bluuebunny/crossref_metadata_2025 huggingface dataset:
Safety and Efficacy of GSK2248761, a Next-Generation Nonnucleoside Reverse Transcriptase Inhibitor, in Treatment-Naive HIV-1-Infected Subjects
Authors: Zala Carlos , St. Clair Marty , Dudas Kathleen , Kim Joseph , Lou Yu , White Scott , Piscitelli Steve , Dumont Etienne , Pietropaolo Keith , Zhou Xiao-Jian , Mayers Douglas
Published: February 2012

GSK2248761 is a novel, once-daily (QD), next-generation nonnucleoside reverse transcriptase inhibitor (NNRTI) with activity against efavirenz-resistant strains. Two phase I/IIa, double-blind, randomized, placebo-controlled studies investigated the antiviral activity, safety, and pharmacokinetics (PK) of several doses of GSK2248761 monotherapy in treatment-naive HIV-infected subjects. In the initial study, 10 subjects (8 active and 2 placebo) per dose received sequentially descending GSK2248761 monotherapy regimens of 800, 400, 200, and 100 mg QD for 7 days. Because a dose-response relationship was not identified, a second study examined a lower, 30-mg QD dose in 8 subjects (6 active and 2 placebo). Adverse events, viral load (VL), PK, and reverse transcriptase mutations were assessed and combined for analysis. Treatment with GSK2248761 for 7 days was well tolerated with no serious adverse events or discontinuations. The mean VL reductions from baseline on day 8 were 0.97, 1.87, 1.84, 1.81, and 1.78 log
10
copies/ml for GSK2248761 doses of 30, 100, 200, 400, and 800 mg QD, respectively. GSK2248761 PK (maximum drug concentration in serum [
C
max
], area under the plasma concentration-time curve from 0 h to the end of the dosing interval [AUC
0-τ
], and concentration at the end of the dosing interval [
C
τ
]) increased proportionally over the dose range of 30 to 800 mg QD. The relationship between short-term VL change and GSK2248761 PK was best described by a maximum-effect (
E
max
) model using
C
τ
(
E
max
= 2.0; 50% effective concentration [EC
50
] = 36.9 ng/ml). No NNRTI resistance mutations emerged during the study. GSK2248761 at 100 to 800 mg QD for 7 days was well tolerated, demonstrated potent antiviral activity in treatment-naive HIV-infected subjects, and had favorable PK and resistance profiles. GSK2248761 is no longer in clinical development.
Campylobacter jejuni Disrupts Protective Toll-Like Receptor 9 Signaling in Colonic Epithelial Cells and Increases the Severity of Dextran Sulfate Sodium-Induced Colitis in Mice
Authors: O'Hara Jennifer R. , Feener Troy D. , Fischer Carrie D. , Buret Andre G.
Published: February 2012

Inflammatory bowel disease (IBD) is characterized by chronic intestinal inflammation associated with a dysregulated immune response to commensal bacteria in susceptible individuals. The relapse of IBD may occur following an infection with
Campylobacter jejuni
. Apical epithelial Toll-like receptor 9 (TLR9) activation by bacterial DNA is reported to maintain colonic homeostasis. We investigated whether a prior
C. jejuni
infection disrupts epithelial TLR9 signaling and increases the severity of disease in a model of mild dextran sulfate sodium (DSS) colitis in mice. In a further attempt to identify mechanisms, T84 monolayers were treated with
C. jejuni
followed by a TLR9 agonist. Transepithelial resistance (TER) and dextran flux across confluent monolayers were monitored. Immunohistochemistry, Western blotting, and flow cytometry were used to examine TLR9 expression. Mice colonized by
C. jejuni
lacked any detectable pathology; however, in response to low levels of DSS, mice previously exposed to
C. jejuni
exhibited significantly reduced weight gain and increased occult blood and histological damage scores. Infected mice treated with DSS also demonstrated a significant reduction in levels of the anti-inflammatory cytokine interleukin-25.
In vitro
studies indicated that apical application of a TLR9 agonist enhances intestinal epithelial barrier function and that this response is lost in
C. jejuni
-infected monolayers. Furthermore, infected cells secreted significantly more CXCL8 following the basolateral application of a TLR9 agonist. Surface TLR9 expression was reduced in
C. jejuni
-infected monolayers subsequently exposed to a TLR9 agonist. In conclusion, infection by
C. jejuni
disrupts TLR9-induced reinforcement of the intestinal epithelial barrier, and colonization by
C. jejuni
increases the severity of mild DSS colitis.
SCHRÖDINGER SYSTEMS ARISING IN NONLINEAR OPTICS AND QUANTUM MECHANICS: PART I
Authors: HAJAIEJ H.
Published: February 2012

In this first part, we study the existence and uniqueness of solutions of a general nonlinear Schrödinger system in the presence of diamagnetic field, local and nonlocal nonlinearities. This kind of systems models many important phenomena in nonlinear optics; multimodal optical fibers, optical pulse propagation, ferromagnetic film and optical pulse propagation in the birefringent fibers. They also govern the interaction of electron and nucleii through Coulombic potential and under the action of external magnetic field in quantum mechanics.
MIXED hp-DISCONTINUOUS GALERKIN FEM FOR LINEAR ELASTICITY AND STOKES FLOW IN THREE DIMENSIONS
Authors: WIHLER THOMAS P. , WIRZ MARCEL
Published: February 2012

We consider mixed hp-discontinuous Galerkin FEM for linear elasticity in polyhedral domains Ω ⊂ ℝ3. In order to resolve possible corner, edge, and corner–edge singularities, anisotropic axiparallel geometric edge meshes consisting of hexahedral elements are applied. We show inf–sup stability results on both the continuous and the discrete level which are robust with respect to the Poisson ratio as it tends to the incompressible limit of ½. Furthermore, in the subsequent a priori error analysis we derive a quasi-optimality result, including the case of singular solutions. In addition, under certain realistic assumptions (for analytic data) on the regularity of the exact solution, we prove that the proposed DG schemes converge at an exponential rate in terms of the fifth root of the number of degrees of freedom.
STM OBSERVATION OF GRAPHENE FORMATION USINGSiC-ON-INSULATOR SUBSTRATES
Authors: NAITOH M. , OKANO M. , KITADA Y. , SASAKI Y. , OKUBO Y. , EDAMOTO D. , NAKAO M. , OMURA I. , IKARI T.
Published: February 2012

We used scanning tunneling microscopy to investigate graphene formation on an SiC -on-insulator (SiC-OI) substrate. Annealing of an SiC-OI substrate with an SiC thickness of 1500 nm produced a graphene layer on the SiC surface. When the thickness of the SiC film was 5 nm, a graphene layer was not formed on the SiC surface. However, after annealing a C-covered SiC-OI substrate with an SiC thickness of 5 nm, a graphene layer formed on the SiO2surface.
THE EFFECTS OF TEMPERATURE AND HYDROSTATIC PRESSURE ON THE DIAMAGNETIC SUSCEPTIBILITY OF A DONOR IN A QUANTUM WELL
Authors: YESILGUL U. , UNGAN F. , KASAPOGLU E. , SARI H. , SÖKMEN I.
Published: February 2012

Using the effective-mass approximation within a variational scheme, we have calculated the diamagnetic susceptibility and binding energy of a hydrogenic donor in a quantum well under different temperatures and hydrostatic pressure conditions. Our calculation have revealed the dependence of the diamagnetic susceptibility and the impurity binding on temperature and hydrostatic pressure.
CONTROLLING THE MOVEMENT OF WATER DROPLETS WITH MICRO- AND HIERARCHICAL MICRO/NANOSTRUCTURES
Authors: RASILAINEN TIINA , KIRVESLAHTI ANNA , NEVALAINEN PAULIINA , SUVANTO MIKA , PAKKANEN TAPANI A.
Published: February 2012

Anisotropic surfaces with micropillar- or micropillar/nanobump structures and anisotropic wetting behavior were fabricated. Structures were arranged as three parallel zones where the structure of the middle zone differed from that of the edge zones. The widths of the middle zones were increased systematically, and the effects of the middle zone structures and widths on the contact and sliding angles of water were investigated. Structures were fabricated on PP by injection molding. Microstructured mold inserts for injection molding were obtained by structuring aluminum foils with a microworking robot, and hierarchically structured mold inserts by anodizing the microstructured foils. It was possible to create surfaces where the microstructure in the middle zone was lower or higher than on the edges, or where the middle zone had only nanostructure or was unstructured. The behavior of water on the surfaces was characterized by measuring the dynamic contact angles and sliding angles parallel and perpendicular to the zones. Hydrophobic surfaces were achieved. With appropriate middle zone widths, clearly differing parallel and perpendicular contact angles were measured and elongation of droplets along the middle zones was detected.
RAMAN AND OPTOELECTRONIC PROPERTIES OF Zn1-xMgxO THIN FILMS PREPARED BY RF MAGNETRON SPUTTERING
Authors: HUANG Q. L. , FANG L. , RUAN H. B. , GUO B. D. , WU F. , KONG C. Y.
Published: February 2012

A series of Zn 1-x Mg x O (x = 0 ~ 0.16) films have been prepared on glass substrates by RF magnetron sputtering. The structure, surface morphology, composition, optical and electrical properties of the films were investigated by X-ray diffraction (XRD), scanning electron microscope (SEM), energy dispersive X-ray spectroscopy (EDX), Raman spectroscopy, UV-Vis spectrophotometer and Hall measurement, respectively. It reveals that the obtained films are uniform hexagonal wurtzite polycrystalline with grain size about 100 nm.The optical transmittance are over 80% and the band gap (Eg) has linear relationship with Mg content: Eg = 1.67x + 3.274 (eV) (0 < x < 0.16). The resistivity of the films increases with the increase of Mg content. The Raman spectra of the films show that the position of E2 peaks (473 cm-1) has not changed, but the A1(LO) mode (577 cm-1) frequency shifts to lower wavenumbers with the increase of Mg content, indicating that Mg -doping does not cause intensive lattice deformation, but results in the decrease of the carrier concentration, which is corresponding to the degradation of the conductivity of ZnMgO films with the increase of Mg content.
THE EXCITATION OF PLASMON MODES AT A MISMATCHED SILVER/COPPER INTERFACE
Authors: POLITANO A.
Published: February 2012

The influence of structural, thermal and electronic properties on collective electronic excitations (plasmon modes) has been investigated for thin Ag films grown at room temperature on Cu(111) . For the (9 × 9)-Ag/Cu(111) structure the excitation of the two-dimensional plasmon, observed in Ag/Si(111) , is forbidden by both the high corrugation of the Ag layer and the presence of the underlying metal substrate. The increase of the sp density of states at the Fermi energy induces the appearance of a broad peak a 7–8eV, assigned to a free-electron collective excitation. For increasing Ag coverage (above 20 layers), surface plasmon is confined within Ag grains, as indicated by the analysis of its dispersion relation, which is dispersionless up to a critical wave-vector. Surface plasmon confinement is removed upon annealing at 400 K. The thermal treatment induces a flattening of the Ag adlayer with a merging of Ag islands, and moreover, a strong enhancement of surface conductivity.
NONLINEAR SYMPLECTIC GRASSMANNIANS AND HAMILTONIAN ACTIONS IN PREQUANTUM LINE BUNDLES
Authors: MARTÍNEZ TORRES DAVID
Published: February 2012

In this paper we extend to the Fréchet setting the following well-known fact about finite-dimensional symplectic geometry: if a Lie group G acts on a symplectic manifold in a Hamiltonian fashion with momentum map μ, given x ∈ M the isotropy group Gxacts linearly on the tangent space in a Hamiltonian fashion, with momentum map the Taylor expansion of μ up to degree 2. We use this result to give a conceptual explanation for a formula of Donaldson in [Scalar curvature and projective embeddings. I, J. Differential Geom.59(3) (2001) 479–522], which describes the momentum map of the Hamiltonian infinitesimal action of the Lie algebra of the group of Hamiltonian diffeomorphisms of a closed integral symplectic manifold, on sections of its prequantum line bundle.
THE CAUCHY PROBLEM FOR f(R)-GRAVITY: AN OVERVIEW
Authors: CAPOZZIELLO S. , VIGNOLO S.
Published: February 2012

We review the Cauchy problem for f(R) theories of gravity, in metric and metric-affine formulations, pointing out analogies and differences with respect to General Relativity. The role of conformal transformations, effective scalar fields and sources in the field equations is discussed in view of the well-formulation and the well-position of the problem. Finally, criteria of viability of the f(R)-models are considered according to the various matter fields acting as sources.
NOTES ON PARA-HERMITE–EINSTEIN SPACETIMES
Authors: PRZANOWSKI MACIEJ , FORMAŃSKI SEBASTIAN , CHUDECKI ADAM
Published: February 2012

Para-Hermite–Einstein spacetimes are considered. It is shown that any para-Hermite–Einstein metric is locally defined by one nonlinear partial differential equation of the second order for one function.
GOLD NANOPARTICLES IN CANCER IMAGING AND THERAPEUTICS
Authors: HUANG HUANG-CHIAO , RAMOS JAMES , GRANDHI TARAKA SAI PAVAN , POTTA THRIMOORTHY , REGE KAUSHAL
Published: February 2012

The use of nanomedicine in the war on cancer diseases has progressed significantly in the recent past. Liposomal- and albumin-based chemotherapeutic agents as well as tumor contrast agents (e.g. Gd-DTPA, ferumoxides) have received FDA approval for human clinical use, while many other agents are in different phases of pre-clinical investigation and clinical trials. Plasmonic gold nanoparticles hold great promise as potential theranostic devices for detection and ablation of cancer diseases. This review discusses recent progress in the imaging, photothermal therapy, and nucleic acid/drug delivery using gold nanoparticles (spheres, shells, rods, cages) in vitro and in vivo. Issues relating to toxicity, biocompatibility, biodistribution, cellular uptake, and targeting efficiency are also discussed.
FEASIBILITY STUDY OF A CLINICAL BLOOD–BRAIN BARRIER OPENING ULTRASOUND SYSTEM
Authors: MARQUET FABRICE , TUNG YAO-SHENG , KONOFAGOU ELISA E.
Published: February 2012

In this paper, we investigate the focalization properties of single-element transducers at intermediate frequencies (500 kHz) through primate and human skulls. The study addresses the transcranial targeting involved in ultrasound-induced blood–brain barrier (BBB) opening with clinically relevant targets such as the hippocampus and the basal ganglia, which are typically affected by early Alzheimer's and Parkinson's disease, respectively. The targeted brain structures were extracted from three-dimensional (3D) brain atlases registered with the skulls and used to virtually position and orient the transducers. The frequency dependence is first investigated and the capability of targeting of different structures is explored. Preliminary in vivo feasibility is investigated in mice at this frequency. A simple, affordable and convenient system is found to be feasible for BBB opening in primates and humans capable of successfully targeting the hippocampus, putamen and substantia nigra and could thus allow for its broader impact and applications.
Going Mainstream
Authors: Tozman Reuben
Published: February 2012

L & D professionals bemoan the unenvious position of being first on the budget slashing table when businesses need to cut back. We believe in the value we can offer to our organizations and yet, regardless of everything we've worked on to prove our value we still seem to be relegated to "nice to have" when push comes to shove. The problem lies squarely on our shoulders. It is up to us to remodel and re-engineer what we do as part of core business operations. To do this, we need to look at the tools we use, the assumptions we make and above all else we need to disperse and integrate.
Parametric assessment of video quality in content
Authors: Mu Mu
Published: February 2012

IP-based packet-switched networks have become one of the main content distribution platforms for emerging multimedia services such as IPTV, thanks to the rapidly growing bandwidth and exclusive inter-networking and interactivity features of IP-based networks. Meanwhile, high quality video content services are becoming particularly popular within content delivery networks (CDN). During content distribution, packets of encoded video streams can be delayed, corrupted or dropped due to network impairments in packet-switched networks. This leads to perceptual quality degradations of the delivered content at receiver. Although network impairments are rare in commercial managed networks, any distortion caused by impairments can be highly detrimental to end users' experience. Consequently the ability to meet customer expectations on video quality has become a critical service differentiator. Quality of Experience (QoE) that was merely recognised as a value-added service of traditional content distribution services is now one of the fundamental requirements and challenges of providing high quality video services. In order to maintain a high level of user experience throughout the life-cycle of a video service, a service quality measurement and management service must be established.
Performance Evaluation of an Object Management Policy Approach for P2P Networks
Authors: Vieira Dario , Melo Cesar A. V. , Ghamri-Doudane Yacine
Published: February 2012

The increasing popularity of network-based multimedia applications poses many challenges for content providers to supply efficient and scalable services. Peer-to-peer (P2P) systems have been shown to be a promising approach to provide large-scale video services over the Internet since, by nature, these systems show high scalability and robustness. In this paper, we propose and analyze an object management policy approach for video web cache in a P2P context, taking advantage of object's metadata, for example, video popularity, and object's encoding techniques, for example, scalable video coding (SVC). We carry out trace-driven simulations so as to evaluate the performance of our approach and compare it against traditional object management policy approaches. In addition, we study as well the impact of churn on our approach and on other object management policies that implement different caching strategies. A YouTube video collection which records over 1.6 million video's log was used in our experimental studies. The experiment results have showed that our proposed approach can improve the performance of the cache substantially. Moreover, we have found that neither the simply enlargement of peers' storage capacity nor a zero replicating strategy is effective actions to improve performance of an object management policy.
About Nodal Systems for Lagrange Interpolation on the Circle
Authors: Berriochoa E. , Cachafeiro A. , García Amor J. M.
Published: February 2012

We study the convergence of the Laurent polynomials of Lagrange interpolation on the unit circle for continuous functions satisfying a condition about their modulus of continuity. The novelty of the result is that now the nodal systems are more general than those constituted by the n roots of complex unimodular numbers and the class of functions is different from the usually studied. Moreover, some consequences for the Lagrange interpolation on [−1,1] and the Lagrange trigonometric interpolation are obtained.
Pleomorphic Adenoma of the Cervical Heterotopic Salivary Gland: A Case Report
Authors: Vegari Saman , Naderpour Masoud , Hemmati Alireza , Baybordi Hosein
Published: February 2012

Introduction. Although pleomorphic adenoma is the most common neoplasm of the salivary glands, this tumor most commonly involves the minor salivary glands of palatal and rarely occurs in cervical region.Case Report. A 21-year-old female referred to our clinic due to painless mass of right upper region of neck. After paraclinical and pathologic evaluation, it was diagnosed as cervical pleomorphic adenoma.Conclusion. Pleomorphic adenoma may be rarely involving the neck. Although the prognosis is good, the choice treatment is the complete resection of the tumor.
Working with Mild Traumatic Brain Injury: Voices from the Field
Authors: Buck Page Walker , Laster Rebecca G. , Sagrati Jocelyn Spencer , Kirzner Rachel Shapiro
Published: February 2012

Mild traumatic brain injury (mTBI), also known as concussion, is an emerging public health issue in the United States. The estimated annual 1.2 million individuals who sustain this injury face a range of cognitive, psychological, and physical consequences for which rehabilitation protocols are being developed and implemented. On the frontlines of this developing area of rehabilitation work are professionals in a range of therapeutic settings whose practice wisdom has yet to be shared in the professional literature. This qualitative study aimed to fill this gap by exploring the experiences and insights of rehabilitation professionals serving mTBI patients in outpatient, civilian settings. An analysis of the qualitative data revealed five themes common in mTBI work, providing an in-depth look at this often challenging field of rehabilitation.
Effect of PGC-1αon Proliferation, Migration, and Transdifferentiation of Rat Vascular Smooth Muscle Cells Induced by High Glucose
Authors: Qi Xiaoqiang , Zhang Yujing , Li Jing , Hou Dongxia , Xiang Yang
Published: February 2012

We assessed the role of PGC-1α (PPARγ coactivator-1 alpha) in glucose-induced proliferation, migration, and inflammatory gene expression of vascular smooth muscle cells (VSMCs). We carried out phagocytosis studies to assess the role of PGC-1α in transdifferentiation of VSMCs by flow cytometry. We found that high glucose stimulated proliferation, migration and inflammatory gene expression of VSMCs, but overexpression of PGC-1α attenuated the effects of glucose. In addition, overexpression of PGC-1α decreased mRNA and protein level of VSMCs-related genes, and induced macrophage-related gene expression, as well as phagocytosis of VSMCs. Therefore, PGC-1α inhibited glucose-induced proliferation, migration and inflammatory gene expression of VSMCs, which are key features in the pathology of atherosclerosis. More importantly, PGC-1α transdifferentiated VSMCs to a macrophage-like state. Such transdifferentiation possibly increased the portion of VSMCs-derived foam cells in the plaque and favored plaque stability.
Retinoic Acid/Alpha-Interferon Combination Inhibits Growth and Promotes Apoptosis in Mantle Cell Lymphoma through Akt-Dependent Modulation of Critical Targets
Authors: Dal Col Jessica , Mastorci Katy , Faè Damiana Antonia , Muraro Elena , Martorelli Debora , Inghirami Giorgio , Dolcetti Riccardo
Published: February 2012

Mantle cell lymphoma (MCL) is characterized by a profound deregulation of the mechanisms controlling cell-cycle progression and survival. We herein show that the combination of 9-cis-retinoic acid (RA) and IFN-α induces marked antiproliferative and proapoptotic effects in MCL cells through the modulation of critical targets. Particularly, IFN-α enhances RA-mediated G0–G1 cell accumulation by downregulating cyclin D1 and increasing p27Kip1 and p21WAF1/Cip1 protein levels. Furthermore, RA/IFN-α combination also induces apoptosis by triggering both caspases-8 and -9 resulting in Bax and Bak activation. In particular, RA/IFN-α treatment downregulates the antiapoptotic Bcl-xL and Bfl-1 proteins and upregulates the proapoptotic BH3-only Noxa protein. Sequestration of Mcl-1 and Bfl-1 by upregulated Noxa results in the activation of Bid, and the consequent induction of apoptosis is inhibited by Noxa silencing. Noxa upregulation is associated with nuclear translocation of the FOXO3a transcription factor as consequence of RA/IFN-α–induced Akt inhibition. Pharmacologic suppression of Akt, but not of TORC1, increases Noxa protein levels and downregulates Bfl-1 protein supporting the conclusion that the inhibition of the Akt pathway, the resulting FOXO3a activation and Noxa upregulation are critical molecular mechanisms underlying RA/IFN-α—dependent MCL cell apoptosis. These results support the potential therapeutic value of RA/IFN-α combination in MCL management. Cancer Res; 72(7); 1825–35. ©2012 AACR.
Workplace-Based Breast Cancer Screening Intervention in China
Authors: Ma Grace X. , Yin Lihong , Gao Wanzhen , Tan Yin , Liu Ran , Fang Carolyn , Ma Xiang S.
Published: February 2012

Background: Breast cancer continues to be the primary cause of death among East and Southeast Asian women. Although China, the most populous country in the world, is experiencing unprecedented economic growth, its health care system has yet to benefit from the current economic prosperity. Indeed, studies have shown a consistent increase in breast cancer rates among Chinese women over the past two decades in the absence of breast cancer screening guidelines.

Methods: The primary objective of this study was to examine the impact of a workplace intervention on increasing breast cancer screening rates. The study was implemented at eight worksites in Nanjing, four of which were assigned to the intervention group (n = 232) and four to the control group (n = 221). The intervention group received breast cancer education and screening navigation. The control group was provided with general cancer education and received a delayed intervention after completion of the study. Study measures were completed at pre- and postprogram and at 6-month follow-up to assess uptake of mammography.

Results: Baseline mammography use was low among both intervention and control groups. However, exposure to the workplace intervention dramatically increased the uptake of mammography from 10.3% at baseline to 72.6% at 6-month follow-up in the intervention group (P < 0.001).

Conclusions: Findings provide preliminary evidence that the implementation of a comprehensive workplace breast cancer screening intervention program in China can lead to increased uptake of mammography. These data may help facilitate the development of theory-based workplace cancer prevention programs and screening guidelines in China.

Impact: A workplace-based multifaceted intervention could have a strong impact in breast cancer prevention and early detection among women in China. Cancer Epidemiol Biomarkers Prev; 21(2); 358–67. ©2011 AACR.
Variation in Age at Cancer Diagnosis in Familial versus Nonfamilial Barrett's Esophagus
Authors: Chak Amitabh , Chen Yanwen , Vengoechea Jaime , Canto Marcia I. , Elston Robert , Falk Gary W. , Grady William M. , Guda Kishore , Kinnard Margaret , Markowitz Sanford , Mittal Sumeet , Prasad Ganapathy , Shaheen Nicholas , Willis Joseph E. , Barnholtz-Sloan Jill S.
Published: February 2012

Background: Genetic influences may be discerned in families that have multiple affected members and may manifest as an earlier age of cancer diagnosis. In this study, we determine whether cancers develop at an earlier age in multiplex Familial Barrett's Esophagus (FBE) kindreds, defined by 3 or more members affected by Barrett's esophagus (BE) or esophageal adenocarcinoma (EAC).

Methods: Information on BE/EAC risk factors and family history was collected from probands at eight tertiary care academic hospitals. Age of cancer diagnosis and other risk factors were compared between nonfamilial (no affected relatives), duplex (two affected relatives), and multiplex (three or more affected relatives) FBE kindreds.

Results: The study included 830 nonfamilial, 274 duplex, and 41 multiplex FBE kindreds with 274, 133, and 43 EAC and 566, 288, and 103 BE cases, respectively. Multivariable mixed models adjusting for familial correlations showed that multiplex kindreds were associated with a younger age of cancer diagnosis (P = 0.0186). Median age of cancer diagnosis was significantly younger in multiplex compared with duplex and nonfamilial kindreds (57 vs. 62 vs. 63 years, respectively, P = 0.0448). Mean body mass index was significantly lower in multiplex kindreds (P = 0.0033), as was smoking (P < 0.0001), and reported regurgitation (P = 0.0014).

Conclusions: Members of multiplex FBE kindreds develop EAC at an earlier age compared with nonfamilial EAC cases. Multiplex kindreds do not have a higher proportion of common risk factors for EAC, suggesting that this aggregation might be related to a genetic factor.

Impact: These findings indicate that efforts to identify susceptibility genes for BE and EAC will need to focus on multiplex kindreds. Cancer Epidemiol Biomarkers Prev; 21(2); 376–83. ©2011 AACR.
Spin-Labeling Magnetic Resonance Imaging Detects Increased Myocardial Blood Flow After Endothelial Cell Transplantation in the Infarcted Heart
Authors: Zhang Hualei , Qiao Hui , Frank Rachel S. , Huang Bin , Propert Kathleen J. , Margulies Susan , Ferrari Victor A. , Epstein Jonathan A. , Zhou Rong
Published: February 2012

Background—

We quantified absolute myocardial blood flow (MBF) using a spin-labeling MRI (SL-MRI) method after transplantation of endothelial cells (ECs) into the infarcted heart. Our aims were to study the temporal changes in MBF in response to EC transplantation and to compare regional MBF with contractile function (wall motion) and microvascular density.

Methods and Results—

We first validated the SL-MRI method with the standard microsphere technique in normal rats. We then induced myocardial infarction in athymic rats and injected 5 million ECs (human umbilical vein endothelial cells) suspended in Matrigel or Matrigel alone (vehicle) along the border of the blanched infarcted area. At 2 weeks after myocardial infarction, MBF averaged over the entire slice (
P
=0.038) and in the infarcted region (
P
=0.0086) was significantly higher in EC versus vehicle group; the greater MBF was accompanied by an increase of microvasculature density in the infarcted region (
P
=0.0105 versus vehicle). At 4 weeks after myocardial infarction, MBF in the remote region was significantly elevated in EC-treated hearts (
P
=0.0277); this was accompanied by increased wall motion in this region assessed by circumferential strains (
P
=0.0075). Intraclass correlation coefficients and Bland-Altman plot revealed a good reproducibility of the SL-MRI method.

Conclusions—

MBF in free-breathing rats measured by SL-MRI is validated by the standard color microsphere technique. SL-MRI allows quantification of temporal changes of regional MBF in response to EC treatment. The proof-of-principle study indicates that MBF is a unique and sensitive index to evaluate EC-mediated therapy for the infarcted heart.
Ouabain and Insulin Induce Sodium Pump Endocytosis in Renal Epithelium
Authors: Gupta Shalini , Yan Yanling , Malhotra Deepak , Liu Jiang , Xie Zijian , Najjar Sonia M. , Shapiro Joseph I.
Published: February 2012

Cardiotonic steroids signaling through the basolateral sodium pump (Na/K-ATPase) have been shown to alter renal salt handling in intact animals. Because the relationship between renal salt handling and blood pressure is a key determinant of hypertension, and patients with insulin resistance are frequently hypertensive, we chose to examine whether there might be competition for resources necessary for receptor-mediated endocytosis. In LLC-PK1 cells, the Na/K-ATPase-α1 and carcinoembryonic antigen cell adhesion molecule 1, a plasma membrane protein that promotes receptor-mediated endocytosis, colocalized in the plasma membranes and translocated to the intracellular region in response to ouabain. Either ouabain or insulin alone caused accumulation of and carcinoembryonic antigen cell adhesion molecule, as well as insulin receptor-β, and epidermal growth factor receptor in early endosomes, but no synergy was demonstrable. Like ouabain, insulin also caused c-Src activation. When caveolin or Na/K-ATPase-α1 expression was knocked down with small interfering RNA, insulin but not ouabain induced carcinoembryonic antigen cell adhesion molecule 1, insulin receptor-β, and epidermal growth factor receptor endocytosis. To determine whether this might be relevant to salt handling in vivo, we examined salt loading in mice with null renal carcinoembryonic antigen cell adhesion molecule 2 expression. The null renal carcinoembryonic antigen cell adhesion molecule 2 animals demonstrated greater increases in blood pressure with increases in dietary salt than control animals. These data demonstrate that cardiotonic steroids and insulin compete for cellular endocytosis resources and suggest that, under conditions where circulating insulin concentrations are high, cardiotonic steroid-mediated natriuresis could be impaired.
Down-regulated expression of hsa-miR-181c in Fanconi anemia patients: implications in TNFα regulation and proliferation of hematopoietic progenitor cells
Authors: Río Paula , Agirre Xabier , Garate Leire , Baños Rocío , Álvarez Lara , San José-Enériz Edurne , Badell Isabel , Casado José A. , Garín Marina , Prósper Felipe , Bueren Juan A.
Published: February 2012

Fanconi anemia (FA) is an inherited genetic disorder associated with BM failure and cancer predisposition. In the present study, we sought to elucidate the role of microRNAs (miRNAs) in the hematopoietic defects observed in FA patients. Initial studies showed that 3 miRNAs, hsa-miR-133a, hsa-miR-135b, and hsa-miR-181c, were significantly down-regulated in lymphoblastoid cell lines and fresh peripheral blood cells from FA patients. In vitro studies with cells expressing the luciferase reporter fused to the TNFα 3′-untranslated region confirmed in silico predictions suggesting an interaction between hsa-miR-181c and TNFα mRNA. These observations were consistent with the down-regulated expression of TNFα mediated by hsa-miR-181c in cells from healthy donors and cells from FA patients. Because of the relevance of TNFα in the hematopoietic defects of FA patients, in the present study, we transfected BM cells from FA patients with hsa-miR-181c to evaluate the impact of this miRNA on their clonogenic potential. hsa-miR-181c markedly increased the number and size of the myeloid and erythroid colonies generated by BM cells from FA patients. Our results offer new clues toward understanding the biologic basis of BM failure in FA patients and open new possibilities for the treatment of the hematologic dysfunction in FA patients based on miRNA regulation.
Functional analysis of hepatitis B virus pre-s deletion variants associated with hepatocellular carcinoma
Authors: Lin Chih-Ming , Wang Gen-Ming , Jow Guey-Mei , Chen Bing-Fang
Published: February 2012

Background

Naturally occurring pre-S deletion mutants have been identified in hepatitis B carriers and shown to be associated with the development of hepatocellular carcinoma. The phenotypes of these pre-S deletion genomes remain unclear, and they were investigated in this study.

Methods

The pre-S deletion genomes: (1) pre-S1 deletion, (2) deletion spanning pre-S1 and pre-S2, (3) pre-S2 N-terminal deletion, and (4) pre-S2 internal deletion were constructed and analyzed by transfection into Huh-7 cells.

Results

Functional analyses reveal that these mutants were divided into two groups: S promoter deletion and non-S promoter deletion variants. Compared with the wild-type genome, S promoter deletion variants led to an inverse ratio of pre-S1 mRNA and pre-S2/S mRNA, and intracellular accumulation of surface proteins. An interesting finding is that a small amount of L proteins was detected in the medium from S promoter deletion variant-transfected cells. Non-S promoter deletion variants conversely displayed a wild-type like mRNA and protein pattern. The secretion of surface proteins from non-S promoter deletion variants was inhibited less than from S promoter deletion variant. Immunofluorescence analysis showed mutant surface proteins colocalized with ER and exhibited an atypical distribution: granular staining pattern in the S-promoter deletion variants and perinuclear staining pattern in the non-S promoter deletion variants.

Conclusion

This study shows that these pre-S deletion genomes exhibit two different phenotypes in mRNA transcription, surface protein expression and secretion. This diversity seems to result from the deletion of S promoter rather than result from the deletion of pre-S1 or pre-S2.
Defining the "core microbiome" of the microbial communities in the tonsils of healthy pigs
Authors: Lowe Beth A , Marsh Terence L , Isaacs-Cosgrove Natasha , Kirkwood Roy N , Kiupel Matti , Mulks Martha H
Published: February 2012

Background

Porcine tonsils are the colonization site for many pathogenic as well as commensal microorganisms and are the primary lymphoid tissue encountered by organisms entering through the mouth or nares. The goal of this study was to provide an in-depth characterization of the composition and structure of the tonsillar microbial communities and to define the core microbiome in the tonsils of healthy pigs, using high throughput bar-coded 454-FLX pyrosequencing.

Results

Whole tonsils were collected at necropsy from 12 16-week-old finisher pigs from two healthy herds. Tonsil brushes were also used to collect samples from four of these animals. Bacterial DNA was isolated from each sample, amplified by PCR with universal primers specific for the bacterial 16S rRNA genes, and the PCR products sequenced using pyrosequencing. An average of 13,000 sequences were generated from each sample. Microbial community members were identified by sequence comparison to known bacterial 16S rRNA gene sequences.

The microbiomes of these healthy herds showed very strong similarities in the major components as well as distinct differences in minor components. Pasteurellaceae dominated the tonsillar microbiome in all animals, comprising ~60% of the total, although the relative proportions of the genera Actinobacillus, Haemophilus, and Pasteurella varied between the herds. Also found in all animals were the genera Alkanindiges, Peptostreptococcus, Veillonella, Streptococcus and Fusobacterium, as well as Enterobacteriaceae and Neisseriaceae. Treponema and Chlamydia were unique to Herd 1, while Arcanobacterium was unique to Herd 2.

Tonsil brushes yielded similar results to tissue specimens, although Enterobacteriaceae and obligate anaerobes were more frequently found in tissue than in brush samples, and Chlamydia, an obligately intracellular organism, was not found in brush specimens.

Conclusions

We have extended and supported our previous studies with 16S clone libraries, using 16S rRNA gene pyrosequencing to describe the microbial communities in tonsils of healthy pigs. We have defined a core microbiome, dominated by Pasteurellaceae, in tonsil specimens, and have also demonstrated the presence of unique minor components of the tonsillar microbiome present in each herd. We have validated the use of non-invasive tonsil brushes, in comparison to tonsil tissue, which will facilitate future studies.
Anti-malarial drugs: how effective are they against Plasmodium falciparum gametocytes?
Authors: Peatey Christopher L , Leroy Didier , Gardiner Donald L , Trenholme Katharine R
Published: February 2012

Background

Recent renewed emphasis on the eradication of malaria has highlighted the need for more tools with which to achieve this ambitious goal. One high priority area is the need to determine the gametocytocidal activity of both currently used anti-malarial drugs and those in the development pipeline. However, testing the activity of compounds against Plasmodium falciparum gametocytes is technically challenging both in vivo and in vitro.

Methods

Here the use of a simple robust assay to screen a panel of currently used and experimental anti-malarial drugs against mature P. falciparum gametocytes is described.

Results

Eight of 44 compounds tested reduced gametocyte viability by at least 50% and three showed IC50 values in nM range.

Conclusions

There is a need to identify new compounds with activity against late stage gametocytes and the information provided by this in vitro assay is a valuable first step, which can guide future clinical studies.
The establishment of a bank of stored clinical bone marrow stromal cell products
Authors: Sabatino Marianna , Ren Jiaqiang , David-Ocampo Virginia , England Lee , McGann Michael , Tran Minh , Kuznetsov Sergei A , Khuu Hanh , Balakumaran Arun , Klein Harvey G , Robey Pamela G , Stroncek David F
Published: February 2012

Background

Bone marrow stromal cells (BMSCs) are being used to treat a variety of conditions. For many applications a supply of cryopreserved products that can be used for acute therapy is needed. The establishment of a bank of BMSC products from healthy third party donors is described.

Methods

The recruitment of healthy subjects willing to donate marrow for BMSC production and the Good Manufacturing Practices (GMP) used for assessing potential donors, collecting marrow, culturing BMSCs and BMSC cryopreservation are described.

Results

Seventeen subjects were enrolled in our marrow collection protocol for BMSC production. Six of the 17 subjects were found to be ineligible during the donor screening process and one became ill and their donation was cancelled. Approximately 12 ml of marrow was aspirated from one posterior iliac crest of 10 donors; one donor donated twice. The BMSCs were initially cultured in T-75 flasks and then expanded for three passages in multilayer cell factories. The final BMSC product was packaged into units of 100 × 106 viable cells, cryopreserved and stored in a vapor phase liquid nitrogen tank under continuous monitoring. BMSC products meeting all lot release criteria were obtained from 8 of the 11 marrow collections. The rate of growth of the primary cultures was similar for all products except those generated from the two oldest donors. One lot did not meet the criteria for final release; its CD34 antigen expression was greater than the cut off set at 5%. The mean number of BMSC units obtained from each donor was 17 and ranged from 3 to 40.

Conclusions

The production of large numbers of BMSCs from bone marrow aspirates of healthy donors is feasible, but is limited by the high number of donors that did not meet eligibility criteria and products that did not meet lot release criteria.
Sensitive and rapid quantification of C-reactive protein using quantum dot-labeled microplate immunoassay
Authors: Luo Yang , Zhang Bo , Chen Ming , Jiang Tianlun , Zhou Daiyang , Huang Junfu , Fu Weiling
Published: February 2012

Background

High-sensitivity C-reactive protein (hs-CRP) assay is of great clinical importance in predicting risks associated with coronary heart disease. Existing hs-CRP assays either require complex operation or have low throughput and cannot be routinely implemented in rural settings due to limited laboratory resources.

Methods

We developed a novel hs-CRP assay capable of simultaneously quantifying over 90 clinical samples by using quantum dots-labeled immunoassay within a standard 96-well microplate. The specificity of the assay was enhanced by adopting two monoclonal antibodies (mAbs) that target distinct hs-CRP epitopes, serving as the coating antibody and the detection antibody, respectively. In the presence of hs-CRP antigen, the fluorescence intensity of the mAb-Ag-mAb sandwich complex captured on the microplate can be read out using a microplate reader.

Results

The proposed hs-CRP assay provides a wide analytical range of 0.001-100 mg/L with a detection limit of 0.06 (0.19) μg/L within 1.5 h. The accuracy of the proposed assay has been confirmed for low coefficient of variations (CVs), 2.27% (intra-assay) and 8.52% (inter-assay), together with recoveries of 96.7-104.2%. Bland-Altman plots of 104 clinical samples exhibited good consistency among the proposed assay, commercial high-sensitivity ELISA, and nephelometry, indicating the prospects of the newly developed hs-CRP assay as an alternative to existing hs-CRP assays.

Conclusion

The developed assay meets the needs of the rapid, sensitive and high-throughput determination of hs-CRP levels within a short time using minimal resources. In addition, the developed assay can also be used to detect and quantify other diagnostic biomarkers by immobilizing specific monoclonal antibodies.
A power efficient MAC protocol for wireless body area networks
Authors: Al Ameen Moshaddique , Ullah Niamat , Chowdhury M Sanaullah , Islam SM Riazul , Kwak Kyungsup
Published: February 2012

Applications of wearable and implanted wireless sensor devices are hot research area. A specialized field called the body area networks (BAN) has emerged to support this area. Managing and controlling such a network is a challenging task. An efficient media access control (MAC) protocol to handle proper management of media access can considerably improve the performance of such a network. Power consumption and delay are major concerns for MAC protocols in a BAN. Low cost wakeup radio module attached with sensor devices can help reduce power consumption and prolong the network lifetime by reducing idle state power consumption and increasing sleep time of a BAN node. In this article, we propose a new MAC protocol for BAN using out of band (on-demand) wakeup radio through a centralized and coordinated external wakeup mechanism. We have compared our method against some existing MAC protocols. Our method is found to be efficient in terms of power consumption and delay.
An improved vacuum formulation for 2D finite-difference modeling of Rayleigh waves including surface topography and internal discontinuities
Authors: Zeng Chong , Xia Jianghai , Miller Richard D. , Tsoflias Georgios P.
Published: February 2012

Rayleigh waves are generated along the free surface and their propagation can be strongly influenced by surface topography. Modeling of Rayleigh waves in the near surface in the presence of topography is fundamental to the study of surface waves in environmental and engineering geophysics. For simulation of Rayleigh waves, the traction-free boundary condition needs to be satisfied on the free surface. A vacuum formulation naturally incorporates surface topography in finite-difference (FD) modeling by treating the surface grid nodes as the internal grid nodes. However, the conventional vacuum formulation does not completely fulfill the free-surface boundary condition and becomes unstable for modeling using high-order FD operators. We developed a stable vacuum formulation that fully satisfies the free-surface boundary condition by choosing an appropriate combination of the staggered-grid form and a parameter-averaging scheme. The elastic parameters on the topographic free surface are updated with exactly the same treatment as internal grid nodes. The improved vacuum formulation can accurately and stably simulate Rayleigh waves along the topographic surface for homogeneous and heterogeneous elastic models with high Poisson’s ratios ([Formula: see text]). This method requires fewer grid points per wavelength than the stress-image-based methods. Internal discontinuities in a model can be handled without modification of the algorithm. Only minor changes are required to implement the improved vacuum formulation in existing 2D FD modeling codes.