bluuebunny/crossref_metadata_2025 huggingface dataset:
Flame Deposition of the Electrolyte and Cathode for High and Stable Performance of Low-Temperature SOFCs
Authors: Maric Radenka , Neagu Roberto , Zhang-Steenwinkel Ye , van Berkel Frans P. F. , Rietveld Bert
Published: December 2010

The key obstacles to the development of low operating temperature (LT) SOFCs are high ohmic resistance and high electrode overpotentials. In the present work, we demonstrate excellent cell performance at 600 °C on a anode supported bi-layer electrolyte SOFC having a thin RSDT-made cerium gadolinium oxide (Gd0.2Ce0.8O2−δ, CGO) and a lanthanum strontium cobaltite (La0.6Sr0.4CoO3−δ, LSC) perovskite cathode. The measured ohmic resistance of the ASE cell with CGO layer deposited by RSDT was 0.24 ohm.cm2, which is close to the expected theoretical value of 0.17 ohm.cm2 for a 5 micron thick 8YSZ electrolyte at 600 °C. This indicates that the obtained peak power output density is approaching what is theoretically possible. This work is based on the lab scale use of Reactive Spray Deposition Technology (RSDT) which is an open atmosphere, cost efficient technique that does not require high vapor precursors and is an effective way to deposit thin ceramic layers of YSZ/CGO/LSC onto Ni-YSZ substrates. It has the potential to chain successive coating steps thus, significantly simplifying the production of multilayered ceramic structures as the SOFCs and reducing the cost associated with manufacturing of the cells.
An Efficient Approximation Method for an Individual Fuel Cell Impedance Characterization
Authors: Han Taehee , Haagenson Tessa A. , Salehfar Hossein , Dahal Samir , Mann Mike D.
Published: December 2010

In this study, an efficient method of approximating individual fuel cell impedances in a stack is proposed and experimentally verified. Two different proton exchange membrane (PEM) fuel cell stacks (600 W with 24 cells and 1.2 kW with 47 cells) were used to develop and verify the method. Both PEM fuel cell stacks were operated using room air and pure hydrogen (99.999%). Impedance and current - voltage (I-V) data were collected for stack and individual cell levels under various operating conditions. The experimental result shows that the individual cell impedance is directly proportional to the corresponding cell voltage. Therefore individual cell impedance can be accurately estimated by performing only stack impedance and individual cell voltage measurements.
Corrosion, Contact Resistance, and Surface Characteristics of Stamped and Hydroformed Metallic Bipolar Plates for PEMFC
Authors: Turan Cabir , Dur Ender , Peker Mevlu¨t Fatih , Cora O¨mer Necati , Koc¸ Muammer
Published: December 2010

In a quest for achieving sustainable mobility, improved fuel efficiency, enhanced driving performance and drastically reduced the tail-pile emissions necessitate the replacement of conventional energy conversion systems with environmentally-friendly technologies as well as lightweighting in transportation vehicles. Fuel cell technology is believed to be a promising avenue to achieve such a long desired sustainable transportation goal. However, for its widespread commercial success, there are some issues that need to be addressed. This study aims to investigate two of these underlying issues: corrosion and contact resistance in bipolar plates, which arise during the use fuel cell stacks, and are direct effects of production, material, surface, and coating conditions. Repeatability and robustness of manufacturing method (stamping, and hydroforming), corrosion and contact resistance of stainless steel bipolar plates (BPP), and tribological issues of forming dies in which bipolar plates are formed were investigated in this study. First, the effects of manufacturing conditions on formed bipolar plate quality and process repeatability were investigated. Second, corrosion and contact resistance tests for manufactured bipolar plates as well as blank stainless steel sheets were performed. Based on the corrosion test results, a faster stamping speed is found to be preferable for higher corrosion resistance and shorter production time. On the contrary, higher pressure rates in hydroforming are found to lower the corrosion resistance. Thus, a compromise between corrosion performance and production rate is needed in hydroforming for mass production purposes. According to the preliminary contact resistance tests, hydroformed bipolar plates showed better interfacial electrical conductivity than stamped plates. Also, the test results confirmed that surface coating is necessary to improve corrosion and contact properties to meet the DOE goals. Finally, relatively larger surface topography changes were observed on the manufactured bipolar plates compared to the forming die surfaces after several hundreds of BPP production.
Water Management Concepts in PEMFC With Biomimetic and TRIZ Design Methods
Authors: Fung Keith , Wallace J. S. , Shu L. H.
Published: December 2010

Excessive water accumulation at the cathode can cause cathode flooding in a fuel cell. Two design methodologies, TRIZ (Theory of Inventive Problem Solving) and biomimetic design, were applied to address the problem. A concept generated from TRIZ involves reversing the direction of cathode flow periodically to introduce dryer gas to the previous outlet, where it is previously saturated, with the humidified gas exiting the previous inlet. The concept is intended to reduce the potential for a channel to flood. A prototype apparatus was created to evaluate the concept. It consisted of a cell with a bare Nafion™ membrane pressurized by water on one side and with air flowing on the other side. The prototype apparatus demonstrated a potential loss of overall water removal efficiency in air. Therefore, the flow direction reversal concept may not benefit an actual fuel cell. A second concept generated from the biomimetic design method involves gathering liquid water with cavities and directing the liquid water out of the flow channels. Cavities for water collection in the flow channels of a bipolar plate are created in two configurations. In the first configuration the cavity is created by extending a straight channel from the u-bend in the channel. In the second configuration, the cavity is created by a hole perpendicular to the channel into the bipolar plate. Once the liquid water is collected at cavities, the water is directed out of the cell with wicking materials. A prototype with injected liquid water demonstrated the potential benefits for a fuel cell.
Design Improvements on a Bipolar Plate With Passive Water Management Using the Biomimetic Design Method
Authors: Ke Ji , Wallace J. S. , Shu L. H.
Published: December 2010

Liquid water build up in the cathode flow channels of a polymer electrolyte membrane fuel cell (PEMFC) can limit performance. A mechanism that removes accumulating liquid water continuously from the flow channels is required. While a number of water management strategies have been demonstrated, the search for improvements continues. This paper describes a novel technique of using biomimetic design to systematically generate a passive water management system concept for PEMFCs. Studies have shown that biology is a good source of analogies for engineering design. We believe that biomimetic design is an effective design methodology for PEMFC designs due to several common characteristics of biological systems, such as efficient use of material and energy, a self-regulating characteristic, and high tolerance to a wide range of operating conditions. A passive water management solution was generated based on two biological phenomena identified using the biomimetic design method. The biological phenomena inspired use of design elements such as random abrasions and polyethersulfone strands to remove water from the flow channels. The design was demonstrated on a simple test apparatus with low air flow rates and low inlet pressure. Preliminary experiments with the test apparatus have shown total recovery from flow channel catastrophic flooding within seconds. The present paper discusses the biomimetic design process, implementation, and prototype results.
Implementing Thermal Management Modeling Into SOFC System-Level Design
Authors: Kattke K. J. , Braun R. J.
Published: December 2010

Effective thermal management is critical to the successful design of small (<10 kW) solid oxide fuel cell (SOFC) power systems. While separate unit processes occur within each component of the system, external heat transport from or to components must be optimally managed and taken into account in system-level design. In this paper, we present a modeling approach that captures thermal interactions among hot zone components and couples this information with system process design. The resulting thermal model is then applied to a mobile SOFC power system concept in the 1–2 kW range to enable a better understanding of how component heat loss affects process gas temperature and flow requirements throughout the flowsheet. The thermal performance of the system is examined for various thermal management strategies that involve altering the convective and radiative heat transfer in the enclosure. The impact of these measures on internal temperature distributions within the cell-stack is also presented. A comparison with results from traditional adiabatic, zero-dimensional thermodynamic system modeling reveals that oxidant flow requirements can be over-predicted by as much as 110% and that important design constraints, such as the magnitude of the maximum cell temperature gradient within the stack, are under-predicted by over 40%.
Characterization of Bioelectrochemical Fuel Cell Fabricated With Agriculture Wastes and Surface Modified Electrode Materials
Authors: Paul Subir , Nandi Saptarshi , Mridha Sanghita
Published: December 2010

A Bioelectrochemical fuel cell was fabricated with pretreated and fermented rice husks. The fuel was characterized with variation of process variables by determination of chemical oxygen demand (COD) which is a measure of the oxygen equivalent of electrochemically oxidizable organic fuel to produce electrical energy. The electrodes of the cell were made with nano porous anodized Al coated with Platinum, Platinum-Ruthenium and Platinum-Ruthenium-Carbon. Anodization parameters were optimized by studying E-I characteristics in sulphuric and oxalic acids with variation of concentration and temperature. Pore size in the order of 30–50 nm was obtained by a two stage anodization. The performance of the cell was evaluated by determining open circuit potential, E-I characteristics, polarization studies and cyclic voltammetry. A steady onload potential of 600–800 mV was obtained with current density in the order of 15–25 mA/cm2. High power density of 10–15 mW/cm2 has been obtained with electrode materials coated with Pt+Ru or Pt+Ru+C. The performance of coating on nanoporous structure was much reflected in the polarization studies, which showed a huge reduction of polarization resistance and increase of exchange current density by many times, the effect being more for anode in anodic solution, fermented rice husk, than with cathode in phosphate buffer cathodic solution. The surface morphology examined by SEM, showed nano deposits of Pt, Pt-Ru and the presence of carbon like structure. XRD peaks clearly reveal presence of Pt, Pt-Ru and carbon.
Gene from a Psoriasis Susceptibility Locus Primes the Skin for Inflammation
Authors: Wolf Ronald , Mascia Francesca , Dharamsi Alif , Howard O. M. Zack , Cataisson Christophe , Bliskovski Val , Winston Jason , Feigenbaum Lionel , Lichti Ulrike , Ruzicka Thomas , Chavakis Triantafyllos , Yuspa Stuart H.
Published: December 2010

Psoriasis candidate genes promote susceptibility to skin inflammation and provide a treatment approach for psoriasis-related inflammation.
Summun Bonum
Authors: Ash Caroline
Published: December 2010

Scientists and policy-makers must help to achieve a public consensus about the value of vaccination to individuals and society.
Thinking Outside the Box in Prostate Cancer
Authors: Alumkal Joshi
Published: December 2010

Targeting the N-cadherin protein prevents the emergence of the lethal, castration-resistant form of prostate cancer.
Bio-Creep in Clinical Trials
Authors: Carlson Nichole
Published: December 2010

Approval of ineffective new treatments is rare, but can occur in certain circumstances.
A WELL-POSEDNESS THEORY IN MEASURES FOR SOME KINETIC MODELS OF COLLECTIVE MOTION
Authors: CAÑIZO J. A. , CARRILLO J. A. , ROSADO J.
Published: December 2010

We present existence, uniqueness and continuous dependence results for some kinetic equations motivated by models for the collective behavior of large groups of individuals. Models of this kind have been recently proposed to study the behavior of large groups of animals, such as flocks of birds, swarms, or schools of fish. Our aim is to give a well-posedness theory for general models which possibly include a variety of effects: an interaction through a potential, such as a short-range repulsion and long-range attraction; a velocity-averaging effect where individuals try to adapt their own velocity to that of other individuals in their surroundings; and self-propulsion effects, which take into account effects on one individual that are independent of the others. We develop our theory in a space of measures, using mass transportation distances. As consequences of our theory, we show also the convergence of particle systems to their corresponding kinetic equations, and the local-in-time convergence to the hydrodynamic limit for one of the models.
ADIABATIC EVOLUTION OF 1D SHAPE RESONANCES: AN ARTIFICIAL INTERFACE CONDITIONS APPROACH
Authors: FARAJ ALI , MANTILE ANDREA , NIER FRANCIS
Published: December 2010

Artificial interface conditions parametrized by a complex number θ0 are introduced for 1D-Schrödinger operators. When this complex parameter equals the parameter θ ∈ iℝ of the complex deformation which unveils the shape resonances, the Hamiltonian becomes dissipative. This makes possible an adiabatic theory for the time evolution of resonant states for arbitrarily large time scales. The effect of the artificial interface conditions on the important stationary quantities involved in quantum transport models is also checked to be as small as wanted, in the polynomial scale (hN)N∈ℕ as h → 0, according to θ0.
Synthesis and characterization of new tetra-substituted porphyrins with exo-donor carboxylic groups as building blocks for supramolecular architectures: Catalytic and structural studies of their metalated derivatives
Authors: Carlucci Lucia , Ciani Gianfranco , Maggini Simona , Proserpio Davide M. , Ragaini Fabio , Gallo Emma , Ranocchiari Marco , Caselli Alessandro
Published: December 2010

We report herein the synthesis of the porphyrins 5,10,15,20-tetrakis(4-carboxybiphenyl)-porphyrin (H2TCBP) and 5,10,15,20-tetrakis(4-carboxy-2,6-dimethylbiphenyl)porphyrin (H2TCDMBP) bearing diphenyl units on meso-positions, and of their cobalt and silver derivatives. The silver complexes of H2TCDMBP and of H2TCPP ( H2TCPP = 5 ,10,15,20-tetrakis(4-carboxyphenyl)porphyrin) were investigated by X-ray crystallography and their supramolecular organization elucidated. Co(TCBP) was reacted with copper formate, yielding a polymeric compound that showed a catalytic activity in the benzylic amination of hydrocarbons using arylazide as aminating agent.
Synthesis and properties of styryl-substituted tetrapyrazinoporphyrazines [St8PyzPzM],M = 2NaI,MgII(H2O)andZnII
Authors: Pia Donzello Maria , Viola Elisa , Tomachinskaya Larisa A. , Ercolani Claudio , Corsini Maddalena , Zanello Piero , Stuzhin Pavel A.
Published: December 2010

New styryl-substituted tetrapyrazinoporphyrazines [St8PyzPzM] (M = 2NaI, MgII(H2O) and ZnII; St = -CH=CHAr , where Ar = phenyl or cumyl) were prepared by template cyclotetramerization of 5,6-distyrylpyrazine-2,3-dicarbonitriles available from condensation of diaminomaleodinitrile with the substituted cinnamils (StCO)2obtained from biacetyl and arylaldehydes ArCHO . The new porphyrazine macrocycles were characterized by electronic absorption and emission spectra, which provide evidence of efficient π-interaction of the peripheral styryl moieties with the central pyrazinoporphyrazine framework. The electronic excitation of the stylbenoid chromophore in the near UV-region (400 nm) leads to strong emission of the porphyrazine chromophore near 700 nm, allowing to consider the styryl-substituted porphyrazines as efficient light-harvesting species. Their spectral properties and electrochemical behavior are compared with those of stylbenoid phthalocyanines and peripherally substituted tetrapyrazinoporphyrazines.
EXTERNAL R&D: EXPLORING THE FUNCTIONS AND QUALIFICATIONS OF R&D PERSONNEL
Authors: SPITHOVEN ANDRÉ , TEIRLINCK PETER
Published: December 2010

Knowledge has become an important production factor. Tacit knowledge is embodied in the minds of people, and is part and parcel of their skills. Since businesses concentrate on strategic tasks, many others are outsourced. This also applies to R&D. External knowledge sources help firms to leverage their internal R&D efforts. Internal and external knowledge have to be knitted together on the work floor giving rise to innovative products and processes. Since tacit knowledge is embodied in personnel, it is interesting to look at the role of the functions and the qualifications of R&D personnel in relation to activities developed in the framework of technical collaboration agreements. Using the OECD business R&D survey for Belgium, insights are offered in the way that external knowledge impacts on the organisation of the internal division of labour. It is demonstrated that absorptive capacity, embodied in people, is a key element in using external knowledge.
β-Arrestin mediates oxytocin receptor signaling, which regulates uterine contractility and cellular migration
Authors: Grotegut Chad A. , Feng Liping , Mao Lan , Heine R. Phillips , Murtha Amy P. , Rockman Howard A.
Published: December 2010

Desensitization of the oxytocin receptor (OXTR) in the setting of prolonged oxytocin exposure may lead to dysfunctional labor, which increases the risk for cesarean delivery, and uterine atony, which may result in postpartum hemorrhage. The molecular mechanism for OXTR desensitization is through the agonist-mediated recruitment of the multifunctional protein β-arrestin. In addition to its desensitizing function, β-arrestins have recently been shown to simultaneously activate downstream signaling. We tested whether oxytocin stimulation promotes β-arrestin-mediated OXTR desensitization in vivo and activates β-arrestin-mediated mitogen-activated protein kinase (MAPK) growth signaling. Uterine muscle strips isolated from wild-type mice exhibited diminished uterine contractility following repeated exposure to oxytocin, whereas uterine muscle strips from β-arrestin-1 and β-arrestin-2 knockout mice showed no desensitization. Utilizing siRNA knockdown of β-arrestin-1 and β-arrestin-2 in HEK-293 cells expressing the OXTR, we demonstrated oxytocin-mediated MAPK signaling that was dependent on β-arrestin-1 and β-arrestin-2. Wild-type and β-arrestin-1 and β-arrestin-2 knockout mice receiving intravenous oxytocin also demonstrated oxytocin-mediated MAPK signaling that was dependent on β-arrestin-1 and β-arrestin-2. Finally, to test the significance of β-arrestin-mediated signaling from the OXTR, HEK-293 cells expressing the OXTR showed β-arrestin-dependent proliferation in a cell migration assay following oxytocin treatment. In conclusion, β-arrestin is a multifunctional scaffold protein that mediates both desensitization of the OXTR, leading to decreases in uterine contractility, and MAPK growth signaling following stimulation by oxytocin. The development of unique OXTR ligands that prevent receptor desensitization may be a novel approach in the treatment of adverse clinical events secondary to prolonged oxytocin therapy.
Vocal Pathway Degradation in Gonadectomized Xenopus laevis Adults
Authors: Zornik Erik , Yamaguchi Ayako
Published: December 2010

Reproductive behaviors of many vertebrate species are activated in adult males by elevated androgen levels and abolished by castration. Neural and muscular components controlling these behaviors contain numerous hormone-sensitive sites including motor initiation centers (such as the basal ganglia), central pattern generators (CPGs), and muscles; therefore it is difficult to confirm the role of each hormone-activated target using behavioral assays alone. Our goal was to address this issue by determining the site of androgen-induced vocal activation using male Xenopus laevis, a species in which androgen dependence of vocal activation has been previously determined. We compared in vivo calling patterns and functionality of two in vitro preparations—the isolated larynx and an isolated brain from which fictive courtship vocalizations can be evoked—in castrated and control males. The isolated larynx allowed us to test whether castrated males were capable of transducing male-typical nerve signals into vocalizations and the fictively vocalizing brain preparation allowed us to directly examine vocal CPG function separate from the issue of vocal initiation. The results indicate that all three components—vocal initiation, CPG, and larynx—require intact gonads. Vocal production decreased dramatically in castrates and laryngeal contractile properties of castrated males were demasculinized, whereas no changes were observed in control animals. In addition, fictive calls of castrates were degraded compared with those of controls. To our knowledge, this finding represents the first demonstration of gonad-dependent maintenance of a CPG for courtship behavior in adulthood. Because previous studies showed that androgen-replacement can prevent castration-induced vocal impairments, we conclude that degradation of vocal initiation centers, larynx, and CPG function are most likely due to steroid hormone deprivation.
MiRNA in innate immune responses: novel players in wound inflammation
Authors: Roy Sashwati , Sen Chandan K.
Published: December 2010

Chronic wounds represent a major and rising socioeconomic threat affecting over 6.5 million people in the United States costing in excess of US $25 billion annually. Wound healing is a physiological response to injury that is conserved across tissue systems. In humans, wounding is followed by instant response aimed at hemostasis, which in turn provides the foundation for inflammatory processes that closely follow. Inflammation is helpful and a prerequisite for healing as long as it is mounted and resolved in a timely manner. Chronic inflammation derails the healing cascade resulting in impaired wound closure. Disruption of Dicer, the RNase III enzyme that generates functional miRNAs, has a major impact on the overall immune system. Emerging studies indicate that miRNAs, especially miR-21, miR-146a/b, and miR-155, play a key role in regulating several hubs that orchestrate the inflammatory process. Direct evidence from studies addressing wound inflammation being limited, the current work represents a digest of the relevant literature that is aimed at unveiling the potential significance of miRNAs in the regulation of wound inflammation. Such treatment would help establish new paradigms highlighting a central role of miRs in the understanding and management of dysregulated inflammation as noted in conjunction with chronic wounds.
A Newly Developed Variable Stiffness Duodenoscope for Diagnostic and Therapeutic Endoscopic Retrograde Cholangiopancreatography
Authors: Itoi Takao , Sofuni Atsushi , Itokawa Fumihide , Kurihara Toshio , Tsuchiya Takayoshi , Ishii Kentaro , Tsuji Shujiro , Ikeuchi Nobuhito , Umeda Junko , Moriyasu Fuminori , Kasuya Kazuhiko , Tsuchida Akihiko
Published: December 2010

The aim of this study is to evaluate a prototype variable stiffness duodenoscope (VSD) for diagnostic and therapeutic ERCP in comparison with standard duodenoscopes. We performed retrospective analysis on the success rate of intubation of the second duodenum, overall procedural success rate, and comparative frequency of the necessity to change duodenoscopes from standard JF-260V and TJF 260V or to change stiffness using the VSD. A total of 213 nonconsecutive procedures in 196 patients with pancreaticobiliary diseases. There was no statistically significant difference in endoscope intubation rate or technical success rate between the different duodenoscopes. In one patient with severe duodenal stenosis, the VSD using the moderately stiff mode allowed the major papilla to be reached when the TJF-260V endoscope could not. There were no serious procedure-related adverse events. In conclusion, while the VSD performed well, the present models do not appear to offer obvious advantages over the standard duodenoscopes for routine diagnostic and therapeutic ERCP. Prospective studies may be warranted to identify those patients who would benefit from this new technology.
Corrosion Resistance of Electroless Ni-Cu-P Ternary Alloy Coatings in Acidic and Neutral Corrosive Mediums
Authors: Cissé Mbouillé , Abouchane Mohamed , Anik Tayeb , Himm Karima , Belakhmima Rida Allah , Ebn Touhami Mohamed , Touir Rachid , Amiar Abderrahmane
Published: December 2010

Electroless Ni-Cu-P alloy coatings were deposited on the ordinary steel substrate in an acidic hypophosphite-type plating bath. These coatings were characterized by a scanning electron microscope (SEM) and an X-ray diffraction. The micrograph shows that coating presents a nodular aspect and is relatively homogeneous and very smooth. The EDX analysis shows that the coating contains 12 wt.% of phosphorus element with a predominance of nickel element. In addition, the anticorrosion properties of the Ni-Cu-P coatings in 1 M HCl, 1 M H2SO4, and 3% NaCl solutions were investigated using Tafel polarization curves, electrochemical impedance spectroscopy, and SEM/EDX analysis. The result showed a marginal improvement in corrosion resistance in 3% NaCl solution compared to acidic medium. It also showed that the corrosion mechanism depends on the nature of the solution.
Weighted Iterated Radial Composition Operators between Some Spaces of Holomorphic Functions on the Unit Ball
Authors: Stević Stevo
Published: December 2010

The boundedness and compactness of weighted iterated radial composition operators from the mixed‐norm space to the weighted‐type space and the little weighted‐type space on the unit ball are characterized here. We also calculate the Hilbert‐Schmidt norm of the operator on the weighted Bergman‐Hilbert space as well as on the HardyH2space.
Iterative Approaches to Find Zeros of Maximal Monotone Operators by Hybrid Approximate Proximal Point Methods
Authors: Ceng LuChuan , Liou YeongCheng , Naraghirad Eskandar
Published: December 2010

The purpose of this paper is to introduce and investigate two kinds of iterative algorithms for the problem of finding zeros of maximal monotone operators. Weak and strong convergence theorems are established in a real Hilbert space. As applications, we consider a problem of finding a minimizer of a convex function.
Why and How Meet n-3 PUFA Dietary Recommendations?
Authors: Molendi-Coste Olivier , Legry Vanessa , Leclercq Isabelle A.
Published: December 2010

Obesity and the metabolic syndrome are systemic inflammatory diseases reaching epidemic proportions. Contemporary changes in human nutrition occurred characterized by increased consumption of fat and of vegetable oils rich in n-6 polyunsaturated fatty acids (PUFAs) together with decrease in n-3 PUFA-rich foods, resulting in an n-6/n-3 ratio of 10–20/1 in Western diet for a ratio around 1/1 in the diet of our ancestors. The literature provides compelling evidence for the health benefit of n-3 PUFA consumption on inflammation and metabolic syndrome prevention and treatment. Such evidence led to the establishment of comprehensive recommendations. However, we show here that, both in collective catering proposed to children and in hospital diet, it is not straightforward to meet such recommendations. Willingness of governments to institute changes, with accountable decisions on catering, nutritional education, and food processing, is required to face our neglected responsibility in promoting balanced diet and consumption of foods rich in essential nutrients in the general population.
[Retracted] Psorinum Therapy in Treating Stomach, Gall Bladder, Pancreatic, and Liver Cancers: A Prospective Clinical Study
Authors: Chatterjee Aradeep , Biswas Jaydip , Chatterjee Ashim , Bhattacharya Sudin , Mukhopadhyay Bishnu , Mandal Syamsundar
Published: December 2010

We prospectively studied the clinical efficacy of an alternative cancer treatment “Psorinum Therapy” in treating stomach, gall bladder, pancreatic and liver cancers. Our study was observational, open level and single arm. The participants′ eligibility criteria included histopathology/cytopathology confirmation of malignancy, inoperable tumor, and no prior chemotherapy or radiation therapy. The primary outcome measures of the study were (i) to assess the radiological tumor response (ii) to find out how many participants survived at least 1 year, 2 years, 3 years, 4 years and finally 5 years after the beginning of the study considering each type of cancer. Psorinum‐6x was administered orally to all the participants up to 0.02 ml/Kg body weight as a single dose in empty stomach per day for 2 years along with allopathic and homeopathic supportive cares. 158 participants (42 of stomach, 40 of gall bladder, 44 of pancreatic, 32 of liver) were included in the final analysis of the study. Complete tumor response occurred in 28 (17.72%) cases and partial tumor response occurred in 56 (35.44%) cases. Double‐blind randomized controlled clinical trial should be conducted for further scientific exploration of this alternative cancer treatment.
Inhibition of Epidermal Growth Factor Receptor and PI3K/Akt Signaling Suppresses Cell Proliferation and Survival through Regulation of Stat3 Activation in Human Cutaneous Squamous Cell Carcinoma
Authors: Bito Toshinori , Sumita Nahoko , Ashida Masashi , Budiyanto Arief , Ueda Masato , Ichihashi Masamitsu , Tokura Yoshiki , Nishigori Chikako
Published: December 2010

Recent studies have emphasized the important role of Stat3 activation in a number of human tumors from the viewpoint of its oncogenic and antiapoptotic activity. In this study, we examined the role and related signaling molecules of Stat3 in the carcinogenesis of human cutaneous squamous cell carcinoma (SCC). In 35 human cutaneous SCC samples, 86% showed overexpression of phosphorylated (p)-Stat3, and most of those simultaneously overexpressed p-EGFR or p-Akt. Constitutive activation of EGFR and Stat3 was observed in three SCC cell lines and four of five SCC tissues. AG1478, an inhibitor of the EGFR, downregulated Stat3 activation in HSC-1 human SCC cells. AG1478 inhibited cell proliferation and induced apoptosis of HSC-1 cells but did not inhibit the growth of normal human epidermal keratinocytes that did not show Stat3 activation. Furthermore, a PI3K inhibitor also suppressed Stat3 activation in HSC-1 cells to some degree. Combined treatment with the PI3K inhibitor and AG1478 strongly suppressed Stat3 activity and dramatically induced apoptosis of HSC-1 cells. These data suggest that Stat3 activation through EGFR and/or PI3K/Akt activation plays a critical role in the proliferation and survival of human cutaneous SCC.
Longitudinal Evaluation of Fatty Acid Metabolism in Normal and Spontaneously Hypertensive Rat Hearts with Dynamic MicroSPECT Imaging
Authors: Reutter Bryan W. , Huesman Ronald H. , Brennan Kathleen M. , Boutchko Rostyslav , Hanrahan Stephen M. , Gullberg Grant T.
Published: December 2010

The goal of this project is to develop radionuclide molecular imaging technologies using a clinical pinhole SPECT/CT scanner to quantify changes in cardiac metabolism using the spontaneously hypertensive rat (SHR) as a model of hypertensive-related pathophysiology. This paper quantitatively compares fatty acid metabolism in hearts of SHR and Wistar-Kyoto normal rats as a function of age and thereby tracks physiological changes associated with the onset and progression of heart failure in
the SHR model. The fatty acid analog, 123I-labeled BMIPP, was used in longitudinal metabolic pinhole SPECT imaging studies performed every seven months for 21 months. The uniqueness of this project is the development of techniques for estimating the blood input function from projection data acquired by a slowly rotating camera that is imaging fast circulation and the quantification of the kinetics of 123I-BMIPP by fitting compartmental models to the blood and tissue time-activity curves.
Regulation of HMGA1 Expression by MicroRNA-296 Affects Prostate Cancer Growth and Invasion
Authors: Wei Jian-Jun , Wu Xinyu , Peng Yi , Shi Guizhi , Olca Basturk , Yang Ximing , Daniels Garrett , Osman Iman , Ouyang Jiangyong , Hernando Eva , Pellicer Angel , Rhim Johng S. , Melamed Jonathan , Lee Peng
Published: December 2010

Purpose: High-motility group AT-hook gene 1 (HMGA1) is a non-histone nuclear binding protein that is developmentally regulated. HMGA1 is significantly overexpressed in and associated with high grade and advance stage of prostate cancer (PC). The oncogenic role of HMGA1 is at least mediated through chromosomal instability and structural aberrations. However, regulation of HMGA1 expression is not well understood. Identification of microRNA-mediated HMGA1 regulation will provide a promising therapeutic target in treating PC.

Experimental Design: In this study, we examined the functional relation between miR-296 and HMGA1 expression in several PC cell lines and a large PC cohort. We further examined the oncogenic property of HMGA1 regulated by miR-296.

Results: Here we report that miR-296, a microRNA predicted to target HMGA1, specifically represses HMGA1 expression by promoting degradation and inhibiting HMGA1translation. Repression of HMGA1 by miR-296 is direct and sequence specific. Importantly, ectopic miR-296 expression significantly reduced PC cell proliferation and invasion, in part through the downregulation of HMGA1. Examining PC patient samples, we found an inverse correlation between HMGA1 and miR-296 expression: high levels of HMGA1 were associated with low miR-296 expression and strongly linked to more advanced tumor grade and stage.

Conclusions: Our results indicate that miR-296 regulates HMGA1 expression and is associated with PC growth and invasion. Clin Cancer Res; 17(6); 1297–305. ©2010 AACR.
Reduced Dose and Intermittent Treatment with Lapatinib and Trastuzumab for Potent Blockade of the HER Pathway in HER2/neu-Overexpressing Breast Tumor Xenografts
Authors: Rimawi Mothaffar F. , Wiechmann Lisa S. , Wang Yen-Chao , Huang Catherine , Migliaccio Ilenia , Wu Meng-Fen , Gutierrez Carolina , Hilsenbeck Susan G. , Arpino Grazia , Massarweh Suleiman , Ward Robin , Soliz Robert , Osborne C. Kent , Schiff Rachel
Published: December 2010

Purpose: We have shown that incomplete blockade of the human epidermal growth factor (HER) pathway is a mechanism of resistance to treatment with trastuzumab (T) in HER2-overexpressing tumor xenografts. We now investigate whether the addition of lapatinib (L), a dual HER1/2 kinase inhibitor, to T results in more potent inhibition of the pathway and therefore inhibition of tumor growth, and whether reduced dose and intermittent treatment with the combination is equally effective.

Experimental Design: Nude mice bearing HER2-overexpressing MCF7/HER2–18 or BT-474 xenograft tumors were treated with L and T, alone or in various combinations with other HER inhibitors. L + T for short duration (14 and 42 days), intermittent administration (14 days on/off), and reduced dosing (half dose) was also investigated. Inhibition of tumor growth, downstream signaling, proliferation, and induction of apoptosis were assessed. All statistical tests were two-sided.

Results: L + T was the most effective regimen in both MCF7/HER2–18 and BT-474 xenografts with complete regression (CR) of tumor observed in all mice. Intermittent and reduced dose treatment (½ dose) resulted in high rates of CR and low rates of tumor recurrence that were comparable to full dose continuous treatment. L + T resulted in significantly reduced downstream signaling and proliferation, and increased apoptosis.

Conclusions: L + T is a potent and effective combination even when given in reduced dose or intermittent schedule potentially resulting in lower toxicity and reduced cost if translated to patients. These findings warrant timely clinical testing. Clin Cancer Res; 17(6); 1351–61. ©2011 AACR.
Hypermethylation of CpG Islands and Shores around Specific MicroRNAs and Mirtrons Is Associated with the Phenotype and Presence of Bladder Cancer
Authors: Dudziec Ewa , Miah Saiful , Choudhry Hani M.Z , Owen Helen C. , Blizard Sheila , Glover Maggie , Hamdy Freddie C. , Catto James W.F.
Published: December 2010

Purpose: To analyze the role and translational potential for hypermethylation of CpG islands and shores in the regulation of small RNAs within urothelial cell carcinoma (UCC). To examine microRNAs (miR) and mirtrons, a new class of RNA located within gene introns and processed in a Drosha-independent manner.

Experimental design: The methylation status of 865 small RNAs was evaluated in normal and malignant cell lines by using 5-azacytidine and microarrays. Bisulfite sequencing was used for CpG regions around selected RNAs. Prognostic and diagnostic associations for epigenetically regulated RNAs were examined by using material from 359 patients, including 216 tumors and 121 urinary samples (68 cases and 53 controls). Functional analyses examined the effect of silencing susceptible RNAs in normal urothelial cells.

Results: Exonic/UTR-located miRs and mirtons are most susceptible to epigenetic regulation. We identified 4 mirtrons and 16 miRs with CpG hypermethylation across 35 regions in normal and malignant urothelium. For several miRs, hypermethylation was more frequent and dense in CpG shores than islands (e.g., miRs-9/149/210/212/328/503/1224/1227/1229), and was associated with tumor grade, stage, and prognosis (e.g., miR-1224 multivariate analysis OR = 2.5; 95% CI, 1.3–5.0; P = 0.006). The urinary expression of epigenetically silenced RNAs (miRs-152/328/1224) was associated with the presence of UCC (concordance index, 0.86; 95% CI, 0.80–0.93; ANOVA P < 0.016).

Conclusions: Hypermethylation of mirtrons and miRs is common in UCC. Mirtrons appear particularly susceptible to epigenetic regulation. Aberrant hypermethylation of small RNAs is associated with the presence and behavior of UCC, suggesting potential roles as diagnostic and prognostic biomarkers. Clin Cancer Res; 17(6); 1287–96. ©2010 AACR.
Rb–Raf-1 Interaction Disruptor RRD-251 Induces Apoptosis in Metastatic Melanoma Cells and Synergizes with Dacarbazine
Authors: Singh Sandeep , Davis Rebecca , Alamanda Vignesh , Pireddu Roberta , Pernazza Daniel , Sebti Said , Lawrence Nicholas , Chellappan Srikumar
Published: December 2010

Metastatic melanoma is an aggressive cancer with very low response rate against conventional chemotherapeutic agents such as dacarbazine (DTIC). Inhibitor of Rb–Raf-1 interaction RRD-251 was tested against the melanoma cell lines SK-MEL-28, SK-MEL-5, and SK-MEL-2. RRD-251 was found to be a potent inhibitor of melanoma cell proliferation, irrespective of V600E B-Raf mutation status of the cell lines. In a SK-MEL-28 xenograft experiment, RRD-251 exerted a significant suppression of tumor growth compared with vehicle (P = 0.003). Similar to in vitro effects, tumors from RRD-251–treated animals showed decreased Rb–Raf-1 interaction in vivo. Growth suppressive effects of RRD-251 were associated with induction of apoptosis as well as a G1 arrest, with an accompanying decrease in S-phase cells. RRD-251 inhibited Rb phosphorylation and downregulated E2F1 protein levels in these cells. Real-time PCR analysis showed that RRD-251 caused downregulation of cell-cycle regulatory genes thymidylate synthase (TS) and cdc6 as well as the antiapoptotic gene Mcl-1. Combinatorial treatment of RRD-251 and DTIC resulted in a significantly higher apoptosis in DTIC resistant cell lines SK-MEL-28 and SK-MEL-5, as revealed by increased caspase-3 activity and PARP cleavage. Because aberrant Rb/E2F pathway is associated with melanoma progression and resistance to apoptosis, these results suggest that the Rb–Raf-1 inhibitor could be an effective agent for melanoma treatment, either alone or in combination with DTIC. Mol Cancer Ther; 9(12); 3330–41. ©2010 AACR.
Population Trends of Recurrent Coronary Heart Disease Event Rates Remain High
Authors: Briffa Tom G. , Hobbs Michael S. , Tonkin Andrew , Sanfilippo Frank M. , Hickling Siobhan , Ridout Stephen C. , Knuiman Matthew
Published: December 2010

Background—

Survivors of nonfatal coronary heart disease (CHD) can reduce their risk of further events by various preventive interventions. The impact of such measures as delivered over 11 years, on population rates of subsequent major CHD events, has not been extensively studied. This study determined population trends in the prevalence of clinically manifest CHD and the proportion of major CHD events that occur in this population.

Methods and Results—

A population longitudinal person-based event-linked file of CHD extracted from State Hospital Morbidity Data and Death Registry for 1980 to 2005 was used to identify, for each year from 1995 to 2005, survivors who had a hospitalization for CHD over the previous 15 years (population with established CHD), and to examine the occurrence of CHD death and hospitalization with a principal diagnosis of myocardial infarction in both populations with and without established CHD. The average annual age-standardized prevalence of CHD in the Perth metropolitan region (population 1.6 million) was 28 373 (8.8%) in men and 14 966 (4.0%) in women. Age-specific prevalence increased exponentially with age, from <1% in 35 to 39 age group to 42% in 80 to 84 age group in men and half that in women. The percentage of total CHD events (n=28 941) that occurred in the population with established CHD was approximately 43% in both men and women, 55% and 51%, respectively, for CHD death and 35% and 36% for nonfatal myocardial infarction.

Conclusions—

More than 40% of major CHD events annually occur in persons with manifest disease, highlighting the imperative to implement systems of care that support effective secondary prevention.
Numerical Study of Horizontal Shear Instability Waves along Narrow Cold Frontal Rainbands
Authors: Kawashima Masayuki
Published: December 2010

The effects of variations in low-level ambient vertical shear and horizontal shear on the alongfront variability of narrow cold frontal rainbands (NCFRs) that propagate into neutral and slightly unstable environments are investigated through a series of idealized cloud-resolving simulations.

In cases initialized with slightly unstable sounding and weak ambient cross-frontal vertical shears, core-gap structures of precipitation along NCFRs occur that are associated with wavelike disturbances that derive their kinetic energy mainly from the mean local vertical shear and buoyancy. However, over a wide range of environmental conditions, core-gap structures of precipitation occur because of the development of a horizontal shear instability (HSI) wave along the NCFRs.

The growth rate and amplitude of the HSI wave decrease significantly as the vertical shear of the ambient cross-front wind is reduced. These decreases are a consequence of the enhancement of the low-level local vertical shear immediately behind the leading edge. The strong local vertical shear acts to damp the vorticity edge wave on the cold air side of the shear zone, thereby suppressing the growth of the HSI wave through the interaction of the two vorticity edge waves. It is also noted that the initial wavelength of the HSI wave increases markedly with increasing horizontal shear. The local vertical shear around the leading edge is shown to damp long HSI waves more strongly than short waves, and the horizontal shear dependency of the wavelength is explained by the decrease in the magnitude of the vertical shear relative to that of the horizontal shear.
Vegetation Dynamics within the North American Monsoon Region
Authors: Forzieri Giovanni , Castelli Fabio , Vivoni Enrique R.
Published: December 2010

The North American monsoon (NAM) leads to a large increase in summer rainfall and a seasonal change in vegetation in the southwestern United States and northwestern Mexico. Understanding the interactions between NAM rainfall and vegetation dynamics is essential for improved climate and hydrologic prediction. In this work, the authors analyze long-term vegetation dynamics over the North American Monsoon Experiment (NAME) tier I domain (20°–35°N, 105°–115°W) using normalized difference vegetation index (NDVI) semimonthly composites at 8-km resolution from 1982 to 2006. The authors derive ecoregions with similar vegetation dynamics using principal component analysis and cluster identification. Based on ecoregion and pixel-scale analyses, this study quantifies the seasonal and interannual vegetation variations, their dependence on geographic position and terrain attributes, and the presence of long-term trends through a set of phenological vegetation metrics. Results reveal that seasonal biomass productivity, as captured by the time-integrated NDVI (TINDVI), is an excellent means to synthesize vegetation dynamics. High TINDVI occurs for ecosystems with a short period of intense greening tuned to the NAM or with a prolonged period of moderate greenness continuing after the NAM. These cases represent different plant strategies (deciduous versus evergreen) that can be adjusted along spatial gradients to cope with seasonal water availability. Long-term trends in TINDVI may also indicate changing conditions favoring ecosystems that intensively use NAM rainfall for rapid productivity, as opposed to delayed and moderate greening. A persistence of these trends could potentially result in the spatial reorganization of ecosystems in the NAM region.
Sensitivity of the Aerosol Indirect Effect to Subgrid Variability in the Cloud Parameterization of the GFDL Atmosphere General Circulation Model AM3
Authors: Golaz Jean-Christophe , Salzmann Marc , Donner Leo J. , Horowitz Larry W. , Ming Yi , Zhao Ming
Published: December 2010

The recently developed GFDL Atmospheric Model version 3 (AM3), an atmospheric general circulation model (GCM), incorporates a prognostic treatment of cloud drop number to simulate the aerosol indirect effect. Since cloud drop activation depends on cloud-scale vertical velocities, which are not reproduced in present-day GCMs, additional assumptions on the subgrid variability are required to implement a local activation parameterization into a GCM.

This paper describes the subgrid activation assumptions in AM3 and explores sensitivities by constructing alternate configurations. These alternate model configurations exhibit only small differences in their present-day climatology. However, the total anthropogenic radiative flux perturbation (RFP) between present-day and preindustrial conditions varies by ±50% from the reference, because of a large difference in the magnitude of the aerosol indirect effect. The spread in RFP does not originate directly from the subgrid assumptions but indirectly through the cloud retuning necessary to maintain a realistic radiation balance. In particular, the paper shows a linear correlation between the choice of autoconversion threshold radius and the RFP.

Climate sensitivity changes only minimally between the reference and alternate configurations. If implemented in a fully coupled model, these alternate configurations would therefore likely produce substantially different warming from preindustrial to present day.