bluuebunny/crossref_metadata_2025 huggingface dataset:
Examining Differences in Local Collagen Fiber Crimp Frequency Throughout Mechanical Testing in a Developmental Mouse Supraspinatus Tendon Model
Authors: Miller Kristin S. , Connizzo Brianne K. , Feeney Elizabeth , Tucker Jennica J. , Soslowsky Louis J.
Published: April 2012

Crimp morphology is believed to be related to tendon mechanical behavior. While crimp has been extensively studied at slack or nondescript load conditions in tendon, few studies have examined crimp at specific, quantifiable loading conditions. Additionally, the effect of the number of cycles of preconditioning on collagen fiber crimp behavior has not been examined. Further, the dependence of collagen fiber crimp behavior on location and developmental age has not been examined in the supraspinatus tendon. Local collagen fiber crimp frequency is quantified throughout tensile mechanical testing using a flash freezing method immediately following the designated loading protocol. Samples are analyzed quantitatively using custom software and semi-quantitatively using a previously established method to validate the quantitative software. Local collagen fiber crimp frequency values are compared throughout the mechanical test to determine where collagen fiber frequency changed. Additionally, the effect of the number of preconditioning cycles is examined compared to the preload and toe-region frequencies to determine if increasing the number of preconditioning cycles affects crimp behavior. Changes in crimp frequency with age and location are also examined. Decreases in collagen fiber crimp frequency were found at the toe-region at all ages. Significant differences in collagen fiber crimp frequency were found between the preload and after preconditioning points at 28 days. No changes in collagen fiber crimp frequency were found between locations or between 10 and 28 days old. Local collagen fiber crimp frequency throughout mechanical testing in a postnatal developmental mouse SST model was measured. Results confirmed that the uncrimping of collagen fibers occurs primarily in the toe-region and may contribute to the tendon’s nonlinear behavior. Additionally, results identified changes in collagen fiber crimp frequency with an increasing number of preconditioning cycles at 28 days, which may have implications on the measurement of mechanical properties and identifying a proper reference configuration.
ADITEC: Joining Forces for Next-Generation Vaccines
Authors: Rappuoli Rino , Medaglini Donata
Published: April 2012

Through the Advanced Immunization Technologies project, scientists join forces to fashion next-generation vaccines with technologies that no lab can master alone.
COBRA Insures Against Flu
Authors: Barnabas Ruanne V.
Published: April 2012

Genomics and computational biology couple to build better broader flu vaccines.
Diseases of Resistance
Authors: Nakamura Takahisa
Published: April 2012

Can preventing insulin resistance in the brain help stop Alzheimer’s disease?
Effect of the orientation of records on displacement ductility demand
Authors: García-Soto A.D. , Hong H.P. , Gómez R.
Published: April 2012

Effects of the ground motion record orientation on the estimated pseudo-spectral acceleration (PSA) have been investigated and reported in the literature; the statistics of the PSA along the major and minor principal axes differ from that for a random orientation. This is true for California as well as for Mexican records. However, a statistical assessment of the effect of record orientation on the displacement ductility demand is lacking. Such an assessment could be important for gaining confidence in and understanding of using the ductility demand rules for seismic hazard and risk evaluations. The statistical analyses of the effect of orientation on the estimated displacement ductility demand for elastic-perfectly-plastic and bilinear hysteretic (single degree of freedom) systems is carried out in the present study using sets of records from Mexican inslab and interplate earthquakes, and California earthquakes. Based on the obtained statistics, it is suggested that the consideration that the ductility demand is independent of the orientation of the records can be adequate, especially for Tn greater than 0.3 s and elastic-perfectly-plastic hysteretic single degree of freedom systems.
Application of artificial neural networks and adaptive neuro-fuzzy inference system models to short-term streamflow forecasting
Authors: Vafakhah Mehdi
Published: April 2012

The present article aims to forecast streamflow by using artificial neural networks (ANNs), adaptive neuro-fuzzy inference system (ANFIS), and autoregressive moving average (ARMA). For this purpose, the daily streamflow time series of two hydrometry stations of Hajighoshan and Tamar on Gorgan River are used for two periods of 1983–2007 and 1974–2007, respectively. Root mean square error (RMSE) and correlation coefficient (R) statistics are employed to evaluate the performance of the ANNs, ANFIS, and ARMA models for forecasting streamflow (1 day ahead). Comparison of the results reveals that the ANFIS model outperforms the ARMA model. Based on the results of validation stage, for the forecasting 1 day ahead streamflow, ANN with RMSE = 0.028 m3/s and R = 0.59 for the Hajighoshan station and RMSE = 0.013 m3/s and R = 0.44 for the Tamar station were found to be superior to the ANFIS with RMSE = 1.98 m3/s and R = 0.42 for the Hajighoshan station and RMSE = 2.18 m3/s and R = 0.22 for the Tamar station. In addition, for 2 day and 3 day ahead streamflow forecasts, the ANN models show superiority in the accuracy of forecasting streamflow compared with the ANFIS models.
A design of experiment aided sensitivity analysis and parameterization for hydrological modeling
Authors: Wu Hongjing , Lye Leonard M. , Chen Bing
Published: April 2012

To provide a better understanding of the water balance in the Deer River watershed of the Hudson Bay lowlands, the Semi-distributed Land Use-based Runoff Process hydrological model was applied to simulate the runoff over a 20 year period. The purpose of this study is to develop an approach to examine the sensitivity of the ten parameters and their interactions via statistical design of experiment methodology. Using the proposed approach, the contribution of each parameter and how they interact with one another were evaluated. The results indicated that the interaction between “retention constant for fast storage” and “precipitation factor” had the greatest positive impact on the Nash–Sutcliffe efficiency (NSE) and the quadratic factor term of “precipitation factor” had the greatest negative effect on the NSE. The proposed approach provided an effective tool for evaluating the contribution of the input parameters and could also be applied for calibration of other hydrological models.
Standardization and characterization of antigens for the diagnosis of aspergillosis
Authors: Stopiglia Cheila Denise Ottonelli , Arechavala Alicia , Carissimi Mariana , Sorrentino Julia Medeiros , Aquino Valério Rodrigues , Daboit Tatiane Caroline , Kammler Luana , Negroni Ricardo , Scroferneker Maria Lúcia
Published: April 2012

The aim of this study was to develop and characterize antigens for the diagnosis of aspergillosis. Nine strains of Aspergillus species Aspergillus fumigatus , Aspergillus flavus , and Aspergillus niger were grown in Sabouraud and Smith broth to produce exoantigens. The antigens were tested by immunodiffusion against sera from patients with aspergillosis and other systemic mycoses. The protein fraction of the antigens was detected by SDS–PAGE; Western blot and representative bands were assessed by mass spectrometry coupled to a nano Acquity UltraPerformance LC and analyzed by the Mascot search engine. Concurrently, all sera were tested with Platelia Aspergillus EIA. The most reactive antigens to sera from patients infected by A. fumigatus were produced by A. fumigatus MG2 Sabouraud and pooled A. fumigatus Sabouraud samples, both with a sensitivity of 93% and specificity of 100% and 97%, respectively. Aspergillus niger and A. flavus antigens were reactive against A. niger and A. flavus sera, each one with a sensitivity and specificity of 100%. Two proteins, probably responsible for antigenic activity, β-glucosidase in A. fumigatus and α-amylase in A. niger were attained. The commercial kit had a specificity of 22%, sensitivity of 100%, positive predictive value of 48%, and negative predictive value of 100%. The antigens produced showed high sensitivity and specificity and can be exploited for diagnostics of aspergilloma.
Phylogenetic diversity of the dddP gene for dimethylsulfoniopropionate-dependent dimethyl sulfide synthesis in mangrove soils
Authors: Peng Mengjun , Xie Qingyi , Hu Huo , Hong Kui , Todd Jonathan D. , Johnston Andrew W.B. , Li Youguo
Published: April 2012

The dddP gene encodes an enzyme that cleaves dimethylsulfoniopropionate (DMSP) into dimethyl sulfide (DMS) plus acrylate and has been identified in various marine bacteria and some fungi. The diversity of dddP genes was investigated by culture-independent PCR-based analysis of metagenomic DNA extracted from 4 mangrove soils in Southern China. A phylogenetic tree of 144 cloned dddP sequences comprised 7 groups, 3 of which also included dddP genes from previously identified Ddd+ (DMSP-dependent DMS production) bacteria. However, most (69%) of the DddP sequences from the mangroves were in 4 other subgroups that did not include sequences from known bacteria, demonstrating a high level of diversity of this gene in these environments. Each clade contained clones from all of the sample sites, suggesting that different dddP types are widespread in mangroves of different geographical locations. Furthermore, it was found the dddP genotype distribution was remarkably influenced by the soil properties pH, available sulfur, salt, and total nitrogen.
SIMULATING NETWORK STRUCTURES USING BERNOULLI'S PRINCIPLE
Authors: HAN YICHEOL , GOETZ STEPHAN J. , LEE JEONGJAE , YOON SEONGSOO
Published: April 2012

Using the fact that connections between vertices of a network often represent directed and weighted flows, we apply hydraulic principles to develop novel insights into network structure and growth. We develop a network model based on Bernoulli's principle and use it to analyze changes in network properties. Simulation results show that velocity of flow, resistance, fitness and existing connections in a system determine network connections of a vertex as well as overall network structure. We demonstrate how network structure is affected by changes in velocity and resistance, and how one vertex can monopolize connections within a network. Using Bernoulli's principle, we are able to independently reproduce key results in the network literature.
MODELING AND ANALYSIS OF BIOPATHWAYS DYNAMICS
Authors: LIU BING , THIAGARAJAN P. S.
Published: April 2012

Cellular processes are governed and coordinated by a multitude of biopathways. A pathway can be viewed as a complex network of biochemical reactions. The dynamics of this network largely determines the functioning of the pathway. Hence the modeling and analysis of biochemical networks dynamics is an important problem and is an active area of research. Here we review quantitative models of biochemical networks based on ordinary differential equations (ODEs). We mainly focus on the parameter estimation and sensitivity analysis problems and survey the current methods for tackling them. In this context we also highlight a recently developed probabilistic approximation technique using which these two problems can be considerably simplified.
A 3-DIMENSIONAL SASAKIAN METRIC AS A YAMABE SOLITON
Authors: SHARMA RAMESH
Published: April 2012

If a 3-dimensional Sasakian metric on a complete manifold (M, g) is a Yamabe soliton, then we show that g has constant scalar curvature, and the flow vector field V is Killing. We further show that, either M has constant curvature 1, or V is an infinitesimal automorphism of the contact metric structure on M.
DIRAC STRUCTURES FROM LIE INTEGRABILITY
Authors: CRASMAREANU MIRCEA
Published: April 2012

We prove that a pair (F = vector sub-bundle of TM, its annihilator) yields an almost Dirac structure which is Dirac if and only if F is Lie integrable. Then a flat Ehresmann connection on a fiber bundle ξ yields two complementary, but not orthogonally, Dirac structures on the total space M of ξ. These Dirac structures are also Lagrangian sub-bundles with respect to the natural almost symplectic structure of the big tangent bundle of M. The tangent bundle in Riemannian geometry is discussed as particular case and the 3-dimensional Heisenberg space is illustrated as example. More generally, we study the Bianchi–Cartan–Vranceanu metrics and their Hopf bundles.
DEVELOPMENT OF ANALYSIS PROGRAM FOR INCOMPRESSIBLE LOOPED FLOW NETWORK USING CONSTITUTIVE TOPOLOGIC MATRIX EQUATION
Authors: KIM BUM-SHIN , YOO SEONG-YEON , CHO WOONG-SUN
Published: April 2012

Flow network which consists of a number of flow paths and their junctions is popularly used in analysis of flow and pressure distribution for complicated pipe or channel flow structure. In order to analyze flow network, it is required to resolve mass conservation equation at each junction and energy conservation equation on all independent closed loops of the flow network. Topologic matrix which reflects characteristics of network connectivity simply transforms continuity equations into linear algebraic equations. However, typical solving procedure based on topologic matrix and linear analysis includes complicated algorithm to retrieve basic closed loop for energy conservation equations. It must confront the problem of nondeterministic polynomial completion. To resolve the problem of typical flow network analysis, the theory of constitutive topologic matrix equation is known to be effective. This paper describes a program algorithm of flow network analysis based on constitutive topological matrix theory and shows user interface of the program. Additionally, comparing analysis results of developed program with commercial software is provided to prove accuracy and reliability of developed program.
Deterministic Assembly of Functional Nanostructures Using Nonuniform Electric Fields
Authors: Smith Benjamin D. , Mayer Theresa S. , Keating Christine D.
Published: April 2012

The force induced on anisotropic nanoparticles in a nonuniform electric field can be used to attract, orient, and position the nanoparticles with respect to microelectrodes on a surface. For polarizable nanomaterials, such as nanowires, carbon nanotubes, or graphene sheets suspended in solvent, this dielectrophoretic force results in movement to regions of highest electric field strength. This review discusses the origin of this force, its production by different microelectrode designs, and its use for nanomaterials assembly, with a focus on efforts toward heterogeneous integration with on-chip electronics for single-particle characterization and device structures.
The Polymer/Colloid Duality of Microgel Suspensions
Authors: Lyon L. Andrew , Fernandez-Nieves Alberto
Published: April 2012

Colloidal dispersions have been studied for decades as a result of their utility in numerous applications and as models for molecular and atomic condensed phases. More recently, a number of groups have exploited in such studies submicrometer-sized hydrogel particles (microgels) that have environmentally tunable sizes. The experimental convenience of tuning the dispersion's colloidal volume fraction while maintaining a constant number density of particles provides a clear advantage over more tedious studies that employ traditional hard-sphere particles. However, as studies delved deeper into the fundamental physics of colloidal dispersions comprising microgel particles, it became abundantly clear that a microgel's utility as a tunable hard sphere was limited and that the impact of softness was more profound than previously appreciated. Herein we review the brief history of microgel-based colloidal dispersions and discuss their transition from tunable hard spheres to a class of soft matter that has revealed a landscape of physics and chemistry notable for its extraordinary richness and diversity.
Nonlinear Light Scattering and Spectroscopy of Particles and Droplets in Liquids
Authors: Roke Sylvie , Gonella Grazia
Published: April 2012

Nano- and microparticles have optical, structural, and chemical properties that differ from both their building blocks and the bulk materials themselves. These different physical and chemical properties are induced by the high surface-to-volume ratio. As a logical consequence, to understand the properties of nano- and microparticles, it is of fundamental importance to characterize the particle surfaces and their interactions with the surrounding medium. Recent developments of nonlinear light scattering techniques have resulted in a deeper insight of the underlying light-matter interactions. They have shed new light on the molecular mechanism of surface kinetics in solution, properties of interfacial water in contact with hydrophilic and hydrophobic particles and droplets, molecular orientation distribution of molecules at particle surfaces in solution, interfacial structure of surfactants at droplet interfaces, acid-base chemistry on particles in solution, and vesicle structure and transport properties.
Relativistic Effects in Chemistry: More Common Than You Thought
Authors: Pyykkö Pekka
Published: April 2012

Relativistic effects can strongly influence the chemical and physical properties of heavy elements and their compounds. This influence has been noted in inorganic chemistry textbooks for a couple of decades. This review provides both traditional and new examples of these effects, including the special properties of gold, lead-acid and mercury batteries, the shapes of gold and thallium clusters, heavy-atom shifts in NMR, topological insulators, and certain specific heats.
Single-Molecule Surface-Enhanced Raman Spectroscopy
Authors: Le Ru Eric C. , Etchegoin Pablo G.
Published: April 2012

A general overview of the field of single-molecule (SM) surface-enhanced Raman spectroscopy (SERS) as it stands today is provided. After years of debates on the basic aspects of SM-SERS, the technique is emerging as a well-established subfield of spectroscopy and SERS. SM-SERS is allowing the observation of subtle spectroscopic phenomena that were not hitherto accessible. Examples of the latter are natural isotopic substitutions in single molecules, observation of the true homogeneous broadening of Raman peaks, Raman excitation profiles of individual molecules, and SM electrochemistry. With background examples of the contributions produced by our group, properly interleaved with results by other practitioners in the field, we present some of the latest developments and promising new leads in this new field of spectroscopy.
Tip-Enhanced Raman Spectroscopy: Near-Fields Acting on a Few Molecules
Authors: Pettinger Bruno , Schambach Philip , Villagómez Carlos J. , Scott Nicola
Published: April 2012

Tip-enhanced Raman spectroscopy (TERS) is a very powerful variant of surface-enhanced Raman spectroscopy (SERS). In a sense, TERS overcomes most of the drawbacks of SERS but keeps its advantages, such as its high sensitivity. TERS offers the additional advantages of high spatial resolution, much beyond the Abbe limit, and the possibility to correlate TER and other scanning probe microscope images, i.e., to correlate topographic and chemical data. TERS finds application in a number of fields, such as surface science, material science, and biology. Single-molecule TERS has been observed even for TERS enhancements of “only” 106–107. In this review, TERS enhancements are discussed in some detail, including a condensed overview of measured contrasts and estimated total enhancements. Finally, recent developments for TERS under ultrahigh vacuum conditions are presented, including TERS on a C60 island with a diameter of a few tens of nanometers, deposited on a smooth Au(111) surface.
Progress in Modeling of Ion Effects at the Vapor/Water Interface
Authors: Netz Roland R. , Horinek Dominik
Published: April 2012

The behavior of halide salts at the vapor/water interface has been the focus of a tremendous amount of work in the past ten years. A molecular view of the interface has been introduced with the observation that large anions have some affinity for the interface, but a quantitative description of the driving forces that determine ion adsorption or repulsion at the interface is still missing. This review discusses recent developments that are based on classical and quantum-chemical molecular simulations as well as developments that are based on simple potential models.
Synthesis of Antenna Arrays and Parasitic Antenna Arrays with Mutual Couplings
Authors: Thevenot M. , Menudier C. , El Sayed Ahmad A. , Zakka El Nashef G. , Fezai F. , Abdallah Y. , Arnaud E. , Torres F. , Monediere T.
Published: April 2012

A synthesis method to design multielement antennas with couplings is presented. The main objective is to perform a rigorous determination of the electromagnetic characteristics involved in the design, especially with arrays of moderate sizes. The aim is to conceive jointly and efficiently the antenna and the circuits to connect (feed distribution network, power amplifiers, reactive loads, etc.). The subsequent objective is to improve the understanding and capabilities of strongly coupled antennas. As a whole, the synthesis procedure is then applied to different antenna architectures in order to show its efficiency and versatility. A focus on some antenna concepts where the management of couplings is a key factor to improve the performances is presented. After describing the synthesis procedure, the first category of coupled multielement antenna studied concerns radiating arrays in linear or circular polarization. A design including couplings effects on an active array is also presented. Then, the method is applied to parasitic antenna arrays and a specific investigation on reflectarray antenna is performed as they can be considered as a particular case of parasitic arrays.
A Rare Form of Melanoma Masquerading as a Diabetic Foot Ulcer: A Case Report
Authors: Thomas Susan , Meng Yuan-Xiang , Patel Vijaykumar G. , Strayhorn Gregory
Published: April 2012

Background. Acral lentiginous melanoma (ALM) is a less-common form of melanoma in US, and it accounts for about 5% of all diagnosed melanomas in US. ALM is often overlooked until it is well advanced because of the lesion’s location and its atypical appearance in the early stages. We present a case of ALM initially presented as a diabetic foot ulcer.Case Report. An 81-year-old man initially presented to the primary care clinic with a right foot diabetic ulcer. There was a large plantar, dark-colored ulcer that bled easy. Initial excision biopsy revealed Clark’s Level IV ALM. Subsequent definitive wide excision and sentinel node biopsy confirmed ALM with metastasis to inguinal lymph nodes (stage IIIb). The treatment included wide margin excision of the lesion with en bloc amputations of 4th and 5th toes, followed by adjuvant chemotherapy.Discussion. The development of ALM may potentially relate to diabetes as a reported higher prevalence of diabetes with ALM patients.Conclusion. The difficulty in early diagnosing of ALM remains as a formidable challenge particularly in diabetic patients who commonly develop plantar foot ulcers due to the diabetic neuropathy. This case reiterates the importance of a thorough foot exam in such patients.
Towards Elimination of Mother-to-Child Transmission of HIV: The Impact of a Rapid Results Initiative in Nyanza Province, Kenya
Authors: Dillabaugh Lisa L. , Lewis Kulzer Jayne , Owuor Kevin , Ndege Valerie , Oyanga Arbogast , Ngugi Evelyne , Shade Starley B. , Bukusi Elizabeth , Cohen Craig R.
Published: April 2012

Many HIV-positive pregnant women and infants are still not receiving optimal services, preventing the goal of eliminating mother-to-child transmission (MTCT) and improving maternal child health overall. A Rapid Results Initiative (RRI) approach was utilized to address key challenges in delivery of prevention of MTCT (PMTCT) services including highly active antiretroviral therapy (HAART) uptake for women and infants. The RRI was conducted between April and June 2011 at 119 health facilities in five districts in Nyanza Province, Kenya. Aggregated site-level data were compared at baseline before the RRI (Oct 2010–Jan 2011), during the RRI, and post-RRI (Jul–Sep 2011) using pre-post cohort analysis. HAART uptake amongst all HIV-positive pregnant women increased by 40% (RR 1.4, 95% CI 1.2–1.7) and continued to improve post-RRI (RR 1.6, 95% CI 1.4–1.8). HAART uptake in HIV-positive infants remained stable (RR 1.1, 95% CI 0.9–1.4) during the RRI and improved by 30% (RR 1.3, 95% CI 1.0–1.6) post-RRI. Significant improvement in PMTCT services can be achieved through introduction of an RRI, which appears to lead to sustained benefits for pregnant HIV-infected women and their infants.
Minimal Invasive Decompression for Lumbar Spinal Stenosis
Authors: Popov Victor , Anderson David G.
Published: April 2012

Lumbar spinal stenosis is a common condition in elderly patients and may lead to progressive back and leg pain, muscular weakness, sensory disturbance, and/or problems with ambulation. Multiple studies suggest that surgical decompression is an effective therapy for patients with symptomatic lumbar stenosis. Although traditional lumbar decompression is a time-honored procedure, minimally invasive procedures are now available which can achieve the goals of decompression with less bleeding, smaller incisions, and quicker patient recovery. This paper will review the technique of performing ipsilateral and bilateral decompressions using a tubular retractor system and microscope.
Sulfotanshinone Sodium Injection for Unstable Angina Pectoris: A Systematic Review of Randomized Controlled Trials
Authors: Qiu Xuelan , Miles Andrew , Jiang Xuehua , Sun Xin , Yang Nan
Published: April 2012

Objective. To assess the effect of sulfotanshinone sodium injection for unstable angina.Methods. We searched for published and unpublished studies up to June 2011. We included randomized controlled trials that confoundedly addressed the effect of sulfotanshinone sodium injection in the treatment of unstable angina.Results. Twenty-five studies involving 2,377 people were included. There was no evidence that sulfotanshinone sodium alone had better or worse effects to routine western medicine treatments in improving clinical symptoms (RR 1.00, 95% CI 0.90 to 1.11) and ECG (RR 0.97, 95% CI 0.87 to 1.09). However, there was evidence that sulfotanshinone sodium combined with western medications was a better treatment option than western medications alone in improving clinical symptoms (RR 1.28, 95% CI 1.23 to 1.3), ECG (RR 1.26, 95% CI 1.18 to 1.35), C-reaction protein (mean difference 2.10, 95% CI 1.63 to 2.58), and IL-6 (mean difference −3.85, 95% CI −4.10 to −3.60). There was no difference between sulfotanshinone sodium plus western medications and western medications alone affecting mortality (RR 0.50, 95% CI 0.02 to 12.13).Conclusion. Compared with western medications alone, sulfotanshinone sodium combined with western medications may provide more benefits for patients with unstable angina. Further large-scale high-quality trials are warranted.
Histone Deacetylase Inhibitors Influence Chemotherapy Transport by Modulating Expression and Trafficking of a Common Polymorphic Variant of the ABCG2 Efflux Transporter
Authors: Basseville Agnes , Tamaki Akina , Ierano Caterina , Trostel Shana , Ward Yvona , Robey Robert W. , Hegde Ramanujan S. , Bates Susan E.
Published: April 2012

Histone deacetylase inhibitors (HDI) have exhibited some efficacy in clinical trials, but it is clear that their most effective applications have yet to be fully determined. In this study, we show that HDIs influence the expression of a common polymorphic variant of the chemotherapy drug efflux transporter ABCG2, which contributes to normal tissue protection. As one of the most frequent variants in human ABCG2, the polymorphism Q141K impairs expression, localization, and function, thereby reducing drug clearance and increasing chemotherapy toxicity. Mechanistic investigations revealed that the ABCG2 Q141K variant was fully processed but retained in the aggresome, a perinuclear structure, where misfolded proteins aggregate. In screening for compounds that could correct its expression, localization, and function, we found that the microtubule-disrupting agent colchicine could induce relocalization of the variant from the aggresome to the cell surface. More strikingly, we found that HDIs could produce a similar effect but also restore protein expression to wild-type levels, yielding a restoration of ABCG2-mediated specific drug efflux activity. Notably, HDIs did not modify aggresome structures but instead rescued newly synthesized protein and prevented aggresome targeting, suggesting that HDIs disturbed trafficking along microtubules by eliciting changes in motor protein expression. Together, these results showed how HDIs are able to restore wild-type functions of the common Q141K polymorphic isoform of ABCG2. More broadly, our findings expand the potential uses of HDIs in the clinic. Cancer Res; 72(14); 3642–51. ©2012 AACR.
Prevention of Mutagenesis: New Potential Mechanisms of Metformin Action in Neoplastic Cells
Authors: Bost Frédéric , Ben-Sahra Issam , Tanti Jean-François
Published: April 2012

Several experimental and epidemiologic studies have shown that the antidiabetes drug metformin has antitumor properties. The report by Algire and colleagues in this issue of the journal (beginning on page 536) shows for the first time that metformin reduces mutagenesis induced by reactive oxygen species. This report offers new perspectives on metformin in cancer prevention and provides a new mechanism for the reduction of cancer risk in diabetic patients treated with this drug. Cancer Prev Res; 5(4); 503–6. ©2012 AACR.
Diagnosing Lynch Syndrome: More Light at the End of the Tunnel
Authors: Burt Randall W.
Published: April 2012

Since the recognition of Lynch syndrome, which confers a high risk of colorectal, uterine, and other cancers, approaches to its diagnosis have included a family history of associated cancers and web-based algorithms. Identification of causative genes now allows a precise diagnosis, thus focusing present efforts on who should have genetic testing. Testing for cancer tissue changes can determine who should have germline genetic testing. Indeed, such tumor testing is now generally recommended for all newly diagnosed colorectal cancer cases. As reported in this issue of the journal by Yurgelun and colleagues (beginning on page 574), large colorectal adenomatous polyps (≥10 mm) from patients with Lynch syndrome exhibit findings similar to those in Lynch syndrome colorectal cancer tissues. This finding indicates that testing larger adenomas in persons at a significant risk for Lynch syndrome can now determine the need for germline genetic testing. Although further study is needed for general application, the present study justifies large polyp testing in high-risk families when cancer tissue is unavailable, albeit negative polyp tissue would not rule out Lynch syndrome, as would negative cancer tissue. Cancer Prev Res; 5(4); 507–10. ©2012 AACR.
Whole Genome Expression Differences in Human Left and Right Atria Ascertained by RNA Sequencing
Authors: Hsu Jeffrey , Hanna Peter , Van Wagoner David R. , Barnard John , Serre David , Chung Mina K. , Smith Jonathan D.
Published: April 2012

Background—

The left and right atria have different susceptibilities toward developing arrhythmias, with left atrial arrhythmias more commonly observed. To understand the molecular basis for such differences, we catalogued micro (mi)RNA and mRNA expression differences by next generation sequencing.

Methods and Results—

Four human left-right atrial pairs were subjected to whole-genome expression analyses via next-generation sequencing of small RNAs, including miRNAs, and poly-A–enriched mRNAs. Using a paired sample design, significant differences in the expression of 32 miRNAs were found in between the left and right atria at a probability value of <0.01. Hsa-miR-143 was the most highly expressed miRNA in the atria, as quantified by RNA sequencing. There were 746 and 2292 differentially expressed mRNAs between the left and right atria at false discovery rates of <0.001 and <0.05, respectively. Transcription factor binding elements within 2 kb of RefSeq genes were determined and specific motifs were identified that were enriched in differentially expressed genes. Similarly, specific miRNA target sequences in 3′ UTRs were also enriched in differentially expressed genes. In addition, 11 novel noncoding RNAs of unknown function were found to be differentially expressed between the left and right atria.

Conclusions—

There are significant differences in miRNA and mRNA expression profiles between the left and right atria, which may yield insight into increased the arrhythmogenesis of the left atria.
High-Density Lipoprotein and Mortality Before Age 90 in Male Physicians
Authors: Rahilly-Tierney Catherine , Sesso Howard D. , Michael Gaziano J. , Djoussé Luc
Published: April 2012

Background—

In cross-sectional and some cohort studies with shorter follow-up, high-density lipoprotein cholesterol (HDL-C) has been associated with longer life. We sought to examine the relationship between HDL-C and death before age 90 in the Physicians' Health Study (PHS).

Methods and Results—

Of PHS enrollees who had blood collected at PHS II baseline (approximately 1997), we selected 1351 men old enough to reach age 90 by March 4, 2009, and with complete data on HDL-C and total cholesterol, lifestyle factors, and comorbidities. We used Cox proportional hazards to determine the hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause, cardiovascular disease (CVD), and non-CVD mortality before age 90, adjusting for potential confounders.

After a mean (SD) follow-up of 6.8 (3.2) years, 44.1% of men in the lowest baseline HDL-C quartile (<32.8 mg/dL) compared with 32.9% (11.2% absolute risk reduction) in the highest HDL-C quartile (≥54.1 mg/dL) died before age 90. In multivariable adjusted analyses, men in the highest HDL-C quartile had a 28% lower risk (HR, 0.72; 95% CI, 0.55 to 0.94) of death before age 90 compared with men in the lowest HDL-C quartile. In age-adjusted analyses, increasing baseline HDL-C was significantly associated with a lower risk of CVD death. No association was found between HDL-C and non-CVD mortality.

Conclusion—

In male physicians, higher baseline HDL-C levels were associated with a lower risk of all-cause and CVD mortality before age 90.
Triggers of Hospitalization for Venous Thromboembolism
Authors: Rogers Mary A.M. , Levine Deborah A. , Blumberg Neil , Flanders Scott A. , Chopra Vineet , Langa Kenneth M.
Published: April 2012

Background—

The rate of hospitalization for venous thromboembolism (VTE) is increasing in the United States. Although predictors of hospital-acquired VTE are well-known, triggers of VTE before hospitalization are not as clearly defined. The objective of this study was to evaluate triggers of hospitalization for VTE.

Methods and Results—

A case-crossover study was conducted. Subjects were participants in the Health and Retirement Study, a nationally representative sample of older Americans. Data were linked to Medicare files for hospital and nursing home stays, emergency department visits, outpatient visits including physician visits, and home health visits from years 1991 to 2007 (n=16 781). The outcome was hospitalization for venous thromboembolism (n=399). Exposures during the 90-day period before hospitalization for VTE were compared with exposures occurring in 4 comparison periods. Infection was the most common trigger of hospitalization for VTE, occurring in 52.4% of the risk periods before hospitalization. The adjusted incidence rate ratios (IRRs; 95% confidence interval) were 2.90 (2.13, 3.94) for all infection, 2.63 (1.90, 3.63) for infection without a previous hospital or skilled nursing facility stay, and 6.92 (4.46, 10.72) for infection with a previous hospital or skilled nursing facility stay. Erythropoiesis-stimulating agents and blood transfusion were also associated with VTE hospitalization (IRR=9.33, 95% confidence interval: 1.19, 73.42; IRR=2.57, 95% confidence interval: 1.17, 5.64; respectively). Other predictors included major surgeries, fractures (IRR=2.81), immobility (IRR=4.23), and chemotherapy (IRR=5.70). These predictors, combined, accounted for a large proportion (69.7%) of exposures before VTE hospitalization as opposed to 35.3% in the comparison periods.

Conclusions—

Risk prediction algorithms for VTE should be reevaluated to include infection, erythropoiesis-stimulating agents, and blood transfusion.
Vascular Occlusion Enables Selecting Acute Ischemic Stroke Patients for Treatment With Desmoteplase
Authors: Fiebach Jochen B. , Al-Rawi Yasir , Wintermark Max , Furlan Anthony J. , Rowley Howard A. , Lindstén Annika , Smyej Jamal , Eng Paul , Warach Steven , Pedraza Salvador
Published: April 2012

Background and Purpose—

Desmoteplase is a novel and highly fibrin-specific thrombolytic agent. Evidence of safety and efficacy was obtained in 2 phase II trials (Desmoteplase In Acute Ischemic Stroke [DIAS] and Desmoteplase for Acute Ischemic Stroke [DEDAS]). The DIAS-2 phase III trial did not replicate the positive phase II efficacy findings. Post hoc analyses were performed with the aim of predicting treatment responders based on CTA and MRA.

Methods—

Patients were grouped according to vessel status (Thrombolysis In Myocardial Infarction [TIMI] grade) for logistic regression of clinical response, applying the data from DIAS-2 as well as the pooled data from DIAS, DEDAS, and DIAS-2.

Results—

In DIAS-2, a substantial number of mismatch-selected patients (126/179; 70%) presented with a normal flow/low-grade stenosis (TIMI 2–3) at screening, with the majority having a favorable outcome at day 90. In contrast, favorable outcome rates in patients with vessel occlusion/high-grade stenosis (TIMI 0–1) were 18% with placebo versus 36% and 27% with desmoteplase 90 and 125 μg/kg, respectively. The clinical effect based on the pooled data from DIAS, DEDAS, and DIAS-2 was favorable for desmoteplase-treated patients presenting with TIMI 0 to 1 at baseline (OR, 4.144; 95% CI, 1.40–12.23;
P
=0.010). There was no desmoteplase treatment benefit in patients presenting with TIMI 2 to 3 (OR, 1.109).

Conclusions—

In this sample of patients with a mismatch diagnosed, proximal vessel occlusion or severe stenosis was associated with clinically beneficial treatment effects of desmoteplase. Selecting patients using CTA or MRA in clinical trials of thrombolytic therapy is justifiable.

Clinical Trial Registration Information—

URL:
http://www.clinicaltrials.gov
. Unique identifiers: NCT00638781, NCT00638248, NCT00111852.
Resolution of Intraventricular Hemorrhage Varies by Ventricular Region and Dose of Intraventricular Thrombolytic
Authors: Webb Alastair J.S. , Ullman Natalie L. , Mann Sarah , Muschelli John , Awad Issam A. , Hanley Daniel F.
Published: April 2012

Background and Purpose—

The Clot Lysis: Evaluating Accelerated Resolution of IVH (CLEAR IVH) program is assessing the efficacy of intraventricular recombinant tissue-type plasminogen activator (rtPA) for spontaneous intraventricular hemorrhage (IVH). This subanalysis assesses the effect of dose of rtPA by region on clearance of IVH.

Methods—

Sixty-four patients within 12 to 24 hours of spontaneous IVH were randomized to placebo or 0.3 mg, 1 mg, or 3 mg of rtPA twice daily through an extraventricular drain. Twelve subregions of the ventricles were scored from 0 to 4. Effect of dose on IVH clearance to 50% of baseline score was compared by survival analysis for all regions combined and by subregion. Models including ventricular region, dose, and baseline score were compared by Cox proportional hazards.

Results—

IVH score reduced faster across all regions with increasing rtPA dose (clearance to 50%: log-rank
P
<0.0001; placebo—11.43 days, 95% CI, 5.68–17.18; 0.3 mg—3.19 days, 1.00–5.38; 1 mg—3.54 days, 0.45–6.64; 3 mg—2.59 days, 1.72–3.46). In the combined models, dose and baseline score were independently associated with reduction in IVH score, which was quickest in the midline ventricles, then the anterior half of the lateral ventricles and slowest in the posterior half of the lateral ventricles (clearance to 50%:
P
<0.0001; rtPA dose: hazard ratio, 1.47, 1.30–1.67; midline versus anterolateral hazard ratio, 1.71, 1.08–2.71; midline versus posterolateral hazard ratio, 4.05, 2.46–6.65; baseline score hazard ratio, 0.96, 0.91–1.01) with a significant interaction between dose and ventricular region (
P
=0.005).

Conclusions—

rtPA accelerates resolution of IVH. This effect is dose-dependent, is greatest in the midline ventricles, and least in the posterolateral ventricles.

Clinical Trial Registration—

URL:
www.clinicaltrials.gov
. Unique identifier: NCT00650858.
The American Public's Energy Choice
Authors: Ansolabehere Stephen , Konisky David M.
Published: April 2012

Public opinion about energy can be understood in a unified framework. First, people evaluate key attributes of energy sources, particularly a fuel's cost and environmental harms. Americans, for example, view coal as relatively inexpensive but harmful, natural gas as less harmful but more expensive, and wind as inexpensive and not harmful. Second, people place different weights on the economic and environmental attributes associated with energy production, which helps explain why some fuels are more popular than others. Americans' attitudes toward energy are driven more by beliefs about environmental harms than by perceived economic costs. In addition, attitudes about energy sources are largely unrelated to views about global warming. These findings suggest that a politically palatable way to reduce greenhouse gas emissions is through regulation of traditional pollutants associated with fossil fuels, rather than a wholly new carbon policy.
God in the Fractals: Recursiveness as a Key to Religious Behavior
Authors: Czachesz István
Published: April 2012

Abstract

Many religious traditions embrace ideas that include boundless elements (i.e., beings that are omnipresent, omniscient, etc.). The origin of ideas with such boundless qualities has not yet been successfully accounted for in the cognitive science of religion. In this study I suggest that the domain-general use of recursion underlies the mental representation of boundless qualities. I also examine the contribution of recursive patterns to other aspects of religiosity: the conceptualization of divine agency and the emergence of magical rituals. I suggest that the human ability to use recursion in a domain-general way is minimally required for the human Faculty of Religion in a Narrow Sense.
Introduction to the Yale Roundtable on Belief
Authors: Lofton Kathryn
Published: April 2012

Abstract

What is belief? Is it a usable categorical for analysis in the study of religion? This was the subject of a one-day workshop hosted by the Department of Religious Studies at Yale University on April 15, 2011. The participating scholars were asked to present comments on the meaning of belief for their own research. This text introduces a sampling of these responses prompted in part by a set of advance readings that represented the bibliography of belief in contemporary religious studies.
Ubiquity Scorned: Belief’s Strange Survivals
Authors: Bivins Jason C.
Published: April 2012

Abstract

This paper attempts not to continue the methodological interrogation of “belief” as a category central to Religious Studies, but to problematize and analyze the ubiquity of such interrogations. Investigations of “belief,” I argue, are also occasions to explore the discipline’s less obvious investments in intellectual and institutional traditions still shackled to the very category under scrutiny. The stand-alone category “religion” that is so central to political culture and disciplinary formation depends on “belief” to facilitate recognition. Thus, while Religious Studies now habitually discredits “belief” as a ubiquitous analytical category, it also partly depends on “belief’s” presences for its disciplinary self-justification.
Development and Psychometric Properties of the Homophobic Bullying Scale
Authors: Prati Gabriele
Published: April 2012

The study aimed to develop the Homophobic Bullying Scale and to investigate its psychometric properties. The items of the Homophobic Bullying Scale were created to measure high school students’ bullying behaviors motivated by homophobia, including verbal bullying, relational bullying, physical bullying, property bullying, sexual harassment, and cyberbullying. Five scales were developed from viewpoints of bullies (toward supposed gay men and lesbians), victims, and witnesses (toward supposed gay men and lesbians). A sample of 863 students enrolled in Grades 9 to 13 in 10 Italian public high schools were involved in this study. The coefficients of internal consistency were greater than .80 for all the scales. Construct validity of its factor structure was demonstrated using confirmatory factor analysis. Discriminant validity was demonstrated by comparatively low correlations with homophobic attitudes and the Homophobic Content Agent Target scale. Results showed the existence of homophobic bullying in various forms other than the use of homophobic epithets. Future research should examine the experience of bullying behaviors motivated by homophobia in schools.
A National Survey of American Higher Education Capstone Practices in Sociology and Psychology
Authors: Hauhart Robert C. , Grahe Jon E.
Published: April 2012

Previous research on capstones in sociology and psychology has suggested that there is a typical capstone experience required by three quarters of all four-year colleges and universities in the United States. This article reports results from a national survey that confirm that sociology and psychology capstone courses conform generally to a common format. The findings further indicate that factors related to student limits and time limits predominate with respect to those variables that produce less successful course outcomes. A review of the social science capstone literature and the pedagogical best practices literature suggests that student limitations and time limitations can be attenuated by curricular, structural, and resource-allocation changes.