bluuebunny/crossref_metadata_2025 huggingface dataset:
PHOTOPHYSIOLOGY IN TWO SOUTHERN OCEAN PHYTOPLANKTON TAXA: PHOTOSYNTHESIS OF PHAEOCYSTIS ANTARCTICA (PRYMNESIOPHYCEAE) AND FRAGILARIOPSIS CYLINDRUS (BACILLARIOPHYCEAE) UNDER SIMULATED MIXED‐LAYER IRRADIANCE1
Authors: Mills Matthew M. , Kropuenske Lindsey R. , van Dijken Gert L. , Alderkamp Anne‐Carlijn , Berg Gry Mine , Robinson Dale H. , Welschmeyer Nicholas A. , Arrigo Kevin R.
Published: November 2010

In the Ross Sea, the prymnesiophyte Phaeocystis antarctica G. Karst. dominates deeply mixed water columns, while diatoms dominate shallower mixed layers. Understanding what controls the dynamics of these two phytoplankton taxa is essential because they dominate virtually all coastal polar waters, have different nutrient utilization characteristics, and support dissimilar food webs. We cultured two strains of P. antarctica and one strain of the diatom Fragilariopsis cylindrus (Grunow) Willi Krieg under three dynamic irradiance regimes that simulated different mixed‐layer depths and measured their photosynthetic characteristics, cellular pigment concentrations, and cellular carbon and nitrogen content. In both species, chl a–normalized maximum carbon uptake rate (Pm* ) and specific growth rate were highest in the deeply mixed treatment that had a dark period. In all irradiance treatments, both (Pm* ) and photosynthetic efficiency (α*) were greater for the two P. antarctica strains than for the F. cylindrus strain. In contrast, P. antarctica strains were more susceptible to photoinhibition (β*) than the F. cylindrus strain. When photosynthetic rates of each phytoplankton taxon were normalized by cellular particulate organic carbon (POC), the difference in the maximal photosynthetic rate () was generally reduced. In the dynamic irradiance treatment that simulated the shallowest mixed‐layer irradiance, all three phytoplankton had similar ; however, the diatom had a 2‐fold higher POC‐normalized photosynthetic efficiency (αC). Finally, we performed calculations using the measured POC‐normalized photosynthetic parameters to show that αC and can play a greater role than βC in determining the competitive outcome between P. antarctica and F. cylindrus in both shallow and deep mixed‐layer environments of the Ross Sea.
Novel Synthesis of Hierarchical Tungsten Carbide Micro‐/Nanocrystals from a Single‐Source Precursor
Authors: Chen Deliang , Wen Hejing , Zhai Haitao , Wang Hailong , Li Xinjian , Zhang Rui , Sun Jing , Gao Lian
Published: November 2010

Hierarchical tungsten carbide (WC) micro‐/nanocrystals were synthesized by thermal treating a single‐source precursor of the tungstate‐based inorganic–organic hybrid compound in a sealed quartz tube at 1000°–1050°C. The hybrid precursor was synthesized by an acid–base reaction of H2O‐moistened H2WO4 and n‐octylamine in a nonpolar solvent. The X‐ray diffraction results indicated that the product obtained at 1050°C for 2 h consisted of a hexagonal WC phase, and the products obtained at temperatures lower than 1000°C had other phases (e.g., α‐W2C, W or β‐W40.9N9.1) besides the major phase of hexagonal WC. The scanning electron microscopy observations indicated that the hexagonal WC obtained at 1050°C consisted of hierarchical microparticles with a size range of 4–18 μm, and the above microparticles were porous aggregates of WC nanoparticles with crystal sizes of 100–250 nm. The newly developed process could achieve pure WC materials at relative low temperatures using a single‐source precursor, and the porous and hierarchical WC micro‐/nanoparticles would have potential applications in catalysis and superhard composites.
Surface Chemistry and Dispersion Property of TiO2 Nanoparticles
Authors: Li Chia‐Chen , Chang Shinn‐Jen , Tai Ming‐Yu
Published: November 2010

The effect of a foreign substance, silica (SiO2), on the surface chemistry, chemical reactivity, and dispersibility of titania (TiO2) nanoparticles was investigated. SiO2 covers 90% of the surface of commercially available TiO2 nanoparticles and provides higher acidity, which facilitates the absorption of alkaline surfactant, oleylamine, onto TiO2 nanoparticles, leading to more efficient nanoparticle dispersion. By removing the surface SiO2 with an acid treatment, the acidity of TiO2 was highly reduced and became favorable to being adsorbed and dispersed by the acidic surfactant, oleic acid.
Mesothelial cell differentiation into osteoblast‐ and adipocyte‐like cells
Authors: Lansley Sally M. , Searles Richelle G. , Hoi Aina , Thomas Carla , Moneta Helena , Herrick Sarah E. , Thompson Philip J. , Mark Newman , Sterrett Gregory F. , Prêle Cecilia M. , Mutsaers Steven E.
Published: November 2010

Serosal pathologies including malignant mesothelioma (MM) can show features of osseous and/or cartilaginous differentiation although the mechanism for its formation is unknown. Mesothelial cells have the capacity to differentiate into cells with myofibroblast, smooth muscle and endothelial cell characteristics. Whether they can differentiate into other cell types is unclear. This study tests the hypothesis that mesothelial cells can differentiate into cell lineages of the embryonic mesoderm including osteoblasts and adipocytes. To examine this, a functional assay of bone formation and an adipogenic assay were performed in vitro with primary rat and human mesothelial cells maintained in osteogenic or adipogenic medium (AM) for 0–26 days. Mesothelial cells expressed increasing levels of alkaline phosphatase, an early marker of the osteoblast phenotype, and formed mineralized bone‐like nodules. Mesothelial cells also accumulated lipid indicative of a mature adipocyte phenotype when cultured in AM. All cells expressed several key osteoblast and adipocyte markers, including osteoblast‐specific runt‐related transcription factor 2, and demonstrated changes in mRNA expression consistent with epithelial‐to‐mesenchymal transition. In conclusion, these studies confirm that mesothelial cells have the capacity to differentiate into osteoblast‐ and adipocyte‐like cells, providing definitive evidence of their multipotential nature. These data strongly support mesothelial cell differentiation as the potential source of different tissue types in MM tumours and other serosal pathologies, and add support for the use of mesothelial cells in regenerative therapies.
Melatonin induces neural SOD2 expression independent of the NF‐kappaB pathway and improves the mitochondrial population and function in old mice
Authors: García‐Macia Marina , Vega‐Naredo Ignacio , De Gonzalo‐Calvo David , Rodríguez‐González Susana M. , Camello Pedro J. , Camello‐Almaraz Cristina , Martín‐Cano Francisco E. , Rodríguez‐Colunga María J. , Pozo María J. , Coto‐Montes Ana M.
Published: November 2010

Abstract:  Aging is commonly defined as a physiological phenomenon associated with morphological and functional deleterious changes in which oxidative stress has a fundamental impact; therefore, readjusting the oxidative balance should have beneficial effects. In our study, we tested the antioxidant melatonin in old mouse brains and showed positive effects at the cellular and mitochondrial levels. Melatonin attenuated β‐amyloid protein expression and α‐synuclein deposits in the brain compared to aged group. Furthermore, oxidative stress was increased by aging and induced the nuclear translocation of nuclear factor‐kappa B (NF‐κB), which was suppressed by melatonin treatment. The antioxidant mitochondrial expression, superoxide dismutase 2 (SOD2), was increased in both control and melatonin‐treated old mice, despite the different activation states of the NF‐κB pathway. The NF‐κB pathway was activated in the old mice, which may be explained by this group’s response to the increased oxidative insult; this insult was inhibited in melatonin‐treated animals, showing this group an increase in active mitochondria population that was not observed in old group. We also report that melatonin is capable of restoring the mitochondrial potential of age‐damaged neurons. In conclusion, melatonin’s beneficial effects on brain aging are linked to the increase in mitochondrial membrane potential and SOD2 expression, which probably reduces the mitochondrial contribution to the oxidative stress imbalance.
Efficacy of melatonin, mercaptoethylguanidine and 1400W in doxorubicin‐ and trastuzumab‐induced cardiotoxicity
Authors: Ozturk Mustafa , Ozler Mehmet , Kurt Yasemin Gulcan , Ozturk Bekir , Uysal Bulent , Ersoz Nail , Yasar Mehmet , Demirbas Seref , Kurt Bulent , Acikel Cengizhan , Oztas Yesim , Arpaci Fikret , Topal Turgut , Ozet Ahmet , Ataergin Selmin , Kuzhan Okan , Oter Sukru , Korkmaz Ahmet
Published: November 2010

Abstract:  Doxorubicin (DOX) and Trastuzumab (TRAST) are effective agents for the treatment of many neoplastic diseases. Cardiotoxicity is a major side effect of these drugs and limit their use. In this study, the possible protective effects of melatonin (MEL), mercaptoethylguanidine (MEG), or N‐(3‐(aminomethyl) benzyl) acetamidine (1400W) against the cardiotoxicity of DOX and TRAST were tested. Male Sprague‐Dawley rats received an injection of DOX (20 mg/kg) alone or in combination with TRAST (10 mg/kg) to induce cardiotoxicity; daily treatments with MEL (10 mg/kg × 2), MEG (10 mg/kg × 2), or 1400W (10 mg/kg × 2) were begun 36 hr before and continued for 72 hr after DOX and TRAST administration. Oxidant/antioxidant indices of the cardiac tissue, namely, malondialdehyde, superoxide dismutase (SOD) and glutathione peroxidase (GSH‐Px), as well as serum levels of creatine phosphokinase (CK‐MB) were measured. Additionally, the injury scores were evaluated histopathologically. Malondialdehyde levels were significantly higher, while SOD and GSH‐Px activities were significantly reduced in rats with DOX‐ or DOX+TRAST‐induced cardiotoxicity compared to normal values. All three treatment agents significantly reversed oxidative stress markers. Serum CK‐MB levels were significantly increased after treatment with DOX and DOX+TRAST; these changes were also reversed by each of the treatments and resulted in near normal levels. Both the DOX‐ and DOX+TRAST‐treated rats presented similar histopathologic injuries; in the animals treated with the protective agents, histologic protection of the cardiac tissue was apparent. These results suggested that MEL, MEG, as well as 1400W are effective in preventing DOX‐ or DOX+TRAST‐induced cardiotoxicity.
Applying a knowledge‐to‐action framework for primary prevention of spina bifida in tropical Africa
Authors: Claude Kasereka M. , Juvenal Kwibuka L. , Hawkes Michael
Published: November 2010

Maternal periconceptual folate supplementation reduces the incidence of neural tube defects; however, in settings where population‐level food fortification is not available, it is not clear how best to promote this prevention strategy. Guided by a knowledge‐to‐action methodology, we used mixed quantitative and qualitative methods to define the local disease burden, then designed, implemented and evaluated a culturally tailored educational intervention in eastern Democratic Republic of Congo, where resource limitations and threats to human security contribute to restricted capacity for the prevention and management of congenital malformations. A descriptive case series of 27 patients undergoing surgery for spina bifida demonstrated a short‐term mortality of 15% and long‐term disability in survivors. A survey of knowledge, attitudes and practices demonstrated a low level of folate awareness (53%) among women of reproductive age. Focus group discussions revealed exotic aetiologic views, significant gender issues and several barriers to folate use. A culturally tailored radio broadcast and an educational video were designed and produced locally based on qualitative and quantitative findings. Evaluation of the video documented high levels of viewer satisfaction and unequivocal knowledge gain (P ≤ 0.001). We conclude that spina bifida poses a significant burden on affected patients and their families in the African context, but folate is underutilized as a prevention strategy. Patient education through video media results in increased awareness and understanding of spina bifida and folate, a first step in empowering women to reduce the risk of spina bifida in their children in the absence of population‐wide food fortification.
Conserved Residues in the Subunit Interface of tau Glutathione S‐transferase Affect Catalytic and Structural Functions
Authors: Wang Cai‐Ling , Yang Hai‐Ling
Published: November 2010

The tau class glutathione S‐transferases (GSTs) have important roles in stress tolerance and the detoxification of herbicides in crops and weeds. Structural investigations of a wheat tau GST (TaGSTU4) show two subunit interactions: a hydrogen bond between the Tyr93 and Pro65 from another subunit of the dimer, and two salt bridges between residues Glu78 and side chains of Arg95 and Arg99 in the opposite subunit. By investigating enzyme activities, kinetic parameters and structural characterizations, this study showed the following results: (i) the hydrogen bond interaction between the Tyr93 and Pro65 was not essential for dimerization, but contributed to the enzyme's catalytic activity, thermal stability and affinity towards substrates glutathione and 1‐chloro‐2, 4‐dinitrobenzene; and (ii) two salt bridges mainly contributed to the protein structure stability and catalysis. The results of this study form a structural and functional basis for rational design of more selective and environmentally friendly herbicides.
Enzymatic Hydrolysis of Blue Whiting (Micromesistius poutassou); Functional and Bioactive Properties
Authors: Geirsdottir Margret , Sigurgisladottir Sjofn , Hamaguchi Patricia Y. , Thorkelsson Gudjon , Johannsson Ragnar , Kristinsson Hordur G. , Kristjansson Magnus M.
Published: November 2010

Abstract:  Functional and biochemical properties of fish protein hydrolysates (FPH) from blue whiting (BW) were studied. FPH (2.5%, 5%, 10%, and 15% degree of hydrolysis [DH]) were made from isolated proteins from headed and gutted BW with Alcalase 2.4 L. The properties of dried BW mince and protein isolate compared to 4 reference proteins (soy and milk protein) were studied: color, solubility, water‐holding capacity (WHC), oil‐binding capacity (OBC), emulsion capacity (EC), and emulsion stability (ES). The angiotensin I‐converting enzyme (ACE) inhibitory activities of the soluble fraction of BW powders were also investigated. Furthermore, the products were characterized by analyzing their chemical composition. Chemical composition, solubility, OBC, and EC of the BW powders was significantly (P < 0.05) different with different DH, while color, ES, and WHC were not significantly (P > 0.05) different. Salt content of the FPH was high (4% to 19%) and increased with increased DH. Protein solubility varied from 10% to 70% and increased with increased DH. WHC of the FPH was around 97% and was higher than that of all the reference proteins tested. OBC decreased with increased DH (from 3.5 to 2.1 g oil/g protein) and was higher than OBC of the soy and milk proteins (1.6 to 1.9 g oil/g protein). EC of FPH was similar or lower than the reference proteins. ES of FPH (60% to 90%) was similar to or lower than soy and whey proteins (60% to 98%) but higher than casein (20%). ACE inhibition activity increased as DH was increased.

Practical Application:  The results from this study demonstrate that a functional bioactive hydrolysate can be produced from BW, which is an underutilized fish species, and may aid the industry in better utilizing this raw material. The novelty of this research was the use of BW as a raw material where the protein has been isolated with the pH shift method. Furthermore, it was novel that bioactivity and functionality was measured in the same samples.
Rheology and Microstructure of Carrot and Tomato Emulsions as a Result of High‐Pressure Homogenization Conditions
Authors: Lopez‐Sanchez Patricia , Svelander Cecilia , Bialek Lucy , Schumm Stephan , Langton Maud
Published: November 2010

Abstract:  High‐pressure homogenization, as a way to further mechanically disrupt plant cells and cell walls compared to conventional blending, has been applied to thermally treated and comminuted carrot and tomato material in the presence of 5% olive oil. Mixes of both vegetables in a 1:1 ratio were also included. Both the effect of homogenization pressure and the effect of multiple process cycles were studied. The different microstructures generated were linked to different rheological properties analyzed by oscillatory and steady state measurements. The results showed that while carrot tissue requires a high shear input to be disrupted into cells and cell fragments, tomato cells were broken across the cell walls already at moderate shear input, and the nature of the tomato particles changed to amorphous aggregates, probably composed of cell contents and cell wall polymers. All the plant stabilized emulsions generated were stable against creaming under centrifugation. While for tomato a low‐pressure multiple cycle and a high‐pressure single‐cycle process led to comparable microstructures and rheological properties, carrot showed different rheological properties after these treatments linked to differences in particle morphology. Mixes of carrot and tomato showed similar rheological properties after homogenizing in a single or in a split‐stream process.

Practical Application:  Following consumers’ demand, the food industry has shown a growing interest in manufacturing products free of gums and stabilizers, which are often perceived as artificial. By tailored processing, fresh plant material could be used to structure food products in a more natural way while increasing their nutritional quality.
Refrigerated Dough Quality: Effect of Environment and Genotypes of Hard Red Spring Wheat
Authors: Simsek S. , Whitney K.L. , Ohm J.B. , Anderson J. , Mergoum M.
Published: November 2010

Abstract:  Refrigerated dough products use wheat flour as their primary ingredient, so the quality and chemical composition of the flour determine the quality of the final product. Six varieties of hard red spring wheat, grown in 3 locations in Minnesota, U.S.A., were evaluated for use in refrigerated dough products. Total arabinoxylan percentages in the flours ranged from 0.97 to 1.54. Xylanase activity of the flour was measured and ranged from 0.20 to 0.84 mU/g. An important factor in the suitability for refrigerated dough is the syruping during storage. A large amount of variability in dough syruping was observed among the varieties and locations when the extent of dough syruping was measured over a period of 10 d. The mean dough syruping on day 10 ranged from 2.05% to 14.83%. Despite the significant interaction effect of genotype and environment, 2 varieties, Glenn and Oklee, had lower dough syrup formation with greater stability across growing locations and storage days than other varieties.

Practical Application:  Refrigerated dough production is one of the fastest growing segments of the ready‐to‐use food industry. Well‐formulated and processed refrigerated doughs are practical to consume and should stay fresh during extended periods of storage; thus, maintenance of dough quality during refrigeration is critical. This study was designed to perform the research on genotypic and environmental effects on variations in dough syruping during refrigeration storage of doughs from hard red spring wheats.
Reapplication Improves the Amount of Sunscreen, not its Regularity, Under Real Life Conditions†
Authors: De Villa Damiê , da Silva Nagatomi Aline Rodrigues , Paese Karina , Guterres Silvia , Cestari Tania Ferreira
Published: November 2010

The sun protection factor (SPF) of sunscreens is determined using samples applied with a thickness of 2 mg cm−2. Sunscreen users, however, typically apply sunscreen nonuniformly and in smaller amounts. The objective of our study was to verify whether sunscreen reapplication increases the amount and regularity of the product on the skin. Volunteers were asked to apply an SPF 6 sunscreen on their forearms and reapply it 30 min later on one forearm. Tape‐strips were used to collect five samples from two different sites on each forearm. The concentration of benzophenone‐3 in the samples was measured and the total amount of sunscreen was estimated using high‐performance liquid chromatography. The median amount of sunscreen film was 0.43 mg cm−2 (0.17–1.07) after one application and 0.95 mg cm−2 (0.18–1.91) after two applications (P = 0.002). No significant difference was found in the film uniformity. Though sunscreen reapplication increases the amount of product on the skin, levels are still lower than the recommended amount, confirming that the protection level is less than the product‐stated SPF. Our results are the first in the literature to support the recommendation for reapplying sunscreens. Based on our results, we recommend that sunscreens be labeled using qualitative measures.
Interior textures, chemical compositions, and noble gas signatures of Antarctic cosmic spherules: Possible sources of spherules with long exposure ages
Authors: OSAWA Takahito , YAMAMOTO Yukio , NOGUCHI Takaaki , IOSE Akari , NAGAO Keisuke
Published: November 2010

Abstract– The interior texture and chemical and noble gas composition of 99 cosmic spherules collected from the meteorite ice field around the Yamato Mountains in Antarctica were investigated. Their textures were used to classify the spherules into six different types reflecting the degree of heating: 13 were cryptocrystalline, 40 were barred olivine, 3 were porphyritic A, 24 were porphyritic B, 9 were porphyritic C, and 10 were partially melted spherules. While a correlation exists between the type of spherule and its noble gas content, there is no significant correlation between its chemical composition and noble gas content. Fifteen of the spherules still had detectable amounts of extraterrestrial He, and the majority of them had 3He/4He ratios that were close to that of solar wind (SW). The Ne isotopic composition of 28 of the spherules clustered between implantation‐fractionated SW and air. Extraterrestrial Ar, confirmed to be present because it had a 40Ar/36Ar ratio lower than that of terrestrial atmosphere, was found in 35 of the spherules. An enigmatic spherule, labeled M240410, had an extremely high concentration of cosmogenic nuclides. Assuming 4π exposure to galactic and solar cosmic rays as a micrometeoroid and no exposure on the parent body, the cosmic‐ray exposure (CRE) age of 393 Myr could be computed using cosmogenic 21Ne. Under these model assumptions, the inferred age suggests that the particle might have been an Edgeworth‐Kuiper Belt object. Alternatively, if exposure near the surface of its parent body was dominant, the CRE age of 382 Myr can be estimated from the cosmogenic 38Ar using the production rate of the 2π exposure geometry, and implies that the particle may have originated in the mature regolith of an asteroid.
Posterior resin composite restorations with or without resin‐modified, glass‐ionomer cement lining: a 1‐year randomized, clinical trial
Authors: Banomyong Danuchit , Harnirattisai Choltacha , Burrow Michael F.
Published: November 2010

Aim:  To investigate the effect of resin‐modified, glass‐ionomer cement lining on the quality of posterior resin composite restorations, bonded with a two‐step, total‐etch or self‐etching adhesive, at 1 year.

Methods:  Patients with 1–4 moderate‐to‐deep, primary occlusal caries in molars were informed and recruited. A total of 110 composite restorations were placed in 75 participants, with one of four restorative procedures: (a) bonded with a total‐etch adhesive (Single Bond 2); (b) lined with glass‐ionomer cement (Fuji Lining LC), and then bonded with total‐etch adhesive; (c) bonded with a self‐etching adhesive (Clearfil SE Bond); and (d) lined with glass‐ionomer cement, and then bonded with self‐etching adhesive.

Results:  At 1 year, 57 patients (86 restorations) attended the recall. Each of the restorations was evaluated and scored from 1 (clinically excellent) to 5 (clinically poor) using the following criteria: (a) patient satisfaction; (b) fracture and retention; (c) marginal adaptation; (d) recurrent caries; and (e) post‐operative sensitivity. At 1 year, the qualities of the restorations were not significantly affected by the placement of glass‐ionomer cement lining, regardless of the adhesive used (P > 0.05). Most of the restorations were scored 1 for all criteria.

Conclusions:  The benefit of placing a glass‐ionomer cement liner in resin composite restoration is questionable.
Esophageal changes in oral submucous fibrosis using fiber‐optic endoscopy
Authors: Shilpa Busnur Jayadevappa , Ashok Lingappa , Veerendra Swamy Sanganal Mat
Published: November 2010

Aim:  The aim of this study was to determine the extent of esophageal involvement and the association between the clinical and functional stages of oral submucous fibrosis and esophageal changes in oral submucous fibrosis patients.

Methods:  Thirty of 35 biopsied patients with proven oral submucous fibrosis, and 20 patients with no evidence of disease, underwent upper gastrointestinal endoscopy. Biopsies were taken from upper third, middle third, and lower third of the esophagus and sent for histopathological evaluation. The esophageal changes in the clinical and functional stages were studied both endoscopically and histopathologically.

Results:  We found that most patients had blanching in clinical stage 2, functional stage B, and functional stage C. In most patients, blanching was found in the upper third of the esophagus, followed by the middle third and lower third. Fibrosis in the middle third of the esophagus was found in most patients.

Conclusion:  The present study concludes that oral submucous fibrosis is not only confined to the oral cavity, but also extends to the esophagus. We found that there is an inverse relationship between the opening of the mouth and esophageal involvement.
Friction Factor Estimation for Turbulent Flows in Corrugated Pipes with Rough Walls
Authors: Pisarenco Maxim , van der Linden Bas , Tijsseling Arris , Ory Emmanuel , Dam Jacques
Published: November 2010

The motivation of the investigation is the critical pressure loss in cryogenic flexible hoses used for LNG transport in offshore installations. Our main goal is to estimate the friction factor for the turbulent flow in this type of pipes. For this purpose, two-equation turbulence models (k−ϵ and k−ω) are used in the computations. First, the fully developed turbulent flow in a conventional pipe is considered. Simulations are performed to validate the chosen models, boundary conditions, and computational grids. Then a new boundary condition is implemented based on the “combined” law of the wall. It enables us to model the effects of roughness (and maintain the right flow behavior for moderate Reynolds numbers). The implemented boundary condition is validated by comparison with experimental data. Next, the turbulent flow in periodically corrugated (flexible) pipes is considered. New flow phenomena (such as flow separation) caused by the corrugation are pointed out and the essence of periodically fully developed flow is explained. The friction factor for different values of relative roughness of the fabric is estimated by performing a set of simulations. Finally, the main conclusion is presented: The friction factor in a flexible corrugated pipe is mostly determined by the shape and size of the steel spiral, and not by the type of the fabric, which is wrapped around the spiral.
SYNTHESIS OF PHOTOLUMINESCENT CORE-SHELL SILICA PARTICLES BY SACRIFICIAL POLYMER SHELL METHOD
Authors: GHAHARI MEHDI , FABBRI PAOLA , EBADZADEH TOURADJ , AGHABABAZADEH ROYA , PILATI FRANCESCO , HESARI FREYDOON ALIKHANI
Published: November 2010

A novel approach has been developed for the synthesis of SiO2 @ Y2O3:Eu3+ particles with core-shell structure. In this method the polymer shell is obtained by copolymerization of methacryl oxyethyl isocyanate onto silica particles which are chemically modified by 3-(trimethoxysilyl) propyl methacrylate. The grafted polymer acts as template to prepare the luminescent shell on silica particles. Then, the obtained silica-polymer core-shell particles are dispersed in a solution of Yttrium and Europium nitrates to allow a physical adsorption of the ions by the polymer shell. The sacrificial polymer shell will be removed by thermal treatment to obtain photoluminescent SiO2 @ Y2O3:Eu3+ core-shell particles. Results reveal that the intensity of photoluminescence of these core-shell particles is much higher than intensity of particles prepared without sacrificial polymer shell.
SYNTHESIS OF YTTRIA-STABILIZED CUBIC ZIRCONIA NANOCRYSTALS BY ULTRASONIC–MICROWAVE ROUTE
Authors: WANG JIAN-DONG , LUO CHONG-XIAO , LIU JIN-KU , LU YI , LI GUANG-MING
Published: November 2010

The yttria-stabilized zirconia (YSZ) nanocrystals with uniform size, high purity, and high degree of crystallinity, were prepared by ultrasonic–microwave-assisted method. The structure, optical properties and morphologies of YSZ nanocrystals were characterized by X-ray powder diffraction (XRD), Raman spectroscopy, UV–vis absorption, scanning electron microscope (SEM) and transmission electron microscopy (TEM). The SEM and TEM images of the YSZ nanocrystals indicate that the product is a mono-dispersion structure with an average particle size of about 25 nm.
The Telomerase Inhibitor Imetelstat Depletes Cancer Stem Cells in Breast and Pancreatic Cancer Cell Lines
Authors: Joseph Immanual , Tressler Robert , Bassett Ekaterina , Harley Calvin , Buseman Christen M. , Pattamatta Preeti , Wright Woodring E. , Shay Jerry W. , Go Ning F.
Published: November 2010

Cancer stem cells (CSC) are rare drug-resistant cancer cell subsets proposed to be responsible for the maintenance and recurrence of cancer and metastasis. Telomerase is constitutively active in both bulk tumor cell and CSC populations but has only limited expression in normal tissues. Thus, inhibition of telomerase has been shown to be a viable approach in controlling cancer growth in nonclinical studies and is currently in phase II clinical trials. In this study, we investigated the effects of imetelstat (GRN163L), a potent telomerase inhibitor, on both the bulk cancer cells and putative CSCs. When breast and pancreatic cancer cell lines were treated with imetelstat in vitro, telomerase activity in the bulk tumor cells and CSC subpopulations were inhibited. Additionally, imetelstat treatment reduced the CSC fractions present in the breast and pancreatic cell lines. In vitro treatment with imetelstat, but not control oligonucleotides, also reduced the proliferation and self-renewal potential of MCF7 mammospheres and resulted in cell death after <4 weeks of treatment. In vitro treatment of PANC1 cells showed reduced tumor engraftment in nude mice, concomitant with a reduction in the CSC levels. Differences between telomerase activity expression levels or telomere length of CSCs and bulk tumor cells in these cell lines did not correlate with the increased sensitivity of CSCs to imetelstat, suggesting a mechanism of action independent of telomere shortening for the effects of imetelstat on the CSC subpopulations. Our results suggest that imetelstat-mediated depletion of CSCs may offer an alternative mechanism by which telomerase inhibition may be exploited for cancer therapy. Cancer Res; 70(22); 9494–504. ©2010 AACR.
Global Downstream Pathway Analysis Reveals a Dependence of Oncogenic NF-E2–Related Factor 2 Mutation on the mTOR Growth Signaling Pathway
Authors: Shibata Tatsuhiro , Saito Shigeru , Kokubu Akiko , Suzuki Takafumi , Yamamoto Masayuki , Hirohashi Setsuo
Published: November 2010

In multicellular organisms, adaptive responses to oxidative stress are regulated by NF-E2–related factor 2 (NRF2), a master transcription factor of antioxidant genes and phase II detoxifying enzymes. Aberrant activation of NRF2 by either loss-of-function mutations in the Keap1 gene or gain-of-function mutations in the Nrf2 gene occurs in a wide range of human cancers, but details of the biological consequences of NRF2 activation in the cancer cells remain unclear. Here, we report that mutant NRF2 induces epithelial cell proliferation, anchorage-independent growth, and tumorigenicity and metastasis in vivo. Genome-wide gene expression profiling revealed that mutant NRF2 affects diverse molecular pathways including the mammalian target of rapamycin (mTOR) pathway. Mutant NRF2 upregulates RagD, a small G-protein activator of the mTOR pathway, which was also overexpressed in primary lung cancer. Consistently, Nrf2-mutated lung cancer cells were sensitive to mTOR pathway inhibitors (rapamycin and NVP-BEZ235) in both in vitro and an in vivo xenograft model. The gene expression signature associated with mutant NRF2 was a marker of poor prognosis in patients with carcinoma of the head and neck region and lung. These results show that oncogenic Nrf2 mutation induces dependence on the mTOR pathway during carcinogenesis. Our findings offer a rationale to target NRF2 as an anticancer strategy, and they suggest NRF2 activation as a novel biomarker for personalized molecular therapies or prognostic assessment. Cancer Res; 70(22); 9095–105. ©2010 AACR.
Insulin-Like Growth Factor I Suppresses Bone Morphogenetic Protein Signaling in Prostate Cancer Cells by Activating mTOR Signaling
Authors: Wahdan-Alaswad Reema S. , Song Kyung , Krebs Tracy L. , Shola Dorjee T.N. , Gomez Jose A. , Matsuyama Shigemi , Danielpour David
Published: November 2010

Insulin-like growth factor (IGF) I and bone morphogenetic proteins (BMP) are critical regulators of prostate tumor cell growth. In this report, we offer evidence that a critical support of IGF-I in prostate cancer is mediated by its ability to suppress BMP4-induced apoptosis and Smad-mediated gene expression. Suppression of BMP4 signaling by IGF-I was reversed by chemical inhibitors of phosphoinositide 3-kinase (PI3K), Akt, or mTOR; by enforced expression of wild-type PTEN or dominant-negative PI3K; or by small hairpin RNA–mediated silencing of mTORC1/2 subunits Raptor or Rictor. Similarly, IGF-I suppressed BMP4-induced transcription of the Id1, Id2, and Id3 genes that are crucially involved in prostate tumor progression through PI3K-dependent and mTORC1/2-dependent mechanisms. Immunohistochemical analysis of non-malignant and malignant prostate tissues offered in vivo support for our model that IGF-I–mediated activation of mTOR suppresses phosphorylation of the BMP-activated Smad transcription factors. Our results offer the first evidence that IGF-I signaling through mTORC1/2 is a key homeostatic regulator of BMP4 function in prostate epithelial cells, acting at two levels to repress both the proapoptotic and pro-oncogenic signals of BMP-activated Smads. We suggest that deregulation of this homeostatic control may be pivotal to the development and progression of prostate cancer, providing important implications and new potential targets for the therapeutic intervention of this malignancy. Cancer Res; 70(22); 9106–17. ©2010 AACR.
Synergistic Enhancement of Carboplatin Efficacy with Photodynamic Therapy in a Three-Dimensional Model for Micrometastatic Ovarian Cancer
Authors: Rizvi Imran , Celli Jonathan P. , Evans Conor L. , Abu-Yousif Adnan O. , Muzikansky Alona , Pogue Brian W. , Finkelstein Dianne , Hasan Tayyaba
Published: November 2010

Metastatic ovarian cancer (OvCa) frequently recurs due to chemoresistance, highlighting the need for nonoverlapping combination therapies that mechanistically synergize to eradicate residual disease. Photodynamic therapy (PDT), a photochemistry-based cytotoxic modality, sensitizes ovarian tumors to platinum agents and biologics and has shown clinical promise against ovarian carcinomatosis. We introduce a three-dimensional (3D) model representing adherent ovarian micrometastases and high-throughput quantitative imaging methods to rapidly screen the order-dependent effects of combining benzoporphyrin-derivative (BPD) monoacid A–based PDT with low-dose carboplatin. 3D ovarian micronodules grown on Matrigel were subjected to BPD-PDT either before or after carboplatin treatment. We developed custom fluorescence image analysis routines to quantify residual tumor volume and viability. Carboplatin alone did not eradicate ovarian micrometastases at a dose of 400 mg/m2, leaving surviving cores that were nonsensitive or impermeable to chemotherapy. BPD-PDT (1.25 μmol/L·J/cm2) created punctate cytotoxic regions within tumors and disrupted micronodular structure. Treatment with BPD-PDT prior to low-dose carboplatin (40 mg/m2) produced a significant synergistic reduction [P < 0.0001, analysis of covariance (ANCOVA)] in residual tumor volume [0.26; 95% confidence interval (95% CI), 0.19–0.36] compared with PDT alone (0.76; 95% CI, 0.63–0.92) or carboplatin alone (0.95; 95% CI, 0.83–1.09), relative to controls. This synergism was not observed with the reverse treatment order. Here, we demonstrate for the first time the use of a 3D model for micrometastatic OvCa as a rapid and quantitative reporter to optimize sequence and dosing regimens of clinically relevant combination strategies. This approach combining biological modeling with high-content imaging provides a platform to rapidly screen therapeutic strategies for a broad array of metastatic tumors. Cancer Res; 70(22); 9319–28. ©2010 AACR.
Highly Active Antitumor Therapy (HAATT) for Epidermal Growth Factor Receptor–Mutant Lung Cancer
Authors: Chmielecki Juliann , Pao William
Published: November 2010

In vitro resistance modeling coupled with molecular analysis of autopsy tumor samples from patients with acquired resistance to epidermal growth factor receptor (EGFR) inhibitors in lung cancer reveal novel biological insights into mechanisms of disease progression. These kinds of studies will facilitate the development of rationally targeted therapies in the era of genetically informed cancer medicine. Clin Cancer Res; 16(22); 5371–3. ©2010 AACR.
RITA Inhibits Multiple Myeloma Cell Growth through Induction of p53-Mediated Caspase-Dependent Apoptosis and Synergistically Enhances Nutlin-Induced Cytotoxic Responses
Authors: Saha Manujendra N. , Jiang Hua , Mukai Asuka , Chang Hong
Published: November 2010

Mutations or deletions of p53 are relatively rare in multiple myeloma (MM), at least in newly diagnosed patients. Thus, restoration of p53 tumor suppressor function in MM by blocking the inhibitory role of murine double minute 2 (MDM2) is a promising and applicable therapeutic strategy. RITA and nutlin are two new classes of small molecule MDM2 inhibitors that prevent the p53-MDM2 interaction. Earlier reports showed p53-dependent activity of RITA in solid tumors as well as in leukemias. We and others recently described nutlin-induced apoptosis in MM cells, but it remains unclear whether RITA exerts antimyeloma activity. Here, we found that RITA activates the p53 pathway and induces apoptosis in MM cell lines and primary MM samples, preferentially killing myeloma cells. The activation of p53 induced by RITA was mediated through modulation of multiple apoptotic regulatory proteins, including upregulation of a proapoptotic protein (NOXA), downregulation of an antiapoptotic protein, Mcl-1, and activation of caspases through extrinsic pathways. Moreover, a number of key p53-mediated apoptotic target genes were identified by gene expression profiling and further validated by quantitative real-time PCR. Importantly, the combination of RITA with nutlin displayed a strong synergism on growth inhibition with the combination index ranging from 0.56 to 0.82 in MM cells. Our data support further clinical evaluation of RITA as a potential novel therapeutic intervention in MM. Mol Cancer Ther; 9(11); 3041–51. ©2010 AACR.
Cucurbitacin I Suppressed Stem-Like Property and Enhanced Radiation-Induced Apoptosis in Head and Neck Squamous Carcinoma–Derived CD44+ALDH1+ Cells
Authors: Chen Yi-Wei , Chen Kuan-Hsuan , Huang Pin-I , Chen Yu-Chih , Chiou Guang-Yu , Lo Wen-Liang , Tseng Ling-Ming , Hsu Han-Sui , Chang Kuo-Wei , Chiou Shih-Hwa
Published: November 2010

Head and neck squamous cell carcinoma (HNSCC) is a prevalent cancer worldwide. Signal transducers and activators of transcription 3 (STAT3) signaling is reported to promote tumor malignancy and recurrence in HNSCC. Cucurbitacins, triterpenoid derivatives, are strong STAT3 inhibitors with anticancer properties. Recent studies have shown aldehyde dehydrogenase 1 (ALDH1) to be a marker of cancer stem cells (CSC) in HNSCC. The aim of this study was to investigate the therapeutic effect of cucurbitacin I in HNSCC-derived CSCs. Using immunohistochemical analysis, we firstly showed that CD44, ALDH1, and phosphorylated STAT3 (p-STAT3) were higher in high-grade HNSCCs, and that triple positivity for CD44/ALDH1/p-STAT3 indicated a worse prognosis for HNSCC patients. Secondly, CD44+ALDH1+ cells isolated from seven HNSCC patients showed greater tumorigenicity, radioresistance, and high expression of stemness (Bmi-1/Oct-4/Nanog) and epithelial-mesenchymal-transitional (Snail/Twist) genes as p-STAT3 level increased. Furthermore, we found that cucurbitacin I (JSI-124) can effectively inhibit the expression of p-STAT3 and capacities for tumorigenicity, sphere formation, and radioresistance in HNSCC-CD44+ALDH1+. Notably, 150 nmol/L cucurbitacin I effectively blocked STAT3 signaling and downstream survivin and Bcl-2 expression, and it induced apoptosis in HNSCC-CD44+ALDH1+. Moreover, microarray data indicated that 100 nmol/L cucurbitacin I facilitated CD44+ALDH1+ cells to differentiate into CD44−ALDH1− and enhanced the radiosensitivity of HNSCC-CD44+ALDH1+. Xenotransplant experiments revealed that cucurbitacin I combined with radiotherapy significantly suppressed tumorigenesis and lung metastasis and further improved the survival rate in HNSCC-CD44+ALDH1+-transplanted immunocompromised mice. Taken together, our data show that cucurbitacin I, STAT3 inhibitor, reduces radioresistant, distant-metastatic, and CSC-like properties of HNSCC-CD44+ALDH1+ cells. The potential of cucurbitacin I as a radiosensitizer should be verified in future anti-CSC therapy. Mol Cancer Ther; 9(11); 2879–92. ©2010 AACR.
Evaluation of Sclerotherapy with a New Sclerosing Agent and Stapled Hemorrhoidopexy for Prolapsing Internal Hemorrhoids: Retrospective Comparison with Hemorrhoidectomy
Authors: Tokunaga Yukihiko , Sasaki Hirokazu , Saito Tohru
Published: November 2010

Background: We retrospectively compared the results of sclerotherapy with a new sclerosing agent (aluminum potassium sulphate/tannic acid) and hemorrhoidopexy using an improved type of circular stapler with hemorrhoidectomy. Methods: Between January 2006 and September 2008, we performed hemorrhoidectomy in 416 patients, sclerotherapy in 784 patients and hemorrhoidopexy in 118 patients with prolapsing internal hemorrhoids. Results: The median volume of the agent injected into a hemorrhoid was 7 ml (interquartile range = 4). The operation duration was significantly shorter (p < 0.01) in sclerotherapy, 13 min (interquartile range = 7), than in hemorrhoidectomy, 43 min (interquartile range = 15), and hemorrhoidopexy, 31 min (interquartile range = 16). Postoperative pain, needing pain killer injection, occurred in 59 patients (14%) in hemorrhoidectomy, 14 patients (1.8%) in sclerotherapy and 1 patient (0.8%) in hemorrhoidopexy (p < 0.01). The disappearance rates of prolapse were 100% (416/416 patients) in hemorrhoidectomy, 96% (753/784 patients) in sclerotherapy and 98.3% (116/118 patients) in hemorrhoidopexy. Conclusions: Hemorrhoidectomy, widely applied for hemorrhoids, needs hospitalization, being accompanied by pain. Sclerotherapy could be performed on outpatient bases without any severe pain or complication. Hemorrhoidopexy is a useful alternative treatment with less pain. Less invasive treatments would be useful when performed paying attention to avoid complications.
Myocardial Perfusion Grade After Late Infarct Artery Recanalization Is Associated With Global and Regional Left Ventricular Function at One Year
Authors: Steigen Terje K. , Buller Christopher E. , John Mancini G.B. , Jorapur Vinod , Cantor Warren J. , Rankin James M. , Thomas Boban , Webb John G. , Kronsberg Shari S. , Atchison Deborah J. , Lamas Gervasio A. , Hochman Judith S. , Džavík Vladimír
Published: November 2010

Background—

Whether myocardial perfusion grade (MPG) following late recanalization of infarct-related arteries (IRAs) predicts left ventricular (LV) function recovery beyond the acute phase of myocardial infarction (MI) is unknown.

Methods and Results—

The Total Occlusion Study of Canada-2 enrolled stable patients with a persistently occluded IRA beyond 24 hours and up to 28 days post-MI. We studied the relationship between the initial MPG and changes in LV function and volume as well as the change in MPG from immediate post-percutaneous coronary intervention (PCI) to 1 year in 139 PCI patients with thrombolysis in myocardial infarction grade 3 epicardial flow post-PCI and with paired values grouped into impaired or good MPG groups (MPG 0/1 or MPG 2/3). MPG 0/1 patients were more likely to have received thrombolytic therapy and to have a left anterior descending IRA. They had lower blood pressure and LV ejection fraction (LVEF) and a higher heart rate and systolic sphericity index at baseline. Changes in the MPG 0/1 and MPG 2/3 groups from baseline to 1 year were LVEF, 3.3±9.0% and 4.8±8.9% (
P
=0.42); LV end-systolic volume index (LVESVI), −1.1±9.2 and −4.7±12.3 mL/m
2
(
P
=0.25); LV end-diastolic volume index (LVEDVI), 0.08±19.1 and −2.4±22.2 mL/m
2
(
P
=0.67); and SDs/chord for infarct zone wall motion index (WMI), 0.38±0.70 and 0.84±1.11 (
P
=0.01). By covariate-adjusted analysis, post-PCI MPG 0/1 predicted lower WMI (
P
<0.001), lower LVEF (
P
<0.001), and higher LVESVI (
P
<0.01) but not LVEDVI at 1 year. Of the MPG 0/1 patients, 60% were MPG 2 or 3 at 1 year.

Conclusions—

Preserved MPG is present in a high proportion of patients following late PCI of occluded IRAs post-MI. Poor MPG post-PCI frequently improves MPG over 1 year. MPG graded after IRA recanalization undertaken days to weeks post MI is associated with LV recovery, indicating that MPG determined in the subacute post-MI period remains a marker of viability.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00025766.
Probabilistic Visibility Forecasting Using Bayesian Model Averaging
Authors: Chmielecki Richard M. , Raftery Adrian E.
Published: November 2010

Bayesian model averaging (BMA) is a statistical postprocessing technique that has been used in probabilistic weather forecasting to calibrate forecast ensembles and generate predictive probability density functions (PDFs) for weather quantities. The authors apply BMA to probabilistic visibility forecasting using a predictive PDF that is a mixture of discrete point mass and beta distribution components. Three approaches to developing predictive PDFs for visibility are developed, each using BMA to postprocess an ensemble of visibility forecasts. In the first approach, the ensemble is generated by a translation algorithm that converts predicted concentrations of hydrometeorological variables into visibility. The second approach augments the raw ensemble visibility forecasts with model forecasts of relative humidity and quantitative precipitation. In the third approach, the ensemble members are generated from relative humidity and precipitation alone. These methods are applied to 12-h ensemble forecasts from 2007 to 2008 and are tested against verifying observations recorded at Automated Surface Observing Stations in the Pacific Northwest. Each of the three methods produces predictive PDFs that are calibrated and sharp with respect to both climatology and the raw ensemble.