bluuebunny/crossref_metadata_2025 huggingface dataset:
The sweets standing at the borderline between allo‐ and xenotransplantation
Authors: Jang Kyoung‐Soon , Kim Yun‐Gon , Adhya Mausumi , Park Hae‐Min , Kim Byung‐Gee
Published: April 2013

Animal cells are densely covered with glycoconjugates, such as N‐glycan, O‐glycan, and glycosphingolipids, which are important for various biological and immunological events at the cell surface and in the extracellular matrix. Endothelial α‐Gal carbohydrate epitopes (Galα3Gal‐R) expressed on porcine tissue or cell surfaces are such glycoconjugates and directly mediate hyperacute immunological rejection in pig‐to‐human xenotransplantation. Although researchers have been able to develop α1,3‐galactosyltransferase (GalT) gene knockout (KO) pigs, there remain unclarified non‐Gal antigens that prevent xenotransplantation. Based on our expertise in the structural analysis of xenoantigenic carbohydrates, we describe the immunologically significant non‐human carbohydrate antigens, including α‐Gal antigens, analyzed as part of efforts to assess the antigens responsible for hyperacute immunological rejection in pig‐to‐human xenotransplantation. The importance of studying human, pig, and GalT‐KO pig glycoprofiles, and of developing adequate pig‐to‐human glycan databases, is also discussed.
Comparison of Time Series Models for Predicting Campylobacteriosis Risk in New Zealand
Authors: Al‐Sakkaf A. , Jones G.
Published: April 2013

Predicting campylobacteriosis cases is a matter of considerable concern in New Zealand, after the number of the notified cases was the highest among the developed countries in 2006. Thus, there is a need to develop a model or a tool to predict accurately the number of campylobacteriosis cases as the Microbial Risk Assessment Model used to predict the number of campylobacteriosis cases failed to predict accurately the number of actual cases. We explore the appropriateness of classical time series modelling approaches for predicting campylobacteriosis. Finding the most appropriate time series model for New Zealand data has additional practical considerations given a possible structural change, that is, a specific and sudden change in response to the implemented interventions. A univariate methodological approach was used to predict monthly disease cases using New Zealand surveillance data of campylobacteriosis incidence from 1998 to 2009. The data from the years 1998 to 2008 were used to model the time series with the year 2009 held out of the data set for model validation. The best two models were then fitted to the full 1998–2009 data and used to predict for each month of 2010. The Holt‐Winters (multiplicative) and ARIMA (additive) intervention models were considered the best models for predicting campylobacteriosis in New Zealand. It was noticed that the prediction by an additive ARIMA with intervention was slightly better than the prediction by a Holt‐Winter multiplicative method for the annual total in year 2010, the former predicting only 23 cases less than the actual reported cases. It is confirmed that classical time series techniques such as ARIMA with intervention and Holt‐Winters can provide a good prediction performance for campylobacteriosis risk in New Zealand. The results reported by this study are useful to the New Zealand Health and Safety Authority's efforts in addressing the problem of the campylobacteriosis epidemic.
Influence of Bubbles on the Turbulence Anisotropy
Authors: Bolotnov Igor A.
Published: April 2013

Direct numerical simulation (DNS) with interface tracking of turbulent bubbly flows is becoming a major tool in advancing our knowledge in the area of multiphase modeling research. A comprehensive analysis of the turbulent flow structure allows us to evaluate the state-of-the-art computational multiphase fluid dynamics (CMFD) models and to propose new closure laws. The presented research will demonstrate how the multiphase DNS data can inform the development of computational fluid dynamics (CFD) models. In particular, the Reynolds stress distribution will be evaluated for single- and two-phase bubbly flows and the level of turbulence anisotropy will be measured in several scenarios. The results will help determine if the isotropic turbulent models are suitable for bubbly flow applications or if there is a strong need to apply and develop Reynolds-stress turbulent models for two-phase flow CFD modeling.
Nitrogen actinometry for measurement of nitrogen radical spatial distribution in large-area plasma-enhanced chemical vapor deposition
Authors: Oh Changhoon , Kang Minwook , Nam Seungsuk , Hahn Jae W.
Published: April 2013

Density distributions of radicals in the large-area silicon nitride (Si3N4) plasma-enhanced chemical vapor deposition (PECVD) process were measured using a spatially resolvable optical emission spectrometer (SROES). To determine the qualitative distribution of a target radical, the authors used optical actinometry with nitrogen (N2) gas as an actinometer. To compare the SROES data and process results, the thickness of the deposited Si3N4 thin films using an ellipsometer was measured. By introducing nitrogen-based optical actinometry, the authors obtained very good agreement between the experimental results of the distributions of atomic nitrogen radical and the deposited thicknesses of Si3N4 thin films. Based on these experimental results, the uniformity of the process plasma in the PECVD process at different applied radio frequency powers was analyzed.
Inositol Polyphosphate Multikinase Is a Coactivator of p53-Mediated Transcription and Cell Death
Authors: Xu Risheng , Sen Nilkantha , Paul Bindu D. , Snowman Adele M. , Rao Feng , Vandiver M. Scott , Xu Jing , Snyder Solomon H.
Published: April 2013

By promoting p53 acetylation and activation, IPMK contributes to DNA damage–induced cell death.
The Scientific Drunk and the Lamppost: Massive Sequencing Efforts in Cancer Discovery and Treatment
Authors: Yaffe Michael B.
Published: April 2013

Signaling networks may provide greater return for the investment in cancer research.
Integrative Analysis of Complex Cancer Genomics and Clinical Profiles Using the cBioPortal
Authors: Gao Jianjiong , Aksoy Bülent Arman , Dogrusoz Ugur , Dresdner Gideon , Gross Benjamin , Sumer S. Onur , Sun Yichao , Jacobsen Anders , Sinha Rileen , Larsson Erik , Cerami Ethan , Sander Chris , Schultz Nikolaus
Published: April 2013

The cBioPortal enables integration, visualization, and analysis of multidimensional cancer genomic and clinical data.
Science Signaling
Podcast: 2 April 2013
Authors: Xu Risheng , VanHook Annalisa M.
Published: April 2013

A multifunctional protein promotes acetylation and activation of the tumor suppressor p53.
Emergence of Extensively Drug-Resistant Haemophilus parainfluenzae in Switzerland
Authors: Tinguely Regula , Seiffert Salome N. , Furrer Hansjakob , Perreten Vincent , Droz Sara , Endimiani Andrea
Published: April 2013

Two homosexual men were colonized in the urethra with
Haemophilus parainfluenzae
nonsusceptible to ampicillin (MIC, 8 μg/ml), amoxicillin-clavulanate (MIC, 4 μg/ml), cefotaxime (MIC, 1.5 μg/ml), cefepime (MIC, 3 μg/ml), meropenem (MIC, 0.5 μg/ml), cefuroxime, azithromycin, ciprofloxacin, tetracycline, and chloramphenicol (all MICs, ≥32 μg/ml). Repetitive extragenic palindromic PCR (rep-PCR) showed that the strains were indistinguishable. The isolates had amino acid substitutions in PBP3, L4, GyrA, and ParC and possessed Mef(A), Tet(M), and CatS resistance mechanisms. This is the first report of extensively drug-resistant (XDR)
H. parainfluenzae
.
The Apparent Quorum-Sensing Inhibitory Activity of Pyrogallol Is a Side Effect of Peroxide Production
Authors: Defoirdt Tom , Pande Gde Sasmita Julyantoro , Baruah Kartik , Bossier Peter
Published: April 2013

There currently is more and more interest in the use of natural products, such as tea polyphenols, as therapeutic agents. The polyphenol compound pyrogallol has been reported before to inhibit quorum-sensing-regulated bioluminescence inVibrio harveyi. Here, we report that the addition of 10 mg · liter−1pyrogallol protects both brine shrimp (Artemia franciscana) and giant river prawn (Macrobrachium rosenbergii) larvae from pathogenicVibrio harveyi, whereas the compound showed relatively low toxicity (therapeutic index of 10). We further demonstrate that the apparent quorum-sensing-disrupting activity is a side effect of the peroxide-producing activity of this compound rather than true quorum-sensing inhibition. Our results emphasize that verification of minor toxic effects by using sensitive methods and the use of appropriate controls are essential when characterizing compounds as being able to disrupt quorum sensing.
CD137 Expressed on Neutrophils Plays Dual Roles in Antibacterial Responses against Gram-Positive and Gram-Negative Bacterial Infections
Authors: Nguyen Quang-Tam , Nguyen Thu-Ha T. , Ju Seong-A. , Lee Yea-Sol , Han Seung Hyun , Lee Sang-Chul , Kwon Byoung S. , Yu Rina , Kim Gyu Yeol , Lee Byung Ju , Kim Byung-Sam
Published: April 2013

Severe sepsis and septic shock caused mainly by bacterial infections are life-threatening conditions that urge the development of novel therapies. However, host responses to and pathophysiology of sepsis have not been clearly understood, which remains a major obstacle for the development of effective therapeutics. Recently, we have shown that stimulation of a costimulatory molecule, CD137, enhanced survival of mice infected with the Gram-positive (G
+
) intracellular bacterium
Listeria monocytogenes
but decreased survival in a polymicrobial sepsis model. Herein, we report that CD137 deficiency or blocking of CD137 signaling decreased antibacterial responses of mice infected with G
+
bacteria (
Staphylococcus aureus
,
Streptococcus pneumoniae
, and
Enterococcus faecalis
) but increased these responses in mice infected with Gram-negative (G
−
) bacteria (
Escherichia coli
,
Pseudomonas aeruginosa
, and
Salmonella enterica
serovar Typhimurium). Consistent with these findings, stimulation of CD137 by administration of agonistic antibody enhanced responses against G
+
bacteria, whereas it decreased these responses against G
−
bacteria. Neutrophils were responsible for CD137-mediated opposite roles in control of G
+
and G
−
bacterial infections. Stimulation of CD137 enhanced activities of neutrophils against
S. aureus
but decreased these activities against
E. coli
, while CD137 blocking produced opposite results with the stimulation of CD137
in vivo
and
in vitro
. Furthermore, we found that combined signaling of CD137 and Toll-like receptor 2 (TLR2) induced synergistic production of tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) by neutrophils, but combined signaling of CD137 and TLR4 did not. Our data strongly suggest that CD137 may play a dual role in sepsis in association with TLRs.
Formalin-Inactivated Coxiella burnetii Phase I Vaccine-Induced Protection Depends on B Cells To Produce Protective IgM and IgG
Authors: Zhang Guoquan , Peng Ying , Schoenlaub Laura , Elliott Alexandra , Mitchell William , Zhang Yan
Published: April 2013

To further understand the mechanisms of formalin-inactivatedCoxiella burnetiiphase I (PI) vaccine (PIV)-induced protection, we examined if B cell, T cell, CD4+T cell, or CD8+T cell deficiency in mice significantly affects the ability of PIV to confer protection against aC. burnetiiinfection. Interestingly, compared to wild-type (WT) mice, PIV conferred comparable levels of protection in CD4+T cell- or CD8+T cell-deficient mice and partial protection in T cell-deficient mice but did not provide measurable protection in B cell-deficient mice. These results suggest that PIV-induced protection depends on B cells. In addition, anti-PI-specific IgM was the major detectable antibody (Ab) in immune sera from PIV-vaccinated CD4+T cell-deficient mice, and passive transfer of immune sera from PIV-vaccinated CD4+T cell-deficient mice conferred significant protection. These results suggest that T cell-independent anti-PI-specific IgM may contribute to PIV-induced protection. Our results also suggested that PIV-induced protection may not depend on complement activation and Fc receptor-mediated effector functions. Furthermore, our results demonstrated that both IgM and IgG from PIV-vaccinated WT mouse sera were able to inhibitC. burnetiiinfectionin vivo, but only IgM from PIV-vaccinated CD4+T cell-deficient mouse sera inhibitedC. burnetiiinfection. Collectively, these findings suggest that PIV-induced protection depends on B cells to produce protective IgM and IgG and that T cell-independent anti-PI-specific IgM may play a critical role in PIV-induced protection againstC. burnetiiinfection.
Hookworm Excretory/Secretory Products Induce Interleukin-4 (IL-4)+IL-10+CD4+T Cell Responses and Suppress Pathology in a Mouse Model of Colitis
Authors: Ferreira Ivana , Smyth Danielle , Gaze Soraya , Aziz Ammar , Giacomin Paul , Ruyssers Nathalie , Artis David , Laha Thewarach , Navarro Severine , Loukas Alex , McSorley Henry J.
Published: April 2013

Evidence from human studies and mouse models shows that infection with parasitic helminths has a suppressive effect on the pathogenesis of some inflammatory diseases. Recently, we and others have shown that some of the suppressive effects of hookworms reside in their excretory/secretory (ES) products. Here, we demonstrate that ES products of the hookwormAncylostoma caninum(AcES) suppress intestinal pathology in a model of chemically induced colitis. This suppression was associated with potent induction of a type 2 cytokine response characterized by coexpression of interleukin-4 (IL-4) and IL-10 by CD4+T cells, downregulation of proinflammatory cytokine expression in the draining lymph nodes and the colon, and recruitment of alternatively activated (M2) macrophages and eosinophils to the site of ES administration. Protease digestion and heat denaturation of AcES resulted in impaired induction of CD4+IL-4+IL-10+cell responses and diminished ability to suppress colitis, indicating that protein component(s) are responsible for some of the immunosuppressive effects of AcES. Identification of the specific parasite-derived molecules responsible for reducing pathology during chemically induced colitis could lead to the development of novel therapeutics for the treatment of human inflammatory bowel disease.
Identification of a Peptide-Based Neutralizer That Potently Inhibits Both Shiga Toxins 1 and 2 by Targeting Specific Receptor-Binding Regions
Authors: Tsutsuki Kazue , Watanabe-Takahashi Miho , Takenaka Yasuaki , Kita Eiji , Nishikawa Kiyotaka
Published: April 2013

Shiga toxin (Stx) is a major virulence factor of enterohemorrhagic
Escherichia coli
that occasionally causes fatal systemic complications. We recently developed a tetravalent peptide (PPP-tet) that neutralizes the cytotoxicity of Stx2 using a multivalent peptide library approach. In this study, we used this technique to identify a series of tetravalent peptides that bound to Stx1, another major Stx family member, with high affinity by targeting one receptor-binding site of the B subunit. One peptide, MMA-tet, markedly inhibited Stx1 and Stx2 cytotoxicity with greater potency than PPP-tet. After forming a complex with Stx1 through its specific receptor-binding region, MMA-tet did not affect vesicular transport of the toxin to the endoplasmic reticulum but substantially rescued inhibition of the protein synthesis induced by Stx1. Oral application of MMA-tet protected mice from a fatal dose of an
E. coli
O157:H7 strain producing both toxins. MMA-tet may be a promising therapeutic agent against the infection.
Heterozygosity at the A625C Polymorphic Site of the MyD88 Gene Is Associated with Mycobacterium bovis Infection in Cattle
Authors: Capparelli Rosanna , De Chiara Francesco , Nocerino Nunzia , Medaglia Chiara , Di Costanzo Rosa , Ramunno Luigi , Capuano Federico , Casalinuovo Francesco , Di Matteo Antonio , Iannelli Domenico
Published: April 2013

The study demonstrates that in cattle, animals heterozygous at the MyD88 A625C polymorphic marker have a 5-fold reduced risk for active pulmonary tuberculosis (odds ratio [OR] = 0.19;
P
= 6 × 10
−12
). The reduced risk, however, does not extend to animals with latent pulmonary tuberculosis (OR = 0.83;
P
= 0.40). Heterozygosity at the A625C single nucleotide polymorphism is associated with intermediate levels of tumor necrosis factor alpha, gamma interferon, and nitric oxide synthase (NOS). Accordingly, deficiency as well as overexpression of proinflammatory cytokines or NOS favor tuberculosis, while heterozygosity provides the animals with the optimal level of inflammation.
Towards testing a two-Higgs-doublet model with maximal CP symmetry at the LHC: Monte Carlo event generator implementation
Authors: Brehmer J. , Lendermann V. , Maniatis M. , Nachtmann O. , Schultz-Coulon H.-C. , Stamen R.
Published: April 2013

A Monte Carlo event generator is implemented for a two-Higgs-doublet model with maximal CP symmetry, the MCPM. The model contains five physical Higgs bosons; the ρ′, behaving similarly to the standard-model Higgs boson, two extra neutral bosons h′ and h″, and a charged pair H±. The special feature of the MCPM is that, concerning the Yukawa couplings, the bosons h′, h″ and H± couple directly only to the second-generation fermions but with strengths given by the third-generation-fermion masses. Our event generator allows the simulation of the Drell–Yan-type production processes of h′, h″ and H± in proton–proton collisions at LHC energies. Also the subsequent leptonic decays of these bosons into the μ+μ−, μ+νμ and $\mu^{-} \bar{\nu}_{\mu}$ channels are studied as well as the dominant background processes. We estimate the integrated luminosities needed in pp collisions at center-of-mass energies of 8 and 14 TeV for significant observations of the Higgs bosons h′, h″ and H± in these muonic channels.
Chemical Characterization and In Vivo Anti-Inflammatory Activities of Actinidia callosa var. ephippioides via Suppression of Proinflammatory Cytokines
Authors: Liao Jung-Chun , Huang Shyh-Shyun , Deng Jeng-Shyan , Lee Chao-Ying , Lin Ying-Chih , Huang Guan-Jhong
Published: April 2013

Actinidia callosa var. ephippioides (ACE) has been widely used to treat anti-pyretic, antinociceptive, anti-inflammation, abdominal pain and fever in Taiwan. This study aims to determine the mechanism of anti-inflammatory activities of ethyl acetate fraction of ACE (EA-ACE) using a model of λ-carrageenan (Carr)-induced paw edema in mouse model. In HPLC analysis, chemical characterization of EA-ACE was established. In order to investigate the anti-inflammatory mechanism of EA-ACE, we have detected the activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) and the levels of malondialdehyde (MDA) in the paw edema. Serum NO, tumor necrosis factor α (TNF-α), and interleukin-1β (IL-1β) were evaluated. Chemical characterization from HPLC indicated that EA-ACE contains betulinic acid, ursolic acid and oleanolic acid. In the anti-inflammatory test, EA-ACE decreased the paw edema after Carr administration, increased the activities of CAT, SOD, and GPx and decreased the MDA level in the edema paw at the 5th hr after Carr injection. EA-ACE affects the serum NO, TNF-α, and IL-1β levels at the 5th hr after Carr injection. EA-ACE decreased Carr-induced inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expressions by Western blotting. Actinidia callosa var. ephippioides have the potential to provide a therapeutic approach to inflammation-associated disorders.
MECHANISM STUDY ON OXYGEN VACANCY INDUCED RESISTANCE SWITCHING IN Au/LaMnO3/SrNb0.01Ti0.99O3
Authors: JIN YU-LING , XU ZHONG-TANG , JIN KUI-JUAN , GE CHEN , LU HUI-BIN , YANG GUO-ZHEN
Published: April 2013

Mechanism of resistance switching in heterostructure Au / LaMnO 3/ SrNb 0.01 Ti 0.99 O 3 was investigated. In Au / LaMnO 3/ SrNb 0.01 Ti 0.99 O 3 devices the LaMnO 3 films were fabricated under various oxygen pressures. The content of the oxygen vacancies has a significant impact on the resistance switching performance. We propose that the resistance switching characteristics of Au / LaMnO 3/ SrNb 0.01 Ti 0.99 O 3 arise from the modulation of the Au / LaMnO 3 Schottky barrier due to the change of the oxygen vacancy concentration at Au / LaMnO 3 interface under the external electric field. The effect of the oxygen vacancy concentration on the resistance switching is explained based on the self-consistent calculation. Both the experimental and numerical results confirm the important role of the oxygen vacancies in the resistance switching behavior.
EXACT INHOMOGENEOUS MODELS AND THE DRIFT OF LIGHT RAYS INDUCED BY NONSYMMETRIC FLOW OF THE COSMIC MEDIUM
Authors: KRASIŃSKI ANDRZEJ , BOLEJKO KRZYSZTOF
Published: April 2013

After introducing the Szekeres and Lemaître–Tolman cosmological models, the real-time cosmology program is briefly mentioned. Then, a few widespread misconceptions about the cosmological models are pointed out and corrected. Investigation of null geodesic equations in the Szekeres models shows that observers in favorable positions would see galaxies drift across the sky at a rate of up to 10-6 arc s per year. Such a drift would be possible to measure using devices that are under construction; the required time of monitoring would be ≈10 years. This effect is zero in the FLRW models, so it provides a measure of inhomogeneity of the Universe. In the Szekeres models, the condition for zero drift is zero shear. But in the shearfree normal models, the condition for zero drift is that, in the comoving coordinates, the time dependence of the metric completely factors out.
THE EFFECT OF CURVATURE IN DETERMINING THE PROPERTY OF DARK ENERGY FROM TYPE IA SUPERNOVA WITH A MODEL INDEPENDENT METHOD
Authors: FU XIANGYUN , WU PUXUN , YU HONGWEI , ZHOU BINGJU
Published: April 2013

The effect of spatial curvature in reconstructing the cosmic expansion history and the property of dark energy is studied in this paper by smoothing the noise of the Union2.1 Type Ia Supernovae (SNIa) data with a Gaussian smoothing function. We find that the spatial curvature induces an apparent effect in reconstructing the Hubble parameter H(z), the deceleration parameter q(z), and especially on the equation of state w(z) of dark energy. Thus, when one probes the dark energy property, an assumption of a flat universe may induce critical bias and it is imperative to take account of the spatial curvature.
SIGNATURE CHANGE BY GUP
Authors: GHANEH T. , DARABI F. , MOTAVALLI H.
Published: April 2013

We revisit the issue of continuous signature transition from Euclidean to Lorentzian metrics in a cosmological model described by Friedmann–Robertson–Walker (FRW) metric minimally coupled with a self-interacting massive scalar field. Then, using a noncommutative (NC) phase space of dynamical variables deformed by generalized uncertainty principle (GUP), we show that the signature transition occurs even for a model described by the FRW metric minimally coupled with a free massless scalar field accompanied by a cosmological constant. This indicates that the continuous signature transition might have been easily occurred at early universe just by a free massless scalar field, a cosmological constant and a NC phase space deformed by GUP, without resorting to a massive scalar field having an ad hoc complicate potential. We also study the quantum cosmology of the model and obtain a solution of Wheeler–DeWitt (WD) equation which shows a good correspondence with the classical path.
ACCELERATION OF PARTICLES BY QUASIBLACK HOLES
Authors: ZASLAVSKII O. B.
Published: April 2013

If two particles collide near the black hole horizon, the energy in their center of mass (CM) frame can grow indefinitely (the so-called Bañados, Silk and West (BSW) effect). This requires fine-tuning the parameters (the energy–momentum, angular momentum or electric charge) of one particle. We show that the CM energy can be unbound also for collisions in the spacetime of quasiblack holes (QBHs) (the objects on the threshold of forming the horizon which do not collapse). It does not require special fine-tuning of parameters and occurs when any particle inside a QBH having a finite energy collides with the particle that entered a QBH from the outside region.
Does Analyst Stock Ownership Affect Reporting Behavior?
Authors: Johnston Rick
Published: April 2013

An analyst who owns stock in the company she covers may be tempted to protect or enhance her personal interests. This paper examines how this potential conflict of interest affects the reporting of sell-side analysts by identifying and collecting two samples, the first from Securities and Exchange Commission (SEC) Form 144 filings, and the second from voluntary ownership disclosures. Ordered probit analyses show that owning analyst recommendations are slightly more cautious than those of the control analysts. There is little robust evidence that stock ownership leads to optimistic analyst reporting, however findings indicate that analysts who are consistently optimistic are owners. The results are consistent with a conclusion that analyst stock ownership, unlike other potential incentives, may not be a significant concern since in many cases multiple nonowning analysts also provide reports. Being an outlier potentially reduces any benefit to the owning analyst and risks her personal reputation. In the absence of a detrimental effect, ownership offers a potential benefit as a credible signal of an analyst's conviction in a company's prospects.
EFFECTS OF SIMVASTATIN ON FEMORAL BIOMECHANICS IN OVARIECTOMIZED RATS
Authors: JIAN XIAOCHONG , CHEN JIANG , ZHANG LINLIN , YAN FUHUA , ZENG YANJUN
Published: April 2013

Objective: To investigate the effect of simvastatin on the biomechanical characteristics of the femur in ovariectomized rats.

Material and methods: Fifty-four female Sprague-Dawley rats, aged three months old, were randomly divided into three groups: sham-operated group ( SHAM; n = 18), ovariectomized group (OVX; n = 18), and ovariectomized with simvastatin treatment group (OVX+SIM; n = 18). Eight weeks after being ovariectomized, simvastatin was administered orally at 5 mg/kg each day in the OVX + SIM group. The animals were sacrificed at either four or 12 weeks after administration and femurs were obtained. Biomechanical parameters were measured by the three-point bending test.

Results: There were no significant differences in the maximal strain and flexibility strain between the OVX and OVX + SIM groups at either four or 12 weeks after administration (p > 0.05). In contrast, significant differences in flexibility loading at four weeks and in maximal loading, flexibility loading, and the coefficient of bending ductility between the OVX and OVX + SIM groups at either four or 12 weeks (p < 0.05 and p < 0.01, respectively). Intergroup comparisons showed that maximal loading and flexibility loading have significant differences in the OVX + SIM group (p < 0.01).

Conclusion: Simvastatin shows potential in promoting bone remodeling, changing bone micro-architecture, and influencing the integration and distribution ratio of organic and inorganic constituents in bone tissue of ovariectomized rats. In addition, a longer time of administration with simvastatin could enhance the femoral strength.
ARE HOUSING DEVELOPERS READY FOR INNOVATION? THE CASE FOR A NEW HOUSING DELIVERY SYSTEM IN MALAYSIA
Authors: YUSOF NOR'AINI , SIBLY SUFARDY , OSMAN ZULKIFLI
Published: April 2013

This paper investigates the readiness level of housing developers in Malaysia to adopt a new housing system known as the Build-Then-Sell (BTS) system. We examine whether a firm's characteristics influence its readiness to adopt. We constructed a BTS readiness index, which comprises innovativeness, optimism, discomfort, and insecurity dimensions. We carried out a face-to-face survey with 246 developers in Malaysia's major cities and received a 48.8% response. The data were analyzed using descriptive analysis, factor analysis and correlation analysis. We found that housing developers are partially ready to implement the BTS system, with a slightly high level of optimism and a high level of insecurity. However, there was a very weak relationship between BTS readiness (e.g. optimism and insecurity) and a firm's characteristics (e.g. type of ownership, firm size, age, and land bank). The paper ends by providing some explanations for the results.
GLOBAL SOLUTIONS AND DECAY PROPERTY WITH REGULARITY-LOSS FOR QUASI-LINEAR HYPERBOLIC SYSTEMS WITH DISSIPATION
Authors: DHARMAWARDANE PRIYANJANA M. N.
Published: April 2013

We consider quasi-linear hyperbolic systems that describe the motion of viscoelastic materials. The decay property for this system exhibits a loss of regularity, and we establish a global existence theory together with sharp decay estimates, under a smallness condition and under sufficient regularity on the initial data. We combine together various tools of analysis, especially energy estimates in Fourier space, the time-weighted energy method, and the semi-group method.
HYPERBOLIC SYSTEMS OF BALANCE LAWS WITH WEAK DISSIPATION II
Authors: DAFERMOS CONSTANTINE M.
Published: April 2013

By extending the analysis in [C. M. Dafermos, Hyperbolic systems of balance laws with weak dissipation, J. Hyperbolic Differ. Equ.3 (2006) 505–527], this note constructs global BV solutions to the Cauchy problem for strictly hyperbolic systems of balance laws endowed with a convex entropy, under the assumption that the entropy production is positive definite.
Significant sensitivity and stability enhancement of tetraphenylporphyrin-based optical oxygen sensing material in presence of perfluorochemicals
Authors: Topal Sevinc Z. , Önal Emel , Ertekin Kadriye , Oter Ozlem , Gürek Ayşe G. , Hirel Catherine
Published: April 2013

Emission-based oxygen sensing properties of highly luminescent tetraphenylporphyrin molecules were investigated in polystyrene, ethyl cellulose, poly(1-trimethylsilyl-1-propyne) and poly(isobutylmethacrylate) matrices. The effect of perfluorochemicals (PFCs) on oxygen sensitivity and stability of the sensor materials was also examined. Fluorescence intensity and lifetime measurements of meso-tetraphenylporphyrinato Zn ( II ) (ZnTPP) and meso-tetraphenylporphyrin (H2TPP) materials were performed in the concentration range of 0–100% pO 2. The fluorescence intensity variation of H2TPPvs. oxygen was 86%. H2TPP-based composite also yielded higher Stern–Volmer constant, faster response and regeneration time, excellent long term photostability and larger linear response range with respect to ZnTPP. The detection limit of oxygen for H2TPP was less than 0.5%. When stored in sealed bags protected from sunlight, no decrease in oxygen sensitivity was observed during approximately five months. As far as we know, the gathered utilization of PFCs and H2TPP embedded in polymer matrices was not previously described in literature, and has present amelioration compared to materials already existing.
ASSESSING THE WELFARE EFFECTS OF PROMOTING BIOMASS GROWTH AND THE USE OF BIOENERGY
Authors: LUNDGREN TOMMY , MARKLUND PER-OLOV
Published: April 2013

Using a growth model that accounts for environmental and climate externalities, we take a closer look at the welfare effects of promoting biomass growth and the use of bioenergy, and especially the role of carbon neutrality. As an illustration, a hypothetical intensive forest cultivation project is simulated. Costs and benefits of the project show that only determining the postive effects of promoting biomass growth and the use of bioenergy, such as substitution away from fossil fuels and carbon sequestration is not sufficient. But more importantly, to achieve a balanced measure of the effects on the climate, we must also incorporate all carbon emissions that are associated with bioenergy. Not doing so will over-estimate the positive climate effects of increasing the use of bioenergy.
Pelvic Primary Staphylococcal Infection Presenting as a Thigh Abscess
Authors: Abbas T. O.
Published: April 2013

Intra-abdominal disease can present as an extra-abdominal abscess and can follow several routes, including the greater sciatic foramen, obturator foramen, femoral canal, pelvic outlet, and inguinal canal. Nerves and vessels can also serve as a route out of the abdomen. The psoas muscle extends from the twelfth thoracic and fifth lower lumbar vertebrae to the lesser trochanter of the femur, which means that disease in this muscle group can migrate along the muscle, out of the abdomen, and present as a thigh abscess. We present a case of a primary pelvic staphylococcal infection presenting as a thigh abscess. The patient was a 60-year-old man who presented with left posterior thigh pain and fever. Physical examination revealed a diffusely swollen left thigh with overlying erythematous, shiny, and tense skin. X-rays revealed no significant soft tissue lesions, ultrasound was suggestive of an inflammatory process, and MRI showed inflammatory changes along the left hemipelvis and thigh involving the iliacus muscle group, left gluteal region, and obturator internus muscle. The abscess was drained passively via two incisions in the posterior left thigh, releasing large amounts of purulent discharge. Subsequent bacterial culture revealed profuse growth ofStaphylococcus aureus. The patient recovered uneventfully except for a moderate fever on the third postoperative day.
Acute Pancreatitis Associated with Amoebic Liver Abscess
Authors: Ghosh Jayant Kumar , Dixit Vinod Kumar , Lamtha Sangey Chopel , Goyal Sundeep Kumar , Kaushik Pankaj
Published: April 2013

We present a rare case of acute pancreatitis in a 50-year-old man with amoebic liver abscess. He had a right lobe liver abscess along with markedly elevated serum lipase and amylase levels and edematous pancreas. Liver abscess was aspirated. The patient was managed conservatively with antibiotics and improved without any complications. Acute pancreatitis associated with ALA is not reported in the literature till date.
Correlation of Vernalization Loci VRN-H1 and VRN-H2 and Growth Habit in Barley Germplasm
Authors: Mohammadi Mohsen , Torkamaneh Davoud , Nikkhah Hamid-Reza
Published: April 2013

Vernalization requirement is a key component in determining the overall fitness of developmental patterns of barley to its environment. We have used previously reported markers and spring-sown growth habit nursery to characterize the genotypes of barley germplasm in an applied barley breeding ground to establish a baseline of information required to understand the relationship between adaptation of autumn-sown barley germplasm in diverse regions with warm (W), moderate (M), or cold climates (C). This study revealed that twenty entries were detected with the presence of the vernalization critical region in VRN-H1 locus and complete presence of the three geneclusters ZCCT-Ha, -Hb, and -Hc in VRN-H2 locus represented as genotype vrn-H1/Vrn-H2 (V1w/V2w). Of these genotypes, 17 entries showed winter growth habit whereas the remaining three revealed facultative growth habit indicating reduced vernalization requirements possibly due to VRN-H3 and photoperiod sensitivity loci as compared to the landmark winter growth habit entries in this group. Twenty-four entries were detected with the lack of vernalization critical region in VRN-H1 locus but complete presence of the three geneclusters ZCCT-Ha, -Hb, and -Hc in VRN-H2 locus represented as genotype Vrn-H1/Vrn-H2 (V1s/V2w). However, only half of these germplasms were identified with spring growth habit in spring-sown nursery, and the rest of the germplasms in this group revealed facultative growth habits due to possible variation in the length of deletion in VRN-H1. Four germplasms showed vernalization insensitive phenotype due to the lack of a functional ZCCT-Ha and/or ZCCT-Hb alleles in VRN-H2 and the deletion in the vernalization critical region of VRN-H1. These germplasms revealed acomplete spring type growth habit. Only one entry showed reduced vernalization requirement solely due to the deletion in functional ZCCT-Hb allele in VRN-H2 and not due to the deletion in the vernalization critical region of VRN-H1.
Squamous Dysplasia—The Precursor Lesion for Esophageal Squamous Cell Carcinoma
Authors: Taylor Philip R. , Abnet Christian C. , Dawsey Sanford M.
Published: April 2013

Esophageal squamous cell carcinoma (ESCC) accounts for 80% of all esophageal cancers worldwide, and esophageal squamous dysplasia (ESD) is the only histopathology that predicts the development of ESCC. The prevalence of ESD parallels rates of invasive ESCC and is typically found in 25% or more of adults above the age of 35 years in populations in north central China, where risk for ESCC is among the highest in the world. Results of chemoprevention and early detection studies to prevent progression of ESD suggest that these approaches, coupled with emerging endoscopic therapies, offer promise for the prevention of esophageal cancer mortality in high-risk populations. Future research on ESD and ESCC should focus on finding additional modifiable risk factors and on identifying biomarkers to incorporate into early detection strategies. Cancer Epidemiol Biomarkers Prev; 22(4); 540–52. ©2013 AACR.
Precursors to Lymphoproliferative Malignancies
Authors: Goldin Lynn R. , McMaster Mary L. , Caporaso Neil E.
Published: April 2013

We review monoclonal B-cell lymphocytosis (MBL) as a precursor to chronic lymphocytic leukemia and monoclonal gammopathy of undetermined significance (MGUS) as a precursor to plasma cell disorders. These conditions are present in the general population and increase with age. These precursors aggregate with lymphoproliferative malignancies in families suggesting shared inheritance. MBL and MGUS may share some of the same risk factors as their related malignancies but data are limited. Although these conditions are characterized by enhanced risk for the associated malignancy, the majority of individuals with these conditions do not progress to malignancy. A key focus for current work is to identify markers that predict progression to malignancy. Cancer Epidemiol Biomarkers Prev; 22(4); 533–9. ©2013 AACR.
Human Papillomavirus Infection and the Multistage Carcinogenesis of Cervical Cancer
Authors: Schiffman Mark , Wentzensen Nicolas
Published: April 2013

This short review outlines our understanding of cervical cancer precursors, concentrating on the central etiologic role of persistent human papillomavirus infection. The stages of cervical carcinogenesis are better understood than for most other major cancers, providing a successful cancer etiology and prevention model. Cancer Epidemiol Biomarkers Prev; 22(4); 553–60. ©2013 AACR.
GSK-3α Promotes Oncogenic KRAS Function in Pancreatic Cancer via TAK1–TAB Stabilization and Regulation of Noncanonical NF-κB
Authors: Bang Deepali , Wilson Willie , Ryan Meagan , Yeh Jen Jen , Baldwin Albert S.
Published: April 2013

Mutations in KRAS drive the oncogenic phenotype in a variety of tumors of epithelial origin. The NF-κB transcription factor pathway is important for oncogenic RAS to transform cells and to drive tumorigenesis in animal models. Recently, TGF-β–activated kinase 1 (TAK1), an upstream regulator of IκB kinase (IKK), which controls canonical NF-κB signaling, was shown to be important for chemoresistance in pancreatic cancer and for regulating KRAS-mutant colorectal cancer cell growth and survival. Here, we show that mutant KRAS upregulates glycogen synthase kinase 3α (GSK-3α), leading to its interaction with TAK1 to stabilize the TAK1–TAB complex to promote IKK activity. In addition, GSK-3α is required for promoting critical noncanonical NF-κB signaling in pancreatic cancer cells. Pharmacologic inhibition of GSK-3 suppresses growth of human pancreatic tumor explants, consistent with the loss of expression of oncogenic genes such as c-myc and TERT. These data identify GSK-3α as a key downstream effector of oncogenic KRAS via its ability to coordinately regulate distinct NF-κB signaling pathways.

Significance: GSK-3α functions to promote IKK/NF-κB activity downstream of oncogenic KRAS via stabilization and activation of the TAK1/TAB complex and to promote noncanonical NF-κB activity via control of nuclear levels of NF-κB2. Inhibition of GSK-3 strongly suppresses growth of human pancreatic tumor explants with downregulation of certain oncogenic NF-κB target genes such as c-myc and TERT. Cancer Discov; 3(6); 690–703. ©2013 AACR.

This article is highlighted in the In This Issue feature, p. 591
Prevalence and Predictors of Ischemia and Outcomes in Outpatients With Diabetes Mellitus Referred for Single-Photon Emission Computed Tomography Myocardial Perfusion Imaging
Authors: Bourque Jamieson M. , Patel Chetan A. , Ali Mohamed M. , Perez Margarita , Watson Denny D. , Beller George A.
Published: April 2013

Background—

The prevalence of ischemia and its prediction of events are unclear in outpatients with diabetes mellitus in the modern era of intensive medical management. We sought to identify the prevalence of ischemia, subsequent cardiac events, and impact of sex, stress type, and symptom status on these findings in a cohort of stable outpatients with diabetes mellitus referred for single-photon emission computed tomography myocardial perfusion imaging (MPI).

Methods and Results—

The study cohort included 575 consecutive outpatients with diabetes mellitus who underwent quantitative, gated single-photon emission computed tomography MPI. Clinical information, stress MPI variables, and cardiac events were prospectively collected and analyzed. The study population was at intermediate risk of coronary artery disease or had known coronary artery disease (40.3%); 29% of patients were asymptomatic at the time of stress testing. Scintigraphic ischemia and significant (≥10%) left ventricular ischemia were present in 126 patients (21.9%) and 29 patients (5.0%), respectively, and <1% of patients had early revascularization. The risk of ischemia was increased >2-fold by male sex (
P
<0.001), but was not impacted by pharmacological stress (
P
=0.15) or presence of symptoms (
P
=0.89). During a median 4.4 years follow-up, the rate of cardiac death/nonfatal myocardial infarction was moderate at 2.6%/y (cardiac death 0.8%/y) in the total cohort, but was 5.7%/y in those with ischemia (
P
<0.001). Pharmacological stress predicted a higher cardiac event rate (
P
<0.001) but symptoms did not (
P
=0.55).

Conclusions—

This cohort of stable outpatients with diabetes mellitus referred for single-photon emission computed tomography had low rates of significant ischemia and early revascularization; an initially low cardiac event rate increased after 2 years. Independent predictors of cardiac death/nonfatal myocardial infarction were known coronary artery disease, pharmacological stress, and MPI ischemia. Nearly one third of those with events had a normal MPI, indicating a need for improved risk stratification.
Integrated Proteomics Pipeline Yields Novel Biomarkers for Predicting Preeclampsia
Authors: Myers Jenny E. , Tuytten Robin , Thomas Grégoire , Laroy Wouter , Kas Koen , Vanpoucke Griet , Roberts Claire T. , Kenny Louise C. , Simpson Nigel A.B. , Baker Philip N. , North Robyn A.
Published: April 2013

Preeclampsia, a hypertensive pregnancy complication, is largely unpredictable in healthy nulliparous pregnant women. Accurate preeclampsia prediction in this population would transform antenatal care. To identify novel protein markers relevant to the prediction of preeclampsia, a 3-step mass spectrometric work flow was applied. On selection of candidate biomarkers, mostly from an unbiased discovery experiment (19 women), targeted quantitation was used to verify and validate candidate biomarkers in 2 independent cohorts from the SCOPE (SCreening fOr Pregnancy Endpoints) study. Candidate proteins were measured in plasma specimens collected at 19 to 21 weeks’ gestation from 100 women who later developed preeclampsia and 200 women without preeclampsia recruited from Australia and New Zealand. Protein levels (n=25), age, and blood pressure were then analyzed using logistic regression to identify multimarker models (maximum 6 markers) that met predefined criteria: sensitivity ≥50% at 20% positive predictive value. These 44 algorithms were then tested in an independent European cohort (n=300) yielding 8 validated models. These 8 models detected 50% to 56% of preeclampsia cases in the training and validation sets; the detection rate for preterm preeclampsia cases was 80%. Validated models combine insulin-like growth factor acid labile subunit and soluble endoglin, supplemented with maximally 4 markers of placental growth factor, serine peptidase inhibitor Kunitz type 1, melanoma cell adhesion molecule, selenoprotein P, and blood pressure. Predictive performances were maintained when exchanging mass spectrometry measurements with ELISA measurements for insulin-like growth factor acid labile subunit. In conclusion, we demonstrated that biomarker combinations centered on insulin-like growth factor acid labile subunit have the potential to predict preeclampsia in healthy nulliparous women.
Differential Effects of Nebivolol Versus Metoprolol on Functional Sympatholysis in Hypertensive Humans
Authors: Price Angela , Raheja Prafull , Wang Zhongyun , Arbique Debbie , Adams-Huet Beverley , Mitchell Jere H. , Victor Ronald G. , Thomas Gail D. , Vongpatanasin Wanpen
Published: April 2013

In young healthy humans, sympathetic vasoconstriction is markedly blunted during exercise to optimize blood flow to the metabolically active muscle. This phenomenon known as functional sympatholysis is impaired in hypertensive humans and rats by angiotensin II–dependent mechanisms, involving oxidative stress and inactivation of nitric oxide (NO). Nebivolol is a β1-adrenergic receptor blocker that has NO-dependent vasodilatory and antioxidant properties. We therefore asked whether nebivolol would restore functional sympatholysis in hypertensive humans. In 21 subjects with stage 1 hypertension, we measured muscle oxygenation and forearm blood flow responses to reflex increases in sympathetic nerve activity evoked by lower body negative pressure at rest, and during rhythmic handgrip exercise at baseline, after 12 weeks of nebivolol (5–20 mg/d) or metoprolol (100–300 mg/d), using a double-blind crossover design. We found that nebivolol had no effect on lower body negative pressure–induced decreases in oxygenation and forearm blood flow in resting forearm (from −29±5% to −30±5% and from −29±3% to −29±3%, respectively;
P
=NS). However, nebivolol attenuated the lower body negative pressure–induced reduction in oxygenation and forearm blood flow in exercising forearm (from −14±4% to −1±5% and from −15±2% to −6±2%, respectively; both
P
<0.05). This effect of nebivolol on oxygenation and forearm blood flow in exercising forearm was not observed with metoprolol in the same subjects, despite a similar reduction in blood pressure. Nebivolol had no effect on sympathetic nerve activity at rest or during handgrip, suggesting a direct effect on vascular function. Thus, our data demonstrate that nebivolol restored functional sympatholysis in hypertensive humans by a mechanism that does not involve β1-adrenergic receptors.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01502787.
Model Reductions for Inference: Generality of Pairwise, Binary, and Planar Factor Graphs
Authors: Eaton Frederik , Ghahramani Zoubin
Published: April 2013

We offer a solution to the problem of efficiently translating algorithms between different types of discrete statistical model. We investigate the expressive power of three classes of model—those with binary variables, with pairwise factors, and with planar topology—as well as their four intersections. We formalize a notion of “simple reduction” for the problem of inferring marginal probabilities and consider whether it is possible to “simply reduce” marginal inference from general discrete factor graphs to factor graphs in each of these seven subclasses. We characterize the reducibility of each class, showing in particular that the class of binary pairwise factor graphs is able to simply reduce only positive models. We also exhibit a continuous “spectral reduction” based on polynomial interpolation, which overcomes this limitation. Experiments assess the performance of standard approximate inference algorithms on the outputs of our reductions.