bluuebunny/crossref_metadata_2025 huggingface dataset:
Preparation of New Magnetic Nanocatalysts Based on TiO2 and ZnO and Their Application in Improved Photocatalytic Degradation of Dye Pollutant Under Visible Light
Authors: Nabid Mohammad Reza , Sedghi Roya , Gholami Saeede , Oskooie Hossein Abdi , Heravi Majid M.
Published: July 2012

Photocatalytic degradation of methyl orange (MO) as a model of an organic pollution was accomplished with magnetic and porous TiO2/ZnO/Fe3O4/PANI and ZnO/Fe3O4/PANI nanocomposites under visible light irradiation. The structures of nanocomposites were characterized by various techniques including UV–Vis absorption spectroscopy, XRD, SEM, EDS, BET and TGA. Optical absorption investigations show two λmax at 450 and 590 nm for TiO2/ZnO/Fe3O4/PANI nanocomposites respectively possessing optical band gaps about 2.75 and 2.1 eV smaller than that of the neat TiO2 and ZnO nanoparticles. Due to these optical absorptions, the nanocomposites can be considered promising candidates as visible light photocatalysts to produce more electron‐hole pairs. The degradation of MO, extremely increased using polymeric photocatalysts and decolorization in the presence of visible light achieved up to 90% in less than 20 min in comparison with the neat nanoparticles (about 10%). All these advantages promise a bright future for these composites as useful photocatalysts. The degradation efficiency of MO using stable nanocomposites was still over 70% after ten times reusing. The highest decolorizing efficiencies were achieved with 0.75 g L−1 of catalyst and 10 mg L−1 of MO at natural pH under visible light irradiation in less than 20 min.
A novel primer set for multilocus phylogenetic inference in East African cichlid fishes
Authors: MEYER BRITTA S. , SALZBURGER WALTER
Published: July 2012

The cichlid fishes in the East African Great Lakes are a prime model system for the study of adaptive radiation. Therefore, the availability of an elaborate phylogenetic framework is an important prerequisite. Previous phylogenetic hypotheses on East African cichlids are mainly based on mitochondrial and/or fragment‐based markers, and, to date, no taxon‐rich phylogeny exists that is based on multilocus DNA sequence data. Here, we present the design of an extensive new primer set (24 nuclear makers) for East African cichlids that will be used for multilocus phylogenetic analyses in the future. The primers are designed to work for both Sanger sequencing and next‐generation sequencing with the 454 technology. As a proof of principle, we validate these primers in a phylogenetically representative set of 16 cichlid species from Lake Tanganyika and main river systems in the area and provide a basic evaluation of the markers with respect to marker length and diversity indices.
Conceptualizing functional traits and ecological characteristics of methane‐oxidizing bacteria as life strategies
Authors: Ho Adrian , Kerckhof Frederiek‐Maarten , Luke Claudia , Reim Andreas , Krause Sascha , Boon Nico , Bodelier Paul L. E.
Published: July 2012

Methane‐oxidizing bacteria (MOB) possess the ability to use methane for energy generation and growth, thereby, providing a key ecosystem service that is highly relevant to the regulation of the global climate. MOB subgroups have different responses to key environmental controls, reflecting on their functional traits. Their unique features (C1‐metabolism, unique lipids and congruence between the 16S rRNA and pmoA gene phylogeny) have facilitated numerous environmental studies, which in combination with the availability of cultured representatives, yield the most comprehensive ecological picture of any known microbial functional guild. Here, we focus on the broad MOB subgroups (type I and type II MOB), and aim to conceptualize MOB functional traits and observational characteristics derived primarily from these environmental studies to be interpreted as microbial life strategies. We focus on the functional traits, and the conditions under which these traits will render different MOB subgroups a selective advantage. We hypothesize that type I and type II MOB generally have distinct life strategies, enabling them to predominate under different conditions and maintain functionality. The ecological characteristics implicated in their adopted life strategies are discussed, and incorporated into the Competitor‐Stress tolerator‐Ruderal functional classification framework as put forward for plant communities. In this context, type I MOB can broadly be classified as competitor‐ruderal while type II MOB fit more within the stress tolerator categories. Finally, we provide an outlook on MOB applications by exemplifying two approaches where their inferred life strategies could be exploited thereby, putting MOB into the context of microbial resource management.
HOW BIG AND HOW CLOSE? HABITAT PATCH SIZE AND SPACING TO CONSERVE A THREATENED SPECIES
Authors: MARCOT BRUCE G. , RAPHAEL MARTIN G. , SCHUMAKER NATHAN H. , GALLEHER BETH
Published: July 2012

Abstract.  We present results of a spatially explicit, individual‐based stochastic dispersal model (HexSim) to evaluate effects of size and spacing of patches of habitat of Northern Spotted Owls (NSO; Strix occidentalis caurina) in Pacific Northwest, USA, to help advise recovery planning efforts. We modeled 31 artificial landscape scenarios representing combinations of NSO habitat cluster size (range 4–49 NSO pairs per cluster) and edge‐to‐edge cluster spacing (range 7–101 km), and an all‐habitat landscape. We ran scenarios using empirical estimates of NSO dispersal dynamics and distances and stage class vital rates (representing current population declines) and under adult survival rates adjusted to achieve an initially stationary population. Results suggested that long‐term (100‐yr) habitat occupancy rates are significantly higher with habitat clusters supporting ≥25 NSO pairs and ≤15 km spacing, and with overall landscapes of ≥35–40% habitat. Although habitat provision is key to NSO recovery, no habitat configuration provided for long‐term population persistence when coupled with currently observed vital rates. Results also suggested a key role of floaters (unpaired, nonterritorial, dispersing owls) in recolonizing vacant habitat, and that the floater population segment becomes increasingly depleted with greater population declines. We suggest additional areas of modeling research on this and other threatened species.
Multimember Districts' Effect on Collaboration between U.S. State Legislators
Authors: KIRKLAND JUSTIN H.
Published: July 2012

In this article, I demonstrate that multimember districts form a basis for collaboration between two legislators. In order to maximize the limited incumbency advantages they possess, legislators from multimember districts form coalitions in an effort to generate greater credit‐claiming opportunities and policy benefits for their district. In order to test this conception, I utilize a natural experiment and an opportunity to observe institutional change in North Carolina's elimination of multimember districts during the 2000–2002 redistricting cycle. Coupled with cross‐sectional analysis of several states that use both single‐member and multimember districts, empirical evidence strongly corroborates my conception of multimember districts as a basis for collaboration between representatives.
Beyond the red complex and into more complexity: the polymicrobial synergy and dysbiosis (PSD) model of periodontal disease etiology
Authors: Hajishengallis G. , Lamont R.J.
Published: July 2012

Recent advancements in the periodontal research field are consistent with a new model of pathogenesis according to which periodontitis is initiated by a synergistic and dysbiotic microbial community rather than by select ‘periopathogens’, such as the ‘red complex’. In this polymicrobial synergy, different members or specific gene combinations within the community fulfill distinct roles that converge to shape and stabilize a disease‐provoking microbiota. One of the core requirements for a potentially pathogenic community to arise involves the capacity of certain species, termed ‘keystone pathogens’, to modulate the host response in ways that impair immune surveillance and tip the balance from homeostasis to dysbiosis. Keystone pathogens also elevate the virulence of the entire microbial community through interactive communication with accessory pathogens. Other important core functions for pathogenicity require the expression of diverse molecules (e.g. appropriate adhesins, cognate receptors, proteolytic enzymes and proinflammatory surface structures/ligands), which in combination act as community virulence factors to nutritionally sustain a heterotypic, compatible and proinflammatory microbial community that elicits a non‐resolving and tissue‐destructive host response. On the basis of the fundamental concepts underlying this model of periodontal pathogenesis, that is, polymicrobial synergy and dysbiosis, we term it the PSD model.
Numerical Prediction of Wind Flow Around Irregular Models
Authors: Wang D. Y. , Zhou Y. , Zhu Y. , Tse Tim K. T.
Published: July 2012

This paper presents numerical predictions of flow around irregular-plan buildings (S-, R-, L- and U-shaped models) in high Reynolds number. The adopted computational approach and numerical models are described firstly. Then comparative analysis with the numerical and experimental data has been conducted to verify the reliability of the numerical predictions. Finally, characteristics of mean and fluctuating pressure distributions and vertical and lateral velocity profiles of the flow around the four models have been investigated and assessed thoroughly. The study shows that satisfactory results can be obtained by large eddy simulation (LES), especially when fluctuating wind velocity is considered in the inflow boundary. Distribution of mean pressure coefficients on front faces is relatively regular. Large fluctuating pressure coefficients are induced by strong vortex motion. Velocity profiles of wind flow are disturbed obviously among the four building models, especially in weak flow. The disturbed intensity decreases with increasing of the distance away from bluff body. The suggested MDS (Maximum Disturbance Scopes) away from bluff body are generally 0.25H in inflow zones, 0.4H in roof zones, 0.5H in both side zones and 3H in weak zones.
Differences in erosion mechanism and selectivity between Ti and TiN in fluorocarbon plasmas for dielectric etch
Authors: Weilnboeck Florian , Bartis Elliot , Shachar Sivan , Oehrlein Gottlieb S. , Farber David , Lii Tom , Lenox Chet
Published: July 2012

Metallic masking materials are promising candidates for plasma-based pattern transfer into low-k materials for fabricating integrated circuits. Improving etching selectivity (ES) between the low-k and hardmask material requires a fundamental understanding of material erosion in fluorocarbon (FC) plasmas. The authors have previously reported on the erosion mechanism and plasma parametric dependencies of Ti etch in FC discharges. The present work focuses on elucidating differences in the erosion behavior between Ti and TiN hardmasks. The authors studied erosion of Ti, TiN, and organosilicate glass (OSG), a reference low-k material, in CF4/Ar and C4F8/Ar plasmas. Changes in surface composition, FC surface reaction layer thicknesses, erosion rates, and corresponding ES were established by x-ray photoelectron spectroscopy and in situ ellipsometry. The authors found that the erosion stages and plasma parameter dependent surface compositions were similar for Ti and TiN. The previously established dependence of Ti erosion rates on FC layer thickness and energy deposition on the hardmask surface by ions generally holds for TiN as well. However, TiN etch rates (volumetric removal rates) and etch yields (atomic removal rates) were increased by a factor of 1–1.4 compared to Ti. This difference can be explained by the rapid removal of N from the TiN surface, increasing the Ti atom number density at the surface above values of the Ti hardmask. The resulting increase in surface reactivity is in good agreement with the enhanced erosion rates compared to Ti. Differences in erosion rates have a direct impact on the ES and the highest ES relative to OSG (up to 15) were achieved for Ti hardmasks in CF4/Ar plasmas with low ion energy.
High‐dose MVCT image guidance for stereotactic body radiation therapy
Authors: Westerly David C. , Schefter Tracey E. , Kavanagh Brian D. , Chao Edward , Lucas Dan , Flynn Ryan T. , Miften Moyed
Published: July 2012

Purpose:

Stereotactic body radiation therapy (SBRT) is a potent treatment for early stage primary and limited metastatic disease. Accurate tumor localization is essential to administer SBRT safely and effectively. Tomotherapy combines helical IMRT with onboard megavoltage CT (MVCT) imaging and is well suited for SBRT; however, MVCT results in reduced soft tissue contrast and increased image noise compared with kilovoltage CT. The goal of this work was to investigate the use of increased imaging doses on a clinical tomotherapy machine to improve image quality for SBRT image guidance.

Methods:

Two nonstandard, high‐dose imaging modes were created on a tomotherapy machine by increasing the linear accelerator (LINAC) pulse rate from the nominal setting of 80 Hz, to 160 Hz and 300 Hz, respectively. Weighted CT dose indexes (wCTDIs) were measured for the standard, medium, and high‐dose modes in a 30 cm solid water phantom using a calibrated A1SL ion chamber. Image quality was assessed from scans of a customized image quality phantom. Metrics evaluated include: contrast‐to‐noise ratios (CNRs), high‐contrast spatial resolution, image uniformity, and percent image noise. In addition, two patients receiving SBRT were localized using high‐dose MVCT scans. Raw detector data collected after each scan were used to reconstruct standard‐dose images for comparison.

Results:

MVCT scans acquired using a pitch of 1.0 resulted in wCTDI values of 2.2, 4.7, and 8.5 cGy for the standard, medium, and high‐dose modes respectively. CNR values for both low and high‐contrast materials were found to increase with the square root of dose. Axial high‐contrast spatial resolution was comparable for all imaging modes at 0.5 lp/mm. Image uniformity was improved and percent noise decreased as the imaging dose increased. Similar improvements in image quality were observed in patient images, with decreases in image noise being the most notable.

Conclusions:

High‐dose imaging modes are made possible on a clinical tomotherapy machine by increasing the LINAC pulse rate. Increasing the imaging dose results in increased CNRs; making it easier to distinguish the boundaries of low contrast objects. The imaging dose levels observed in this work are considered acceptable at our institution for SBRT treatments delivered in 3–5 fractions.
Direct aperture optimization for FLEC‐based MERT and its application in mixed beam radiotherapy
Authors: Alexander Andrew , Soisson Emilie , Renaud Marc‐André , Seuntjens Jan
Published: July 2012

Purpose:

Despite promising research in modulated electron radiotherapy (MERT), an applicator to produce modulated electron beams and associated treatment planning software is still not commercially available. This work investigated an optimization process in treatment planning for the McGill few leaf electron collimator (FLEC) MERT delivery device. In addition, the possibility of combining MERT with photon fields was examined to investigate mixed beam radiotherapy.

Methods:

A FLEC direct aperture optimization (DAO) method, in which FLEC apertures and weights were iteratively optimized was created. The authors evaluated the performance of DAO against our previous technique for generating FLEC plans and with commercially available photon beam optimization algorithms using a basic target and organ at risk geometry. The authors applied the DAO technique on a sarcoma treatment to evaluate clinical parameters. Finally, the authors examined the merit of mixing the DAO generated FLEC electron fields with photon fields to improve the dosimetry of the sarcoma treatment.

Results:

In relation to the alternative plans, the DAO generated sarcoma MERT plan was competitive in its ability to reduce the dose to OAR but weaker in its ability to highly conform the dose to the target volume. The addition of photon fields improved the quality of the MERT plan in terms of OAR sparing and target conformality.

Conclusions:

The DAO approach yielded deliverable FLEC‐based MERT plans with a limited number of fields. The approach combined with photon optimization added flexibility, where the mutual benefits of each radiation type was used in unison to improve plan quality.
High resolution 2D dose measurement device based on a few long scintillating fibers and tomographic reconstructiona)
Authors: Goulet Mathieu , Archambault Louis , Beaulieu Luc , Gingras Luc
Published: July 2012

Purpose:

Patient‐specific QA of highly conformal radiotherapy treatments are usually conducted using 2D or 3D dosimetry of the incident dose distribution in a water‐equivalent phantom. However, dosimeters typically used for this task usually lack in either spatial resolution or dose accuracy. The purpose of this work is to develop and validate a novel type of high resolution 2D dosimeter based on the tomographic reconstruction of the dose projections obtained using long scintillating fibers for the quality assurance of modern radiotherapy techniques such as IMRT.

Methods:

Fifty parallel scintillating fibers were aligned in a 30 cm diameter cylindrical masonite phantom with a 95 cm source‐to‐surface distance and a 100 cm source‐to‐fibers distance. The fibers were disposed so that the effective detection area of the scintillating fibers was a 20 cm diameter disk. Both ends of each scintillating fiber were coupled to clear optical fibers to enable light collection by a single CCD camera. Seven IMRT segments and two square fields were acquired using 18 projections over a 170° rotation of the device. Computation of the dose integrals was made for each scintillating fiber using the irradiation of known rectangular reference fields. Dose reconstructions were conducted using a total‐variation minimization iterative reconstruction algorithm. Eight monitor units were programmed for each projection and the reconstructed dose grid pixel resolution was set to 1 × 1 mm2.

Results:

3%/3 mm gamma tests conducted between the reconstructed IMRT dose distributions and the dose calculated with the treatment planning system Pinnacle3 were on average successful for 99.6% of the dose pixels with a predicted dose of at least 10% of the maximum dose. The dose profiles for both square fields and IMRT segments agreed within 2% to the dose calculated with Pinnacle3 except in high dose gradient regions, and were comparable to the dose measured using an ionization chamber array (IBA MatriXX) and radiographic films (Kodak XV2).

Conclusions:

Using tomographic reconstruction on the projections acquired with rotating scintillating fibers, we were able to perform water‐equivalent 2D dosimetry of square fields and IMRT segments with acceptable accuracy and high spatial resolution. The underlying concept of tomographic dosimetry and the small number of fibers needed to reconstruct a given 2D dose distribution offer new dosimetric possibilities, both applicable to 2D and 3D dosimetry.
On the output factor measurements of the CyberKnife iris collimator small fields: Experimental determination of the correction factors for microchamber and diode detectors
Authors: Pantelis E. , Moutsatsos A. , Zourari K. , Petrokokkinos L. , Sakelliou L. , Kilby W. , Antypas C. , Papagiannis P. , Karaiskos P. , Georgiou E. , Seimenis I.
Published: July 2012

Purpose:

To measure the output factors (OFs) of the small fields formed by the variable aperture collimator system (iris) of a CyberKnife (CK) robotic radiosurgery system, and determine the correction factors for a microchamber and four diode detectors.

Methods:

OF measurements were performed using a PTW PinPoint 31014 microchamber, four diode detectors (PTW‐60017, −60012, −60008, and the SunNuclear EDGE detector), TLD‐100 microcubes, alanine dosimeters, EBT films, and polymer gels for the 5 mm, 7.5 mm, 10 mm, 12.5 mm, and 15 mm iris collimators at 650 mm, 800 mm, and 1000 mm source to detector distance (SDD). The alanine OF measurements were corrected for volume averaging effects using the 3D dose distributions registered in polymer gel dosimeters. correction factors for the PinPoint microchamber and the diode dosimeters were calculated through comparison against corresponding polymer gel, EBT, alanine, and TLD results.

Results:

Experimental OF results are presented for the array of dosimetric systems used. The PinPoint microchamber was found to underestimate small field OFs, and a correction factor ranging from 1.127 ± 0.022 (for the 5 mm iris collimator) to 1.004 ± 0.010 (for the 15 mm iris collimator) was determined at the reference SDD of 800 mm. The PinPoint correction factor was also found to increase with decreasing SDD; values equal to 1.220 ± 0.028 and 1.077 ± 0.016 were obtained for the 5 mm iris collimator at 650 mm and 1000 mm SDD, respectively. On the contrary, diode detectors were found to overestimate small field OFs and a correction factor equal to 0.973 ± 0.006, 0.954 ± 0.006, 0.937 ± 0.007, and 0.964 ± 0.006 was measured for the PTW‐60017, −60012, −60008 and the EDGE diode detectors, respectively, for the 5 mm iris collimator at 800 mm SDD. The corresponding correction factors for the 15 mm iris collimator were found equal to 0.997 ± 0.010, 0.994 ± 0.009, 0.988 ± 0.010, and 0.986 ± 0.010, respectively. No correlation of the diode correction factors with SDD was observed.

Conclusions:

This work demonstrates an experimental procedure for the determination of the correction factors required to obtain small field OF results of increased accuracy.
Optimization of PROPELLER reconstruction for free‐breathing T1‐weighted cardiac imaging
Authors: Huang Teng‐Yi , Tseng Yu‐Shen , Tang Yu‐Wei , Lin Yi‐Ru
Published: July 2012

Purpose:

Clinical cardiac MR imaging techniques generally require patients to hold their breath during the scanning process to minimize respiratory motion‐related artifacts. However, some patients cannot hold their breath because of illness or limited breath‐hold capacity. This study aims to optimize the PROPELLER reconstruction for free‐breathing myocardial T1‐weighted imaging.

Methods:

Eight healthy volunteers (8 men; mean age 26.4 years) participated in this study after providing institutionally approved consent. The PROPELLER encoding method can reconstruct a low‐resolution image from every blade because of k‐space center oversampling. This study investigated the feasibility of extracting a respiratory trace from the PROPELLER blades by implementing a fully automatic region of interest selection and introducing a best template index to account for the property of the human respiration cycle.

Results:

Results demonstrated that the proposed algorithm significantly improves the contrast‐to‐noise ratio and the image sharpness (p < 0.05).

Conclusions:

The PROPELLER method is expected to provide a robust tool for clinical application in free‐breathing myocardial T1‐weighted imaging. It could greatly facilitate the acquisition procedures during such a routine examination.
An unusual cause of a non-functioning stoma in an 87-year-old gentleman
Authors: Ayeni Itunuayo V , Williams Nicholas J
Published: July 2012

Gallstone ileus is a rare but significant cause of intestinal obstruction particularly among the elderly population. Symptoms are often vague and therefore a high suspicious index is required for successful diagnosis. In this report, we present the case of an 87-year-old gentleman with a background history of cholelithiasis and ileostomy for ulcerative colitis who was admitted with a 24-h history of his stoma not functioning. He had an abdominal x-ray and CT which were consistent with small bowel obstruction with no identifiable cause. He underwent an examination of his stoma under general anaesthesia which revealed a 2.5 cm gallstone wedged several centimetres near the entry point of the stoma. The purpose of this report is to highlight the importance of considering gallstones as a potential cause of a non-functioning stoma in any patient with a significant history of cholelithiasis.
Fulminant inflammatory neuropathy mimicking cerebral death: Table 1
Authors: Liik Maarika , Puksa Leena , Lüüs Siiri-Merike , Haldre Sulev , Taba Pille
Published: July 2012

We report a case of a 44-year-old woman who developed rapidly progressive tetraparesis followed by respiratory failure and abolition of brainstem reflexes. Electrodiagnostic studies excluded the possibility of cerebral death and confirmed the diagnosis of acute motor-sensory axonal neuropathy. The initial fulminant course of the disease was followed by slow recovery to independence in daily activities.
Dipeptidyl peptidase IV inhibition potentiates amino acid- and bile acid-induced bicarbonate secretion in rat duodenum
Authors: Inoue Takuya , Wang Joon-Ho , Higashiyama Masaaki , Rudenkyy Sergiy , Higuchi Kazuhide , Guth Paul H. , Engel Eli , Kaunitz Jonathan D. , Akiba Yasutada
Published: July 2012

Intestinal endocrine cells release gut hormones, including glucagon-like peptides (GLPs), in response to luminal nutrients. Luminal l-glutamate (l-Glu) and 5′-inosine monophosphate (IMP) synergistically increases duodenal HCO3− secretion via GLP-2 release. Since L cells express the bile acid receptor TGR5 and dipeptidyl peptidase (DPP) IV rapidly degrades GLPs, we hypothesized that luminal amino acids or bile acids stimulate duodenal HCO3− secretion via GLP-2 release, which is enhanced by DPPIV inhibition. We measured HCO3− secretion with pH and CO2 electrodes using a perfused rat duodenal loop under isoflurane anesthesia. l-Glu (10 mM) and IMP (0.1 mM) were luminally coperfused with or without luminal perfusion (0.1 mM) or intravenous (iv) injection (3 μmol/kg) of the DPPIV inhibitor NVP728. The loop was also perfused with a selective TGR5 agonist betulinic acid (BTA, 10 μM) or the non-bile acid type TGR5 agonist 3-(2-chlorophenyl)- N-(4-chlorophenyl)- N,5-dimethylisoxazole-4-carboxamide (CCDC; 10 μM). DPPIV activity visualized by use of the fluorogenic substrate was present on the duodenal brush border and submucosal layer, both abolished by the incubation with NVP728 (0.1 mM). An iv injection of NVP728 enhanced l-Glu/IMP-induced HCO3− secretion, whereas luminal perfusion of NVP728 had no effect. BTA or CCDC had little effect on HCO3− secretion, whereas NVP728 iv markedly enhanced BTA- or CCDC-induced HCO3− secretion, the effects inhibited by a GLP-2 receptor antagonist. Coperfusion of the TGR5 agonist enhanced l-Glu/IMP-induced HCO3− secretion with the enhanced GLP-2 release, suggesting that TGR5 activation amplifies nutrient sensing signals. DPPIV inhibition potentiated luminal l-Glu/IMP-induced and TGR5 agonist-induced HCO3− secretion via a GLP-2 pathway, suggesting that the modulation of the local concentration of the endogenous secretagogue GLP-2 by luminal compounds and DPPIV inhibition helps regulate protective duodenal HCO3− secretion.
Nonviral gene therapy targeting cardiovascular system
Authors: Su Cheng-Huang , Wu Yih-Jer , Wang Hsueh-Hsiao , Yeh Hung-I
Published: July 2012

The goal of gene therapy is either to introduce a therapeutic gene into or replace a defective gene in an individual's cells and tissues. Gene therapy has been urged as a potential method to induce therapeutic angiogenesis in ischemic myocardium and peripheral tissues after extensive investigation in recent preclinical and clinical studies. A successful gene therapy mainly relies on the development of the gene delivery vector. Developments in viral and nonviral vector technology including cell-based gene transfer will further improve transgene delivery and expression efficiency. Nonviral approaches as alternative gene delivery vehicles to viral vectors have received significant attention. Recently, a simple and safe approach of gene delivery into target cells using naked DNA has been improved by combining several techniques. Among the physical approaches, ultrasonic microbubble gene delivery, with its high safety profile, low costs, and repeatable applicability, can increase the permeability of cell membrane to macromolecules such as plasmid DNA by its bioeffects and can provide as a feasible tool in gene delivery. On the other hand, among the promising areas for gene therapy in acquired diseases, ischemic cardiovascular diseases have been widely studied. As a result, gene therapy using advanced technology may play an important role in this regard. The aims of this review focus on understanding the cellular and in vivo barriers in gene transfer and provide an overview of currently used chemical vectors and physical tools that are applied in nonviral cardiovascular gene transfer.
Assessment of cerebral autoregulation: the quandary of quantification
Authors: Tzeng Y. C. , Ainslie P. N. , Cooke W. H. , Peebles K. C. , Willie C. K. , MacRae B. A. , Smirl J. D. , Horsman H. M. , Rickards C. A.
Published: July 2012

We assessed the convergent validity of commonly applied metrics of cerebral autoregulation (CA) to determine the extent to which the metrics can be used interchangeably. To examine between-subject relationships among low-frequency (LF; 0.07–0.2 Hz) and very-low-frequency (VLF; 0.02–0.07 Hz) transfer function coherence, phase, gain, and normalized gain, we performed retrospective transfer function analysis on spontaneous blood pressure and middle cerebral artery blood velocity recordings from 105 individuals. We characterized the relationships ( n = 29) among spontaneous transfer function metrics and the rate of regulation index and autoregulatory index derived from bilateral thigh-cuff deflation tests. In addition, we analyzed data from subjects ( n = 29) who underwent a repeated squat-to-stand protocol to determine the relationships between transfer function metrics during forced blood pressure fluctuations. Finally, data from subjects ( n = 16) who underwent step changes in end-tidal Pco2 (PetCO2) were analyzed to determine whether transfer function metrics could reliably track the modulation of CA within individuals. CA metrics were generally unrelated or showed only weak to moderate correlations. Changes in PetCO2 were positively related to coherence [LF: β = 0.0065 arbitrary units (AU)/mmHg and VLF: β = 0.011 AU/mmHg, both P < 0.01] and inversely related to phase (LF: β = −0.026 rad/mmHg and VLF: β = −0.018 rad/mmHg, both P < 0.01) and normalized gain (LF: β = −0.042%/mmHg2 and VLF: β = −0.013%/mmHg2, both P < 0.01). However, PetCO2 was positively associated with gain (LF: β = 0.0070 cm·s−1·mmHg−2, P < 0.05; and VLF: β = 0.014 cm·s−1·mmHg−2, P < 0.01). Thus, during changes in PetCO2, LF phase was inversely related to LF gain (β = −0.29 cm·s−1·mmHg−1·rad−1, P < 0.01) but positively related to LF normalized gain (β = 1.3% mmHg−1/rad, P < 0.01). These findings collectively suggest that only select CA metrics can be used interchangeably and that interpretation of these measures should be done cautiously.
Vascular smooth muscle responsiveness to nitric oxide is reduced in healthy adults with increased adiposity
Authors: Christou Demetra D. , Pierce Gary L. , Walker Ashley E. , Hwang Moon-Hyon , Yoo Jeung-Ki , Luttrell Meredith , Meade Thomas H. , English Mark , Seals Douglas R.
Published: July 2012

Vascular smooth muscle responsiveness to nitric oxide, as assessed by nitroglycerin-induced dilation (NID), is impaired in clinical cardiovascular disease, but its relation to adiposity is unknown. We determined the relation of NID to total and abdominal adiposity in healthy adults varying widely in adiposity. In 224 men and women [age, 18–79 years; body mass index (BMI), 16.4–42.2 kg/m2], we measured NID (brachial artery dilation to 0.4 mg sublingual nitroglycerin), total body adiposity [BMI and percent body fat (percent BF via dual-energy X-ray absorptiometry)], and indexes of abdominal adiposity [waist circumference (WC) and waist-to-hip ratio (WHR)]. In a subgroup ( n = 74), we also measured total abdominal fat (TAF), abdominal visceral fat (AVF), and subcutaneous fat (ASF) using computed tomography. Based on multiple linear regression, NID was negatively related to BMI [part correlation coefficient ( rpart) = −0.19, P = 0.004] and abdominal adiposity (WC, rpart = −0.22; WHR, rpart = −0.19; TAF, rpart = −0.36; AVF, rpart = −0.36; and ASF, rpart = −0.30; all P ≤ 0.009) independent of sex, but only tended to be related to total percent BF ( rpart = −0.12, P = 0.07). In a subgroup of subjects with the highest compared with the lowest amount of AVF, NID was 35% lower ( P = 0.003). Accounting for systolic blood pressure, HDL cholesterol, glucose, insulin resistance, adiponectin, and brachial artery diameter reduced or abolished some of the relations between NID and adiposity. In conclusion, NID is or tends to be negatively associated with measures of total adiposity (BMI and percent BF, respectively) but is consistently and more strongly negatively associated with abdominal adiposity. Adiposity may influence NID in part via other cardiovascular risk factors.
Adaptive changes of mesenteric arteries in pregnancy: a meta-analysis
Authors: van Drongelen Joris , Hooijmans Carlijn R. , Lotgering Frederik K. , Smits Paul , Spaanderman Marc E. A.
Published: July 2012

The vascular response to pregnancy has been frequently studied in mesenteric artery models by investigating endothelial cell (EC)- and smooth muscle cell (SMC)-dependent responses to mechanical (flow-mediated vasodilation, myogenic reactivity, and vascular compliance) and pharmacological stimuli (G protein-coupled receptor responses: GqEC, GsSMC, GqSMC). It is unclear to what extent these pathways contribute to normal pregnancy-induced vasodilation across species, strains, and/or gestational age and at which receptor level pregnancy affects the pathways. We performed a meta-analysis on responses to mechanical and pharmacological stimuli associated with pregnancy-induced vasodilation of mesenteric arteries and included 55 (188 responses) out of 398 studies. Most included studies (84%) were performed in Wistar and Sprague-Dawley rats (SDRs) and compared late gestation versus nonpregnant controls (80%). Pregnancy promotes flow-mediated vasodilation in all investigated species. Only in SDRs, pregnancy additionally stimulates both vasodilator GqECsensitivity (EC50reduced by −0.76 [−0.92, −0.60] log[M]) and GsSMCsensitivity (EC50reduced by −0.51 [−0.82, −0.20] log[M]), depresses vasopressor GqSMCsensitivity (EC50increase in SDRs by 0.23 [0.16, 0.31] log[M]), and enhances arterial compliance. We conclude that 1) pregnancy facilitates flow-mediated vasodilation at term among all investigated species, and the contribution of additional vascular responses is species and strain specific, and 2) late pregnancy mediates vasodilation through changes at the receptor level for the substances tested. The initial steps of vasodilation in early pregnancy remain to be elucidated.
Dual Targeting of mTOR and Aurora-A Kinase for the Treatment of Uterine Leiomyosarcoma
Authors: Brewer Savannah Kari J. , Demicco Elizabeth G. , Lusby Kristelle , Ghadimi Markus PH. , Belousov Roman , Young Eric , Zhang Yiqun , Huang Kai-Lieh , Lazar Alexander J. , Hunt Kelly K. , Pollock Raphael E. , Creighton Chad J. , Anderson Matthew L. , Lev Dina
Published: July 2012

Purpose: The significance of mTOR activation in uterine leiomyosarcoma (ULMS) and its potential as a therapeutic target were investigated. Furthermore, given that effective therapies likely require combination mTOR blockade with inhibition of other targets, coupled with recent observations suggesting that Aurora-A kinase (Aurk-A) deregulations commonly occur in ULMS, the preclinical impact of dually targeting both pathways was evaluated.

Experimental Design: Immunohistochemical staining was used to evaluate expression of activated mTOR components in a large (>200 samples) ULMS tissue microarray. Effects of mTOR blockade (using rapamycin) and Aurk-A inhibition (using MLN8237) alone and in combination on human ULMS cell growth, cell-cycle progression, and apoptosis were assessed in cellular assays. Drug interactions were determined via combination index analyses. The antitumor effects of inhibitors alone or in combination were evaluated in vivo.

Results: Enhanced mTOR activation was seen in human ULMS samples. Increased pS6RP and p4EBP1 expression correlated with disease progression; p4EBP1 was found to be an independent prognosticator of patient outcome. Rapamycin inhibited growth and cell-cycle progression of ULMS cell strains/lines in culture. However, only a cytostatic effect on tumor growth was found in vivo. Combining rapamycin with MLN8237 profoundly (and synergistically) abrogated ULMS cells' growth in culture; interestingly, these effects were seen only when MLN8237 was preadministered. This novel therapeutic combination and scheduling regimen resulted in marked tumor growth inhibition in vivo.

Conclusions: mTOR and Aurk-A pathways are commonly deregulated in ULMS. Preclinical data support further exploration of dual mTOR and Aurk-A therapeutic blockade for human ULMS. Clin Cancer Res; 18(17); 4633–45. ©2012 AACR.
BAY 1000394, a Novel Cyclin-Dependent Kinase Inhibitor, with Potent Antitumor Activity in Mono- and in Combination Treatment upon Oral Application
Authors: Siemeister Gerhard , Lücking Ulrich , Wengner Antje M. , Lienau Philip , Steinke Wolfram , Schatz Christoph , Mumberg Dominik , Ziegelbauer Karl
Published: July 2012

Deregulated activity of cyclin-dependent kinases (CDK) results in loss of cell-cycle checkpoint function and increased expression of antiapoptotic proteins, which has been directly linked to the molecular pathology of cancer. BAY 1000394 inhibits the activity of cell-cycle CDKs CDK1, CDK2, CDK3, CDK4, and of transcriptional CDKs CDK7 and CDK9 with IC50 values in the range between 5 and 25 nmol/L. Cell proliferation was inhibited at low nanomolar concentration in a broad spectrum of human cancer cell lines. In cell-based assays, the inhibition of phosphorylation of the CDK substrates retinoblastoma protein, nucleophosmin, and RNA polymerase II was shown. Cell-cycle profiles were consistent with inhibition of CDK 1, 2, and 4 as shown in cell-cycle block and release experiments. The physicochemical and pharmacokinetic properties of BAY 1000394 facilitate rapid absorption and moderate oral bioavailability. The compound potently inhibits growth of various human tumor xenografts on athymic mice including models of chemotherapy resistance upon oral dosing. Furthermore, BAY 1000394 shows more than additive efficacy when combined with cisplatin and etoposide. These results suggest that BAY 1000394 is a potent pan-CDK inhibitor and a novel oral cytotoxic agent currently in phase I clinical trials. Mol Cancer Ther; 11(10); 2265–73. ©2012 AACR.
Abstract 1744: Hsp27 overexpression enhances the chemosensitivity to MCF7 doxorubicin resistance cells
Authors: Kanagasabai Ragu , Krishnamurthy Karthikeyan , Ilangovan Govindasamy
Published: July 2012

Multidrug resistance (MDR) is a major obstacle in cancer chemotherapy and its inhibition is an effective way to reverse cancer drug resistance. In the present study we report that over expression of HSP27 down-regulated MDR1 expression in MCF7/Doxorubicin (MCF7/DOX), a human breast MDR cancer cell line. In MCF7/Dox cells, mutant p53 was found to be accumulated, whereas Hsp27 level is completely depleted. Since Hsp27 was shown to enhance Akt phosphorylation and G2/M cell cycle arrest, a common pathway of Dox-induced cell death in MCF7 cells, we hypothesized that over expression of Hsp27 in resistant cell will sensitize for chemotherapy. HSP27 over expression significantly inhibited mutant p53 and MDR1 (P-gp) expression and MDR1 mRNA. The suppression of MDR1 was accompanied by partial recovery of intracellular drug accumulation and increased cytotoxicity of Doxorubicin, indicating that HSP27 reversed the MDR phenotype by inhibiting the drug efflux function of MDR1. Moreover, nuclear factor-KB activity and IKB degradation were inhibited by HSP27 over expression through down regulation of mutant p53.

Interestingly, the over expression of HSP27 negatively regulated the cell growth with significant G2/M arrest of cell cycle, and it could up-regulate endogenous p21 in a p53 independent manner leading to enhanced caspase activation to promote intracellular apoptotic signaling for cell death. Taken together, our results suggested that HSP27 is down regulated in MCF7/Dox resistant cells, and when re-expressed, it down regulates MDR1 expression via p53 and NF-KB., which results in growth suppression and higher sensitivity to Doxorubicin.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1744. doi:10.1158/1538-7445.AM2011-1744
Abstract 1891: Cigarette smoking and incident colorectal cancer by KRAS mutation status in a population-based cohort of older women
Authors: Samadder Niloy Jewel , Vierkant Robert A. , Wang Alice , Tillmans Lori S. , Lynch Charles F. , Anderson Kristin E. , Haile Robert W. , Harnack Lisa J. , Potter John D. , Slager Susan L. , Smyrk Thomas C. , Thibodeau Stephen N. , Cerhan James R. , Limburg Paul
Published: July 2012

Background: Cigarette smoking (CS) is an established, although relatively modest, colorectal cancer (CRC) risk factor. Emerging data suggest that CS might affect distinct pathways of colorectal carcinogenesis. In this study, we examined CS-associated CRC risks by KRAS mutation status in the population-based Iowa Women's Health Study (IWHS).

Methods: The IIWHS recruited 41,836 randomly selected Iowa women, ages 55-69 years, with a valid driver's license at study entry (1986). CS and other exposure variables were assessed at baseline, by self-report. Incident CRC cases were ascertained by annual linkage with the Iowa Cancer Registry. Archived, paraffin-embedded tissue specimens were collected from 732 representative CRC cases diagnosed through 12/31/2002. CS was categorized by smoking status (current, former), average number of cigarettes per day (1-19, 20-39, > 40) and pack-years (1-19, 20-39, > 40); never smokers were defined as the reference group. KRAS mutation status (wildtype [wt] vs. mutated [mut]) was determined by direct sequence analysis of codons 12 and 13 (exon 2). Multivariate Cox regression models were fit to estimate relative risks (RRs) and 95% confidence intervals (CIs).

Results: Of the 732 available CRC cases, 507 (69%) had complete CS and KRAS data. Each of the CS-related variables was more strongly associated with KRAS-wt vs. KRAS-mut tumors (see Table). However, event rates were relatively small in some cells, and tests for heterogeneity between KRAS-defined subtypes were not statistically significant (p > 0.05 for each comparison).

Conclusions: These findings suggest that CS may affect colorectal carcinogenesis through KRAS-independent pathways, but additional data are needed from larger, more diverse study populations.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1891. doi:10.1158/1538-7445.AM2011-1891
Abstract 1895: Genetic polymorphisms of an innate immune gene, Toll-Like Receptor 4, and aggressive prostate cancer risk: A systematic review and meta-analysis
Authors: Huang Yi-Ling , Page John H. , Chen Jen-Hau , Lin Yen-Ling , Xu Jianfeng , Koutros Stella , Berndt Sonja , Chanock Stephen J. , Witte John S. , Chen Yen-Ching
Published: July 2012

Toll-like receptor 4 (TLR4) is located on the surface of macrophages and is important for the immune response to several pathogens. Chronic inflammation has been implicated in the pathogenesis of prostate cancer (PCa), and genetic polymorphisms of the innate immune gene TLR4 have been related to the risk of PCa. Six studies have explored the association between TLR4 polymorphisms and the risk of PCa. Five studies mainly included men of European ancestry. We conducted a systematic review of all genetic association studies that evaluated the relationship between TLR4 genotypes and aggressive PCa risk. We found the rs11536889 variant was significantly associated with an increased risk of aggressive PCa under a dominant genetic model [odds ratio (OR) = 1.20, 95% CI = 1.05-1.37]. However, rs1927914, rs2149356, or rs10759932 polymorphisms were not associated with the risk of PCa under any inheritance mode. In conclusion, this study found that the polymorphism TLR4 rs11536889 was significantly associated with the risk of aggressive PCa. Additional large-scale genetic association studies are needed to confirm these findings.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1895. doi:10.1158/1538-7445.AM2011-1895
Abstract 190: Targeting ceramide and endoplasmic reticulum-stress in vitamin E induced apoptosis in human breast cancer cells
Authors: Gopalan Archana , Yu Weiping , Sanders Bob , Kline Kimberly
Published: July 2012

Vitamin E consists of eight plant-derived forms classified as tocopherols (α, β, Δ, γ) and tocotrienols (α, β, Δ, γ) which have a chromanol ring and a saturated and unsaturated aliphatic side chain, respectively. The anti-cancer actions of tocopherols and tocotrienols are limited to the gamma and delta forms. Here, we report that both γ-tocopherol (γT) and γ-tocotrienol (γT3) display potent anti-cancer actions with γT3 being more potent. Both forms target similar pro-apoptotic and anti-apoptotic pathways. γT and γT3 induced apoptosis in human breast cancer cells by enhancing death-receptor DR5 mediated activation of caspase-8 and mitochondria dependent caspase-9, as well as by activating ER-stress markers: GADD153/ C/EBP homologous protein (CHOP), GRP-78, ATF-4 and eIF2α. JNK and CHOP are involved in DR5 mediated apoptosis triggered by both vitamin E forms. γT and γT3 decreased protein levels of anti-apoptotic factors c-FLIP, BCl-2 and survivin. Since ceramide is a known upstream inducer of ER-stress and downstream mediator of death receptor apoptotic pathway mediators, treatments with γT and γT3 were conducted in the presence of specific inhibitors of sphingomyelin hydrolysis, de novo ceramide pathways and ER-stress in order to distinguish between the pathways modulated by the vitamin E forms. Data show that both γT and γT3 induced apoptosis via activation of sphingomyelin hydrolysis and the de novo ceramide pathways; however, activation of the ER-stress pathway contributed to apoptosis induced by γT3 only. Taken together, our data suggest that γT3s more potent apoptotic effects in comparison to γT are due to the ability of γT3 to activate ER stress pathways. This better understanding of the anti-cancer properties and mechanistic actions by these two natural occurring agents in vitro provides the necessary impetus to test them in combination with other known anti-cancer agents in pre-clinical xenograft studies to identify novel and safer therapeutic strategies. Research funded by The Clayton Foundation for Research.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 190. doi:10.1158/1538-7445.AM2011-190