bluuebunny/crossref_metadata_2025 huggingface dataset:
Tumor Regression Grades: Can They Influence Rectal Cancer Therapy Decision Tree?
Authors: Santos Marisa D. , Silva Cristina , Rocha Anabela , Matos Eduarda , Nogueira Carlos , Lopes Carlos
Published: September 2013

Background. Evaluating impact of tumor regression grade in prognosis of patients with locally advanced rectal cancer (LARC).Materials and Methods. We identified from our colorectal cancer database 168 patients with LARC who received neoadjuvant therapy followed by complete mesorectum excision surgery between 2003 and 2011: 157 received 5-FU-based chemoradiation (CRT) and 11 short course RT. We excluded 29 patients, the remaining 139 were reassessed for disease recurrence and survival; the slides of surgical specimens were reviewed and classified according to Mandard tumor regression grades (TRG). We compared patients with good response (Mandard TRG1 or TRG2) versus patients with bad response (Mandard TRG3, TRG4, or TRG5). Outcomes evaluated were 5-year overall survival (OS), disease-free survival (DFS), local, distant and mixed recurrence.Results. Mean age was 64.2 years, and median followup was 56 months. No statistically significant survival difference was found when comparing patients with Mandard TRG1 versus Mandard TRG2 (). Mandard good responders (TRG1 + 2) have significantly better OS and DFS than Mandard bad responders (TRG3 + 4 + 5) (OS ; DFS ).Conclusions. Mandard good responders had a favorable prognosis. Tumor response (TRG) to neoadjuvant chemoradiation should be taken into account when defining the optimal adjuvant chemotherapy regimen for patients with LARC.
Development of Orodispersible Tablets of Candesartan Cilexetil-β-cyclodextrin Complex
Authors: Sravya Maddukuri , Deveswaran Rajamanickam , Bharath Srinivasan , Basavaraj Basappa Veerbadraiah , Madhavan Varadharajan
Published: September 2013

The aim of this study was to investigate the use of inclusion complexation technique employing β-cyclodextrin in improving the dissolution profile of candesartan cilexetil, a BCS class-II drug, and to formulate the inclusion complex into orodispersible tablets. The inclusion complexes were formed by physical mixing, kneading, coevaporation, and lyophilisation methods. Inclusion complexes were characterized by FTIR, DSC, XRD, NMR, and mass spectral studies. Inclusion complexes prepared using kneading, and lyophilisation techniques in the molar ratio 1 : 5 with β-cyclodextrin were used for formulating orodispersible tablets by direct compression with different superdisintegrants like croscarmellose sodium, crospovidone, sodium starch glycolate, and low substituted hydroxypropyl cellulose in varying concentrations. The directly compressible powder was evaluated for precompression parameters, and the prepared orodispersible tablets were evaluated for postcompression parameters. Drug-excipient compatibility studies showed no interaction, and characterization proved the formation of inclusion complex. In vitro disintegration time was found to be within 3 minutes, and all the formulations showed complete drug release of 100% within 20 minutes. The optimized formulation was found to be stable after 6 months and showed no significant change in drug content. This work proved β-cyclodextrins to be effective solubilizing agent in improving the solubility of poorly water soluble drugs.
Damage Identification of Trusses with Elastic Supports Using FEM and Genetic Algorithm
Authors: Kim Nam-Il , Lee Jaehong
Published: September 2013

The computationally efficient damage identification technique for truss structures with elastic supports is proposed based on the force method. To transform the truss with supports into the equivalent free-standing model without supports, the novel zero-length dummy members are employed. General equilibrium equations and kinematic relations, in which the reaction forces and the displacements at the elastic supports are taken into account, are clearly formulated. The compatibility equations, in terms of forces in which the flexibilities of elastic supports are considered, are explicitly presented using the singular value decomposition (SVD) technique. Both member and reaction forces are simultaneously and directly obtained. Then, all nodal displacements including constrained nodes are back calculated from the member and reaction forces. Next, the microgenetic algorithm (MGA) is used to properly identify the site and the extent of multiple damages in truss structures. In order to verify the superiority of the current study, the numerical solutions are presented for the planar and space truss models with and without elastic supports. The numerical results indicate that the computational effort required by this study is found to be significantly lower than that of the displacement method.
Analytical Optimization of Piezoelectric Circular Diaphragm Generator
Authors: Mohammadi S. , Abdalbeigi M.
Published: September 2013

This paper presents an analytical study of the piezoelectric circular diaphragm microgenerator using strain energy method. Piezoelectrics are the intelligent materials that can be used as transducer to convert mechanical energy into electrical energy and vice versa. The aim of this paper is to optimize produced electrical energy from mechanical pressure. Therefore, the circular metal plate equipped with piezoelectric circular patch has been considered with simply and clamped supports. A comprehensive modeling, parametrical study and the effect of the boundary conditions on the performance of the microgenerator have been investigated. The system is under variable pressure from an oscillating pressure source. Results are presented for PZT and PMN-PT piezoelectric materials with steel and aluminum substrates. An optimal value for the radius and thickness of the piezoelectric layer with a special support condition has been obtained.
Production of a Lipopeptide Biosurfactant by a Novel Bacillus sp. and Its Applicability to Enhanced Oil Recovery
Authors: Varadavenkatesan Thivaharan , Murty Vytla Ramachandra
Published: September 2013

Biosurfactants are surface-active compounds derived from varied microbial sources including bacteria and fungi. They are secreted extracellularly and have a wide range of exciting properties for bioremediation purposes. They also have vast applications in the food and medicine industry. With an objective of isolating microorganisms for enhanced oil recovery (EOR) operations, the study involved screening of organisms from an oil-contaminated site. Morphological, biochemical, and 16S rRNA analysis of the most promising candidate revealed it to be Bacillus siamensis, which has been associated with biosurfactant production, for the first time. Initial fermentation studies using mineral salt medium supplemented with crude oil resulted in a maximum biosurfactant yield of 0.64 g/L and reduction of surface tension to 36.1 mN/m at 96 h. Characterization studies were done using thin layer chromatography and Fourier transform infrared spectroscopy. FTIR spectra indicated the presence of carbonyl groups, alkyl bonds, and C–H and N–H stretching vibrations, typical of peptides. The extracted biosurfactant was stable at extreme temperatures, pH, and salinity. Its applicability to EOR was further verified by conducting sand pack column studies that yielded up to 60% oil recovery.
3D Molecular Modelling Study of the H7N9 RNA-Dependent RNA Polymerase as an Emerging Pharmacological Target
Authors: Vlachakis Dimitrios , Karozou Argiro , Kossida Sophia
Published: September 2013

Currently not much is known about the H7N9 strain, and this is the major drawback for a scientific strategy to tackle this virus. Herein, the 3D complex structure of the H7N9 RNA-dependent RNA polymerase has been established using a repertoire of molecular modelling techniques including homology modelling, molecular docking, and molecular dynamics simulations. Strikingly, it was found that the oligonucleotide cleft and tunnel in the H7N9 RNA-dependent RNA polymerase are structurally very similar to the corresponding region on the hepatitis C virus RNA-dependent RNA polymerase crystal structure. A direct comparison and a 3D postdynamics analysis of the 3D complex of the H7N9 RNA-dependent RNA polymerase provide invaluable clues and insight regarding the role and mode of action of a series of interacting residues on the latter enzyme. Our study provides a novel and efficiently intergraded platform with structural insights for the H7N9 RNA-dependent RNA Polymerase. We propose that future use and exploitation of these insights may prove invaluable in the fight against this lethal, ongoing epidemic.
Olfactory Dysfunction in Patients with Neuromyelitis Optica
Authors: Schmidt Felix , Göktas Önder , Jarius Sven , Wildemann Brigitte , Ruprecht Klemens , Paul Friedemann , Harms Lutz
Published: September 2013

Background. Neuromyelitis optica (NMO) is a severely disabling autoimmune disorder of the CNS, which mainly affects the optic nerves and spinal cord. However, recent studies have shown that extra-opticospinal are more common in NMO than previously thought.Objective. To investigate olfactory function (OF) in patients with neuromyelitis optica (NMO) versus healthy controls (HC).Methods. Psychophysical testing of the orthonasal OF was performed using theThreshold-Discrimination-Identificationtest (TDI), measuring different qualities of olfaction, in 10 unselected NMO patients and 10 HC.Results. Five of 10 NMO patients (50%) showed hyposmia, while all 10 HC were normosmic. Moreover, NMO patients had significantly lower meanTDI-scores compared to HC, based on a poorer performance in both theDiscriminationand theIdentificationsubtests.Conclusions. Our results suggest that hyposmia might be part of the expanding clinical spectrum of NMO.
Water Vapor Adsorption Capacity of Thermally Fluorinated Carbon Molecular Sieves for CO2 Capture
Authors: Jung Jin-Young , Yu Hye-Ryeon , In Se Jin , Choi Young Chul , Lee Young-Seak
Published: September 2013

The surfaces of carbon molecular sieves (CMSs) were thermally fluorinated to adsorb water vapor. The fluorination of the CMSs was performed at various temperatures (100, 200, 300, and 400°C) to investigate the effects of the fluorine gas (F2) content on the surface properties. Fluorine‐related functional groups formed were effectively generated on the surface of the CMSs via thermal fluorination process, and the total pore volume and specific surface area of the pores in the CMSs increased during the thermal fluorination process, especially those with diameters ≤ 8 Å. The water vapor adsorption capacity of the thermally fluorinated CMSs increased compared with the as‐received CMSs, which is attributable to the increased specific surface area and to the semicovalent bonds of the C–F groups.
Development of a Virtual Maintenance System for Complex Mechanical Product
Authors: Liu Xin-hua , Song Guo-min , Cui Xiao-long , Xu Bi-hong , Wang Kai , Wang Zhong-bin
Published: September 2013

In order to improve the maintenance training effect of complex mechanical product, a virtual maintenance system was developed. The system framework was proposed, and the main functional modules were elaborated. A multilevel information representation model for complex mechanical product was put forward, and the flowchart of model transformation technology was designed. Moreover, a collision detection method based on hierarchical bounding volume was proposed, and the maintainability analysis and evaluation solution based on maintenance knowledge was presented. Finally, a prototype system was developed, and the proposed system was provedto be efficient through an example of hydraulic winch.
Production of Platinum Atom Nanoclusters at One End of Helical Plant Viruses
Authors: Drygin Yuri , Kondakova Olga , Atabekov Joseph
Published: September 2013

Platinum atom clusters (Pt nanoparticles, Pt-NPs) were produced selectively at one end of helical plant viruses, tobacco mosaic virus (TMV) and potato virus X (PVX), when platinum coordinate compounds were reduced chemically by borohydrides. Size of the platinum NPs depends on conditions of the electroless deposition of platinum atoms on the virus. Results suggest that the Pt-NPs are bound concurrently to the terminal protein subunits and the 5′ end of encapsidated TMV RNA. Thus, a special structure of tobacco mosaic virus and potato X virus particles with nanoparticles of platinum, which looks like a push-pin with platinum head and virus needle, was obtained. Similar results were obtained with ultrasonically fragmented TMV particles. By contrast, the Pt-NPs fully filled the central axial hole ofin vitroassembled RNA-free TMV-like particles. We believe that the results presented here will be valuable in the fundamental understanding of interaction of viral platforms with ionic metals and in a mechanism of nanoparticles formation.
A Phase Noise Analysis Method for Millimeter-Wave Passive Imager BHU-2D-U Frequency Synthesizer
Authors: Zhang Jin , Zheng Cheng , Yao Xianxun , Yang Baohua
Published: September 2013

A nontrivial phase noise analysis method is proposed for frequency synthesizer of a passive millimeter-wave synthetic aperture interferometric radiometer (SAIR) imager for concealed weapon detections on human bodies with high imaging rates. The frequency synthesizer provides local oscillator signals for both millimeter-wave front ends and intermediate frequency IQ demodulators for the SAIR system. The influence of synthesizer phase noise in different offset frequency ranges on the visibility phase errors has been systematically investigated with noise requirements drawn, and the integrated RMS phase error could represent uncorrelated phase noise effects in the most critical offset frequency range for visibility error control. An analytical phase noise simulation method is proposed to guide synthesizer design. To conclude, the phase noise effects on SAIR visibility errors have been concretized to noise design requirements, and good agreements have been observed between simulation and measurement results. The frequency synthesizer designed has been successfully in operation in BHU-2D-U system.
A Frame Element Model for the Nonlinear Analysis of FRP-Strengthened Masonry Panels Subjected to In-Plane Loads
Authors: Grande Ernesto , Imbimbo Maura , Rasulo Alessandro , Sacco Elio
Published: September 2013

A frame element model for evaluating the nonlinear response of unstrengthened and FRP-strengthened masonry panels subjected to in-plane vertical and lateral loads is presented. The proposed model, based on some assumptions concerning the constitutive behaviour of masonry and FRP material, considers the panel discretized in frame elements with geometrical and mechanical properties derived on the basis of the different states characterizing the sectional behaviour. The reliability of the proposed model is assessed by considering some experimental cases deduced from the literature.
Frequency and Characteristics of Infections Caused by Extended-Spectrum Beta-Lactamase-Producing Organisms in Neonates: A Prospective Cohort Study
Authors: Vijayakanthi Nandini , Bahl Dheeraj , Kaur Nirmaljit , Maria Arti , Dubey Nand Kishore
Published: September 2013

This prospective cohort study was conducted to determine the frequency of infections caused by extended-spectrum beta-lactamase- (ESBL-) producing organisms, various bacteria producing ESBL, antibiotic susceptibility of these organisms, and the risk factors associated with these infections in a neonatal intensive care unit in a tertiary care hospital in North India. Of the 150 neonates enrolled in the study, 47 culture-positive neonates were included in the study cohort and were divided into two groups: ESBL-positive (8 neonates) and ESBL-negative (39 neonates) cohorts. Various organisms were isolated from 72 culture samples in these 47 neonates. Of these, 10 culture samples grew ESBL-positive organisms and 62 samples grew ESBL-negative organisms. The frequency of ESBL-producing organisms was found to be 5.3%. ESBL infection incidence densities were found to be 3.4 per 1000 patient-days.Klebsiella(60%) was the most common organism producing ESBL followed byEscherichia coli(30%) andPseudomonas(10%). Eighty percent of the ESBL-producing organisms were sensitive to piperacillin-tazobactam. Risk factors found significant by univariate analysis (P<0.05) were preterm, low birthweight, perinatal asphyxia, respiratory distress syndrome, anaemia, metabolic acidosis, prolonged mechanical ventilation (>7 days), length of hospitalization, length of level 3 stay, prior antibiotic use, central venous catheter duration, peripherally inserted central venous catheter duration, and total parenteral nutrition duration. Factors that retained significance in the logistic regression model were duration of hospital stay (adjusted OR: 0.958, CI: 0.920–0.997, andPvalue = 0.037) and gestational age (adjusted OR: 1.39, CI: 1.037–1.865, andPvalue = 0.028). There was no significant difference in the mortality between the two groups.
On the Security of Data Collection and Transmission from Wireless Sensor Networks in the Context of Internet of Things
Authors: Yu Hong , He Jingsha , Liu Ruohong , Ji Dajie
Published: September 2013

In the context of Internet of Things (IoT), multiple cooperative nodes in wireless sensor networks (WSNs) can be used to monitor an event, jointly generate a report and then send it to one or more Internet nodes for further processing. A primary security requirement in such applications is that every event data report be authenticated to intended Internet users and effectively filtered on its way to the Internet users to realize the security of data collection and transmission from the WSN. However, most present schemes developed for WSNs don't consider the Internet scenario while traditional mechanisms developed for the Internet are not suitable due to the resource constraint of sensor nodes. In this paper, we propose a scheme, which we refer to as Data Authentication and En-route Filtering (DAEF), for WSNs in the context of IoT. In DAEF, signature shares are generated and distributed based on verifiable secret sharing cryptography and an efficient ID-based signature algorithm. Our security analysis shows that DAEF can defend against node compromise attacks as well as denial of service (DoS) attacks in the form of report disruption and selective forwarding. We also analyze energy consumption to show the advantages of DAEF over some comparable schemes.
The Split Feasibility Problems for Countable Families of Asymptotically Strict Pseudocontractions
Authors: Deng Wei-Qi
Published: September 2013

An up-to-date algorithm for solving the split feasibility problem for countable families of asymptotically strict pseudocontractions is introduced in the framework of Hilbert spaces. Our results greatly improve and extend those of other authors whose related research studies are restricted to the situation of at most finitely many such mappings.
Entropy Analysis in Relativistic Heavy-Ion Collisions
Authors: Ahmad Shakeel , Ahmad A. , Chandra Anuj , Zafar M. , Irfan M.
Published: September 2013

Entropy creation in multiparticle system is investigated by analysing the experimental data on ion-ion collisions at AGS and SPS energies and the results thus obtained are compared with those predicted by multiphase transport and correlation-free Monte Carlo models. Entropies produced in limited- and full-phase space are observed to increase with increasing beam energy. The entropy values, normalized to the maximum rapidity and plotted against pseudorapidity (bin width also normalized to the maximum rapidity), are found to be energy independent, exhibiting a kind of entropy scaling. Such scaling is observed in the full phase space as well as in the regions confined to the forward or backward hemispheres. The findings also reveal that there exist strong correlations amongst the particles produced in the forward and backward hemispheres around the midrapidity. These correlations are found to be of short range in nature, and the contributions from the long-range correlations seem to be absent. PACS numbers: 25.75-q, 25.75.Gz.
A Study on the Mechanism of Cinobufagin in the Treatment of Paw Cancer Pain by Modulating Localβ-Endorphin ExpressionIn Vivo
Authors: Chen Tao , Hu Wei , He Haibo , Gong Zipeng , Wang Jing , Yu Xueqin , Ai Ting , Zhan Ling
Published: September 2013

Background. Cinobufagin has been widely used in the treatment of carcinoma and plays an important role in the relief of cancer pain. But the involved mechanism remains unknown.Aim. To investigate the changes in thermal and mechanical hyperalgesia in paw cancer pain in mice and the action mechanism of cinobufagin using a paw cancer pain model.Methods. 60 female mice were randomly divided into 5 groups: control group, model group, cinobufagin group, cinobufagin +NAL-M group, and morphine group; except ones in control group, mice were inoculated with H22 hepatoma cells in the right hind paw. From the 9th day after inoculation, mice were administrated drug once daily lasting for 8 days. The pain behavior was determined on the 2nd, 4th, 6th, and 8th days before and after administration. On the last day, they were sacrificed. The levels ofβ-END, CRF, and IL-1βwere analyzed by ELISA; immunohistochemistry was performed to detect the expressions ofβ-END, POMC, andμ-OR in the tumor and adjacent tissue.Results. The thresholds of thermal pain and mechanical pain were significantly increased by cinobufagin. Moreover, the expressions ofβ-END, CRF, POMC, andμ-OR were significantly upregulated by cinobufagin. The analgesic effect of cinobufagin was blocked by the peripheral opioid receptor antagonist NAL-M.Conclusions. Cinobufagin significantly relieved cancer pain in mice and raised their pain threshold, mainly upregulating the expression levels ofβ-END andμ-OR in the hind paw tumor and adjacent tissue.
Polymorphisms of the Homologous Recombination GeneRAD51in Keratoconus and Fuchs Endothelial Corneal Dystrophy
Authors: Synowiec Ewelina , Wojcik Katarzyna A. , Izdebska Justyna , Binczyk Ewelina , Blasiak Janusz , Szaflik Jerzy , Szaflik Jacek P.
Published: September 2013

Purpose. We investigated the association between genotypes and haplotypes of the c.-61G>T (rs 1801320) and c.-98G>C (rs 1801321) polymorphisms of theRAD51gene and the occurrence of keratoconus (KC) and Fuchs endothelial corneal dystrophy (FECD) in dependence on some environmental factors.Methods. The polymorphisms were genotyped in peripheral blood lymphocytes of 100 KC and 100 FECD patients as well as 150 controls with PCR-RFLP.Results. The G/T genotype of the c.-61G>T polymorphism was associated with significantly increased frequency occurrence of KC (crude OR 2.99, 95% CI 1.75–5.13). On the other hand, the G/G genotype of this polymorphism was positively correlated with a decreased occurrence of this disease (crude OR 0.52, 95% CI 0.31–0.88). We did not find any correlation between genotypes/alleles of the c.-98G>C polymorphism and the occurrence of KC. We also found that the G/G genotype and G allele of the c.-98G>C polymorphism had a protective effect against FECD (crude OR 0.51, 95% CI 0.28–0.92; crude OR 0.53, 95% CI 0.30–0.92, resp.), while the G/C genotype and the C allele increased FECD occurrence (crude OR 1.85, 95% CI 1.01–3.36; crude OR 1.90, 95% CI 1.09–3.29, resp.).Conclusions. The c.-61T/T and c.-98G>C polymorphisms of theRAD51gene may have a role in the KC and FECD pathogenesis and can be considered as markers in these diseases.
In Vitro Effect of Sodium Fluoride on Malondialdehyde Concentration and on Superoxide Dismutase, Catalase, and Glutathione Peroxidase in Human Erythrocytes
Authors: Gutiérrez-Salinas José , García-Ortíz Liliana , Morales González José A. , Hernández-Rodríguez Sergio , Ramírez-García Sotero , Núñez-Ramos Norma R. , Madrigal-Santillán Eduardo
Published: September 2013

The aim of this paper was to describe the in vitro effect of sodium fluoride (NaF) on the specific activity of the major erythrocyte antioxidant enzymes, as well as on the membrane malondialdehyde concentration, as indicators of oxidative stress.
For this purpose, human erythrocytes were incubated with NaF (0, 7, 28, 56, and 100 μg/mL) or NaF (100 μg/mL) + vitamin E (1, 2.5, 5 and 10 μg/mL). The malondialdehyde (MDA) concentration on the surface of the erythrocytes was determined, as were the enzymatic activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GlPx). Our results demonstrated that erythrocytes incubated with increasing NaF concentrations had an increased MDA concentration, along with decreased activity of antioxidant enzymes. The presence of vitamin E partially reversed the toxic effects of NaF on erythrocytes. These findings suggest that NaF induces oxidative stress in erythrocytes in vitro, and this stress is partially reversed by the presence of vitamin E.
Ballistic Resistance of Honeycomb Sandwich Panels under In‐Plane High‐Velocity Impact
Authors: Qi Chang , Yang Shu , Wang Dong , Yang Li-Jun
Published: September 2013

The dynamic responses of honeycomb sandwich panels (HSPs) subjected to in‐plane projectile impact were studied by means of explicit nonlinear finite element simulations using LS‐DYNA. The HSPs consisted of two identical aluminum alloy face‐sheets and an aluminum honeycomb core featuring three types of unit cell configurations (regular, rectangular‐shaped, and reentrant hexagons). The ballistic resistances of HSPs with the three core configurations were first analyzed. It was found that the HSP with the reentrant auxetic honeycomb core has the best ballistic resistance, due to the negative Poisson’s ratio effect of the core. Parametric studies were then carried out to clarify the influences of both macroscopic (face‐sheet and core thicknesses, core relative density) and mesoscopic (unit cell angle and size) parameters on the ballistic responses of the auxetic HSPs. Numerical results show that the perforation resistant capabilities of the auxetic HSPs increase as the values of the macroscopic parameters increase. However, the mesoscopic parameters show nonmonotonic effects on the panels′ ballistic capacities. The empirical equations for projectile residual velocities were formulated in terms of impact velocity and the structural parameters. It was also found that the blunter projectiles result in higher ballistic limits of the auxetic HSPs.
Vegetable‐Oil‐Based Hyperbranched Polyester‐Styrene Copolymer Containing Silver Nanoparticle as Antimicrobial and Corrosion‐Resistant Coating Materials
Authors: Alam Manawwer , Shaik Mohammed Rafi , Alandis Naser M.
Published: September 2013

Pongamia oil (PO) was converted to Pongamia oil hydroxyl (POH) via epoxidation process. The esterification of POH with linolenic acid was carried out to form hyperbranched polyester (HBPE), and further styrenation was performed at the conjugated double bond in the chain of linolenic acid. After styrenation, silver nanoparticle was added in different weight percentages (0.1–0.4 wt%). The structural elucidation of POH, HBPE, and HBPE‐St was carried out by FT‐IR, 1H‐NMR, and 13C‐NMR spectroscopic techniques. Physicochemical and physicomechanical analyses were performed by standard method. Thermal behavior of the HBPE‐St was analyzed by using thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). The coatings of HBPE‐St were prepared on mild steel strips. The anticorrosive behavior of HBPE‐St resin‐based coatings in acid, saline, and tap water was evaluated, and the molecular weight of HBPE‐St was determined by gel permeation chromatography (GPC). The antibacterial activities of the HBPE‐St copolymers were tested in vitro against bacteria and fungi by disc diffusion method. The HBPE‐St copolymers exhibited good antibacterial activities and can be used as antimicrobial and corrosion‐resistant coating materials.
Alzheimer’s Disease: Screening Biomarkers Using Frequency Doubling Technology Visual Field
Authors: Valenti Denise A.
Published: September 2013

This study was to investigate the feasibility of frequency doubling technology (FDT) visual field testing in Alzheimer’s disease (AD) in order to identify early biomarkers of AD in patients already diagnosed with AD and compare the findings to participants not having Alzheimer’s disease. This biomarker would be useful in a battery of tests for the early identification of those with AD. It was not the intent to correlate the visual system biomarker with severity of disease, but to determine if the biomarker was present in pass or fail screening criteria. The study showed with very strong significance that the FDT can identify biomarkers of those with AD compared to an age-matched population that does not have AD. FDT is a simple test to take and administer and has been used to screen for eye and retinal diseases such as glaucoma, retinal macular degeneration, and diabetic retinopathy. The results obtained in the FDT readout are analyzed and compared to the age normative database within the system. The FDT ability to screen for AD biomarker in the visual system was significant in those with AD compared to the controls, and the deficits were not related to any ocular pathology.
First-in-human, Pharmacokinetic and Pharmacodynamic Phase I Study of Resminostat, an Oral Histone Deacetylase Inhibitor, in Patients with Advanced Solid Tumors
Authors: Brunetto André T. , Ang Joo Ern , Lal Rohit , Olmos David , Molife L. Rhoda , Kristeleit Rebecca , Parker Ann , Casamayor Isabel , Olaleye Muyibat , Mais Anna , Hauns Bernhard , Strobel Vera , Hentsch Bernd , de Bono Johann S.
Published: September 2013

Purpose: This first-in-human dose-escalating trial investigated the safety, tolerability, maximum tolerated dose (MTD), dose-limiting toxicities (DLT), pharmacokinetics, and pharmacodynamics of the novel histone deacetylase (HDAC) inhibitor resminostat in patients with advanced solid tumors.

Experimental Design: Resminostat was administered orally once-daily on days 1 to 5 every 14 days at 5 dose levels between 100 and 800 mg. Safety, pharmacokinetics, pharmacodynamics including histone acetylation and HDAC enzyme activity, and antitumor efficacy were assessed.

Results: Nineteen patients (median age 58 years, range 39–70) were treated. At 800 mg, 1 patient experienced grade 3 nausea and vomiting, grade 2 liver enzyme elevation, and grade 1 hypokalemia and thrombocytopenia; these were declared as a combined DLT. No other DLT was observed. Although an MTD was not reached and patients were safely dosed up to 800 mg, 3 of 7 patients treated with 800 mg underwent dose reductions after the DLT-defining period due to cumulative gastrointestinal toxicities and fatigue. All toxicities resolved following drug cessation. No grade 4 treatment-related adverse event was observed. The pharmacokinetic profile was dose-proportional with low inter-patient variability. Pharmacodynamic inhibition of HDAC enzyme was dose-dependent and reached 100% at doses ≥400 mg. Eleven heavily pretreated patients had stable disease and 1 patient with metastatic thymoma had a 27% reduction in target lesion dimensions.

Conclusions: Resminostat was safely administered with a dose-proportional pharmacokinetic profile, optimal on-target pharmacodynamic activity at dose levels ≥400 mg and signs of antitumor efficacy. The recommended phase II dose is 600 mg once-daily on days 1 to 5 every 14 days. Clin Cancer Res; 19(19); 5494–504. ©2013 AACR.
Discovery of a Mutant-Selective Covalent Inhibitor of EGFR that Overcomes T790M-Mediated Resistance in NSCLC
Authors: Walter Annette O. , Sjin Robert Tjin Tham , Haringsma Henry J. , Ohashi Kadoaki , Sun Jing , Lee Kwangho , Dubrovskiy Aleksandr , Labenski Matthew , Zhu Zhendong , Wang Zhigang , Sheets Michael , St Martin Thia , Karp Russell , van Kalken Dan , Chaturvedi Prasoon , Niu Deqiang , Nacht Mariana , Petter Russell C. , Westlin William , Lin Kevin , Jaw-Tsai Sarah , Raponi Mitch , Van Dyke Terry , Etter Jeff , Weaver Zoe , Pao William , Singh Juswinder , Simmons Andrew D. , Harding Thomas C. , Allen Andrew
Published: September 2013

Patients with non–small cell lung cancer (NSCLC) with activating EGF receptor (EGFR) mutations initially respond to first-generation reversible EGFR tyrosine kinase inhibitors. However, clinical efficacy is limited by acquired resistance, frequently driven by the EGFRT790M mutation. CO-1686 is a novel, irreversible, and orally delivered kinase inhibitor that specifically targets the mutant forms of EGFR, including T790M, while exhibiting minimal activity toward the wild-type (WT) receptor. Oral administration of CO-1686 as single agent induces tumor regression in EGFR-mutated NSCLC tumor xenograft and transgenic models. Minimal activity of CO-1686 against the WT EGFR receptor was observed. In NSCLC cells with acquired resistance to CO-1686 in vitro, there was no evidence of additional mutations or amplification of the EGFR gene, but resistant cells exhibited signs of epithelial–mesenchymal transition and demonstrated increased sensitivity to AKT inhibitors. These results suggest that CO-1686 may offer a novel therapeutic option for patients with mutant EGFR NSCLC.

Significance: We report the preclinical development of a novel covalent inhibitor, CO-1686, that irreversibly and selectively inhibits mutant EGFR, in particular the T790M drug-resistance mutation, in NSCLC models. CO-1686 is the first drug of its class in clinical development for the treatment of T790M-positive NSCLC, potentially offering potent inhibition of mutant EGFR while avoiding the on-target toxicity observed with inhibition of the WT EGFR. Cancer Discov; 3(12); 1404–15. ©2013 AACR.

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The Role of Reflectance Confocal Microscopy as an Aid in the Diagnosis of Collision Tumors
Authors: Moscarella Elvira , Rabinovitz Harold , Oliviero Margaret C. , Brown Lise , Longo Caterina , Zalaudek Iris , Piana Simonetta , Farnetani Francesca , Lallas Aimilios , Argenziano Giuseppe , Pellacani Giovanni
Published: September 2013

Background: The term ‘collision tumor' refers to the association of 2 or more different neoplasms within the same lesion. The association of a benign neoplasm with a malignant neoplasm is of particular significance and warrants diagnostic accuracy. Objective: The purpose of our study was to see if reflectance confocal microscopy (RCM) was a valuable tool when dealing with collision tumors. Methods: We retrospectively evaluated 24 histologically confirmed cases of collision tumors, which were initially assessed using dermoscopy and RCM. Results: The malignancy most commonly detected in association with collision tumors was basal cell carcinoma (BCC) (n = 13), followed by melanoma (n = 5, of which 2 collided with BCC) and squamous cell carcinoma in situ (n = 4). Seborrheic keratoses were the most common benign neoplasms found in association with collision tumors (n = 18), followed by nevi (n = 7). Dermoscopy revealed the malignant component in 14 out of 20 lesions compared to RCM, which revealed a malignant component in 19 out of 20 neoplasms. There was excellent concordance between RCM and histopathology with regard to the identification of a malignant component within a tumor (kappa value >0.9). Conclusion: The dermatoscope and the reflectance confocal microscope, when used in conjunction, are valuable tools aiding in the diagnosis of collision tumors.
An Evaluation of Nest-Building Behavior by Sanctuary Chimpanzees with Access to Forested Habitats
Authors: Fultz Amy , Brent Linda , Breaux Sarah D. , Grand Alison P.
Published: September 2013

All of the great apes build nests, but captive chimpanzees rarely have vegetation from which to build nests. The forested environment at Chimp Haven does allow captive chimpanzees to build nests of natural vegetation. Between February 2007 and December 2010, 238 nests were found in 2 forested habitats. Nests were made of naturally available vegetation, and more nests were made on the ground than in the trees (Z = 7.27, p < 0.001); nests were also built in the interior forest rather than on the periphery (Z = 7.06, p < 0.001). There was no correlation between the number of months in the habitat and the nests built per chimpanzee (rs= -0.07, p = 0.52). More nests were observed when more wild-born females were in the group (rs= 0.27, p = 0.01), and during warmer temperatures (rs= 0.45, p < 0.001). These findings support the goal of naturalistic environments in suitable climates for captive chimpanzees.
Nerve Fiber Layer Thickness in Eyes Treated with Red versus Green Laser in Proliferative Diabetic Retinopathy: Short-Term Results
Authors: Ghassemi Fariba , Ebrahimiadib Nazanin , Roohipoor Ramak , Moghimi Sasan , Alipour Fateme
Published: September 2013

Purpose: To evaluate changes of retinal nerve fiber layer (RNFL) thickness after panretinal photocoagulation (PRP) in red versus green laser-treated eyes. Procedure: This is a prospective, randomized, fellow-eye controlled clinical trial conducted on 60 eyes of 30 patients (mean age 52.3 ± 7.8 years; 57% male) with early- to high-risk proliferative diabetic retinopathy type II diabetes who received standard red or green laser treatment. Scanning laser polarimetry (GDx) was performed to evaluate RNFL thickness at baseline and at week 6. Results: Only 22 patients (44 eyes) could perform reliable GDx tests. At week 6 after PRP, the RNFL thickness increased by an average of 3.35 ± 9.18 µm (p = 0.02) and 2.08 ± 4.75 µm (p = 0.04) in the red and green laser groups, respectively. There was no significant correlation between changes in RNFL thickness and the number of laser burns, age, HbA1c or blood pressure. The difference in the change of the RNFL thickness between the red and green laser groups was not significant (p = 0.8). Conclusion: Though RNFL thickness was increased significantly 6 weeks after PRP with red and green laser in comparison to baseline, there was no significant difference in RNFL thickness between red and green laser groups.
The G Protein-Coupled Estrogen Receptor 1 (GPER1/GPR30) Agonist G-1 Regulates Vascular Smooth Muscle Cell Ca2+ Handling
Authors: Holm Anders , Hellstrand Per , Olde Björn , Svensson Daniel , Leeb-Lundberg L.M. Fredrik , Nilsson Bengt-Olof
Published: September 2013

The G protein-coupled estrogen receptor GPER1/GPR30 is implicated in blood pressure regulation but the mechanisms are not identified. Here, we hypothesize that GPER1 controls blood pressure by regulating vascular smooth muscle cell Ca2+ handling. Treatment with the GPER1 agonist G-1 (in the µM concentration range) acutely reduced spontaneous and synchronous Ca2+ spike activity in A7r5 vascular smooth muscle cells expressing mRNA for GPER1. Furthermore, G-1 (1 µM) attenuated the thromboxane A2 analogue U46619-stimulated Ca2+ spike activity but had no effect on the U46619-induced increase in the basal level of Ca2+. The voltage-sensitive L-type Ca2+ channel blocker nifedipine (100 nM) reduced Ca2+ spike activity similar to G-1. Pharmacological, but not physiological, concentrations of the estrogen 17β-estradiol reduced Ca2+ spike activity. The GPER1 antagonist G-15 blocked G-1-induced downregulation of Ca2+ spike activity, supporting a GPER1-dependent mechanism. G-1 (1 µM) and nifedipine (100 nM) attenuated the 30-mM KCl-evoked rise in intracellular Ca2+ concentration, suggesting that G-1 blocks inflow of Ca2+ via voltage-sensitive Ca2+ channels. In conclusion, we demonstrate that the GPER1 agonist G-1 regulates vascular smooth muscle cell Ca2+ handling by lowering Ca2+ spike activity, suggesting a role for this mechanism in GPER1-mediated control of blood pressure.
Genetic Association with Response to Intravitreal Ranibizumab for Neovascular Age-Related Macular Degeneration in the Han Chinese Population
Authors: Yuan Dongqing , Yuan Donglan , Liu Xiaoyi , Yuan Songtao , Xie Ping , Liu Qinghuai
Published: September 2013

Purpose: To investigate a possible association between gene variants and patient response to treatment with intravitreal ranibizumab for neovascular age-related macular degeneration (AMD). Methods: Visual acuity score (VAS) was recorded at baseline and a subsequent visit at 6 months. Genotypes of 3 polymorphisms in known AMD susceptibility loci (rs1061170 in complement factor H (CFH), rs11200638 in HTRA1 and rs1413711 in VEGF) were determined. Central retinal thickness and maximum thickness of the lesion were also measured. Results: A total of 168 neovascular AMD patients treated with intravitreal ranibizumab were included in our study. For HTRA1 rs11200638, mean VAS changes were 3.5, 9.4 and 10.6 letters for the AA, AG and GG genotypes, respectively (p = 0.022). In contrast, for CFH rs1061170 and VEGF rs1413711, mean VAS changes were not significant. However, there was no significant difference in the changes in central retinal thickness and maximum lesion thickness among the genotypes of the tested single-nucleotide polymorphisms. Conclusions: HTRA1 gene polymorphism may influence patient response to treatment with intravitreal ranibizumab for neovascular AMD.
Increased Thin-Cap Neoatheroma and Periprocedural Myocardial Infarction in Drug-Eluting Stent Restenosis
Authors: Ali Ziad A. , Roleder Tomasz , Narula Jagat , Mohanty Bibhu D. , Baber Usman , Kovacic Jason C. , Mintz Gary S. , Otsuka Fumiyuki , Pan Stephen , Virmani Renu , Sharma Samin K. , Moreno Pedro , Kini Annapoorna S.
Published: September 2013

Background—

Re-endothelialization is delayed after drug-eluting stent (DES) implantation. In this setting, neointima is more prone to become lipid laden and develop neoatherosclerosis (NA), potentially increasing plaque vulnerability.

Methods and Results—

Optical coherence tomography and near-infrared spectroscopy with intravascular ultrasound were used to characterize NA in 65 (51 DES and 14 bare-metal stents) consecutive symptomatic patients with in-stent restenosis. Median duration poststent implantation was 33 months. Optical coherence tomography–verified NA was observed in 40 stents with in-stent restenosis (62%), was more prevalent in DES than bare-metal stents (68% versus 36%;
P
=0.02), and demonstrated significantly higher prevalence of thin-cap neoatheroma (47% versus 7%;
P
=0.01) in DES. Near-infrared spectroscopy assessment demonstrated that the total lipid core burden index (34 [interquartile range, 12–92] versus 9 [interquartile range, 0–32];
P
<0.001) and the density of lipid core burden index (lipid core burden index/4 mm, 144 [interquartile range, 60–285] versus 26 [interquartile range, 0–86];
P
<0.001) were higher in DES compared with bare-metal stents. Topographically, NA was classified as I (thin-cap NA), II (thick-cap NA), and III (peri-strut NA). Type I thin-cap neoatheroma was more common in DES (20% versus 3%;
P
=0.01) and in areas of the stented segment without significant in-stent restenosis (71%). Periprocedural myocardial infarction occurred only in DES (11 versus 0;
P
=0.05), of which 6 (55%) could be attributed to segments with >70% in-stent restenosis. By logistic regression, prior DES was the only independent predictor of both NA (odds ratio, 7.0; 95% confidence interval, 1.7–27;
P
=0.006) and periprocedural myocardial infarction (odds ratio, 1.8; 95% confidence interval, 1.1–2.4;
P
=0.05).

Conclusions—

In-stent thin-cap neoatheroma is more prevalent, is distributed more diffusely across the stented segment, and is associated with increased periprocedural myocardial infarction in DES compared with bare-metal stents. These findings support NA as a mechanism for late DES failure.
Long-Term Effects of AAV1/SERCA2a Gene Transfer in Patients With Severe Heart Failure
Authors: Zsebo Krisztina , Yaroshinsky Alex , Rudy Jeffrey J. , Wagner Kim , Greenberg Barry , Jessup Mariell , Hajjar Roger J.
Published: September 2013

Rationale:

The Calcium Up-Regulation by Percutaneous Administration of Gene Therapy In Cardiac Disease (CUPID 1) study was a phase 1/phase 2 first-in-human clinical gene therapy trial using an adeno-associated virus serotype 1 (AAV1) vector carrying the sarcoplasmic reticulum calcium ATPase gene (AAV1/SERCA2a) in patients with advanced heart failure. The study explored potential benefits of the therapy at 12 months, and results were previously reported.

Objective:

To report long-term (3-year) clinical effects and transgene expression in the patients in CUPID 1.

Methods and Results:

A total of 39 patients with advanced heart failure who were on stable, optimal heart failure therapy were randomized to receive intracoronary infusion of AAV1/SERCA2a in 1 of 3 doses (low-dose, 6×10
11
DNase-resistant particles; mid-dose, 3×10
12
DNase-resistant particles; and high-dose, 1×10
13
DNase-resistant particles) versus placebo. The following recurrent cardiovascular and terminal events were tracked for 3 years in all groups: myocardial infarction, worsening heart failure, heart failure–related hospitalization, ventricular assist device placement, cardiac transplantation, and death. The number of cardiovascular events, including death, was highest in the placebo group, high but delayed in the low- and mid-dose groups, and lowest in the high-dose group. Evidence of long-term transgene presence was also observed in high-dose patients. The risk of prespecified recurrent cardiovascular events was reduced by 82% in the high-dose versus placebo group (
P
=0.048). No safety concerns were noted during the 3-year follow-up.

Conclusions:

After a single intracoronary infusion of AAV1/SERCA2a in patients with advanced heart failure, positive signals of cardiovascular events persist for years.
Physiological and Phenotypic Characteristics of Late Survivors of Tetralogy of Fallot Repair Who Are Free From Pulmonary Valve Replacement
Authors: Frigiola Alessandra , Hughes Marina , Turner Mark , Taylor Andrew , Marek Jan , Giardini Alessandro , Hsia Tain-Yen , Bull Kate
Published: September 2013

Background—

Pulmonary valve replacement (PVR) after repair of tetralogy of Fallot is commonly required and is burdensome. Detailed anatomic and physiologic characteristics of survivors free from late PVR and with good exercise capacity are not well described in a literature focusing on the indications for PVR.

Methods and Results—

Survival and freedom from PVR were tracked in 1085 consecutive patients receiving standard tetralogy of Fallot repair in a single institution from 1964 to 2009. Of 152 total deaths, 100 occurred within the first postoperative year. Surviving patients between 10 and 50 years of age had an annual risk of death of 4 (confidence limit, 2.8–5.4) times that of normal contemporaries. To date, 189 patients have undergone secondary PVR at mean age of 20±13 years (36% of those alive at 40 years of age). A random sample of 50 survivors (age, 4–57 years) free from PVR underwent cardiovascular magnetic resonance, echocardiography, and exercise testing. These patients had mildly dilated right ventricles (right ventricular end-diastolic volume=101±26 mL/m
2
) with good systolic function (right ventricular ejection fraction=59±7%). Most had exercise capacity within normal range (
z
peak

o
2
=−0.91±1.3;
z

e
/

co
2
=0.20±1.5). In patients >35 years of age with normal exercise capacity, there was mild residual right ventricular outflow tract obstruction (mean gradient, 24±13 mm Hg), pulmonary annulus diameters <0.5
z
, and unobstructed branch pulmonary arteries.

Conclusions—

An important proportion of patients require PVR late after tetralogy of Fallot repair. Patients surviving to 35 years of age without PVR and with a normal exercise capacity may have had a definitive primary repair; their right ventricular outflow tracts are characterized by mild residual obstruction and pulmonary annulus diameter <0.5
z
.
Presentness in Displaced Sound
Authors: Harris Yolande
Published: September 2013

The author discusses her works that explore sound's influence on creating a sense of presentness and her aim to increase the audience's awareness of this influence.
Sounds in Your Pocket: Composing Live Soundscapes with an App
Authors: van Rijswijk Rob , Strijbos Jeroen
Published: September 2013

The authors present their musical smartphone app that uses GPS data to trigger specific sound events relative to spots within an area predetermined by the artists. Moving through the area, users listen to these events via headphones, completing the soundscape composition. The article outlines the effects and the workings of the app, which combines elements of composition and installation, and which the artists have so far adapted to a number of different areas.