620 xenografts have a higher dependency on the de novo pathway of thymidine utilization than HCT116 xenografts.

Conclusions: AZD1152 treatment showed antitumor efficacy in both colon cancer xenografts. Although [18F]FDG PET was inadequate in monitoring treatment response, [18F]FLT PET was very effective in monitoring response in HCT116 xenografts, but not in SW620 xenografts. These observations suggest that de novo thymidine synthesis could be a limitation and confounding factor for [18F]FLT PET imaging and quantification of tumor proliferation, and this may apply to some clinical studies as well. Clin Cancer Res; 17(5); 1099–110. ©2011 AACR.
A Controlled Naturalistic Study on a Weekly Music Therapy and Activity Program on Disruptive and Depressive Behaviors in Dementia
Authors: Han Peimin , Kwan Melanie , Chen Denise , Yusoff Siti Zubaidah , Chionh Hui Ling , Goh Jenny , Yap Philip
Published: January 2011

Aim: This study explores the effects of a weekly structured music therapy and activity program (MAP) on behavioral and depressive symptoms in persons with dementia (PWD) in a naturalistic setting. Methods: PWD attended a weekly group MAP conducted by a qualified music therapist and occupational therapist for 8 weeks. Two validated scales, the Apparent Emotion Scale (AES) and the Revised Memory and Behavioral Problems Checklist (RMBPC), were used to measure change in outcomes of mood and behavior. Results: Twenty-eight subjects completed the intervention, while 15 wait-list subjects served as controls. Baseline AES and RMBPC scores were not significantly different between the intervention and control groups. After intervention, RMBPC scores improved significantly (p = 0.006) with 95% CI of the difference between the mean intervention and control group scores compared to baseline at –62.1 to –11.20. Total RMBPC scores in the intervention group improved from 75.3 to 54.5, but worsened in the control group, increasing from 62.3 to 78.6. AES scores showed a nonsignificant trend towards improvement in the intervention group. Conclusion: The results suggest that a weekly MAP can ameliorate behavioral and depressive symptoms in PWD.
Sociodemographic Risk Factors and Correlates of Dementia in Older Malaysians
Authors: Hamid Tengku Aizan , Krishnaswamy Saroja , Abdullah Siti Suhailah , Momtaz Yadollah Abolfathi
Published: January 2011

Objective: The rapid expansion of the aged population in Malaysia is expected to greatly increase the number of persons with dementia in the country. However, data on dementia prevalence at the national level is lacking, and little is known about the sociodemographic risk factors and correlates of dementia. This paper describes a nationwide study of dementia prevalence and its sociodemographic risk factors and health correlates among older Malaysians. Methods: In the nationwide study, the Mental Health and Quality of Life of Older Malaysians, AGECAT-GMS was used to diagnose dementia in a nationally representative sample of 2,980 persons aged 60 and above. Results: The prevalence rate of dementia was 14.3%. Higher dementia prevalences were found in oldest age (26.3%), women (19.7%), no formal education (24.1%), Bumiputeras (32.2%), unmarried (19.4%), unemployed (31.3%) and very poor on self-rated health (33.3%). Multivariate logistic regression analyses showed that older age, female gender, no formal education, ethnicity and very poor self-rated health were independent risk factors and correlates of dementia. Conclusions: Relatively higher prevalence rates of dementia in older Malaysians were accounted for by greater proportions without education, Malay and Bumiputera ethnicity, and other unknown factors which should be further investigated.
Family Caregiving in Dementia: The Asian Perspective of a Global Problem
Authors: Chan Sally Wai-Chi
Published: January 2011

Background/Aims: With an increasing life expectancy, the number of people suffering from dementia globally will rise to about 115.4 million by 2050. It is projected that in the 21st century, the majority of the world’s older people will be living in Asia. This paper examines the global issues of family caregiving for older persons with dementia from an Asian perspective. Methods: Literature review of published empirical studies from 1990 to October 2010. Results: A full understanding of the specific way that culture could influence family caregivers’ burdens may play an important part in the development of a holistic model for family-centered care. Well-designed psychoeducation interventions or multicomponent interventions could help in reducing caregivers’ burden. With socio-economical and demographical changes, families need to be supported when taking on the caregiving role and be offered alternatives of care. Conclusion: There is a need for future trials with more rigorous randomization and longitudinal follow-up to assess family caregiver burdens at different illness stages. Future studies could focus on protective factors that promote caregivers’ resilience. It is essential to develop psychometrically robust measures for family caregiver burden and gain.
Systemic Inflammation Is Associated with MCI and Its Subtypes: The Sydney Memory and Aging Study
Authors: Trollor Julian N. , Smith Evelyn , Baune Bernhard T. , Kochan Nicole A. , Campbell Lesley , Samaras Katherine , Crawford John , Brodaty Henry , Sachdev Perminder
Published: January 2011

Background/Aims: Raised low-grade systemic inflammation has been associated with dementia, and preliminary studies suggest an association with mild cognitive impairment (MCI). This study examines the relationship between systemic inflammation and MCI subtypes. Methods: We measured the inflammatory markers C-reactive protein, interleukins (IL)-1β, -6, -8, -10 and -12, plasminogen activator inhibitor-1 (PAI-1), serum amyloid A (SAA), tumor necrosis factor-α (TNF-α) and vascular adhesion molecule-1 (VCAM-1) in the Sydney Memory and Ageing Study (MAS) cohort, a longitudinal study of 1,037 Australians aged 70–90 years. Results: After adjusting for possible confounding variables, levels of TNF-α and SAA were higher in participants with MCI compared to cognitively normal individuals, and some sex differences were apparent. Nonamnestic multiple domain MCI was associated with higher levels of IL-1β and IL-12, TNF-α and SAA compared to cognitively normal, amnestic MCI (single and multiple domain) and nonamnestic single domain MCI. PAI-1 levels were higher in cognitively normal and nonamnestic multiple domain MCI than in amnestic multiple domain MCI. Conclusion: Our findings suggest an association between specific inflammatory markers and MCI subtypes, highlight sex differences in the association with MCI, and point to a discrete impact of systemic inflammation on cognition.
Apolipoprotein E Polymorphism and Dementia: A Hospital-Based Study from Southern India
Authors: Bharath Srikala , Purushottam Meera , Mukherjee Odity , Bagepally Bhavani Shankara , Prakash Om , Kota Lakshminarayanan , Krishnappa Srinivas Brahmadevarahalli , Sivakumar Palanimuthu Thangaraju , Jain Sanjeev , Varghese Mathew
Published: January 2011

Background/Aims: To evaluate the ApoE gene polymorphism among patients with dementia from southern India. Methods: Persons with dementia attending a geriatric clinic in a hospital setting located in southern India and matched controls were recruited. All subjects were evaluated on standard assessments and were diagnosed according to the ICD-10; genotyping was done at the apolipoprotein E (ApoE) locus. Results: The study comprised 212 cases and 195 controls. The ApoE4 allele was significantly more prevalent in dementia (λ = 0.18 vs. λ = 0.07; p = 0.0018), especially in the Alzheimer’s disease subgroup (n = 137; λ = 0.21 vs. λ = 0.07; p < 0.001), with a trend in vascular dementia subtype (n = 31; λ = 0.17 vs. λ = 0.07) in comparison with the control group. ApoE4 carrier status did not differ between the other dementia group (n = 44) and controls (p > 0.20), or between the Alzheimer’s group and vascular dementia groups. Cognitive and functional deficits were not correlated to the presence ApoE4 polymorphism in the dementia group. Conclusion: The study confirmed the positive association of the ApoE4 polymorphism in dementia, both in the Alzheimer’s and vascular etiology subgroups. Influence of this polymorphism on various clinical phenotypes, including extent of cognitive and functional deficits, needs further evaluation.
Apolipoprotein E Polymorphism and Age at Onset of Alzheimer’s Disease in a Quadriethnic Sample
Authors: Kwon Oh Dae , Khaleeq Aisha , Chan Wenyaw , Pavlik Valory N. , Doody Rachelle S.
Published: January 2011

Background: The relationship between the apolipoprotein E (ApoE) genotype and the risk for developing Alzheimer’s disease (AD) or age at onset of AD is relatively well established in Caucasians, but less established in other ethnicities. We examined the association between the ApoE genotype and age at onset of AD in a quadriethnic group of community-dwelling AD patients. Methods: AD patients were evaluated at 2 university-based outpatient memory disorder clinics. The ethnic distribution was as follows: Caucasians (n = 1,083), Hispanics (n = 55), African Americans (n = 84) and Koreans (n = 87). All were diagnosed with probable AD according to NINCDS-ADRDA diagnostic criteria. Results: After adjusting for ethnicity, the Ε4 allele was significantly associated with earlier age at onset (p < 0.0001) for the combined group. Within ethnic groups, the effect of Apo Ε4 on age at onset was significant in Caucasians (p < 0.0001) and African Americans (p < 0.05), but nonsignificant in Koreans (p = 0.43) and in the smaller Hispanic (p = 0.07) group. Conclusions: The association between Apo Ε4 and younger age at onset was significant in Caucasians and African Americans, where the Ε4 allele was also most frequent. This study suggests that the impact of ApoE polymorphism on age at onset of AD may be different among distinct ethnic groups.