bluuebunny/crossref_metadata_2025 huggingface dataset:
Hypoxia Promotes the Production and Inhibits the Destruction of Human Articular Cartilage
Authors: Thoms Brendan L. , Dudek Katarzyna A. , Lafont Jérôme E. , Murphy Christopher L.
Published: January 2013

Objective

To determine the effects of hypoxia on both anabolic and catabolic pathways of metabolism in human articular cartilage and to elucidate the roles played by hypoxia‐inducible factors (HIFs) in these responses.

Methods

Normal human articular cartilage from a range of donors was obtained at the time of above‐the‐knee amputations due to sarcomas not involving the joint space. Fresh cartilage tissue explants and isolated cells were subjected to hypoxia and treatment with interleukin‐1α. Cell transfections were performed on isolated human chondrocytes.

Results

Using chromatin immunoprecipitation, we found that hypoxia induced cartilage production in human tissue explants through direct binding of HIF‐2α to a specific site in the master‐regulator gene SOX9. Importantly, hypoxia also suppressed spontaneous and induced destruction of human cartilage in explant culture. We found that anticatabolic responses were predominantly mediated by HIF‐1α. Manipulation of the hypoxia‐sensing pathway through depletion of HIF‐targeting prolyl hydroxylase–containing protein 2 (PHD‐2) further enhanced cartilage responses as compared to hypoxia alone. Hypoxic regulation of tissue‐specific metabolism similar to that in human cartilage was observed in pig, but not mouse, cartilage.

Conclusion

We found that resident chondrocytes in human cartilage are exquisitely adapted to hypoxia and use it to regulate tissue‐specific metabolism. Our data revealed that while fundamental regulators, such as SOX9, are key molecules both in mice and humans, the way in which they are controlled can differ. This is all the more important since it is upstream regulators such as this that need to be directly targeted for therapeutic benefit. HIF‐specific hydroxylase PHD‐2 may represent a relevant target for cartilage repair.
Curcumin and aging
Authors: Shen Li‐Rong , Parnell Laurence D. , Ordovas Jose M. , Lai Chao‐Qiang
Published: January 2013

Turmeric has been used commonly as a spice, food additive, and an herbal medicine worldwide. Known as a bioactive polyphenolic extract of Turmeric, curcumin has a broad range of health benefit properties for humans. Recently, active research on curcumin with respect to aging and related traits in model organisms has demonstrated that curcumin and its metabolite, tetrahydrocurcumin (THC), increase mean lifespan of at least three model organisms: nematode roundworm, fruit flyDrosophila,and mouse. Nematodes grown on media containing curcumin showed a significantly increased lifespan by reducing the production of reactive oxygen species. Genesosr‐1, sek‐1, mek‐1, skn‐1, unc‐43, sir‐2.1, andage‐1are required for curcumin‐mediated lifespan extension. The lifespan extension ofDrosophilaby curcumin supplementation was associated with increased superoxide dismutase (SOD) activity, and decreased lipofuscin and malondialdehyde levels. Curcumin up‐regulated expression of SOD genes and down‐regulated expression of several age‐related genes, such asdInR, ATTD, Def, CecB,andDptB.In addition, THC extended lifespan inDrosophilaand inhibited the oxidative stress response by regulatingFOXOandSir2.Mice fed diets containing THC starting at the age of 13 months had significantly increased mean lifespan. In summary, the positive effects of curcumin on lifespan extension likely arise from beneficial regulation of common oxidative stress responses and age‐related genes. Understanding the molecular mechanism(s) of curcumin action has provided base knowledge and rationale for future human clinical trials, and for nutritional intervention in aging and age‐associated disorders in humans. © 2013 BioFactors, 39(1):133–140, 2013
Crystal structure of the collagen model peptide (Pro‐Pro‐Gly)4‐Hyp‐Asp‐Gly‐(Pro‐Pro‐Gly)4 at 1.0 Å resolution
Authors: Okuyama Kenji , Kawaguchi Tatsuya , Shimura Masaki , Noguchi Keiichi , Mizuno Kazunori , Bächinger Hans Peter
Published: January 2013

The single‐crystal structure of the collagen‐like peptide (Pro‐Pro‐Gly)4‐Hyp‐Asp‐Gly‐(Pro‐Pro‐Gly)4, was analyzed at 1.02 Å resolution. The overall average helical twist (θ = 49.6°) suggests that this peptide adopts a 7/2 triple‐helical structure and that its conformation is very similar to that of (Gly‐Pro‐Hyp)9, which has the typical repeating sequence in collagen. High‐resolution studies on other collagen‐like peptides have shown that imino acid‐rich sequences preferentially adopt a 7/2 triple‐helical structure (θ = 51.4°), whereas imino acid‐lean sequences adopt relaxed conformations (θ < 51.4°). The guest Gly‐Hyp‐Asp sequence in the present peptide, however, has a large helical twist (θ = 61.1°), whereas that of the host Pro‐Pro‐Gly sequence is small (θ = 46.7°), indicating that the relationship between the helical conformation and the amino acid sequence of such peptides is complex. In the present structure, a strong intermolecular hydrogen bond between two Asp residues on the A and B strands might induce the large helical twist of the guest sequence; this is compensated by a reduced helical twist in the host, so that an overall 7/2‐helical symmetry is maintained. The Asp residue in the C strand might interact electrostatically with the N‐terminus of an adjacent molecule, causing axial displacement, reminiscent of the D‐staggered structure in fibrous collagens. © 2013 Wiley Periodicals, Inc. Biopolymers 99: 436–447, 2013.
Biotinylated Phosphoproteins from Kinase‐Catalyzed Biotinylation are Stable to Phosphatases: Implications for Phosphoproteomics
Authors: Senevirathne Chamara , Pflum Mary Kay H.
Published: January 2013

Kinase‐catalyzed protein phosphorylation is involved in a wide variety of cellular events. Development of methods to monitor phosphorylation is critical to understand cell biology. Our lab recently discovered kinase‐catalyzed biotinylation, where ATP‐biotin is utilized by kinases to label phosphopeptides or phosphoproteins with a biotin tag. To exploit kinase‐catalyzed biotinylation for phosphoprotein purification and identification in a cellular context, the susceptibility of the biotin tag to phosphatases was characterized. We found that the phosphorylbiotin group on peptide and protein substrates was relatively insensitive to protein phosphatases. To understand how phosphatase stability would impact phosphoproteomics research applications, kinase‐catalyzed biotinylation of cell lysates was performed in the presence of kinase or phosphatase inhibitors. We found that biotinylation with ATP‐biotin was sensitive to inhibitors, although with variable effects compared to ATP phosphorylation. The results suggest that kinase‐catalyzed biotinylation is well suited for phosphoproteomics studies, with particular utility towards monitoring low‐abundance phosphoproteins or characterizing the influence of inhibitor drugs on protein phosphorylation.
Synthesis and Reactivity of Cationic Triruthenium Clusters Derived from 2‐Methyl‐ and 4‐Methylpyrimidines: From Conventional Cyclometalated Ligands to Novel Types of N‐Heterocyclic Carbenes
Authors: Cabeza Javier A. , García‐Álvarez Pablo , Pérez‐Carreño Enrique , Pruneda Vanessa
Published: January 2013

The methylation of the uncoordinated nitrogen atom of the cyclometalated triruthenium cluster complexes [Ru3(μ‐H)(μ‐κ2N1,C6‐2‐Mepyr)(CO)10] (1; 2‐MepyrH=2‐methylpyrimidine) and [Ru3(μ‐H)(μ‐κ2N1,C6‐4‐Mepyr)(CO)10] (9; 4‐MepyrH=4‐methylpyrimidine) gives two similar cationic complexes, [Ru3(μ‐H)(μ‐κ2N1,C6‐2,3‐Me2pyr)(CO)10]+(2+) and [Ru3(μ‐H)(μ‐κ2N1,C6‐3,4‐Me2pyr)(CO)10]+ (9+), respectively, whose heterocyclic ligands belong to a novel type of N‐heterocyclic carbenes (NHCs) that have the Ccarbene atom in 6‐position of a pyrimidine framework. The position of the C‐methyl group in the ligands of complexes 2+ (on C2) and 9+ (on C4) is of key importance for the outcome of their reactions with K[N(SiMe3)2], K‐selectride, and cobaltocene. Although these reagents react with 2+ to give [Ru3(μ‐H)(μ‐κ2N1,C6‐2‐CH2‐3‐Mepyr)(CO)10] (3; deprotonation of the C2‐Me group), [Ru3(μ‐H)(μ3‐κ3N1,C5,C6‐4‐H‐2,3‐Me2pyr)(CO)9] (4; hydride addition at C4), and [Ru6(μ‐H)2{μ6‐κ6N1,N1′,C5,C5′,C6,C6′‐4,4′‐bis(2,3‐Me2pyr)}(CO)18] (5; reductive dimerization at C4), respectively, similar reactions with 9+ have only allowed the isolation of [Ru3(μ‐H)(μ3‐κ2N1,C6‐2‐H‐3,4‐Me2pyr)(CO)9] (11; hydride addition at C2). Compounds 3 and 11 also contain novel six‐membered ring NHC ligands. Theoretical studies have established that the deprotonation of 2+ and 9+ (that have ligand‐based LUMOs) are charge‐controlled processes and that both the composition of the LUMOs of these cationic complexes and the steric protection of their ligand ring atoms govern the regioselectivity of their nucleophilic addition and reduction reactions.
Giant Fullerene Polyelectrolytes Composed of C60 Building Blocks with an Octahedral Addition Pattern and Discovery of a New Cyclopropanation Reaction Involving Dibromomalonates
Authors: Hörmann Frank , Hirsch Andreas
Published: January 2013

We report here on the facile synthetic access of a new family of bis‐, tetra‐, hexa‐, and heptafullerenes (prototypes I–IV), which can be easily converted into very water soluble polyelectrolytes with up to 60 charges located on their periphery. Their very regioselective formation is based on the use of C2v‐symmetrical pentakisadducts 3 and hexakisadducts 2 as key intermediates. All fullerene moieties incorporated in these macromolecular structures involve a complete or partial octahedral addition pattern. Tripod‐shaped tetrafullerenes 9 a,b (type II), which can accumulate up to thirty positive or negative charges, are very soluble in acidic or basic water, respectively. Hexafullerenes 13 a,b (type III) were synthesized via isoxazolinofullerenes 10 followed by photolytic cleavage of the isoxazoline group. The giant heptafullerene 1 b (type IV) representing the anionic counterpart of the previously synthesized polyelectrolyte 1 a can store up to 60 negative charges on its periphery within a defined three‐dimensional structure. We also discovered a new cyclopropanation reaction of C60 involving dibromomalonates and 1,8‐diazabicyclo[5.4.0]undec‐7‐ene (DBU). This reaction allows even for the highly regioselective formation of hexakisadducts with an octahedral addition pattern without requiring activation with reversibly binding addends such as 9,10‐dimethylanthracene (DMA).
Folic Acid Functionalized Nanoprobes for Fluorescence‐, Dark‐Field‐, and Dual‐Imaging‐Based Selective Detection of Cancer Cells and Tissue
Authors: Maity Amit Ranjan , Saha Arindam , Roy Arun , Jana Nikhil R.
Published: January 2013

Folate‐functionalized quantum dots, gold/silver nanoparticles, and magnetic quantum dots have been synthesized and used as fluorescence, dark‐field, and dual‐imaging probes for the detection of cancer cells and tissues. A very efficient and generalized folate‐functionalization method has been developed for various amine‐terminated nanoparticles. The advantages of the presented approach are that it can be used to synthesize a wide range of folate‐functionalized nanoparticles and the number of folate molecules per nanoparticle can be controlled easily to tune their interaction with folate receptors present at the cell surface. These folate‐functionalized nanoparticles have been used as cellular and tissue‐imaging bioprobes. Results show that folate‐functionalized nanoparticles act as efficient and selective imaging probes in targeting cancer cells and tissues and labeled cells/tissues can be detected by using different imaging modalities.
Executive functioning and behavioral impulsivity of young women who binge eat
Authors: Kelly Nichole R. , Bulik Cynthia M. , Mazzeo Suzanne E.
Published: January 2013

Objective:

To examine the link between binge eating, executive functioning, and behavioral impulsivity.

Method:

Fifty women who reported engaging in weekly binge eating in the absence of regular compensatory behaviors and 66 women with no history of binge eating completed several self‐report questionnaires and a brief neuropsychological battery, including the Wisconsin Card Sorting Task and Conner's Continuous Performance Task.

Results:

Hierarchical regression analyses revealed that groups did not differ in executive functioning after controlling for depression, anxiety, body mass, general intelligence, and psychotropic medication use. Correlation analyses suggest that individuals who endorse more frequent binge eating might have greater difficulties thinking flexibly or shifting attention. Individuals who binge eats are also more likely to behave impulsively, but only for emotional reasons.

Discussion:

Although this study is unable to determine whether these cognitive and behavioral factors precede or follow binge‐eating episodes, outcomes have implications for treatment and prevention. © 2013 by Wiley Periodicals, Inc. (Int J Eat Disord 2013)
Simulating evolutionary responses of an introgressed insect resistance trait for ecological effect assessment of transgene flow: a model for supporting informed decision‐making in environmental risk assessment
Authors: Meier Matthias S. , Trtikova Miluse , Suter Matthias , Edwards Peter J. , Hilbeck Angelika
Published: January 2013

Predicting outcomes of transgene flow from arable crops requires a system perspective that considers ecological and evolutionary processes within a landscape context. In Europe, the arable weed Raphanus raphanistrum is a potential hybridization partner of oilseed rape, and the two species are ecologically linked through the common herbivores Meligethes spp. Observations in Switzerland show that high densities of Meligethes beetles maintained by oilseed rape crops can lead to considerable damage on R. raphanistrum. We asked how increased insect resistance in R. raphanistrum – as might be acquired through introgression from transgenic oilseed rape – would affect seed production under natural herbivore pressure. In simulation experiments, plants protected against Meligethes beetles produced about twice as many seeds as unprotected plants. All stages in the development of reproductive structures from buds to pods were negatively affected by the herbivore, with the transition from buds to flowers being the most vulnerable. We conclude that resistance to Meligethes beetles could confer a considerable selective advantage upon R. raphanistrum in regions where oilseed rape is widely grown.
Co‐Assembly of LDH Nanosheets with Crown Ethers: Structural Transformation and Water‐Adsorption Behavior
Authors: Ma Shulan , Wang Juan , Du Li , Fan Cuihong , Sun Yahong , Sun Genban , Yang Xiaojing
Published: January 2013

Co‐assembly of inorganic LDH nanosheets with an organic azacrown ether carboxylic acid derivative was studied by a flocculation method. The homogeneous structure seen in the wet state changed markedly after drying: a staging structure transformed into a homogeneous one after increased assembly times. The experimental observations, changeover from homogeneous to staging and unequal charges of organic and inorganic guests in gallery, might suggest the Daumas–Hérold model applicable in LDH system. The composites with staging could function as powerful water adsorption materials with facile reversibility.
Concise Total Syntheses of Dipiperidine Alkaloids Virgidivarine and Virgiboidine through Ru‐Mediated Ene‐Ene‐Yne Ring Rearrangement Metathesis (RRM)
Authors: Kress Steffen , Weckesser Jochen , Schulz Sabrina Renate , Blechert Siegfried
Published: January 2013

Herein, we report on the first enantioselective synthesis of the sparteine‐type alkaloids virgidivarine (1) and virgiboidine (2). The stereoselective construction of the challenging dipiperidine core within 1 and 2 was realized by applying an intramolecular ene‐ene‐yne ring‐rearrangement metathesis (RRM) protocol. In combination with this sequence, an unprecedented tandem metathesis/oxidation reaction was established. Subsequent to the RRM event, the Ru‐alkylidene species was converted into the highly potent dihydroxylation catalyst RuO4 by the addition of NaIO4. This transformation rendered five sequential reactions that include an ene‐ene‐yne RRM/dihydroxylation/glycol cleavage in a one‐pot procedure. This approach provides practical and general access to dipiperidines and piperidino‐quinolizidines. Despite their wide use in organic and organometallic chemistry as well as their occurrence in biologically active natural products, methods are still lacking for the stereoselective synthesis of these motifs.
Evaluation of the saltation process of bed materials by video imaging under altered bed roughness
Authors: Bhattacharyya Anindita , Ojha Satya P. , Mazumder Bijoy S.
Published: January 2013

The purpose of this paper is to examine the nature of particle saltation and movement over the beds of fixed roughness from flume experiments. A series of experiments are carried out to study the saltation of individual sand particles of different sizes over rough beds under different flow conditions. A 3‐D acoustic Doppler velocimeter is used to record the fluid velocity components; subsequently, under different flow conditions, the images of released sand particles are recorded using high‐speed video imaging technique. Systematic analysis is made with regard to the forces acting on the grains and the variation of their magnitudes along the saltation trajectories of the grains. Relations between the saltation parameters, flow intensity and bed roughness are developed. The distributions of the angle of orientations during a single saltation follows almost a Gaussian distribution. The shape of the Gaussian distribution depends on the particle size and bed roughness. Particle collisions with rough beds and the resulting coefficients of restitution are also discussed. A theoretical framework is developed to compute the mean particle velocity considering the spin in the energy balance equation. Results of the detailed analysis using the imaging technique are much better than in previously reported studies. Copyright © 2013 John Wiley & Sons, Ltd.
Increasing rainfall, decreasing winds, and historical changes in Santa Catarina dunefields, southern Brazil
Authors: da Silva Graziela Miot , Hesp Patrick A.
Published: January 2013

Morphological and vegetation changes on the Moçambique barrier dunefield system are examined for the period 1938–2002 from aerial photography, and a variety of factors are investigated as possible driving factors. Human factors include a decrease in grazing pressure and tree felling from the early 1960s onwards after 200 years of these activities, and fires. In the 1960s tree planting also took place. During the period 1963 to 1970 there was a marked decline in drift potential (DP – potential sand transport), and then a period of very low DPs (1970–1974). This period falls within the time interval when vegetation cover significantly increased by ~70% along the Moçambique barrier (from 1956 to 1978). During the 1960s to present, the rainfall increased. Analyses of other transgressive dunefields in Santa Catarina and Rio Grande do Sul states show similar trends so it is likely that climatic factors such as increasing rainfall and decreasing DPs are responsible for driving dunefield changes and vegetation colonization of the barriers. Copyright © 2013 John Wiley & Sons, Ltd.
Variation in the Composition and In Vitro Proinflammatory Effect of Urban Particulate Matter from Different Sites
Authors: Manzano‐León Natalia , Quintana Raúl , Sánchez Brisa , Serrano Jesús , Vega Elizabeth , Vázquez‐López Inés , Rojas‐Bracho Leonora , López‐Villegas Tania , O'Neill Marie S. , Vadillo‐Ortega Felipe , De Vizcaya‐Ruiz Andrea , Rosas Irma , Osornio‐Vargas Álvaro R.
Published: January 2013

Spatial variation in particulate matter–related health and toxicological outcomes is partly due to its composition. We studied spatial variability in particle composition and induced cellular responses in Mexico City to complement an ongoing epidemiologic study. We measured elements, endotoxins, and polycyclic aromatic hydrocarbons in two particle size fractions collected in five sites. We compared the in vitro proinflammatory response of J774A.1 and THP‐1 cells after exposure to particles, measuring subsequent TNFα and IL‐6 secretion. Particle composition varied by site and size. Particle constituents were subjected to principal component analysis, identifying three components: C1 (Si, Sr, Mg, Ca, Al, Fe, Mn, endotoxin), C2 (polycyclic aromatic hydrocarbons), and C3 (Zn, S, Sb, Ni, Cu, Pb). Induced TNFα levels were higher and more heterogeneous than IL‐6 levels. Cytokines produced by both cell lines only correlated with C1, suggesting that constituents associated with soil induced the inflammatory response and explain observed spatial differences. © 2013 Wiley Periodicals, Inc. J BiochemMol Toxicol 27:87‐97, 2013; View this article online at wileyonlinelibrary.com. DOI 10.1002/jbt.21471
Ti(Oi‐Pr)4 Mediated Olefination between Julia Reagent and Aldehydes under Mild Conditions: Facile Synthesis of Vinyl Sulfones
Authors: Yang Jinjin , Yin Wei , Liu Renhua , Chu Changhu
Published: January 2013

A novel Ti(Oi‐Pr)4 mediated olifination between Julia reagent and aldehydes has been developed. By this method, a series of substituted vinyl sulfones are prepared under mild conditions, all products are exclusively E isomers. All the structures of these compounds were confirmed by 1H NMR, 13C NMR HRMS and IR.
Imaging features of benign adenomyoepithelioma of the breast
Authors: Park Young Mi , Park Ji Sung , Jung Hyun Seok , Yoon Hye Kyoung , Yang Wei Tse
Published: January 2013

Purpose:

The purpose of our study was to evaluate the imaging features of benign adenomyoepithelioma of the breast with a focus on sonographic (US) appearances.

Methods:

Ten benign adenomyoepitheliomas in 9 patients were included in this study. Mammographic and US findings were analyzed retrospectively by 2 radiologists according to the Breast Imaging–Reporting and Data System (BI‐RADS) lexicon. The BI‐RADS final assessment category was also recorded.

Results:

Of the 8 lesions for which mammography was available, 4 lesions presented with abnormal findings. Two lesions presented with an indistinct, irregular, isodense mass and a circumscribed, oval, isodense mass. The other 2 lesions presented with areas of focal asymmetry and asymmetry, respectively. On US, all of 10 lesions presented as a mass. The masses measured 0.5–1.2 cm (mean, 0.8 cm), were irregular (n = 8) or oval (n = 2) with microlobulated (n = 5), indistinct (n = 3), or angular (n = 2) margins. They were all hypoechoic, had non parallel orientation in 6 cases, and increased peripheral vascularity in 7 cases. The BI‐RADS final assessment category was 4B in 6, and 4A in 4.

Conclusions:

Mammographic findings of benign adenomyoepithelioma were nonspecific. An irregular, non parallel orientation, microlobulated or indistinct margin, hypoechogenicity, and increased peripheral vascularity were the most frequent US features. © 2013 Wiley Periodicals, Inc. J Clin Ultrasound, 2013
Purified collagen I oriented membrane for tendon repair: An ex vivo morphological study
Authors: Gigante Antonio , Busilacchi Alberto , Lonzi Barbara , Cecconi Stefano , Manzotti Sandra , Renghini Chiara , Giuliani Alessandra , Mattioli‐Belmonte Monica
Published: January 2013

Injured tendons have limited repair ability after full‐thickness lesions. Tendon regeneration properties and adverse reactions were assessed ex vivo in an experimental animal model using a new collagen I membrane. The multilamellar membrane obtained from purified equine Achilles tendon is characterized by oriented collagen I fibers and has been shown to sustain cell growth and orientation in vitro. The central third of the patellar tendon (PT) of 10 New Zealand White rabbits was sectioned and grafted with the collagen membrane; the contralateral PT was cut longitudinally (sham‐operated controls). Animals were euthanized 1 or 6 months after surgery, and tendons were subjected to histological and Synchrotron Radiation‐based Computed Microtomography (SRµCT) examination and 3D structure analysis. Histological and SRµCT findings showed satisfactory graft integration with native tendon. Histological examination also showed ongoing angiogenesis. Adverse side‐effects (inflammation, rejection, calcification) were not observed. The multilamellar collagen I membrane can be considered as an effective tool for tendon defect repair and tendon augmentation. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 738–745, 2013
Resurfacing with chemically modified hyaluronic acid and lubricin for flexor tendon reconstruction
Authors: Zhao Chunfeng , Hashimoto Takahiro , Kirk Ramona L. , Thoreson Andrew R. , Jay Gregory D. , Moran Steven L. , An Kai‐Nan , Amadio Peter C.
Published: January 2013

We assessed surface coating with carbodiimide derivatized hyaluronic acid combined with lubricin (cd‐HA‐Lubricin) as a way to improve extrasynovial tendon surface quality and, consequently, the functional results in flexor tendon reconstruction, using a canine in vivo model. The second and fifth flexor digitorum profundus tendons from 14 dogs were reconstructed with autologs peroneus longus (PL) tendons 6 weeks after a failed primary repair. One digit was treated with cd‐HA‐Lubricin, and the other was treated with saline as the control. Six weeks following grafting, the digits and graft tendons were functionally and histologically evaluated. Adhesion score, normalized work of flexion, graft friction in zone II, and adhesion breaking strength at the proximal repair site in zone III were all lower in the cd‐HA‐Lubricin treated group compared to the control group. The strength at the distal tendon/bone interface was decreased in the cd‐HA‐Lubricin treated grafts compared to the control grafts. Histology showed inferior healing in the cd‐HA‐Lubricin group at both proximal and distal repair sites. However, cd‐HA‐Lubricin treatment did not result in any gap or rupture at either the proximal or distal repair sites. These results demonstrate that cd‐HA‐Lubricin can eliminate graft adhesions and improve digit function, but that treatment may have an adverse effect on tendon healing. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 969–975, 2013
Shape optimization for the subsidence resistance of an interbody device using simulation‐based genetic algorithms and experimental validation
Authors: Hsu Ching‐Chi
Published: January 2013

Subsidence of interbody devices into the vertebral body might result in serious clinical problems, especially when the devices are not well designed and analyzed. Recently, some novel designs were proposed to reduce the risk of subsidence, but those designs are based on the researcher's experience. The purpose of this study was to discover the interbody device design with excellent subsidence resistance by changing the device's shape. The three‐dimensional nonlinear finite element models, which consisted of the interbody device and vertebral body, were created first. Then, the simulation‐based genetic algorithm, which combined the finite element model and the searching algorithm, was developed by using ANSYS® Parametric Design Language. Finally, the numerical results were carefully validated with the use of biomechanical tests. The optimum shape design obtained in this study looks like a flower with many petals and it has excellent subsidence resistance when compared with the other designs provided by the past studies. The results of the present study could help surgeons to understand the subsidence resistance of interbody devices in terms of their shapes and has directly provided the design rationales to engineers. © 2013 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 31:1158–1163, 2013
The use of a novel MUC1 antibody to identify cancer stem cells and circulating MUC1 in mice and patients with pancreatic cancer
Authors: Curry Jennifer M. , Thompson Kyle J. , Rao Shanti G. , Besmer Dahlia M. , Murphy Andrea M. , Grdzelishvili Valery Z. , Ahrens William A. , McKillop Iain H. , Sindram David , Iannitti David A. , Martinie John B. , Mukherjee Pinku
Published: January 2013

Background and Objectives

MUC1 is over‐expressed and aberrantly glycosylated in >60% of human pancreatic cancer (PC). Development of novel approaches for detection and/or targeting of MUC1 are critically needed and should be able to detect MUC1 on PC cells (including cancer stem cells) and in serum.

Methods

The sensitivity and specificity of the anti‐MUC1 antibody, TAB 004, was determined. CSCs were assessed for MUC1 expression using TAB 004‐FITC on in vitro PC cell lines, and on lineage− cells from in vivo tumors and human samples. Serum was assessed for shed MUC1 via the TAB 004 EIA.

Results

In vitro and in vivo, TAB 004 detected MUC1 on >95% of CSCs. Approximately, 80% of CSCs in patients displayed MUC1 expression as detected by TAB 004. Shed MUC1 was detected serum in mice with HPAF‐II (MUC1high) but not BxPC3 tumors (MUC1low). The TAB 004 EIA was able to accurately detect stage progression in PC patients.

Conclusions

The TAB 004 antibody may be explored as a therapeutic targeting agent for CSCs in PC. The TAB 004 EIA detected circulating MUC1 in a stage‐dependent manner in patients with PC and thus may be explored as a PC stage diagnostic biomarker. J. Surg. Oncol. 2013;107:713–722. © 2013 Wiley Periodicals, Inc.
Combined pancreas and liver therapies: Resection and ablation in hepato‐pancreatico‐biliary malignancies
Authors: Edwards Jacob , Scoggins Charles , McMasters Kelly , Martin Robert
Published: January 2013

Background

Combined pancreatic and liver resection for hepato‐pancreatico‐biliary disease is generally considered contraindicated since it is thought to provide little if any survival benefit with high risk of morbidity. Our goal was to review our experience with combined pancreatic and liver resections to better define characteristics that increase risk for perioperative complications after combined resections.

Methods

A review of prospectively collected IRB approved hepato‐pancreatico‐biliary database was performed from October 2002 to April 2012.

Results

Twenty‐one cases were identified including all histologies. Perioperative outcomes were examined and the overall mean length of stay was 12.1 days (range: 6–26 days) and no perioperative mortalities (<90 days) were observed. With respect to morbidity 43% of patients experienced any grade of complication, 29% were Grade 3 with no Grade 4 or 5 complications noted. We found a statistically indicated association between BMI > 25 and risk of Grade 3 complications (P = 0.149). The median survival following operation was 11 months (range: 3–148 months).

Conclusion

Combined pancreas and liver resection for metastatic disease should only be considered in highly selected patients. Tumor histology as well as BMI > 25 (overweight and obese patients) should be considered in the decision making process in an effort to minimize surgical morbidity while potentially improving survival. J. Surg. Oncol. 2013;107:709–712. © 2013 Wiley Periodicals, Inc.
The ToxBank Data Warehouse: Supporting the Replacement of In Vivo Repeated Dose Systemic Toxicity Testing
Authors: Kohonen Pekka , Benfenati Emilio , Bower David , Ceder Rebecca , Crump Michael , Cross Kevin , Grafström Roland C. , Healy Lyn , Helma Christoph , Jeliazkova Nina , Jeliazkov Vedrin , Maggioni Silvia , Miller Scott , Myatt Glenn , Rautenberg Michael , Stacey Glyn , Willighagen Egon , Wiseman Jeff , Hardy Barry
Published: January 2013

The aim of the SEURAT‐1 (Safety Evaluation Ultimately Replacing Animal Testing‐1) research cluster, comprised of seven EU FP7 Health projects co‐financed by Cosmetics Europe, is to generate a proof‐of‐concept to show how the latest technologies, systems toxicology and toxicogenomics can be combined to deliver a test replacement for repeated dose systemic toxicity testing on animals. The SEURAT‐1 strategy is to adopt a mode‐of‐action framework to describe repeated dose toxicity, combining in vitro and in silico methods to derive predictions of in vivo toxicity responses. ToxBank is the cross‐cluster infrastructure project whose activities include the development of a data warehouse to provide a web‐accessible shared repository of research data and protocols, a physical compounds repository, reference or “gold compounds” for use across the cluster (available via wiki.toxbank.net), and a reference resource for biomaterials. Core technologies used in the data warehouse include the ISA‐Tab universal data exchange format, REpresentational State Transfer (REST) web services, the W3C Resource Description Framework (RDF) and the OpenTox standards. We describe the design of the data warehouse based on cluster requirements, the implementation based on open standards, and finally the underlying concepts and initial results of a data analysis utilizing public data related to the gold compounds.
Betti numbers in multidimensional persistent homology are stable functions
Authors: Cerri Andrea , Fabio Barbara Di , Ferri Massimo , Frosini Patrizio , Landi Claudia
Published: January 2013

Multidimensional persistence mostly studies topological features of shapes by analyzing the lower level sets of vector‐valued functions, called filtering functions. As is well known, in the case of scalar‐valued filtering functions, persistent homology groups can be studied through their persistent Betti numbers, that is, the dimensions of the images of the homomorphisms induced by the inclusions of lower level sets into each other. Whenever such inclusions exist for lower level sets of vector‐valued filtering functions, we can consider the multidimensional analog of persistent Betti numbers. Varying the lower level sets, we obtain that persistent Betti numbers can be seen as functions taking pairs of vectors to the set of non‐negative integers. In this paper, we prove stability of multidimensional persistent Betti numbers. More precisely, we prove that small changes of the vector‐valued filtering functions imply only small changes of persistent Betti numbers functions. This result can be obtained by assuming the filtering functions to be just continuous. Multidimensional stability opens the way to a stable shape comparison methodology based on multidimensional persistence. In order to obtain our stability theorem, some other new results are proved for continuous filtering functions. They concern the finiteness of persistent Betti numbers for vector‐valued filtering functions and the representation via persistence diagrams of persistent Betti numbers, as well as their stability, in the case of scalar‐valued filtering functions. Finally, from the stability of multidimensional persistent Betti numbers, we obtain a lower bound for the natural pseudo‐distance. Copyright © 2013 John Wiley & Sons, Ltd.
Age‐related treatment patterns in sickle cell disease patients and the associated sickle cell complications and healthcare costs
Authors: Blinder Morey A. , Vekeman Francis , Sasane Medha , Trahey Alex , Paley Carole , Duh Mei Sheng
Published: January 2013

Background

This study explored the blood transfusion patterns, SCD complications, utilization of iron chelation therapies (ICT), healthcare resource use, and costs in pediatric, transitioning (18 years old) and adult patients with SCD.

Procedure

Data from Florida (1998–2009), New Jersey (1996–2009), Missouri (1997–2010), Kansas (2001–2009), and Iowa (1998–2010) state Medicaid were used. Patients with ≥2 SCD diagnoses and ≥1 transfusion event were included. Rates of transfusion events, SCD complications, and proportion of eligible patients receiving ICT were calculated. ICT eligibility was defined as receiving ≥10 transfusions over lifetime. SCD complications included pain, pulmonary event, infection event, renal, cardiovascular, stroke, leg ulcers, and avascular necrosis. Regressions were used to assess risk factors for transfusion and identify the main drivers of costs.

Results

The sample included 3,208 patients. The transfusion rate increased from 1‐year‐old to a peak at 16 years old, then dropped until age 26 and remained stable thereafter. In contrast the frequency of diagnoses for SCD complications increased markedly after age 16. Post‐transition patients (≥18 years old) were significantly associated with fewer transfusions (odds ratio: 0.80, P = 0.002). Among eligible patients for ICT, there was no statistically significant difference in total cost between the ICT and no ICT groups (adjusted cost difference, $136, P = 0.114).

Conclusions

Patients transitioning to adult care received less transfusions and hydroxyurea, less ICT when eligible for chelation therapy, had higher healthcare costs and suffered from more frequent SCD related complications than pediatric patients. These findings highlight the changes in treatment patterns corresponding to transition to adult care. Pediatr Blood Cancer 2013; 60: 828–835. © 2013 Wiley Periodicals, Inc.
Cyclosporine 0.05% ophthalmic emulsion for the treatment of radiation‐associated dry eye in children
Authors: Hoehn Mary Ellen , Kelly Steven R. , Wilson Matthew W. , Walton R. Christopher
Published: January 2013

Dry eye disease is a well‐known late complication of radiation therapy and is often difficult to treat. We evaluated the usefulness of cyclosporine 0.05% ophthalmic emulsion for the treatment of radiation‐associated dry eye in children. Eleven children received cyclosporine 0.05% emulsion twice daily after failure of conventional therapy. After 6 months, dry eye manifestations improved in three children (27.3%). The remaining eight children showed no improvement with cyclosporine 0.05% ophthalmic emulsion. These results suggest that twice‐daily cyclosporine 0.05% ophthalmic emulsion has limited use in children with refractory radiation‐associated chronic dry eye. Pediatr Blood Cancer 2013; 60: E35–E37. © 2013 Wiley Periodicals, Inc.
A cyclic selenium‐based reversible addition‐fragmentation chain transfer agent mediated polymerization of vinyl acetate
Authors: Zhan Yiyu , Zhang Zhengbiao , Pan Xiangqiang , Zhu Jian , Zhou Nianchen , Zhu Xiulin
Published: January 2013

A cyclic selenium‐based reversible addition‐fragmentation chain transfer (RAFT) agent, 5,5‐dimethyl‐3‐phenyl‐2‐selenoxo‐1,3‐selenazolidin‐4‐one (RAFT‐Se), was synthesized and utilized in the RAFT polymerizations of vinyl acetate (VAc). Its analog, 5,5‐dimethyl‐3‐phenyl‐2‐thioxothiazolidin‐4‐one (RAFT‐S), was also used in RAFT polymerizations for comparison under identical conditions. The RAFT polymerizations of VAc with RAFT‐Se were moderately controlled evidenced by the increase of molecular weights with conversion, despite the slightly high Mw/Mn (less than 1.90), whereas the molecular weights were poorly controlled in the presence of RAFT‐S (2.00 < Mw/Mn < 2.30). Thanks to its unusual cyclic structure of RAFT‐Se, one or more RAFT‐Se species was incorporated into the resultant poly(VAc) as revealed by the results of cleavage of polymer and atomic absorption spectroscopy. Considering the biorelated functions of both poly(VAc) and Se element, this work undoubtedly provided a successful methodology of how to incorporate high content of Se into a molecular weight controlled poly(VAc). © 2013 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2013
The G84E mutation in the HOXB13 gene is associated with an increased risk of prostate cancer in Poland
Authors: Kluźniak Wojciech , Wokołorczyk Dominika , Kashyap Aniruddh , Jakubowska Anna , Gronwald Jacek , Huzarski Tomasz , Byrski Tomasz , Dębniak Tadeusz , Gołąb Adam , Gliniewicz Bartłomiej , Sikorski Andrzej , Świtała Jerzy , Borkowski Tomasz , Borkowski Andrzej , Antczak Andrzej , Wojnar Łukasz , Przybyła Jacek , Sosnowski Marek , Małkiewicz Bartosz , Zdrojowy Romuald , Sikorska‐Radek Paulina , Matych Józef , Wilkosz Jacek , Różański Waldemar , Kiś Jacek , Bar Krzysztof , Bryniarski Piotr , Paradysz Andrzej , Jersak Konrad , Niemirowicz Jerzy , Słupski Piotr , Jarzemski Piotr , Skrzypczyk Michał , Dobruch Jakub , Domagała Paweł , Akbari Mohammad R. , Lubiński Jan , Narod Steven A. , Cybulski Cezary ,   the Polish Hereditary Prostate Cancer Consortium
Published: January 2013

BACKGROUND

The G84E mutation in the HOXB13 gene has been associated with a high lifetime risk of prostate cancer in North America (about 20‐fold). The geographical and ethnic extent of this recurrent allele has not yet been determined.

METHODS

We assayed for the presence of the G84E mutation in 3,515 prostate cancer patients and 2,604 controls from Poland and estimated the odds ratio for prostate cancer associated with the allele.

RESULTS

The G84E mutation was detected in 3 of 2,604 (0.1%) individuals from the general population in Poland and in 20 of 3,515 (0.6%) men with prostate cancer (Odds ratio [OR] = 5.0; 95% CI: 1.5–16.7; P = 0.008). The allele was present in 4 of 416 (1.0%) men with familial prostate cancer (OR = 8.4, 95% CI: 1.9–37.7; P = 0.005).

CONCLUSIONS

The G84E mutation predisposes to prostate cancer in Poland, but accounts for only a small proportion of cases. We expect that the G84E founder mutation might be present in other Slavic populations. Prostate 73: 542–548, 2013. © 2013 Wiley Periodicals, Inc.
Phase II open label, multi‐center clinical trial of modulation of intermediate endpoint biomarkers by 1α‐hydroxyvitamin D2 in patients with clinically localized prostate cancer and high grade pin
Authors: Gee Jason , Bailey Howard , Kim KyungMann , Kolesar Jill , Havighurst Tom , Tutsch Kendra D. , See William , Cohen Michael B. , Street Nick , LeVan Leon , Jarrard David , Wilding George
Published: January 2013

BACKGROUND

Prostate cancer is the most common malignancy and second leading cause of cancer related deaths in American men supporting the study of prostate cancer chemoprevention. Major risk factors for this disease have been associated with low serum levels of vitamin D. Here, we evaluate the biologic activity of a less calcemic vitamin D analog 1α‐hydroxyvitamin D2 [1α‐OH‐D2] (Bone Care International, Inc.) in patients with prostate cancer and high grade prostatic intraepithelial neoplasia (HG PIN).

METHODS

Patients with clinically organ‐confined prostate cancer and HG PIN were randomized to 1α‐OH‐D2 versus placebo for 28 days prior to radical prostatectomy. Intermediate endpoint biomarkers included serum vitamin D metabolites, TGFß 1/2, free/total PSA, IGF‐1, IGFBP‐3, bFGF, and VEGF. Tissue endpoints included histology, MIB‐1 and TUNEL staining, microvessel density and factor VIII staining, androgen receptor and PSA, vitamin D receptor expression and nuclear morphometry.

RESULTS

The 1α‐OH‐D2 vitamin D analog was well tolerated and could be safely administered with good compliance and no evidence of hypercalcemia over 28 days. While serum vitamin D metabolite levels only slightly increased, evidence of biologic activity was observed with significant reductions in serum PTH levels. TGF‐ß2 was the only biomarker significantly altered by vitamin D supplementation. Whether reduced TGF‐ß2 levels in our study is an early indicator of response to vitamin D remains unclear.

CONCLUSIONS

While further investigation of vitamin D may be warranted based on preclinical studies, results of the present trial do not appear to justify evaluation of 1α‐OH‐D2 in larger clinical prostate cancer prevention studies. Prostate 73: 970–978, 2013. © 2013 Wiley Periodicals, Inc.
Sensitivity of deep convection to terrain forcing over Mediterranean islands
Authors: Barthlott Christian , Kirshbaum Daniel J.
Published: January 2013

The influence of mountainous islands on the initiation of deep convection is investigated using the Consortium for Small‐scale Modeling (COSMO) model. A case study and sensitivity analysis is performed for 26 August 2009, when moist convection occurred over both Corsica and Sardinia islands in the western Mediterranean Sea. Sensitivity runs with systematically modified topography are explored to evaluate the relative importance of the land–sea contrast and the terrain height for convection initiation. Whereas no island precipitation is simulated when the islands are completely removed, all simulations that represent these land surfaces develop convective precipitation. Although convection initiates progressively earlier in the day over taller islands, the precipitation rates and accumulations do not show a fixed relationship with terrain height. This is due to the competing effects of different physical processes. Firstly, whereas the forcing for low‐level ascent increases over taller islands the boundary‐layer moisture supply decreases, which diminishes the conditional instability and precipitable water. Secondly, whereas taller islands enhance the inland propagation speeds of sea‐breeze fronts they also block these fronts mechanically and prevent them from reaching the island interior. As a result, the island precipitation is rather insensitive to island terrain height except for one particular case in which the island precipitation increases considerably due to an optimal superposition of the sea breeze and upslope flow. Comparing the two islands, convective precipitation develops earlier over Corsica due to its increased terrain height and reduced convective inhibition. However, precipitation amounts are substantially larger over Sardinia, where a stronger land–sea contrast gives rise to a more intense and organized line of sea‐breeze convergence. These results demonstrate the complexity of interactions between sea breezes and orography and reinforce that an adequate representation of detailed topographic features is necessary to account for thermally induced wind systems that initiate deep convection.
Prepubertal castration causes the age‐dependent changes in hippocampal long‐term potentiation
Authors: Moradpour Farshad , Fathollahi Yaghoub , Naghdi Nasser , Hosseinmardi Nargess , Javan Mohammad
Published: January 2013

The effects of prepubertal castration on hippocampal CA3‐CA1 synaptic transmission and plasticity were studied at different ages in vitro. The field excitatory postsynaptic potentials (fEPSP) and population spikes (PS) were simultaneously recorded from stratum radiatum and stratum pylamidale of area CA1 following stimulation of Schaffer collaterals in slices taken from sham‐castrated and castrated rats at postnatal days (PND) 28, 35, 45, and 60. Castration had no effect on baseline responses at different ages except at PND 60 that a decrease in the fEPSP slope was seen. Prepubertal castration caused age‐specific changes in CA1‐long term potentiation (LTP) induction. The castration did decrease both fEPSP‐LTP and PS‐LTP at PND 35 but a decrease was seen only in PS‐LTP at PND 60. NMDA receptor antagonist AP5 (25 µM) completely blocked both fEPSP‐LTP and PS‐LTP at PND 60 and only PS‐LTP at PND 35 in both sham‐castrated and castrated groups. Although AP5 blocked fEPSP‐LTP at PND 35 in sham‐castrated group, it failed to inhibit fEPSP‐LTP at PND 35 in castrated one. These findings suggest that prepubertal castration causes the age‐dependent changes in CA1‐LTP induction, which might arise from alterations in the NMDA receptors. Synapse 67:235–244, 2013. © 2013 Wiley Periodicals, Inc.