bluuebunny/crossref_metadata_2025 huggingface dataset:
Local tissue temperature increase of a generic implant compared to the basic restrictions defined in safety guidelines
Authors: Kyriakou Adamos , Christ Andreas , Neufeld Esra , Kuster Niels
Published: November 2011

The objective of this study was to investigate if persons with implantable medical devices are intrinsically protected by the current electromagnetic safety guidelines. For inter‐laboratory comparisons, the U.S. Food and Drug Administration has defined a generic implant as consisting of an insulated wire with noninsulated tips, simulating active implants composed of a metallic case, and insulated wires with electric contacts at the tip. In this study, we determined the amplitude of the uniform electric fields induced in body tissues that cause a local increase in the tissue temperature by 1 °C in the presence of this generic implant for a wide range of frequencies and wire lengths. The field amplitudes were compared to the basic restrictions of the current exposure guidelines for both occupational and uncontrolled exposure. Results showed that a 1 °C temperature increase in the tissues around the tips of the generic implant can be reached for field strengths much smaller than 1% of those in the basic restrictions. The simulated results were validated by experimental evaluations. The impact of perfusion was investigated and was found to lead to a reduction in the local temperature peak by only 1.6–3 times. Additional simulations inside an inhomogeneous anatomical model were performed to ascertain whether similar heating as in the generic model was observed. The significant temperature elevations due to the presence of a generic implant indicate that demonstrating compliance with the basic restrictions might not be sufficient for persons with implants. Special considerations may be required, especially in the case of novel, emerging technologies that feature strong near‐fields at frequencies below 10 MHz (e.g., wireless power‐transfer systems). Bioelectromagnetics 33:366–374, 2012. © 2011 Wiley Periodicals, Inc.
Towards dynamic metabolic flux analysis in CHO cell cultures
Authors: Ahn Woo Suk , Antoniewicz Maciek R.
Published: November 2011

Chinese hamster ovary (CHO) cells are the most widely used mammalian cell line for biopharmaceutical production, with a total global market approaching $100 billion per year. In the pharmaceutical industry CHO cells are grown in fed‐batch culture, where cellular metabolism is characterized by high glucose and glutamine uptake rates combined with high rates of ammonium and lactate secretion. The metabolism of CHO cells changes dramatically during a fed‐batch culture as the cells adapt to a changing environment and transition from exponential growth phase to stationary phase. Thus far, it has been challenging to study metabolic flux dynamics in CHO cell cultures using conventional metabolic flux analysis techniques that were developed for systems at metabolic steady state. In this paper we review progress on flux analysis in CHO cells and techniques for dynamic metabolic flux analysis. Application of these new tools may allow identification of intracellular metabolic bottlenecks at specific stages in CHO cell cultures and eventually lead to novel strategies for improving CHO cell metabolism and optimizing biopharmaceutical process performance.
Towards automated production and drug sensitivity testing using scaffold‐free spherical tumor microtissues
Authors: Drewitz Maren , Helbling Marianne , Fried Nicole , Bieri Manuela , Moritz Wolfgang , Lichtenberg Jan , Kelm Jens M.
Published: November 2011

Although the relevance of three‐dimensional (3‐D) culture has been recognized for years and exploited at an academic level, its translation to industrial applications has been slow. The development of reliable high‐throughput technologies is clearly a prerequisite for the industrial implementation of 3‐D models. In this study the robustness of spherical microtissue production and drug testing in a 96‐well hanging‐drop multiwell plate format was assessed on a standard 96‐well channel robotic platform. Microtissue models derived from six different cell lines were produced and characterized according to their growth profile and morphology displaying high‐density tissue‐like reformation and growth over at least 15 days. The colon cancer cell line HCT116 was chosen as a model to assess microtissue‐based assay reproducibility. Within three individual production batches the size variations of the produced microtissues were below 5%. Reliability of the microtissue‐based assay was tested using two reference compounds, staurosporine and chlorambucil. In four independent drug testings the calculated IC50 values were benchmarked against 2‐D multiwell testings displaying similar consistency. The technology presented here for the automated production of a variety of microtissues for efficacy testing in a standard 96‐well format will aid the implementation of more organotypic models at an early time point in the drug discovery process.
Gallionella spp. in trickling filtration of subsurface aerated and natural groundwater
Authors: de Vet W.W.J.M. , Dinkla I.J.T. , Abbas B.A. , Rietveld L.C. , van Loosdrecht M.C.M.
Published: November 2011

The growth of iron‐oxidizing bacteria, generally regarded as obligate microaerophilic at neutral pH conditions, has been reported in a wide range of environments, including engineered systems for drinking water production. This research focused on intensively aerated trickling filters treating deep anaerobic and subsurface aerated groundwater. The two systems, each comprising groundwater abstraction and trickling filtration, were monitored over a period of 9 months. Gallionella spp. were quantified by qPCR with specifically designed 16S rRNA primers and identified directly in the environmental samples using clone libraries with the same primers. In addition, enrichments in gradient tubes were evaluated after DGGE separation with general bacterial primers. No other iron‐oxidizing bacteria than Gallionella spp. were found in the gradient tubes. qPCR provided an effective method to evaluate the growth of Gallionella spp. in these filter systems. The growth of Gallionella spp. was stimulated by subsurface aeration, but these bacteria hardly grew in the trickling filter. In the uninfluenced, natural anaerobic groundwater, Gallionella spp. were only present in low numbers, but they grew extensively in the trickling filter. Identification revealed that Gallionella spp., growing in the trickling filter were phylogenetically distinct from the species found growing during subsurface aeration, indicating that the different conditions in both systems selected for niche organisms, while inhibiting other groups. The results suggest a minor direct significance for inoculation of Gallionella spp. during filtration of subsurface aerated groundwater. Biotechnol. Bioeng. 2012; 109:904–912. © 2011 Wiley Periodicals, Inc.
Multicentre observational study of the natural history of left-sided acute diverticulitis
Authors: Binda G A , Arezzo A , Serventi A , Bonelli L
Published: November 2011

Background

The natural history of acute diverticulitis (AD) is still unclear. This study investigated the recurrence rate, and the risks of emergency surgery, associated stoma and death following initial medical or surgical treatment of AD.

Methods

The Italian Study Group on Complicated Diverticulosis conducted a 4-year multicentre retrospective and prospective database analysis of patients admitted to hospital for medical or surgical treatment of AD and then followed for a minimum of 9 years. The persistence of symptoms, recurrent episodes of AD, new hospital admissions, medical or surgical treatment, and their outcome were recorded during follow-up.

Results

Of 1046 patients enrolled at 17 centres, 743 were eligible for the study (407 recruited retrospectively and 336 prospectively); 242 patients (32·6 per cent) underwent emergency surgery at accrual. After a mean follow-up of 10·7 years, rates of recurrence (17·2 versus 5·8 per cent; P < 0·001) and emergency surgery (6·9 versus 1·3 per cent; P = 0·021) were higher for medically treated patients than for those treated surgically. Among patients who had initial medical treatment, age less than 40 years and a history of at least three episodes of AD were associated with an increased risk of AD recurrence. There was no association between any of the investigated parameters and subsequent emergency surgery. The risk of stoma formation was below 1 per cent and disease-related mortality was zero in this group. The disease-related mortality rate was 0·6 per cent among patients who had surgical treatment.

Conclusion

Long-term risks of recurrent AD or emergency surgery were limited and colectomy did not fully protect against recurrence.
Case-controlled study of critical care or surgical ward care after elective open colorectal surgery
Authors: Swart M , Carlisle J B
Published: November 2011

Background

Evidence for the benefit of critical care after surgery is limited. This study assessed the value of immediate admission to the critical care unit (CCU) after open colorectal surgery.

Methods

Patients aged over 45 years were screened with a cardiopulmonary exercise test to determine their anaerobic threshold. Less fit patients defined by an anaerobic threshold below 11 ml oxygen per kg per min were assigned to either critical care or surgical ward care. Those with an anaerobic threshold of 11 ml oxygen per kg per min or above were assigned to ward care. The outcome measure was the number of cardiac events.

Results

Of 153 patients who underwent exercise testing, 55 had an anaerobic threshold of at least 11 ml oxygen per kg per min (ward care) and 98 had a threshold of less than 11 ml oxygen per kg per min, of whom 39 were allocated to ward care and 51 to critical care. Median length of CCU stay was 31 (range 5–46) h. More cardiac events occurred in patients allocated to ward care (7 of 39) than in those allocated to critical care (0 of 51): absolute difference 18 (95 per cent confidence interval 10 to 26) per cent (P = 0·002). There were no cardiac events in patients with an anaerobic threshold of 11 ml oxygen per kg per min or higher.

Conclusion

Patients with an anaerobic threshold of at least 11 ml oxygen per kg per min and those with a threshold below 11 ml oxygen per kg per min managed in the CCU had fewer cardiac events.
Synthesis of economically viable biodiesel from waste frying oils (WFO)
Authors: Sharma Yogesh C. , Agrawal Shweta , Singh Bhaskar , Frómeta Amado Enrique Navarro
Published: November 2011

In present communication, waste frying oil (WFO) has been used as a feedstock for biodiesel synthesis. WFO, procured from a local Indian restaurant possessed an acid value of 0.84 mg KOH/g, which is low enough for single step transesterification reaction. Biodiesel (fatty acid methyl esters) was washed after transesterification reaction and the yield got lowered substantially (from 96% to 86.36%) after water washing owing to loss of esters. 30:100 vol% (methanol to oil), 0.6 wt% NaOCH3, 60°C temperature and 600 rpm agitation in 1 h reaction time was found to be optimum for transesterification reaction. 1H NMR spectrum showed a high conversion (95.19%) of fatty acids in WFO to biodiesel in 2 h reaction time. Almost complete conversion (99.68%) was attained in 2 h reaction time. © 2011 Canadian Society for Chemical Engineering
Chemical Effects in SERS of Pyrazine Adsorbed on Au–Pd Bimetallic Nanoparticles: A Theoretical Investigation
Authors: Lang Xiu‐Feng , Yin Peng‐Gang , You Ting‐Ting , Guo Lin
Published: November 2011

Chemical enhancement in surface‐enhanced Raman scattering (SERS) of pyrazine adsorbed on Au–Pd nanoclusters is investigated by using density functional theory. Changing Pd content in the bimetallic clusters enables modulation of the direct chemical interactions between the pyrazine and the clusters. The magnitude of chemical enhancement is correlated well with the induced polarizability for the complexes with low Pd content, which fails for the complexes with high Pd content. Furthermore, the dependence of chemical enhancement on cluster size and coupling is also described by the induced polarizability. Additionally, the chemical enhancement in the cluster–molecule–cluster junction is found to account for as much as 103, which suggests that a chemical mechanism might be more important than previously believed, in particular for Au–Pd bimetallic nanoparticle aggregates.
Slope effects on the spatial variations in duff moisture
Authors: Raaflaub L. D. , Valeo C. , Johnson E. A.
Published: November 2011

Investigations were made on the influence of slope on the spatial variations in duff moisture, the decomposing organic matter of the forest floor. Relationships between duff and soil moisture along hillslopes were identified from field measurements over various moisture conditions. Results indicated that duff moisture is not related to soil moisture, nor is it controlled by a hydraulic gradient. The spatial pattern of duff moisture over a 2 week period was established along two 2 m by 60 m hillslope transects that were sampled every 3 m. Because of interception, tree proximity was found to be the primary factor that significantly influenced the spatial variation in duff moisture. As the duff dried, the influence of tree proximity decreased. The distance from the top of the hillslope was not found to be an important factor in duff moisture variability. The spatial variation in duff moisture is more prominent during periods of wetness because of the exponential nature of the duff drying curve. Copyright © 2011 John Wiley & Sons, Ltd.
IL‐23‐dependent IL‐17 drives Th1‐cell responses following Mycobacterium bovis BCG vaccination
Authors: Gopal Radha , Lin Yinyao , Obermajer Nataša , Slight Samantha , Nuthalapati Nikhil , Ahmed Mushtaq , Kalinski Pawel , Khader Shabaana A.
Published: November 2011

The generation of effective type 1 T helper (Th1)‐cell responses is required for immunity against intracellular bacteria. However, some intracellular bacteria require interleukin (IL)‐17 to drive Th1‐cell immunity and subsequent protective host immunity. Here, in a model of Mycobacterium bovis Bacille Calmette–Guerin (BCG) vaccination in mice, we demonstrate that the dependence on IL‐17 to drive Th1‐cell responses is a host mechanism to overcome bacteria‐induced IL‐10 inhibitory effects. We show that BCG‐induced prostaglandin‐E2 (PGE2) promotes the production of IL‐10 which limits Th1‐cell responses, while simultaneously inducing IL‐23 and Th17‐cell differentiation. The ability of IL‐17 to downregulate IL‐10 and induce IL‐12 production allows the generation of subsequent Th1‐cell responses. Accordingly, BCG‐induced Th17‐cell responses precede the generation of Th1‐cell responses in vivo, whereas the absence of the IL‐23 pathway decreases BCG vaccine‐induced Th17 and Th1‐cell immunity and subsequent vaccine‐induced protection upon M. tuberculosis challenge. Importantly, in the absence of IL‐10, BCG‐induced Th1‐cell responses occur in an IL‐17‐independent manner. These novel data demonstrate a role for the IL‐23/IL‐17 pathway in driving Th1‐cell responses, specifically to overcome IL‐10‐mediated inhibition and, furthermore, show that in the absence of IL‐10, the generation of BCG‐induced Th1‐cell immunity is IL‐17 independent.
Pim1 and Myc reversibly transform murine precursor B lymphocytes but not mature B lymphocytes
Authors: Bouquet Corinne , Melchers Fritz
Published: November 2011

The proto‐oncogenes Myc and Pim1, which are deregulated in many types of cancers, are known to cooperate in B lymphoma development. Here we show that overexpression of retrovirally transduced, doxycycline‐inducible Myc alone in IL‐7‐deprived, growth‐arrested pre‐B cells enhanced cell cycle entry without impairing apoptosis. Overexpression of Pim1 decreased apoptosis, but had no effect on cell cycle entry. Co‐expression of Pim1 and Myc inhibited apoptosis and led to IL‐7‐independent proliferation of the transduced pre‐B cells in vitro, while blocking their differentiation to IgM+ immature cells. Transplantation of Pim1/Myc overexpressing pre‐BI cells into B‐cell‐deficient mice expanded the pre‐B‐cell compartments up to 100‐fold within 4–8 weeks. Transformation remained dependent on the expression of both oncogenes, as removal of doxycycline in vitro and in vivo terminated proliferation and induced differentiation to IgM+ B cells. In contrast, Pim1/Myc‐transduced mature B cells that developed from the oncogene‐transduced pre‐BI cells in the absence of oncogene overexpression in vivo were not capable of long‐term proliferation after induction of Pim and Myc overexpression, neither in vivo nor in vitro, neither with nor without stimulation by polyclonal activators.
Improved sample preparation for CE‐LIF analysis of plant N‐glycans
Authors: Nagels Bieke , Santens Francis , Weterings Koen , Van Damme Els J. M. , Callewaert Nico
Published: November 2011

In view of glycomics studies in plants, it is important to have sensitive tools that allow one to analyze and characterize the N‐glycans present on plant proteins in different species. Earlier methods combined plant‐based sample preparations with CE‐LIF N‐glycan analysis but suffered from background contaminations, often resulting in non‐reproducible results. This publication describes a reproducible and sensitive protocol for the preparation and analysis of plant N‐glycans, based on a combination of the ‘in‐gel release method’ and N‐glycan analysis on a multicapillary DNA sequencer. Our protocol makes it possible to analyze plant N‐glycans starting from low amounts of plant material with highly reproducible results. The developed protocol was validated for different plant species and plant cells.
Isolation of metallothionein from cells derived from aggressive form of high‐grade prostate carcinoma using paramagnetic antibody‐modified microbeads off‐line coupled with electrochemical and electrophoretic analysis
Authors: Masarik Michal , Gumulec Jaromir , Sztalmachova Marketa , Hlavna Marian , Babula Petr , Krizkova Sona , Ryvolova Marketa , Jurajda Michal , Sochor Jiri , Adam Vojtech , Kizek Rene
Published: November 2011

Prostate cancer with altered zinc(II) cell metabolism is the second most frequently diagnosed cancer in developed countries. The alterations of zinc(II) metabolism can influence metabolism of other metal ions and can also be associated with the expression and translation of metal‐binding proteins including metallothioneins. The aim of this article was to optimize immunoseparation protocol based on paramagnetic beads conjugated with protein G for the isolation of metallothionein. Isolated metallothionein was determined by differential pulse voltammetry Brdicka reaction and SDS‐PAGE. Optimal conditions: antigen‐binding time – 60 min, temperature − 70°C, and buffer composition and pH – acetate buffer, pH 4.3, were determined. Under the optimized conditions, lysates from 22Rv1 prostate cancer cells treated with various concentrations of cadmium(II) and copper(II) ions were analyzed. We observed strong correlation in all experimental groups and all lysate types (r>0.83 at p<0.041) between metallothionein concentration related to viability and concentration of copper(II) ions and cadmium(II) ions in medium. Moreover, the results were compared with standard sample preparation as heat treatment and SDS‐PAGE analysis.
Simulation of flow‐flexible body interactions with large deformation
Authors: Uddin Emad , Sung Hyung Jin
Published: November 2011

A modified front‐tracking method was proposed for the simulation of fluid‐flexible body interactions with large deformations. A large deformable body was modeled by restructuring the body using a grid adaptation. Discontinuities in the viscosity at the fluid‐structure interface were incorporated by distributing the viscosity across the interface using an indicator function. A viscosity gradient field was created near the interface, and a smooth transition occurred between the structure and the fluid. The fluid motion was defined on the Eulerian domain and was solved using the fractional step method on a staggered Cartesian grid system. The solid motion was described by Lagrangian variables and was solved by the finite element method on an unstructured triangular mesh. The fluid motion and the structure motion were independently solved, and their interaction force was calculated using a feedback law. The interaction force was the restoring force of a stiff spring with damping, and spread from the Lagrangian coordinates to the Eulerian grid by a smoothed approximation of the Dirac delta function. In the numerical simulations, we validated the effect of the grid adaptation on the solid solver using a vibrating circular ring. The effects of the viscosity gradient field were verified by solving the deformation of a circular disk in a linear shear flow, including an elastic ring moving through a channel with constriction, deformation of a suspended catenary, and a swimming jellyfish. A comparison of the numerical results with the theoretical solutions was presented. Copyright © 2011 John Wiley & Sons, Ltd.
Nowcasting with Google Trends in an Emerging Market
Authors: Carrière‐Swallow Yan , Labbé Felipe
Published: November 2011

Most economic variables are released with a lag, making it difficult for policy‐makers to make an accurate assessment of current conditions. This paper explores whether observing Internet browsing habits can inform practitioners about aggregate consumer behavior in an emerging market. Using data on Google search queries, we introduce an index of online interest in automobile purchases in Chile and test whether it improves the fit and efficiency of nowcasting models for automobile sales. Despite relatively low rates of Internet usage among the population, we find that models incorporating our Google Trends Automotive Index outperform benchmark specifications in both in‐sample and out‐of‐sample nowcasts, provide substantial gains in information delivery times, and are better at identifying turning points in the sales data. Copyright © 2011 John Wiley & Sons, Ltd.
Hepatitis C virus and GBV‐C virus prevalence among patients with B‐cell lymphoma in different European regions: a case‐control study of the International Extranodal Lymphoma Study Group
Authors: Nicolosi Guidicelli Sabrina , Lopez‐Guillermo Armando , Falcone Umberto , Conconi Annarita , Christinat Alexandre , Rodriguez‐Abreu Delvys , Grisanti Salvatore , Lobetti‐Bodoni Chiara , Piffaretti Jean Claude , Johnson Peter W. , Mombelli Giorgio , Cerny Andreas , Montserrat Emili , Cavalli Franco , Zucca Emanuele
Published: November 2011

Hepatitis C virus (HCV) infection is associated with some B‐cell non‐Hodgkin lymphoma (B cell‐NHLs). Patients with HCV infection frequently show co‐infections with GB virus C (GBV‐C, formerly known as hepatitis G virus), and some studies have suggested a higher incidence of GBV‐C infection in patients with B cell‐NHLs. The aim of this study was to prospectively evaluate the association between HCV and/or GBV‐C infection and B cell‐NHLs in different geographic areas. One hundred thirty‐seven lymphoma cases and 125 non‐lymphoma matched controls were enrolled in an international case‐control study conducted in Switzerland (Bellinzona), Spain (Barcelona) and England (Southampton) on samples collected from 2001 to 2002. In Bellinzona (41 cases and 81 controls), the overall prevalence of HCV was 3.3% (4.9% in NHLs), and the overall prevalence of GBV‐C was 24% (22% in NHLs). In Barcelona (46 cases and 44 controls), the prevalence of HCV was 10% (8.7% in NHLs) and the prevalence of GBV‐C 20% (13% in NHLs). There was no statistically significant difference in the frequency of both infections between patients with NHL and controls. In Southampton, 50 NHL cases were analysed, none of them was found to be HCV‐positive; therefore, no control group was analysed and GBV‐C analysis was not performed, too. Both in Bellinzona and in Barcelona, the seropositivity rate was significantly lower for HCV than for GBV‐C, suggesting that their transmission can be independent. The incidence of HCV was significantly higher in Barcelona than that in Bellinzona. This study confirmed the existence of marked geographic differences in the prevalence of HCV in NHL but cannot provide any significant evidence for an association between HCV and/or GBV‐C and B‐cell NHLs. Copyright © 2011 John Wiley & Sons, Ltd.
The effects of agomelatine on sexual function in depressed patients and healthy volunteers
Authors: Montejo Angel , Majadas Susana , Rizvi Sakina J. , Kennedy Sidney H.
Published: November 2011

Background

Selective serotonin reuptake inhibitor (SSRI) and serotonin and norepinephrine reuptake inhibitor antidepressants are associated with high rates of treatment‐emergent sexual dysfunction (TESD) due to stimulation of serotonin receptors.

Objective

The objective is to evaluate the effect of agomelatine on sexual function in depressed patients.

Methods

This paper reviews published and unpublished data on sexual function with agomelatine in depressed patients and healthy volunteers.

Results

Agomelatine, an agonist of melatonergic MT1 and MT2 receptors and antagonist of 5‐HT2 receptors, is associated with similar rates of sexual dysfunction compared with placebo and lower rates compared with other antidepressants. Twice as many sexually active depressed patients (n = 193) reported a deterioration of sexual function during 12 weeks of treatment with venlafaxine compared with agomelatine (15.2% vs. 8.2%, p < 0.0001); however, no differences were found with respect to arousal. Using the Arizona Sexual Experience Scale in depressed patients (n = 399), the incidence of treatment‐emergent sexual dysfunction (TESD) with agomelatine (3%) was significantly lower than placebo (8.6%) and selective serotonin reuptake inhibitors (10.1%). Among healthy male volunteers (n = 92), TESD was not increased compared with placebo in either agomelatine (25 and 50 mg/day) group over 8 weeks, and both were significantly lower than TESD with paroxetine (p < 0.0001). Moderate or severe TESD occurred in less than 5% of subjects receiving agomelatine versus 62% who received paroxetine (p < 0.001).

Conclusion

Agomelatine demonstrates favorable sexual acceptability. Copyright © 2011 John Wiley & Sons, Ltd.
GMM with many weak moment conditions: Replication and application of Newey and Windmeijer (2009)
Authors: Farbmacher Helmut
Published: November 2011

In a recent article Newey and Windmeijer (Generalized method of moments with many weak moment conditions. Econometrica 2009; 77(3): 687–719) propose a new variance estimator for generalized empirical likelihood. In Monte Carlo examples they show that t‐statistics based on the new variance estimator have nearly correct size. I have replicated their Monte Carlo simulations and in addition used the new variance estimator to re‐estimate Angrist and Krueger's (Does compulsory school attendance affect schooling and earnings? Quarterly Journal of Economics 1991; 106(4): 979–1014) returns to education. Copyright © 2011 John Wiley & Sons, Ltd.
Alignment and composition of laminin–polycaprolactone nanofiber blends enhance peripheral nerve regeneration
Authors: Neal Rebekah A. , Tholpady Sunil S. , Foley Patricia L. , Swami Nathan , Ogle Roy C. , Botchwey Edward A.
Published: November 2011

Peripheral nerve transection occurs commonly in traumatic injury, causing deficits distal to the injury site. Conduits for repair currently on the market are hollow tubes; however, they often fail due to slow regeneration over long gaps. To facilitate increased regeneration speed and functional recovery, the ideal conduit should provide biochemically relevant signals and physical guidance cues, thus playing an active role in regeneration. To that end, laminin and laminin–polycaprolactone (PCL) blend nanofibers were fabricated to mimic peripheral nerve basement membrane. In vitro assays established 10% (wt) laminin content is sufficient to retain neurite‐promoting effects of laminin. In addition, modified collector plate design to introduce an insulating gap enabled the fabrication of aligned nanofibers. The effects of laminin content and fiber orientation were evaluated in rat tibial nerve defect model. The lumens of conduits were filled with nanofiber meshes of varying laminin content and alignment to assess changes in motor and sensory recovery. Retrograde nerve conduction speed at 6 weeks was significantly faster in animals receiving aligned nanofiber conduits than in those receiving random nanofiber conduits. Animals receiving nanofiber‐filled conduits showed some conduction in both anterograde and retrograde directions, whereas in animals receiving hollow conduits, no impulse conduction was detected. Aligned PCL nanofibers significantly improved motor function; aligned laminin blend nanofibers yielded the best sensory function recovery. In both cases, nanofiber‐filled conduits resulted in better functional recovery than hollow conduits. These studies provide a firm foundation for the use of natural–synthetic blend electrospun nanofibers to enhance existing hollow nerve guidance conduits. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2012.
Design and assessment of a wrapped cylindrical Ca‐P AZ31 Mg alloy for critical‐size ulna defect repair
Authors: Smith Montserrat Rabago , Atkinson Patrick , White Désirée , Piersma Tyler , Gutierrez Gloria , Rossini Gianny , Desai Sapna , Wellinghoff Stephen , Yu Hui , Cheng Xingguo
Published: November 2011

Recently, magnesium has been investigated as a promising bioresorbable orthopedic biomaterial. Its mechanical properties are very similar to natural bone, making it appropriate for load‐bearing orthopedic fracture repair applications. However, significant hurdles remain regarding the design of practical implants and methods to control degradation and enhance biocompatibility. Although attempts have been made to hinder magnesium's rapid corrosion via alloying and coating, these studies have used solid monoliths. In an effort to reduce the amount of alloy used for implantation in a shape that mimics cortical bone shape, this study used a thin sheet of Mg AZ31 which was rolled into hollow cylindrical scaffolds. The scaffold was coated with different amounts of Ca‐P; this implant demonstrated slowed corrosion in simulated body fluid (SBF) as well as enhanced biocompatibility for mesenchymal stem cells (MSC). In vivo implantation of magnesium alloy scaffold adjacent to the rat femur showed significant biointegration with further deposition of complex Mg‐Ca phosphates/carbonates typical of natural bone. Finally, the implant was placed in a critical‐size ulna defect in live rabbits, which lead to radiographic union and partial restoration of biomechanical strength in the defect. This study demonstrated that a thin sheet of coated Mg alloy that was spirally wrapped wound be a promising orthopedic biomaterial for bone repair. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2012.
Structural and in vitro adhesion analysis of a novel covalently coupled bioactive composite
Authors: Khan Abdul S. , Hassan Khawaja R. , Bukhari Syeda F. , Wong Ferranti S. L. , Rehman Ihtesham U.
Published: November 2011

The interfacial adhesion between a restorative composite and tooth is one of the major factors that determine the ultimate performance of composite restoration. A novel polyurethane (PU) composite material was prepared by chemically binding the nano‐hydroxyapatite (nHA) to the diisocyanate component in the PU backbone by utilizing solvent polymerization. The procedure involved stepwise addition of monomeric units of the PU and optimizing the reagent concentrations. The resultant materials were characterized structurally (Raman Spectroscopy) and in vitro bioactive analysis was conducted in modified‐simulated body fluid for periodical time intervals. The in vitro study evaluated the push‐out bond strength of existing obturating material and novel covalently linked PU/nHA composites to dentin after long‐term storage in deionized water and artificial saliva. Human extracted molar roots were filled with experimental samples and analyzed at predetermined time intervals. The shear bond strength of samples was measured and surface morphologies were evaluated. Covalent bond formation was achieved between PU and nHA without intermediate coupling agent. With the increase in concentration of nHA, the composite showed more bioactivity and adhesion toward tooth structure. Bond strength of this new composite were in accordance with obutrating material, therefore, the material can be used as an obturating material because of its direct adhesion with tooth structure. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2012.
Synthesis and characterization of silver/silicon‐cosubstituted nanohydroxyapatite
Authors: Lim Poon Nian , Tay Bee Yen , Chan Cynthia Mingli , Thian Eng San
Published: November 2011

Favorable cell‐material interaction and the absence of undesirable reaction from the host body defence system play a critical role in determining the success and long‐term survival of the implants. Substitution of various elements into hydroxyapatite (HA) has been done to alter its chemical composition, thereby mimicking that of the bone mineral. In this study, a cosubstituted nanosized apatite (Ag/Si‐HA) containing Ag (0.3 wt %) and Si (0.8 wt %) was synthesized by an aqueous precipitation technique. The synthesized Ag/Si‐HA displayed a rod‐like morphology of dimensions ∼50 nm in length and ∼15 nm in width, as observed from the transmission electron microscope image. With an increase in temperature, the aspect ratio of nanosized Ag/Si‐HA decreased, whilst the size increased. Autoclaving was used to achieve sufficient crystallinity while maintaining the rod‐like morphology and size that were comparable to that of the bone apatite. A pure Ag/Si‐HA was produced without any undesirable secondary phases, as evidenced from the X‐ray diffraction and thermal gravimetric results. The Ag/Si cosubstitution affected the lattice cell parameters, in particularly the a‐ and c‐ axes which further led to an expansion of the unit cell volume. In addition, the relative intensity of the hydroxyl vibrational bands was reduced. These results demonstrated that a stable phase‐pure Ag/Si‐HA was produced using an aqueous precipitation reaction. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2012.
Fibrous membrane of nano‐hybrid poly‐L‐lactic acid/silica xerogel for guided bone regeneration
Authors: Jang Tae‐Sik , Lee Eun‐Jung , Jo Ji‐Hoon , Jeon Jong‐Myeong , Kim Mi‐Young , Kim Hyoun‐Ee , Koh Young‐Hag
Published: November 2011

Nanofibrous membranes, consisting of a poly(L‐lactic acid) (PLLA)‐silica xerogel hybrid material, were successfully fabricated from a hybrid sol using the electrospinning technique for guided bone regeneration (GBR) application. These hybrid nanofibers exhibited a homogeneous and continuous morphology, with a nano‐sized dispersed silica xerogel phase in the PLLA fiber matrix. The mechanical properties, such as the tensile strength and the elastic modulus, were improved as the silica xerogel content increased up to 40%. All of the hybrid membranes exhibited highly hydrophilic surfaces and good proliferation levels. After culturing for 13 days, the cells that were cultured on the hybrid membranes exhibited a significantly higher ALP activity compared to the pure PLLA membrane. Moreover, the in vivo animal experiments that used the rat calvarial defect model revealed a remarkably improved bone regeneration ability for the hybrid membrane compared to pure PLLA. These results demonstrated the feasibility of these hybrid membranes for efficient GBR. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 100B: 321–330, 2012.
Biological functionalization of dental implants with collagen and glycosaminoglycans—A comparative study
Authors: Stadlinger Bernd , Hintze Vera , Bierbaum Susanne , Möller Stephanie , Schulz Matthias C. , Mai Ronald , Kuhlisch Eberhard , Heinemann Sascha , Scharnweber Dieter , Schnabelrauch Matthias , Eckelt Uwe
Published: November 2011

Biological implant surface coatings are an emerging technology to increase bone formation. Such an approach is of special interest in anatomical regions like the maxilla. In the present study, we hypothesized that the coating of titanium implants with components of the organic extracellular matrix increases bone formation and implant stability compared to an uncoated reference. The implants were coated using collagen‐I with either two different concentrations of chondroitin sulfate (CS) or two differentially sulfated hyaluronans. Implant coatings were characterized biochemically and with atomic force microscopy. Histomorphometry was used to assess bone‐implant contact (BIC) and bone‐volume density (BVD) after 4 and 8 weeks of submerged healing in the maxilla of 20 minipigs. Further, implant stability was measured by resonance frequency analysis (RFA). Implants containing the lower CS concentration had significantly more BIC, compared to the uncoated reference at both times of interest. No significant increase was measured from week 4 to 8. Differences in BVD and RFA were statistically not significant. A higher concentration of CS and the application of sulfated hyaluronans showed no comparable increase in BIC. This study demonstrates a positive effect of a specific collagen–glycosaminoglycan combination on early bone formation in vivo. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 100B: 331–341, 2012.
Long‐term outcomes of a chitosan hemostatic dressing in laparoscopic partial nephrectomy
Authors: Xie Hua , Lucchesi Lisa , Teach Jeffrey S. , Virmani Renu
Published: November 2011

This study examined the long‐term safety and effectiveness of a chitosan hemostatic dressing (CHD) in a porcine laparoscopic partial nephrectomy (LPN) model. Eighteen miniswine underwent treatment of using CHD or Surgicel® and Tisseel® (S/T) for renal parenchymal hemostasis after LPN. The animals were followed up for 6 and 12 months. Surgical procedure related complications, hematological and blood chemical changes were monitored. Histopathological examination was performed on the treated and untreated tissue and organs. All animals had initial hemostasis and survived without any immediate or delayed complications in both CHD and S/T groups. The animals with CHD treatment left large amounts of chitosan residuals on the resected kidney that associated with greater inflammatory scores when compared to the S/T treated animals. This long‐term study showed that CHD residuals remained for 12 months and resulted in local inflammation in the LPN model. Despite lack of signs and symptoms of clinical significance in the animals, a further investigation should be conducted to understand the risk of slow degradation of CHD. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 100B: 432–436, 2012.
Analysis of lipid surface area in protein–membrane systems combining voronoi tessellation and monte carlo integration methods
Authors: Mori Takaharu , Ogushi Fumiko , Sugita Yuji
Published: November 2011

All‐atom molecular dynamics (MD) simulation has become a powerful research tool to investigate structural and dynamical properties of biological membranes and membrane proteins. The lipid structures of simple membrane systems in recent MD simulations are in good agreement with those obtained by experiments. However, for protein–membrane systems, the complexity of protein–lipid interactions makes investigation of lipid structure difficult. Although the area per lipid is one of the essential structural properties in membrane systems, the area in protein–membrane systems cannot be computed easily by conventional approaches like the Voronoi tessellation method. To overcome this limitation, we propose a new method combining the two‐dimensional Voronoi tessellation and Monte Carlo integration methods. This approach computes individual surface areas of lipid molecules not only in bulk lipids but also in proximity to membrane proteins. We apply the method to all‐atom MD trajectories of the sarcoplasmic reticulum Ca2+‐pump and the SecY protein‐conducting channel. The calculated lipid surface area is in agreement with experimental values and consistent with other structural parameters of lipid bilayers. We also observe changes in the average area per lipid induced by the conformational transition of the SecY channel. Our method is particularly useful for examining equilibration of lipids around membrane proteins and for analyzing the time course of protein–lipid interactions. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2012
Compromised decision making and the effects of manipulating physical states on human judgments
Authors: De Los Reyes Andres , Aldao Amelia , Kundey Shannon M.A. , Lee Bern G. , Molina Sabrina
Published: November 2011

Objectives: Nonmorally based decision making between two equitable objects often involves degrading the unchosen object and promoting the chosen object (“postdecisional dissonance”). One can extinguish these thought processes with the physical act of hand‐washing (“clean slate” effects; [Lee & Schwarz (2010). Washing away postdecisional dissonance. Science, 328, 709.]). However, clean slate effects might not characterize all nonmorally based decision making, particularly for people who mentally “get stuck” making decisions (i.e., compromised decision making). Design: We administered a clean slate task to 48 undergraduates (64.6% females; mean = 21.34 years, standard deviation = 4.06 years; 75% Caucasian), and identified individuals reporting relatively high‐compromised versus low‐compromised decision making (e.g., self‐reported repetitive thought processes and generalized anxiety symptoms). Results: Only individuals reporting relatively high‐compromised decision making continued to express postdecisional dissonance even after hand‐washing. Conclusions: Behavioral markers of clean slate effects might result in identifying phenotypes associated with psychological concerns typified by compromised decision making. © 2011 Wiley Periodicals, Inc. J Clin Psychol 68:1–7, 2012.
Pharmaco‐metabolomics: An emerging “omics” tool for the personalization of anticancer treatments and identification of new valuable therapeutic targets
Authors: Corona Giuseppe , Rizzolio Flavio , Giordano Antonio , Toffoli Giuseppe
Published: November 2011

In the post‐genomics era, metabolomics represents a new “omics” approach that in the last decade has received increased attention in the field of oncology. Metabolomics is based on the holistic study of the metabolic profile that characterizes a specific phenotype in a biological system. The metabolic profile provides a readout of the metabolic state of an individual that cannot be obtained directly from DNA genotyping, gene expression, or proteomic profiling analyses. The translational value of metabonomics in the oncology field has been demonstrated by the identification of diagnostic and prognostic biomarkers. The so‐called pharmaco‐metabolomic approach that is currently emerging aims to identify the individual metabolomic characteristics able to predict drug effectiveness and/or toxicity. This review presents the potential role of pharmaco‐metabolomics in the future of anticancer pharmacology to achieve customized anticancer treatments and new, targeted therapeutic approaches. J. Cell. Physiol. 227: 2827–2831, 2012. © 2011 Wiley Periodicals, Inc.
Unsaturated fatty acids induce mesenchymal stem cells to increase secretion of angiogenic mediators
Authors: Smith Andria N. , Muffley Lara A. , Bell Austin N. , Numhom Surawej , Hocking Anne M.
Published: November 2011

Mesenchymal stem cells (MSC) represent emerging cell‐based therapies for diabetes and associated complications. Ongoing clinical trials are using exogenous MSC to treat type 1 and 2 diabetes, cardiovascular disease and non‐healing wounds due to diabetes. The majority of these trials are aimed at exploiting the ability of these multipotent mesenchymal stromal cells to release soluble mediators that reduce inflammation and promote both angiogenesis and cell survival at sites of tissue damage. Growing evidence suggests that MSC secretion of soluble factors is dependent on tissue microenvironment. Despite the contribution of fatty acids to the metabolic environment of type 2 diabetes, almost nothing is known about their effects on MSC secretion of growth factors and cytokines. In this study, human bone marrow‐derived MSC were exposed to linoleic acid, an omega‐6 polyunsaturated fatty acid, or oleic acid, a monounsaturated fatty acid, for seven days in the presence of 5.38 mM glucose. Outcomes measured included MSC proliferation, gene expression, protein secretion and chemotaxis. Linoleic and oleic acids inhibited MSC proliferation and altered MSC expression and secretion of known mediators of angiogenesis. Both unsaturated fatty acids induced MSC to increase secretion of interleukin‐6, VEGF and nitric oxide. In addition, linoleic acid but not oleic acid induced MSC to increase production of interleukin‐8. Collectively these data suggest that exposure to fatty acids may have functional consequences for MSC therapy. Fatty acids may affect MSC engraftment to injured tissue and MSC secretion of cytokines and growth factors that regulate local cellular responses to injury. J. Cell. Physiol. 227: 3225–3233, 2012. © 2011 Wiley Periodicals, Inc.
The protective role of peroxisome proliferator‐activated receptor γ coactivator‐1α in hyperthyroid cardiac hypertrophy
Authors: Xu Wei , Hou Dongxia , Jiang Xiangrui , Lu Zhiyuan , Guo Ting , Liu Yuan , Wang Dongjin , Zen Ke , Yu Bo , Zhang Chen‐Yu
Published: November 2011

Heart failure is a major cause of death throughout the world. Hyperthyroidism has been shown to induce cardiac hypertrophy, which is a contributing factor to heart failure. However, the mechanism underling effect of thyroid hormone is not completely clear. The present study investigates the role of peroxisome proliferator‐activated receptor (PPAR) γ coactivator‐1α (PGC‐1α) in cardiac hypertrophy induced by Triiodothyronine (T3). We investigated PGC‐1α mRNA expression in rat hearts exposed to T3 in vivo and ex vivo. Surprisingly, we found that the extended periods of T3 treatment led to an increase in PGC‐1α expression compared to shorter treatment times, which resulted in a reduction of PGC‐1α expression. Mechanistic studies showed that suppression of PGC‐1α by small interfering RNA in cardiomyocytes amplified the cellular hypertrophic response to T3 stimulation, whereas overexpression of PGC‐1α was protective. Furthermore, we presented evidence to show that T3 decreased PGC‐1α expression via p38 mitogen‐activated protein kinases (MAPK) pathway. Our studies also revealed that overexpression of PGC‐1α in cardiomyocytes inhibited basal and T3‐induced p38 MAPK phosphorylation. These data indicate for the first time that PGC‐1α plays protective role in T3‐induced cardiac hypertrophy and that hypertrophic growth induced by T3 involves a regulatory pathway between PGC‐1α and p38 MAPK. J. Cell. Physiol. 227: 3243–3253, 2012. © 2012 Wiley Periodicals, Inc.
Proteotoxic stress of cancer: Implication of the heat‐shock response in oncogenesis
Authors: Dai Chengkai , Dai Siyuan , Cao Junyue
Published: November 2011

Organisms frequently encounter a wide variety of proteotoxic stressors. The heat‐shock response, an ancient cytoprotective mechanism, has evolved to augment organismal survival and longevity in the face of proteotoxic stress from without and within. These broadly recognized beneficial effects, ironically, contrast sharply with its emerging role as a culprit in the pathogenesis of cancers. Here, we present an overview of the normal biology of the heat‐shock response and highlight its implications in oncogenic processes, including the proteotoxic stress phenotype of cancer; the function of this stress response in helping cancer survive and adapt to proteotoxic stress; and perturbation of proteome homeostasis in cancer as a potential therapeutic avenue. J. Cell. Physiol. 227: 2982–2987, 2012. © 2011 Wiley Periodicals, Inc.