bluuebunny/crossref_metadata_2025 huggingface dataset:
Corrosion Studies of Austenitic and Ferritic Stainless Steels in Solution Containing Chloride Ions
Authors: Soares Thiago Freitas , Moreira Roberta Rossi , de Andrade Adalgisa Rodrigues , Ribeiro Josimar
Published: October 2014

This paper investigated the corrosion behavior of AISI 304 and AISI 430 stainless steels in 3.0 wt. % NaCl solutions in both the presence and absence of pyridine or benzimidazole as inhibitor. The electrochemical study was performed using the polarization technique. Electrode surface morphology was characterized by Atomic Force Microscopy (AFM) and Scanning Electron Microscopy (SEM). The inhibition efficiency was evaluated at six different inhibitor concentrations (5, 25, 50, 100, 500, and 1000 ppm). The corrosion potential increased at all concentrations. For both alloys AFM showed that the average pit depth obtained in the presence of inhibitor was at least four times smaller than the values obtained in the absence of inhibitor.
Site-Selective Deposition of Ordered Intermetallic PtPb Nanoparticle Co-Catalysts on WO3 Surfaces to Enhance Photocatalytic Activity
Authors: Gunji Takao , Tsuda Takashi , Jeevagan Arockiam John , Hashimoto Masanari , Kaneko Shingo , Tanabe Toyokazu , Matsumoto Futoshi
Published: October 2014

The site-selective deposition of PtPb nanoparticles (PtPb NPs) on oxidation sites and of Pt NPs on reduction sites as co-catalysts was attempted on tungsten oxide (WO3) using a photodeposition reaction and the chemical reduction of Pt and Pb precursors for photoexcited electrons and holes to be efficiently consumed without the recombination of photogenerated carriers during the photochemical decomposition of acetic acid (AcOH). The synthesized PtPb/Pt/WO3 exhibited higher photocatalytic performance for the decomposition of AcOH under visible light irradiation (λ > 420 nm) than that observed using the conventional photodeposited Pt/WO3 or chemically deposited PtPb/WO3. The results of this study highlight the importance of controlling the deposition site for co-catalysts on photocatalyst surfaces.
Photocatalytic Activity of Pt3Ti/WO3 Photocatalyst under Visible-Light Irradiation
Authors: Hashimoto Masanari , Gunji Takao , Jeevagan Arockiam John , Tanabe Toyokazu , Tsuda Takashi , Kaneko Shingo , Miyauchi Masahiro , Matsumoto Futoshi
Published: October 2014

We have prepared Pt-Ti nanoparticles (NPs) loaded tungsten oxide (WO3) composites by hand grinding of WO3 powder with chemically prepared Pt-Ti NPs. The Pt-Ti/WO3 composites exhibited higher efficiency for the decomposition of acetic acid (AcOH) and acetaldehyde (AcH) under visible light irradiation (λ > 420 nm) than that of the composite prepared using WO3 and the conventional cocatalyst of Pt NPs. The higher photocatalytic activity of the composites could be attributed to the efficient oxidative decomposition of organic compounds and/or reduction of O2 on the Pt-Ti NPs surface.
Electromigration Reliability of Passivated Gold Interconnects for GaAs Devices
Authors: Kilgore Steve
Published: October 2014

The electromigration lifetimes of a very large quantity of passivated electroplated Au interconnects were measured utilizing high resolution in-situ resistance monitoring equipment. Application of moderate accelerated stress conditions with current density limited to 2 MA/cm2 and oven temperatures in the range of 300°C to 375°C avoided large Joule-heated temperature gradients and electrical overstress failures. A maximum Joule-heated Au film temperature of 12°C was determined from measured temperature coefficients of resistance (TCRs). All Au interconnect lifetime distributions followed log-normal statistics. An activation energy of 0.80 ± 0.05 eV was measured from constant-current electromigration tests at multiple temperatures. A current density exponent of 1.91 ± 0.03 was extracted from multiple current densities at a single constant temperature. These electromigration model parameters correlate with the observed Au interconnect failure mechanism.
Phase-Field Simulations of Solid Electrolyte Interface Morphology Evolution
Authors: Guan Pengjian , Lin Xianke , Liu Lin
Published: October 2014

Solid electrolyte interface (SEI) layer morphology evolution has not yet been fully understood. A phase field model was employed and developed to simulate the SEI formation, growth and morphology evolution. SEI layer involves many boundaries formation and evolution among reaction products and their phase dynamic boundaries (interfaces). The phase field model can investigate phase boundaries without explicitly tracking the interfaces with sharp composition gradients. It also reveals the profiles of chemical potential and velocity in the electrolyte/SEI interfacial region. Most important, the present dveloped model has great potential to be extended to three dimensional space for SEI layer spatial growth inverstigation. In addition, other interfacial problems with more complex morphology evolution may also be investigated by the developed phase field model.
Electrolyte Optimization of a Substituted-LiCo1-xFexPO4 Cathode
Authors: Allen Joshua L. , Allen Jan L. , Delp Samuel A. , Jow T. Richard
Published: October 2014

Lithium cobalt phosphate (LiCoPO4) is an attractive cathode material due to its high discharge potential (4.8 V vs. Li/Li+) and specific capacity (167 mAh g-1), resulting in an impressive specific energy of ~802 Wh kg-1. The development of LCP has proven difficult owing to the instability of the electrode and the tendency of the electrolyte to perpetually decompose (oxidize), leading to a highly resistive passivation layer. In this report, a substituted lithium cobalt iron phosphate (s-LiCo1-xFexPO4 or s-LCFP) cathode material was tested with various solvents and additives to find an optimized electrolyte that limits electrode polarization and improves cycle life. The s-LCFP cathode performed best with a 1M LiPF6 solution of EC/EMC (3/7 wt%) with 2% of additive ARL1. Comparing ARL1 to the baseline electrolyte, the fade rate was reduced from 0.014% per cycle to 0.005% per cycle and the shift in charge voltage (due to polarization) was reduced from 39mV to 19mV through 50 cycles.
Performances of Lithium-Ion Cells Constituted of NMC // LTO Electrodes and Ionic Liquid or Carbonates-Based Electrolytes
Authors: Chancelier Léa , Santini Catherine C. , Gutel Thibaut , Mailley Sophie
Published: October 2014

Commercial lithium-ion batteries could lead to safety issues related to the use of flammable carbonates as electrolyte solvents. To provide safer cells, ionic liquids are widely studied as they possess negligible vapour pressure and reduced flammability. This paper presents a comparison between carbonates and ionic liquid-based electrolytes, comprising bis(trifluoromethanesulfonyl)imide [NTf2] anion and imidazolium [Im] or pyrrolidinium [PYR] cations. Lithium-ion cells constituted of Li4Ti5O12 (LTO) and LiNi1/3Mn1/3Co1/3O2 (NMC) electrodes were assembled and cycled at 25 and 60 °C with these different electrolytes. These systems were investigated by cyclic voltammetry (CV) and electrochemical cycling. Diffusion coefficients of lithium ions were also determined by CV techniques and by liquid NMR.
Identification of the Parameters in Equivalent Circuit Model of Lithium-Ion Batteries
Authors: Chang Meng-Ting , Lin Yang-Shan , Ling Shou-Hong , Liang SHI-Hao , Lin Chi-Hao , Chen Kuo-Ching
Published: October 2014

A typical impedance spectrum of the lithium-ion cell is composed of two partially overlapped semicircles and a straight line at low frequency end. The overlapped semicircles make the parameters of the two RC circuit in equivalent circuit model of lithium-ion battery hard to be discriminated. To correctly obtain the parameters of the two RC circuit, it is necessary to find a method to distinguish Rct
from R
sei. It is found that the charge transfer resistance Rct
can be determined from the expression, R
ct=RT/nFi
0
, where the exchange current density i
0 is evaluated by the electrochemical model simulation, and R and T respectively denote the gas constant and the Kelvin temperature. As soon as R
ct is achieved, the curve fitting of the impedance spectrum helps us to obtain the other seven parameters.
Extended Electrochemical Reliability Study of All-Solid-State Thin Film Microbatteries
Authors: Grillon Nathanaël , Bouyssou Emilien , Fabre Steve Dimitri , Lestriez Bernard , Guyomard Dominique , Jacques Sébastien , Gautier Gaël
Published: October 2014

The long-term reliability of all-solid-state thin film microbatteries was studied through a deepened electrical characterization of the solid interfaces. After 1,500 cycles, the cells cycled at 60°C showed few changes of the intrinsic parameters at the interfaces of the active layers from the electrochemical stack. Through the implementation of an extended experimental approach incorporating impedance spectroscopy measurements from 1 MHz to 200 mHz, coupled to an equivalent electrical model, charge transfer resistances and exchange currents densities were extracted. The study highlights the reliability performances of the EnFilm™ HiCap microbattery technology. The results were confirmed through the experimental behavior study, the electrochemical integrity of EnFilm™ HiCap technology is preserved in use. Devoid of Solid Electrolyte Interface (SEI) typical of conventional liquid electrolyte Li-ion systems, all-solid-state microbatteries therefore present physical characteristics of good reliability performances.
Post-Test Analysis of Battery Materials: Another Part of the Question
Authors: Bloom Ira , Rago Nancy Dietz , Jansen Andrew N. , Polzin Bryant J , Trask Steve E , Bareno Javier
Published: October 2014

Post-test analyses of cells consisting of a layered-layered cathode, a graphite anode and an organic carbonate-based electrolyte were performed. Many changes in the cell components were visible. Gas analysis revealed possible evidence of oxygen evolution from cathode and electrolyte degradation, including likely reaction products between electrolyte solvents and salt or binder. The anode surface was highly inhomogeneous and was comprised of a surface film of varying thickness, white precipitates, and dendritic growth of metallic Li and/or deliquescent salts. Manganese was incorporated into the anode and P, C, and O were preferentially incorporated into some areas of the anode surface. Analysis of the composition of the SEI layer shows that, unsurprisingly, it was complex.
Improved Parameterization of an Ethylene Carbonate Molecular Dynamics Model in Li-Air Batteries for Accurate Density and Transition Temperatures
Authors: Ward Donald , Jones Reese , Templeton Jeremy , Reyes Karla , Kane Marie
Published: October 2014

Li-air batteries are at the forefront of advanced battery technologies because of their tremendous theoretical energy density. However, before reaching this potential several technical issues must be understood including optimal electrolytes for Li+ transport. With a vast library of potential electrolytes it is highly impractical to test all materials. Fortunately, atomistic models can assist in selecting optimal electrolyte candidates and thus decrease experimental time. In order for such models to effectively screen electrolyte materials, an interatomic potential must accurately reproduce relevant material properties such as density, viscosity, and transition temperatures. This work presents an approach to calibrate molecular dynamics models to capture these quantities. As a case study we explore the ability of an interatomic potential to correctly predict the transition temperature of ethylene-propylene carbonate mixtures. Here, we modify an available CHARMM potential parameterization to correctly reproduce the relative transition temperatures by modifying the long-range interactions between molecules. In doing this, we can improve the predicted transport properties of carbonate electrolytes which affect battery performance.
Construction of All-Solid-State Nickel-Zinc Rechargeable Cell with Hybrid Hydrogel Electrolyte
Authors: Inoue Hiroshi , Tomita Shoji , Higuchi Eiji , Tsai Jie-Shen , Chiku Masanobu
Published: October 2014

Organic-inorganic hybrid hydrogel electrolyte with ionic conductivity and electrochemical window comparable to the corresponding electrolyte solution was used for assembling an all solid-state rechargeable Ni-Zn cell. The all solid-state rechargeable Ni-Zn cell was superior in charge-discharge performance to the conventional Ni-Zn cell when the distance between the positive and negative electrodes became shorter. Charge retention at the first cycle of this cell was almost 100% even at 2 C discharge rate, but discharge capacity was decreased with repeating charge-discharge cycle.
Tailoring Porphyrin (Nano)Structures
Authors: Ryan Aoife A. , Letchford Kristie A. , Senge Mathias O.
Published: October 2014

Porphyrins present one of the most ubiquitous classes of compounds in chemistry, optics, medicine, and materials science. This is a result of their multifaceted roles in nature and the wide range of tunable molecular properties. Further advances in translational research and a more detailed understanding of their biological function require a specific tailoring of the macrocycle to the desired task. Using examples from our own research we illustrate how a targeted molecular design combining the aspects of conformational flexibility with rational chemical synthesis in porphyrins can be used to advance our knowledge of cofactor function and to develop novel and highly efficient materials.
Microwave-Assisted Hydrothermal Synthesis of NiO-Ce1-XEuxO2-δ Powders for Fuel Cell Catalytic Anodes
Authors: Medeiros Amanda Lucena de , Martinelli Antonio Eduardo , Melo Dulce Maria de Araujo , Orlandi Marcelo Ornaghi , Macedo Daniel Araujo
Published: October 2014

CeO2-based materials doped with rare earth (TR +3) can be used as alternative to traditional NiO-YSZ anodes in solid oxide fuel cells as they have higher ionic conductivity and lower ohmic losses compared to YSZ. Moreover, they allow fuel cell operation at lower temperatures (500-800°C). In the anode composition, the concentration of NiO acting as catalyst in YSZ provides high electrical conductivity and high electrochemical activity of reactions, promoting internal reform in the cell. In this work, NiO - Ce1-xEuxO2-δ compounds (x = 0.1, 0.2 and 0.3) have been synthesized by microwave-assisted hydrothermal method. The materials were characterized by TG, XRD, TPR and SEM-FEG techniques. The refinement of data obtained by X-ray diffraction showed the presence of ceria doped with europium crystallized in a cubic phase with fluorite structure, in addition to the presence of NiO. The microwave-assisted hydrothermal method showed significant reduction in the average particle size and good mass control of phase compositions compared to other chemical synthesis techniques.
Examining the Cellular Uptake and Toxicity of Engineered Nanomaterials
Authors: Kosaraju Karshak , Tarannum Mubin , Crawford Steven , Garde Komal , Aravamudhan Shyam
Published: October 2014

Engineered Nanomaterials (ENs) such as silica, ceria and alumina nanoparticles have been extensively used in health care, energy and electronics. However, their toxicity and cellular uptake, which are strongly dependent on their physiochemical properties and on cell interaction, are largely unknown. The objective of this work is to study and quantify the cellular uptake of silica, ceria and alumina ENs. First, comprehensive characterization using DLS, zeta potential, BET, XRD, FTIR, Raman, SEM and TEM was done. Then, cell exposure studies were carried out on A549 lung epithetical cells to study cell viability and membrane integrity. Lastly, cellular uptake of ENs was studied by using techniques such as Confocal Raman Spectroscopy and ICP-OES and Electrochemical Cell-substrate Impedance Sensing (ECIS). ICP-OES analysis showed uptake of silica, ceria and alumina, while Confocal Raman indicated the uptake of Ceria ENs. Time-course effects of EN on A549 cells were studied using ECIS measurements.
SIM2 maintains innate host defense of the small intestine
Authors: Chen Kuan-Jung , Lizaso Analyn , Lee Ying-Hue
Published: October 2014

The single-minded 2 (SIM2) protein is a basic helix-loop-helix transcription factor regulating central nervous system (CNS) development in Drosophila. In humans, SIM2 is located within the Down syndrome critical region on chromosome 21 and may be involved in the development of mental retardation phenotype in Down syndrome. In this study, knockout of SIM2 expression in mice resulted in a gas distention phenotype in the gastrointestinal tract. We found that SIM2 is required for the expression of all cryptdins and numerous other antimicrobial peptides (AMPs) expressed in the small intestine. The mechanism underlying how SIM2 controls AMP expression involves both direct and indirect regulations. For the cryptdin genes, SIM2 regulates their expression by modulating transcription factor 7-like 2, a crucial regulator in the Wnt/β-catenin signaling pathway, while for other AMP genes, such as RegIIIγ, SIM2 directly activates their promoter activity. Our results establish that SIM2 is a crucial regulator in controlling expression of intestinal AMPs to maintain intestinal innate immunity against microbes.
Retention and interference of learned dexterous manipulation: interaction between multiple sensorimotor processes
Authors: Fu Qiushi , Santello Marco
Published: October 2014

An object can be used in multiple contexts, each requiring different hand actions. How the central nervous system builds and maintains memory of such dexterous manipulations remains unclear. We conducted experiments in which human subjects had to learn and recall manipulations performed in two contexts, A and B. Both contexts involved lifting the same L-shaped object whose geometry cued its asymmetrical mass distribution. Correct performance required producing a torque on the vertical handle at object lift onset to prevent it from tilting. The torque direction depended on the context, i.e., object orientation, which was changed by 180° object rotation about a vertical axis. With an A1B1A2 context switching paradigm, subjects learned A1 in the first block of eight trials as indicated by a torque approaching the required one. However, subjects made large errors in anticipating the required torque when switching to B1 immediately after A1 (negative transfer), as well as when they had to recall A1 when switching to A2 after learning B through another block of eight lifts (retrieval interference). Classic sensorimotor learning theories attribute such interferences to multi-rate, multi-state error-driven updates of internal models. However, by systematically changing the interblock break duration and within-block number of trials, our results suggest an alternative explanation underlying interference and retention of dexterous manipulation. Specifically, we identified and quantified through a novel computational model the nonlinear interaction between two sensorimotor mechanisms: a short-lived, context-independent, use-dependent sensorimotor memory and a context-sensitive, error-based learning process.
Background complexity affects response of a looming-sensitive neuron to object motion
Authors: Silva Ana C. , McMillan Glyn A. , Santos Cristina P. , Gray John R.
Published: October 2014

An increasing number of studies show how stimulus complexity affects the responses of looming-sensitive neurons across multiple animal taxa. Locusts contain a well-described, descending motion-sensitive pathway that is preferentially looming sensitive. However, the lobula giant movement detector/descending contralateral movement detector (LGMD/DCMD) pathway responds to more than simple objects approaching at constant, predictable trajectories. In this study, we presented Locusta migratoria with a series of complex three-dimensional visual stimuli presented while simultaneously recording DCMD activity extracellularly. In addition to a frontal looming stimulus, we used a combination of compound trajectories (nonlooming transitioning to looming) presented at different velocities and onto a simple, scattered, or progressive flow field background. Regardless of stimulus background, DCMD responses to looming were characteristic and related to previously described effects of azimuthal approach angle and velocity of object expansion. However, increasing background complexity caused reduced firing rates, delayed peaks, shorter rise phases, and longer fall phases. DCMD responded to transitions to looming with a characteristic drop in a firing rate that was relatively invariant across most stimulus combinations and occurred regardless of stimulus background. Spike numbers were higher in the presence of the scattered background and reduced in the flow field background. We show that DCMD response time to a transition depends on unique expansion parameters of the moving stimulus irrespective of background complexity. Our results show how background complexity shapes DCMD responses to looming stimuli, which is explained within a behavioral context.
Effect of Formalin Fixation on Surgical Margins in Breast Cancer Surgical Specimen
Authors: Zaidi Masooma , Khan Shaista , Farooqi Najiha Bilal , Abbas Kashif , Idrees Romana
Published: October 2014

Margin analysis in breast surgery is an important predictor of local recurrence and can have vital impact on the postoperative treatment planning.Objective. The aim was to assess the mean reduction in the closest tumor-free surgical margin in millimeters of breast cancer specimens following formalin fixation.Materials and Methods. We conducted a cross-sectional study at the Aga Khan University Hospital from March 30, 2010 to January 20, 2011. One hundred consecutive breast tumour surgical specimens which had macroscopically visible tumour were included. The cancer type included both in situ and invasive cancers. Excluded were the patients who had previous surgery or systemic/radiation therapy. The closest tumor-free margin was recorded and compared with the margin after formalin fixation.Pvalue of <0.05 was considered significant.Results. The mean age of our 100 patients was 53 years with the majority of the patients having undergone mastectomy for predominantly invasive ductal carcinoma. Following formalin fixation, the mean reduction of the closest tumor-free margin was noted as 2.14 mm which was found statistically significant.Conclusion. Considerable shrinkage of tumor-free surgical margins of breast cancer specimen was noted after formalin fixation. This inference can have implications on the postoperative management plan.
The Evaluation of Various Restoration Techniques on Internal Adaptation of Composites in Class V Cavities
Authors: Dionysopoulos D. , Papadopoulos C. , Koliniotou-Koumpia E.
Published: October 2014

Aim.The aim of this study was to evaluate the effect of different restoration techniques on the formation of internal microgaps between materials and dentin in class V restorations.Materials and Methods.Twenty-five extracted human premolars were prepared with standardized class V cavity outlines (3 mm × 2 mm × 2 mm). The cavities were randomly divided into 5 groups of 10 cavities each and restored according to manufacturer’s instructions: Group 1: preheating (55°C) conventional composite (Filtek Z250), Group 2: flowable composite (Filtek Flow), Group 3: Filtek Flow + Filtek Z250 light-cured separately, Group 4: Filtek Flow + Filtek Z250 light-cured simultaneously, and Group 5 (control): Filtek Z250 at room temperature (23°C). The specimens were then thermocycled and cross-sectioned through the center of the restoration. Subsequently, impressions were taken, and epoxy resin replicas were made. The internal adaptation of the materials to the axial wall was analyzed under SEM.Results.The preheated Filtek Z250 (Group 1) showed better internal adaptation than the room temperature groups(P<0.05). The combination of Filtek Flow with Filtek Z250 which was light-cured separately (Group 3) exhibited better internal adaptation than control group(P<0.05).Conclusion.Different restoration techniques exhibit different behavior regarding internal adaptation to dentin after photopolymerization.
Differences inIn VitroDisintegration Time among Canadian Brand and Generic Bisphosphonates
Authors: Olszynski Wojciech P. , Adachi Jonathan D. , Davison K. Shawn
Published: October 2014

The objective of this study was to compare the disintegration times among Canadian-marketed brand (alendronate 70 mg, alendronate 70 mg plus vitamin D 5600 IU, and risedronate 35 mg) and generic (Novo-alendronate 70 mg and Apo-alendronate 70 mg) once-weekly dosed bisphosphonates. All disintegration tests were performed with a Vanderkamp Disintegration Tester. Disintegration was deemed to have occurred when no residue of the tablet, except fragments of insoluble coating or capsule shell, was visible. Eighteen to 20 samples were tested for each bisphosphonate group. The mean (±standard deviation) disintegration times were significantlyP<0.05faster for Apo-alendronate (26±5.6seconds) and Novo-alendronate (13±1.1seconds) as compared to brand alendronate (147±50.5seconds), brand alendronate plus vitamin D (378±60.5seconds), or brand risedronate (101±20.6seconds). The significantly faster disintegration of the generic tablets as compared to the brand bisphosphonates may have concerning safety and effectiveness implications for patients administering these therapies.
Tumor-Derived Osteopontin Suppresses Antitumor Immunity by Promoting Extramedullary Myelopoiesis
Authors: Kim Eun-Kyung , Jeon Insu , Seo Hyungseok , Park Young-Jun , Song Boyeong , Lee Kyoo-A , Jang Yongwoo , Chung Yeonseok , Kang Chang-Yuil
Published: October 2014

Extramedullary myelopoiesis occurs commonly in tumor-bearing animals and is known to lead to accumulation of peripheral myeloid-derived suppressor cells (MDSC), which play an important role in immune escape. However, the cellular and molecular mechanisms by which tumors induce extramedullary myelopoiesis are poorly understood. In this study, we found that osteopontin expressed by tumor cells enhances extramedullary myelopoiesis in a CD44-dependent manner through the Erk1/2–MAPK pathway. Osteopontin-mediated extramedullary myelopoiesis was directly associated with increased MDSCs in tumor-bearing hosts. More importantly, osteopontin silencing in tumor cells delayed both tumor growth and extramedullary myelopoiesis, while the same treatment did not affect tumor growth in vitro. Finally, treatment with an antibody against osteopontin inhibited tumor growth and synergized with cell-based immunotherapeutic vaccines in mediating antitumor immunity. Our findings unveil a novel immunosuppressive role for tumor-derived osteopontin and offer a rationale for its therapeutic targeting in cancer treatment. Cancer Res; 74(22); 6705–16. ©2014 AACR.
Evaluation of Human Papillomavirus Type Replacement Postvaccination Must Account for Diagnostic Artifacts: Masking of HPV52 by HPV16 in Anogenital Specimens
Authors: Tota Joseph E. , Ramanakumar Agnihotram V. , Villa Luisa L. , Richardson Harriet , Burchell Ann N. , Koushik Anita , Mayrand Marie-Hélène , Coutlée François , Franco Eduardo L.
Published: October 2014

It has been hypothesized that, following a reduction in human papillomavirus (HPV) vaccine–targeted genotypes, an increase in prevalence of other HPV types may occur due to reduced competition during natural infection. Any apparent postvaccination increase must be distinguished from diagnostic artifacts consequent to consensus PCR assays failing to detect HPV types present in low copy numbers in coinfected specimens (under the assumption that with a drop in vaccine-preventable types there may be increased detection of previously “masked” types). We reanalyzed anogenital specimens to evaluate unmasking of HPV52 that may be caused by elimination of HPV16. Using highly sensitive type-specific real-time HPV52 PCR, we retested 1,200 anogenital specimens (all HPV52 negative according to consensus PCR assays) from six epidemiologic studies (200 specimens/study; 100 HPV16+/study). Multivariate logistic regression, with adjustment for age and number of sexual partners, was used to evaluate the association between HPV16 positivity and detection of HPV52. In our pooled analysis (n = 1,196), the presence of HPV16 was positively associated with HPV52 detection [adjusted OR, 1.47; 95% confidence interval (CI), 0.76–2.82]. In our separate (study specific) analyses, a statistically significant association was observed in one study that included HIV-infected males (HIPVIRG study; adjusted OR, 3.82; 95% CI, 1.19–12.26). We observed a positive association between HPV16 viral load (tertiles) and detection of HPV52 (P for trend = 0.003). These results indicate that diagnostic artifacts, resulting from unmasking of HPV52, may occur in some settings in the evaluation of HPV type replacement. Additional studies exploring the extent and severity of unmasking are needed. Cancer Epidemiol Biomarkers Prev; 24(1); 286–90. ©2014 AACR.
A Phase I, Dose-Escalation Study of the Multitargeted Receptor Tyrosine Kinase Inhibitor, Golvatinib, in Patients with Advanced Solid Tumors
Authors: Molife L. Rhoda , Dean Emma Jane , Blanco-Codesido Montserrat , Krebs Matthew G. , Brunetto Andre T. , Greystoke Alastair Peter , Daniele Gennaro , Lee Lucy , Kuznetsov Galina , Myint Khin Than , Wood Karen , de las Heras Begoña , Ranson Malcolm Richard
Published: October 2014

Purpose: Receptor tyrosine kinases c-Met and Ron transduce signals regulating cell migration and matrix invasion. This phase I dose-escalation trial tested golvatinib, a highly potent, small-molecule, ATP-competitive inhibitor of c-Met and multiple members of the Eph receptor family plus c-Kit and Ron.

Experimental Design: Patients with advanced solid tumors received golvatinib orally, once daily, continuously. Using a “3+3” design, dosing started at 100 mg once daily, escalating to the maximum tolerated dose (MTD) defined by dose-limiting toxicities. Pharmacokinetic, pharmacodynamic, and preliminary antitumor activity was assessed during dose escalation and in a MTD expansion cohort.

Results: Thirty-four patients were treated at six dose levels. The MTD was determined as 400 mg once daily. Three dose-limiting toxicities were observed: grade 3 increased γ-glutamyltransferase and alkaline phosphatase (200 mg), repeated grade 2 fatigue, and grade 3 fatigue (50.0%). Frequent treatment-related adverse events (with incidence >10%) included diarrhea (58.8%), nausea (50%), vomiting (44.1%), fatigue (41.2%), decreased appetite (32.4%), elevated alanine aminotransferase (32.4%), elevated aspartate aminotransferase (20.6%), dry skin (11.8%), and dysgeusia (11.8%). Best overall response was stable disease (median duration 85 days, range 85–237). Pharmacokinetics demonstrated high variability, although maximum plasma concentration and area under the plasma concentration–time curve increased with dose. Soluble urokinase-type plasminogen activator receptor, VEGFR2, c-Met, and angiopoietin-2 levels increased after dose. Posttreatment decrease in either p-c-Met or p-ERK was observed in 3 of 4 paired biopsies at MTD.

Conclusions: Golvatinib at the MTD of 400 mg once daily was well tolerated with pharmacodynamic evidence of c-Met target modulation. Clin Cancer Res; 20(24); 6284–94. ©2014 AACR.
Doxycycline as an Inhibitor of the Epithelial-to-Mesenchymal Transition and Vasculogenic Mimicry in Hepatocellular Carcinoma
Authors: Meng Jie , Sun Baocun , Zhao Xiulan , Zhang Danfang , Zhao Xueming , Gu Qiang , Dong Xueyi , Zhao Nan , Liu Peimei , Liu Yanrong
Published: October 2014

This study was conducted to examine the effects of doxycycline on the survival time and proliferation of hepatocellular carcinoma (HCC) in vivo and on the biologic functions of HCC in vitro. This study was also designed to evaluate the effects of doxycycline on epithelial-to-mesenchymal transition (EMT)– and vasculogenic mimicry (VM)–related protein expression and on matrix metalloproteinase (MMP) and DNA methyltransferase (DNMT) activity in vitro. Human MHCC97H cells were injected into BALB/c mice, which were divided into treatment and control groups. Doxycycline treatment prolonged the mouse survival time and partly suppressed the growth of engrafted HCC tumor cells, with an inhibition rate of 43.39%. Higher amounts of VM and endothelium-dependent vessels were found in the control group than the treatment group. IHC indicated that epithelial (E)-cadherin expression was increased in the doxycycline-treated mice compared with the control group. In in vitro experiments, doxycycline promoted HCC cell adhesion but inhibited HCC cell viability, proliferation, migration, and invasion. Western blot analysis, semiquantitative RT-PCR, qRT-PCR, and immunofluorescence demonstrated that doxycycline inhibited the degradation of the epithelial marker E-cadherin and downregulated the expression levels of EMT promoters, the mesenchymal marker vimentin, and the VM-associated marker vascular endothelial (VE)-cadherin. Furthermore, the activities of MMPs and DNMTs were examined in different groups via gelatin zymography and a DNMT activity assay kit. A methylation-specific PCR was performed to assess the promoter methylation of CDH1 (the gene encoding E-cadherin). Doxycycline prolonged the mouse survival time by inhibiting EMT progression and VM formation. Mol Cancer Ther; 13(12); 3107–22. ©2014 AACR.
The Path to Reactivation of Antitumor Immunity and Checkpoint Immunotherapy
Authors: Kim Hye-Jung , Cantor Harvey
Published: October 2014

Cancer immunology has recently made major therapeutic inroads that represent clinical application of basic insights into mechanisms that govern immunity against tumors. Research into fundamental elements of T-cell and natural killer–cell biology, including the basis of antigen recognition, activation, proliferation, and survival, has informed the design of new therapeutic approaches to augment the body's natural anticancer immune response. Here, we describe some of the key steps that have provided the foundation for current strategies of immunotherapy. Cancer Immunol Res; 2(10); 926–36. ©2014 AACR.
The Wage of Fame: How Non-Epistemic Motives Have Enabled the Phenomenal Success of Modern Science
Authors: Franck Georg
Published: October 2014

This paper ventures an economic view of modern science. It points out how science works as a closed economy of attention where researchers invest their own attention in order to get the attention of fellow researchers. Attention thus enters economy in two properties: (1) as a scarce resource energising scientific production and (2) as a means of gratification rewarding the effort of the working scientist. Economising on attention as a scarce resource is another expression of thought economy. The income of expert attention is what gives rise to reputation, renown, prominence and eventually fame. By its being conceived as a closed economy of attention, science shows to be capable of self-organising a tendency towards overall efficiency and thus towards collective rationality.
Are Respiratory Abnormalities Specific for Panic Disorder? A Meta-Analysis
Authors: Grassi Massimiliano , Caldirola Daniela , Di Chiaro Nunzia Valentina , Riva Alice , Daccò Silvia , Pompili Maurizio , Perna Giampaolo
Published: October 2014

Objectives: There is evidence of baseline respiratory abnormalities in panic disorder (PD), but whether they are specific to PD remains unclear. To investigate this issue, we meta-analyzed results from studies comparing baseline respiratory and hematic variables between subjects with PD and subjects with other anxiety disorders. Methods: A literature search in bibliographic databases was performed. Fixed-effects models were applied. Several moderator analyses and publication bias diagnostics were performed. Results: We found: (1) significantly lower mean end-tidal partial pressure of CO2 (et-pCO2) in subjects with PD than in those with social phobia (SP) or generalized anxiety disorder (GAD), and (2) higher mean respiratory rate, lower venous et-pCO2 and HCO3- concentration in subjects with PD than in those with SP. No publication bias was found. Conclusions: Subjects with PD show a condition of baseline hyperventilation when compared to subjects with SP or GAD. Hematic variables suggest that the hyperventilation may be chronic. These results support the idea that baseline respiratory abnormalities are specific to PD pathophysiology. Further studies are needed to clarify whether these abnormalities are related to a malfunction of the respiratory system or to specific cognitive/emotional/behavioral factors in this population.
Assessing the Public Health Impact of Developmental Origins of Health and Disease (DOHaD) Nutrition Interventions
Authors: Garmendia Maria Luisa , Corvalan Camila , Uauy Ricardo
Published: October 2014

Investing in the maternal and early-infancy periods (the first 1,000 days, i.e. from -1 to +2 years) is presently acknowledged as a key priority to ensure good nutrition and prevent all forms of malnutrition. The concept is to invest during this period to maximize the human development potential, and the early-life agenda includes prevention of stunting and promotion of optimal brain development as well as ensuring the quality of life of those who survive. Thus, public health assessments of specific interventions need to go beyond the traditional indices of prevention of death and disease. We need to consider including a full range of outcomes such as disability-adjusted life years (DALY) and quality-adjusted life years (QALY) and not only the number of deaths. The long-term outcomes of maternal and infant interventions to prevent obesity and related noncommunicable diseases remain uncertain in terms of their biological impact even under ideal conditions (efficacy); we need interventions with proven effectiveness under real-world conditions (effectiveness). Conversely, interventions to prevent undernutrition have already been proven effective and are considered cost-effective based on rigorous economic analyses. Continuous evaluation of interventions implemented using the developmental origins of health and disease (DOHaD) model needs to be undertaken, as this will allow progressive improvement and thus maximize the potential impact on the health and well-being of populations. We need to consider the population-attributable risk of obesity and chronic disease and conduct an economic evaluation of the lifelong impact of chronic diseases not only in terms of lives lost but also in relation to lost DALY and QALY. This should help to prioritize preventive actions in line with patterns of disease and disability considering the existing resources and demands.
Reduced Bone Mass in 7-Year-Old Children with Asymptomatic Idiopathic Hypercalciuria
Authors: Escribano Joaquin , Rubio-Torrents Carmen , Ferré Natalia , Luque Veronica , Grote Veit , Zaragoza-Jordana Marta , Gispert-Llauradó Mariona , Closa-Monasterolo Ricardo ,   for the European Childhood Obesity Project Group
Published: October 2014

Background: Idiopathic hypercalciuria (IHC), i.e. an elevated urinary calcium excretion without concomitant hypercalcemia, is a common disorder in children and can have a range of urinary clinical presentations and decreased bone mineral density (BMD). Aim: To assess the effect of IHC on bone mineral content in children without urological symptoms. Methods: Calcium excretion, BMD (by dual-energy X-ray absorptiometry), and anthropometry were assessed in 175 seven-year-old children who were classified as IHC or controls. Calcium intake and physical activity were measured as confounding factors. Results: The prevalence of IHC was 17.7%. Both groups (controls and IHC) showed similar baseline characteristics in terms of their anthropometry, gender distribution, and protein and calcium dietary intakes as well as physical activity scores. Urinary calciuria was independent of the calcium dietary intake and anthropometry. BMD correlated with anthropometry and physical activity but not with calcium dietary intake. IHC children had lower whole-body BMD z-scores compared to controls. The role of IHC in reducing the whole-body BMD z-score was still significant even when anthropometry, physical activity, and calcium intake were included as confounders in multivariate analyses. Conclusions: The prevalence of IHC in this population of 7-year-old children was about 17%. IHC diagnosis was associated with lower BMD z-scores and osteopenia in 22% of them.
Metabolomic Biomarkers for Obesity in Humans: A Short Review
Authors: Rauschert Sebastian , Uhl Olaf , Koletzko Berthold , Hellmuth Christian
Published: October 2014

Background: The prevalence and incidence of obesity have become a major public health problem during the last decades, but the underlying biochemical and metabolic processes are not fully understood. Metabolomics, the science of small molecules of the metabolism, is helping to unravel these mechanisms via the identification of markers related to obesity. These biomarkers are used to prevent diseases in later life or for the early diagnosis of diseases. This review focuses on articles dealing with biomarkers for obesity. Key Messages: Branched-chain amino acids (BCAA), nonesterified fatty acids, organic acids, acylcarnitines, and phospholipids were identified as potential biomarkers for obesity. This indicates a relation between elevated BCAA, and other amino acids, and the obese state. Furthermore, deregulation of β-oxidation is associated with the development of obesity. The results have several limitations, including the differing ages of the subjects in the studies, the fact that all of the studies had a case-control design and therefore no causal explanatory power, and that most looked for similar metabolites and reported almost equal results. Conclusion: The strength of this review is that it gives a comprehensive overview of the current status of the knowledge on metabolomics biomarkers for obesity, but further research is needed because the methods used in the studies to date are very homogenous, e.g. most used a targeted approach and therefore analyzed almost the same group of metabolites. Moreover, prospective studies are lacking since all of the studies are either case-control or cross-sectional studies.
Western Dietary Pattern Interaction with APOC3 Polymorphism in the Risk of Metabolic Syndrome: Tehran Lipid and Glucose Study
Authors: Hosseini-Esfahani Firoozeh , Mirmiran Parvin , Daneshpour Maryam S. , Mehrabi Yadollah , Hedayati Mehdi , Zarkesh Maryam , Azizi Fereidoun
Published: October 2014

Background/Aims: Gene-dietary pattern interactions may contribute to the determination of a susceptibility to metabolic syndrome (MetS). The aim of this study was to evaluate the potential interactions of dietary patterns with the common genetic variant of APOC3 in relation to MetS in adults. Methods: In this individual matched nested case-control study, 755 MetS subjects and 755 controls were selected from among participants in the Tehran Lipid and Glucose Study. Dietary patterns were determined by factor analysis. APOC3 3238C>G rs5128 was genotyped by polymerase chain reaction and restriction fragment length polymorphism. Results: Fat-sweet, healthy and Western dietary patterns (WDP) were extracted from the data. In the joint analysis, the associations of the WDP and APOC3 rs5128 with MetS risk tended to be dependent on APOC3 3238C>G gene variants (p for interaction = 0.009) in women. The MetS risk was increased in women with the CC genotype with increasing tertiles of WDP scores compared with women with the CG + GG genotype, whose MetS risk was decreased with increasing tertiles of WDP scores. In addition, we found that intakes of fast food, salty snacks and soft drinks showed significant interactions with the rs5128 genotypes in relation to MetS risk (p for interactions <0.05). Conclusion: The results obtained demonstrate a diet-gene interaction between APOC3 rs5128 polymorphism and the WDP in relation to MetS risk.
Protein Biomarkers Identify Patients Unlikely to Benefit From Primary Prevention Implantable Cardioverter Defibrillators
Authors: Cheng Alan , Zhang Yiyi , Blasco-Colmenares Elena , Dalal Darshan , Butcher Barbara , Norgard Sanaz , Eldadah Zayd , Ellenbogen Kenneth A. , Dickfeld Timm , Spragg David D. , Marine Joseph E. , Guallar Eliseo , Tomaselli Gordon F.
Published: October 2014

Background—

Primary prevention implantable cardioverter defibrillators (ICDs) reduce all-cause mortality, but the benefits are heterogeneous. Current risk stratification based on left ventricular ejection fraction has limited discrimination power. We hypothesize that biomarkers for inflammation, neurohumoral activation, and cardiac injury can predict appropriate shocks and all-cause mortality in patients with primary prevention ICDs.

Methods and Results—

The Prospective Observational Study of Implantable Cardioverter Defibrillators (PROSe-ICD) enrolled 1189 patients with systolic heart failure who underwent ICD implantation for primary prevention of sudden cardiac death. The primary end point was an ICD shock for adjudicated ventricular tachyarrhythmia. The secondary end point was all-cause mortality. After a median follow-up of 4.0 years, 137 subjects experienced an appropriate ICD shock and 343 participants died (incidence rates of 3.2 and 5.8 per 100 person-years, respectively). In multivariable-adjusted models, higher interleukin-6 levels increased the risk of appropriate ICD shocks. In contrast, C-reactive protein, interleukin-6, tumor necrosis factor-α receptor II, pro–brain natriuretic peptide (pro-BNP), and cardiac troponin T showed significant linear trends for increased risk of all-cause mortality across quartiles. A score combining these 5 biomarkers identified patients who were much more likely to die than to receive an appropriate shock from the ICD.

Conclusions—

An increase in serum biomarkers of inflammation, neurohumoral activation, and myocardial injury increased the risk for death but poorly predicted the likelihood of an ICD shock. These findings highlight the potential importance of serum-based biomarkers in identifying patients who are unlikely to benefit from primary prevention ICDs.

Clinical Trial Registration—

URL:
clinicaltrials.gov
; Unique Identifier: NCT00733590.
Transforming Growth Factor β–Activated Kinase 1 Signaling Pathway Critically Regulates Myocardial Survival and Remodeling
Authors: Li Lei , Chen Yi , Doan Jessica , Murray Jason , Molkentin Jeffery D. , Liu Qinghang
Published: October 2014

Background—

Programmed necrosis (necroptosis) plays an important role in development, tissue homeostasis, and disease pathogenesis. The molecular mechanisms that regulate necroptosis in the heart and its physiological relevance in myocardial remodeling and heart failure remain largely unknown.

Methods and Results—

Here, we identified an obligate function for TAK1 (transforming growth factor β–activated kinase 1, gene name
Map3k7
) in regulating necroptotic myocyte death, myocardial remodeling, and heart failure propensity. Cardiac-specific ablation of
Map3k7
in mice induced spontaneous apoptosis and necroptosis that led to adverse remodeling and heart failure, and these effects were abolished by ablation of tumor necrosis factor receptor-1. Mechanistically, TAK1 functions as a molecular switch in tumor necrosis factor receptor-1 signaling by regulating the formation of 2 cell death complexes, RIP 1 (receptor-interacting protein 1)–FADD (Fas-associated protein with death domain)–caspase 8 and RIP1-RIP3, a process that is dependent on FADD and caspase 8 as scaffolding molecules. Importantly, inhibition of RIP1 or RIP3 largely blocked necroptotic cell death, adverse remodeling, and heart failure in TAK1-deficient mice.

Conclusions—

These results indicate that TAK1 functions as a key survival factor in the heart by directly antagonizing necroptosis, which is critical for the maintenance of myocardial homeostasis and the prevention of adverse myocardial remodeling.