bluuebunny/crossref_metadata_2025 huggingface dataset:
Does a standard measure of self‐reported physical disability correlate with clinician perception of impairment related to cancer screening?
Authors: Buckley David I. , Davis Melinda M. , Andresen Elena M.
Published: August 2011

BACKGROUND:

Adults with physical disabilities are less likely than others to receive cancer screening. It is not known, however, whether commonly used measures assess elements of physical ability necessary for successful screening. The objective of this exploratory study was to determine whether patients who reported limitations in activities of daily living (ADLs) or instrumental ADLs (IADLs) are perceived by their primary care clinicians to have physical limitations that may impede cancer screening.

METHODS:

Patients at 2 rural primary care clinics were surveyed about ADLs and IADLs and about their up‐to‐date status for breast, cervical, and/or colorectal cancer screening. Clinicians and office staff were asked whether they believed each patient had a physical limitation that might impede screening. The agreement between patient and clinician assessments was evaluated.

RESULTS:

Clinicians believed that 43% of patients with severe disability (ADLs) and 30% of patients with moderate disability (IADLs) had limitations that might affect screening. Agreement between patient and clinician assessments was low according to the kappa statistic (κ = 0.355), but had a high percentage of negative agreement (92.3%) and a low percentage of positive agreement (42.7%). Patients with ADL/IADL‐related disability were less likely than nondisabled patients to be current for cervical and breast cancer screening. Patients who were viewed by clinicians as having limitations relevant for screening were less likely to be current for cervical cancer screening.

CONCLUSIONS:

These results indicate that a common measure of general disability may not capture all factors relevant for cancer screening. An instrument designed to include these factors may help identify and accommodate patients who have disabilities that may impede screening. Cancer 2012;. © 2011 American Cancer Society.
Epidermal growth factor receptor protein expression and genomic alterations in renal cell carcinoma
Authors: Minner Sarah , Rump Dorothea , Tennstedt Pierre , Simon Ronald , Burandt Eike , Terracciano Luigi , Moch Holger , Wilczak Waldemar , Bokemeyer Carsten , Fisch Margit , Sauter Guido , Eichelberg Christian
Published: August 2011

BACKGROUND:

Epidermal growth factor receptor (EGFR) is involved in the progression of many cancer types and represents an important therapeutic target.

METHODS:

To determine the role of EGFR in renal cell carcinoma (RCC), the authors analyzed 1088 tumors in a tissue microarray format by using immunohistochemistry and fluorescence in situ hybridization (FISH). A subset of 63 cancers was sequenced for EGFR exon 18 through 21 mutations.

RESULTS:

EGFR expression was observed in 83.8% of clear cell carcinomas, in 68.2% of papillary carcinomas, in 75% of chromophobe carcinomas, and in 50% of oncocytomas. Within clear cell carcinomas, the expression level of EGFR was associated with high tumor grade (P < .0001), advanced pathologic tumor classification (P < .0001), and, to a lesser extent, lymph node status (P = .0326). FISH analysis revealed increased EGFR copy numbers (high polysomy) in 5.5% of tumors and amplification in 0.1% of tumors. EGFR copy number increases were associated with EGFR protein expression (P = .0015). Within clear cell carcinomas, EGFR copy number increases were associated with high tumor grade (P < .0001), advanced pathologic tumor classification (P = .0472), and lymph node status (P = .0065). No exon 18 through 21 mutations were identified in 63 sequenced tumors.

CONCLUSIONS:

The authors concluded that increased EGFR expression occurs in a fraction of patients who have RCC with an unfavorable histologic phenotype. EGFR copy number gain represents 1 possible cause for EGFR overexpression; however, many over expressing tumors have a normal genotype. High polysomy (which is suggested to be predictive of a response to tyrosine kinase inhibitors) occurs in 5.6% of RCCs. Thus, the potential utility of anti‐EGFR medications may be worth further investigation in a small but significant subset of patients with RCC. Cancer 2012;. © 2011 American Cancer Society.
Body mass index, long‐term weight change, and esophageal squamous cell carcinoma
Authors: Lahmann Petra H. , Pandeya Nirmala , Webb Penelope M. , Green Adèle C. , Whiteman David C. ,   for the Australian Cancer Study
Published: August 2011

BACKGROUND:

Observational studies suggest that body mass index (BMI) is inversely associated with esophageal squamous cell carcinoma (ESCC). However, questions remain regarding reverse causation and confounding, especially by smoking, as alternative explanations.

METHODS:

The authors examined the association between BMI and measures of weight history and risk of ESCC in a population‐based Australian case‐control study (from 2002 to 2005) comprising 287 patients with ESCC (cases) and a control group of 1544 individuals who were sampled from a population registry. Stratified analyses were performed specifically to explore whether this association was influenced by smoking. Multivariable logistic regression models were used to derive odds ratios (ORs).

RESULTS:

After adjusting for smoking, significant inverse associations with ESCC for BMI and weight 1 year before diagnosis, maximum adult BMI, and weight gain since age 20 years were observed (all Ptrend < .001). The risk of ESCC was reduced by 35% (range, 23%‐44%) per 5‐unit increase in recent BMI. Participants who gained weight after age 20 years had a lower risk than those who maintained their weight during adult life (OR for gain of >20 kg, 0.51; 95% confidence interval [CI], 0.33‐0.77). In stratified analyses, higher BMI was associated with a decreasing risk of ESCC both in never‐smokers (OR, 0.32; 95% CI 0.13‐0.76) and smokers (OR 0.22, 95%CI 0.07‐0.67) comparing the highest versus the lowest BMI quintile.

CONCLUSIONS:

In this study, the inverse associations between BMI, long‐term weight gain, and other body measures and ESCC appeared to be robust and could not be explained by smoking status or potential confounding factors. Cancer 2012;. © 2011 American Cancer Society.
CFD and PIV analysis of hemodynamics in a growing intracranial aneurysm
Authors: Raschi Marcelo , Mut Fernando , Byrne Greg , Putman Christopher M. , Tateshima Satoshi , Viñuela Fernando , Tanoue Tetsuya , Tanishita Kazuo , Cebral Juan R.
Published: August 2011

Hemodynamics is thought to be a fundamental factor in the formation, progression, and rupture of cerebral aneurysms. Understanding these mechanisms is important to improve their rupture risk assessment and treatment. In this study, we analyze the blood flow field in a growing cerebral aneurysm using experimental particle image velocimetry (PIV) and computational fluid dynamics (CFD) techniques. Patient‐specific models were constructed from longitudinal 3D computed tomography angiography images acquired at 1‐y intervals. Physical silicone models were constructed from the computed tomography angiography images using rapid prototyping techniques, and pulsatile flow fields were measured with PIV. Corresponding CFD models were created and run under matching flow conditions. Both flow fields were aligned, interpolated, and compared qualitatively by inspection and quantitatively by defining similarity measures between the PIV and CFD vector fields. Results showed that both flow fields were in good agreement. Specifically, both techniques provided consistent representations of the main intra‐aneurysmal flow structures and their change during the geometric evolution of the aneurysm. Despite differences observed mainly in the near wall region, and the inherent limitations of each technique, the information derived is consistent and can be used to study the role of hemodynamics in the natural history of intracranial aneurysms. Copyright © 2011 John Wiley & Sons, Ltd.
Registration of plantar pressure images
Authors: Oliveira Francisco P.M. , Tavares João Manuel R.S.
Published: August 2011

In this work, five computational methodologies to register plantar pressure images are compared: (1) the first methodology is based on matching the external contours of the feet; (2) the second uses the phase correlation technique; (3) the third addresses the direct maximization of cross‐correlation using the Fourier transform; (4) the fourth minimizes the sum of squared differences using the Fourier transform; and (5) the fifth methodology iteratively optimizes an intensity (dis)similarity measure based on Powell's method. The accuracy and robustness of the five methodologies were assessed by using images from three common plantar pressure acquisition devices: a Footscan system, an EMED system, and a light reflection system. Using the residual error as a measure of accuracy, all methodologies revealed to be very accurate even in the presence of noise. The most accurate was the methodology based on the iterative optimization, when the mean squared error was minimized. It achieved a residual error inferior to 0.01 mm and 0.6 mm for non‐noisy and noisy images, respectively. On the other hand, the methodology based on image contour matching was the fastest, but its accuracy was the lowest. Copyright © 2011 John Wiley & Sons, Ltd.
Modulation and coding scheme selection in multimedia broadcast over a single frequency network‐enabled long‐term evolution networks
Authors: Alexiou Antonios , Bouras Christos , Kokkinos Vasileios , Papazois Andreas , Tsichritzis George
Published: August 2011

Long term evolution constitutes the next generation cellular network beyond 3G that is designed to support the explosion in demand for bandwidth‐hungry multimedia services in wireless networks by providing an extremely high performance radio access technology. To support multimedia broadcast/multicast services (MBMS), long term evolution offers the functionality to transmit MBMS over a single frequency network, where a time‐synchronized common waveform is transmitted from multiple cells for a given duration. This enables over‐the‐air combining, thus significantly improving the spectral efficiency (SE) compared with conventional MBMS operations. In MBMS over a single frequency network transmissions, the achieved SE is mainly determined by the modulation and coding scheme selected. This study proposes and evaluates four approaches for the selection of the modulation and coding scheme. Each approach corresponds to different users' distribution and multimedia traffic conditions. On the basis of SE measurements, we determine the approach that either maximizes or achieves a target SE for the corresponding users' distribution and traffic conditions. Copyright © 2011 John Wiley & Sons, Ltd.
An optimal energy‐efficient clustering method in wireless sensor networks using multi‐objective genetic algorithm
Authors: Peiravi Ali , Mashhadi Habib Rajabi , Hamed Javadi S.
Published: August 2011

In this study, an optimal method of clustering homogeneous wireless sensor networks using a multi‐objective two‐nested genetic algorithm is presented. The top level algorithm is a multi‐objective genetic algorithm (GA) whose goal is to obtain clustering schemes in which the network lifetime is optimized for different delay values. The low level GA is used in each cluster in order to get the most efficient topology for data transmission from sensor nodes to the cluster head. The presented clustering method is not restrictive, whereas existing intelligent clustering methods impose certain conditions such as performing two‐tiered clustering. A random deployed model is used to demonstrate the efficiency of the proposed algorithm. In addition, a comparison is made between the presented algorithm other GA‐based clustering methods and the Low Energy Adaptive Clustering Hierarchy protocol. The results obtained indicate that using the proposed method, the network's lifetime would be extended much more than it would be when using the other methods. Copyright © 2011 John Wiley & Sons, Ltd.
Focused attention, heart rate deceleration, and cognitive development in preterm and full‐term infants
Authors: Petrie Thomas Julianne H. , Whitfield Michael F. , Oberlander Tim F. , Synnes Anne R. , Grunau Ruth E.
Published: August 2011

The majority of children who are born very preterm escape major impairment, yet more subtle cognitive and attention problems are very common in this population. Previous research has linked infant focused attention during exploratory play to later cognition in children born full‐term and preterm. Infant focused attention can be indexed by sustained decreases in heart rate (HR). However there are no preterm studies that have jointly examined infant behavioral attention and concurrent HR response during exploratory play in relation to developing cognition. We recruited preterm infants free from neonatal conditions associated with major adverse outcomes, and further excluded infants with developmental delay (Bayley Mental Development Index [MDI < 70]) at 8 months corrected age (CA). During infant exploratory play at 8 months CA, focused attention and concurrent HR response were compared in 83 preterm infants (born 23–32 weeks gestational age [GA]) who escaped major impairment to 46 full‐term infants. Focused attention and HR response were then examined in relation to Bayley MDI, after adjusting for neonatal risk. MDI did not differ by group, yet full‐term infants displayed higher global focused attention ratings. Among the extremely preterm infants born <29 weeks, fewer days on mechanical ventilation, mean longest focus, and greater HR deceleration during focused attention episodes, accounted for 49% of adjusted variance in predicting concurrent MDI. There were no significant associations for later‐born gestational age (29–32 weeks) or full‐term infants. Among extremely preterm infants who escape major impairment, our findings suggest unique relationships between focused attention, HR deceleration, and developing cognition. © 2011 Wiley Periodicals, Inc. Dev Psychobiol 54:383–400, 2012.
Attachment security and HPA axis reactivity to positive and challenging emotional situations in child–mother dyads in naturalistic settings
Authors: Roque Lisa , Veríssimo Manuela , Oliveira Tania F. , Oliveira Rui F.
Published: August 2011

This study investigated adrenocortical activity in response to different challenging and positive affect emotional contexts in child–mother dyads, as function of attachment security (children's secure base behaviors and mothers' attachment representations). Fifty‐one children ranging in age from 18 to 26 months and their mothers participated in this study. Secure children showed significant increases in their cortisol levels after fear episodes and significant decreases, after positive affect ones. No significant changes were found for frustration/anger episodes. Insecure children did not show significant differences in cortisol levels in any of the episodes, which suggests that insecure attachment may be related to hypothalamic–pituitary–adrenal axis suppression in response to challenging and positive contexts. Mothers of insecure children showed significantly higher cortisol concentrations in pre‐ and post‐session samples, than mothers of secure children. Mothers' personal attachment representations influenced their own cortisol responses, as well as their children's (in a marginal significant way). © 2011 Wiley Periodicals, Inc. Dev Psychobiol 54:401–411, 2012.
Increased expression of Syne1/nesprin‐1 facilitates nuclear envelope structure changes in embryonic stem cell differentiation
Authors: Smith Elizabeth R. , Zhang Xiao‐Ying , Capo‐Chichi Callinice D. , Chen Xiongwen , Xu Xiang‐Xi
Published: August 2011

We found by electron microscopy that the inter‐membrane space of embryonic stem cells is irregular and generally wider than in differentiated cells. Among a panel of nuclear envelope structural proteins examined, the expression of Syne1/nesprin‐1 was found to be greatly induced upon differentiation. Down‐regulation of Syne1 by siRNA in differentiated embryonic stem cells caused the nuclear envelope to adopt a configuration resembling that found in undifferentiated embryonic stem cells. Suppression of Syne1 expression did not produce a detectable impact on the retinoic acid–induced differentiation of embryonic stem cells; however, forced expression of Syne1 enhanced the tendency of the cells to lose pluripotency. Thus, we found that low expression of Syne1 splicing isoforms accounts for the wider and irregular nuclear envelope inter‐membrane space in embryonic stem cells. We conclude that the nuclear envelope structural change accompanying differentiation likely participates in promoting the differential chromatin organization of the differentiated cells. Developmental Dynamics 240:2245–2255, 2011. © 2011 Wiley‐Liss, Inc.
Octahedral Molybdenum(0) Monodinitrogen Complexes Facially Coordinated by the Tripodal Ligand 1,1,1‐Tris(diphenylphosphanylmethyl)ethane – Influence of Diphosphane Coligands on the Activation of N2
Authors: Krahmer Jan , Broda Henning , Näther Christian , Peters Gerhard , Thimm Wulf , Tuczek Felix
Published: August 2011

The synthesis and physicochemical properties of the new molybdenum dinitrogen complexes [Mo(N2)(tdppme)(dmpm)] (2) and [Mo(N2)(tdppme)(dppm)] (3) are reported. Complexes 2 and 3 are facially coordinated by the tripodal ligand 1,1,1‐tris(diphenylphosphanylmethyl)ethane (tdppme) and contain the bidentate coligands bis(dimethylphosphanyl)methane (dmpm) and bis(diphenylphosphanyl)methane (dppm), respectively. They are accessible by amalgam reduction of the MoIII precursor [MoBr3(tdppme)] (1) under nitrogen in the presence of dppm and dmpm, respectively. Protonation of 2 with trifluoromethanesulfonic acid (triflic acid, HOTf) leads to the NNH2 complex [Mo(NNH2)(tdppme)(dmpm)](OTf)2 (4) with retention of the pentaphosphane coordination. The structural, electronic and vibrational properties of 2, 3 and 4 have been investigated by NMR, IR and Raman spectroscopy coupled with DFT calculations. The crystal structure of 2 has been determined and is discussed in relation to the calculated structures of 2 and 3. The results of the investigations are compared with those obtained earlier for the pentaphosphane complexes [Mo(N2)(dpepp)(dppm)] and [Mo(NNH2)(dpepp)(dppm)](OTf)2 [dpepp = bis(diphenylphosphanylethyl)phenylphosphane].
Systematic Expansion of Supercubane Cores in Manganese Oxo Clusters with Tricarboxylate Ligands
Authors: Okui Yayoi , Catusanu Florina Aurelia , Kubota Ryoko , Kure Bunsho , Nakajima Takayuki , Tanase Tomoaki , Kajiwara Takashi , Mikuriya Masahiro , Miyasaka Hitoshi , Yamashita Masahiro
Published: August 2011

A novel class of high‐nuclearity Mn17 and Mn19 mixed‐valent complexes, [Mn17(μ‐O)12(μ‐OMe)2(μ‐kta)6(MeOH)4] (1), [Mn17(μ‐O)14(μ‐kta)6L4] [L = bpy (2a), phen (2b), 4,7‐Ph2phen (2c), dmf (3)], and [Mn19(μ‐O)14(μ‐kta)6(bpy)6]X3 [X = PF6 (4a), BF4 (4b)], were synthesized by utilizing Kemp's tricarboxylate ligands (H3kta = cis,cis‐1,3,5‐trimethylcyclohexane‐1,3,5‐tricarboxylic acid). The complexes were characterized by X‐ray crystallography and reveal mineralomimetic Mn13 supercubane units, [Mn13(μ‐O)14], in which their oxidation states systematically altered, depending on their vertex face‐capping ligands and MnII satellite fragments. Complex 2a was converted by treatment with benzoic acid and [Mn2O2(bpy)4](BF4)3 to a cage‐type Mn14 complex, [Mn14(μ‐O)12(μ‐OH)6(μ‐Hkta)6(bpy)6](BF4)4 (5), which show ferro‐ and antiferromagnetic interactions and slow magnetic relaxation at low temperature.
Lipid storage: Yeast we can!
Authors: Athenstaedt Karin , Daum Günther
Published: August 2011

Waste not, want not! This saying also applies to the yeast. In times of excess this microorganism synthesizes non‐polar lipids, triacylglycerols (TAG) and steryl esters (SE), which serve as energy source and/or as a source of building blocks for the formation of membrane phospholipids when nutriments become limiting. Due to the lack of charged groups substantial amounts of non‐polar lipids cannot be incorporated into cellular membranes, whereas the hydrophobic nature of these molecules also deprives cytosolic localization. Consequently, TAG and SE are stored in specialized compartments known as lipid particles or lipid droplets. TAG synthases and SE synthases which catalyze the final steps in storage lipid formation occur redundantly. Hydrolytic enzymes, TAG lipases and SE hydrolases, initiate the breakdown of storage lipids and make sterols, diacylglycerols, and free fatty acids available for anabolic processes and energy production. In this paper we describe routes of non‐polar lipid metabolism, focus on molecular properties of enzymes involved and discuss regulatory aspects of the respective pathways. The value of the yeast as a eukaryotic model system is advocated.
Oxidative stability of 70% fish oil‐in‐water emulsions: Impact of emulsifiers and pH
Authors: Horn Anna Frisenfeldt , Nielsen Nina Skall , Andersen Ulf , Søgaard Louise Helene , Horsewell Andy , Jacobsen Charlotte
Published: August 2011

The objective of this study was to evaluate the protective effects of five different emulsifiers on lipid oxidation in 70% fish oil‐in‐water emulsions to be used as delivery systems for long chain polyunsaturated omega‐3 fatty acids to foods. The emulsifiers were either phospholipid (PL) based or protein based. The PL‐based emulsifiers were soy lecithin and two milk PL concentrates (with either 20 or 75% PL). The protein‐based emulsifiers were whey protein isolate and sodium caseinate. Lipid oxidation was studied at two pH values (pH 4.5 and 7.0) and results were compared to lipid oxidation in neat fish oil. Lipid oxidation was followed by determination of peroxide values and volatile oxidation products. Emulsions were furthermore imaged by confocal and cryo‐scanning electron microscopy. Results showed that emulsions prepared at high pH with proteins oxidized less than or equally to neat oil, whereas, all other emulsions oxidized more. In addition, there was a tendency toward a faster progression in lipid oxidation at low pH compared to high pH for emulsions prepared with protein‐based emulsifiers. The opposite was observed for emulsions prepared with PL‐based emulsifiers. Hence, at low pH PL‐based emulsions may be more suitable as delivery systems than protein‐based emulsions. Moreover, the quality of the PL‐based emulsifiers seemed to affect lipid oxidation.

Practical applications: Results from the present study give an insight into the physical and oxidative stability of 70% fish oil‐in‐water emulsions prepared with whey protein isolate, sodium caseinate, milk phospholipids, or soy lecithin. The emulsions can be used as delivery systems for fish oil to foods. However, only emulsions prepared with proteins at high pH offered advantages with respect to better oxidative stability during storage compared to neat fish oil. Thus, when fish oil is added to a food product in a delivery emulsion, the type of emulsion used should be carefully considered.
New Austalides from the Sponge‐Associated Fungus Aspergillus sp.
Authors: Zhou Yaming , Mándi Attila , Debbab Abdessamad , Wray Victor , Schulz Barbara , Müller Werner E. G. , Lin WenHan , Proksch Peter , Kurtán Tibor , Aly Amal H.
Published: August 2011

Chromatographic separation of a crude extract obtained from the fungus Aspergillus sp., isolated from the Mediterranean sponge Tethya aurantium, yielded five new meroterpenoid metabolites, austalides M–Q (1–5), together with nine known compounds (6–13). The structures of the new compounds were unambiguously elucidated on the basis of extensive 1D and 2D NMR methods and by mass spectral analysis. Furthermore, the absolute configurations of 1 and 4 were determined by time‐dependent density functional theory electronic circular dichroism (TDDFT ECD) calculations, allowing the assignment of the absolute configuration of analogous compounds 2, 3, and 5. The calculations revealed that the conformation of the benzene‐fused phthalide chromophore, which is sensitive to even minor changes in its proximity, is decisive for the ECD parameters, rendering a simple ECD comparison of related homochiral austalides difficult. All compounds were evaluated for their cytotoxic activity against murine cancer cell line L5178Y by using the MTT method. Compounds 8 and 11 exhibited moderate to pronounced cytotoxicity, with IC50 values of 39.4 and 0.2 μM, respectively, whereas the remaining investigated compounds showed either weak or no activity in this assay.
Recent Developments in Synthesis and Applications of Triptycene and Pentiptycene Derivatives
Authors: Jiang Yi , Chen Chuan‐Feng
Published: August 2011

Iptycenes are a class of aromatic compounds with arene units fused to the [2.2.2]bicyclooctatriene bridgehead system. As a result of their unique structures, more and more iptycenes, especially triptycene and pentiptycene derivatives, have been efficiently synthesized. These compounds have wide applications in many research areas, including molecular machines, molecular balances, catalysis, materials chemistry, molecular assembly, host–guest chemistry, and so on. This microreview mainly describes the developments in the synthesis and applications of triptycene and pentiptycene derivatives during the last ten years. Particular attention is paid to the synthesis and applications of hosts derived from triptycene and pentiptycene systems in recent years.
Heterogeneous Bisoxazoline/Copper Complex: A Green Catalyst for the Enantioselective Reaction of Nitromethane with Substituted Benzaldehydes
Authors: Maggi Raimondo , Lanari Daniela , Oro Chiara , Sartori Giovanni , Vaccaro Luigi
Published: August 2011

Polystyrene‐supported chiral 2,2′‐methylenebis[(4S)‐4‐tert‐butyl‐2‐oxazoline] is a promising heterogeneous catalyst for the enantioselective Henry reaction of nitromethane with substituted benzaldehydes. The process is carried out in ethanol as a green solvent, and the corresponding chiral β‐nitroalcohols are obtained in 56–95 % yield with 49–88 % ee.
Selective Synthesis of New Fluorinated Alicyclic β‐Amino Ester Stereoisomers (Eur. J. Org. Chem. 26/2011)
Authors: Kiss Loránd , Forró Enikő , Fustero Santos , Fülöp Ferenc
Published: August 2011

The cover picture shows a waterfall located in the Eastern Carpathians in Transylvania, near Bicaz Canyon. Although fluorinated organic compounds are nonexistent in nature, an increasing number of drugs (25 %) on the market contain at least one fluorine atom. Cyclic fluorinated β‐amino acid derivatives have been synthesized by selective hydroxylation and hydroxy?fluorine exchange. Details are discussed in the article by F. Fülöp et al. on p. 4993 ff.
Fast‐responding thermal‐death‐time tubes for the determination of thermal bacteria inactivation
Authors: Büchner Christin , Thomas Susann , Jaros Doris , Rohm Harald
Published: August 2011

The knowledge of thermal inactivation kinetics, usually expressed in terms of D‐ and z‐values, is of crucial importance for the design of sanitation and sterilization processes. In this study, we designed a simple, fast‐responding, and mechanically stable aluminum tube for inactivation measurements and compared these experiments with the successive‐sampling method at different temperatures. Up to 65°C, we determined a come‐up time of approximately 15 s for the tubes, which is lower than the corresponding values of other devices, presumably because of lower wall thickness, material properties, and a higher surface to volume ratio. D‐values of Escherichia coli calculated from tube inactivation experiments by first‐order kinetics were 370 s (56°C), 126 s (58°C), 53.2 s (60°C), 33.8 s (62°C), and 3.22 s (65°C), and the corresponding values determined with the successive‐sampling flask method were insignificantly different (417, 138, 48.6, and 29.1 s for 56, 58, 60, and 62°C, respectively). These data as well as those measured for Enterobacter cloacae, Pseudomonas putida, Serratia odorifera, and Yersinia rhodei were in close accordance with literature values.
Cytokine production using membrane adsorbers: Human basic fibroblast growth factor produced by Escherichia coli
Authors: Chen Ran , John Jinu , Lavrentieva Antonina , Müller Susann , Tomala Magda , Zhao Yangxi , Zweigerdt Robert , Beutel Sascha , Hitzmann Bernd , Kasper Cornelia , Martin Ulrich , Rinas Ursula , Stahl Frank , Scheper Thomas
Published: August 2011

Basic fibroblast growth factor (FGF‐2) is a multifunctional cytokine that regulates various cellular processes both in vitro and in vivo. FGF‐2 is extensively used in embryonic stem cell cultures since it can maintain the cells in an undifferentiated state. However, the high price of FGF‐2 has limited its application in stem cell research. Here we present a fast and efficient process for the purification of FGF‐2 from recombinant Escherichia coli cultures using reusable membrane adsorbers. A high expression level of FGF‐2 (42 mg/g dry cell) was achieved by fed‐batch cultivation of E. coli BL21(DE3). A new combination of cation exchange membrane chromatography and heparin‐sepharose affinity chromatography was used for the purification of the protein. A novel anion exchange membrane chromatography was used in the polishing step to remove endotoxins and DNA. In this new process, about 200 mg soluble FGF‐2 was yielded from 1.9 L culture broth with a purity of 98%. The purified protein was identified to be endotoxin‐free and bioactive. It was successfully tested to keep primate embryonic stem cell and human‐induced pluripotent stem cell pluripotent. Our approach, in which a controlled cultivation process is combined with an optimized fast and versatile downstreaming process, is suitable for low‐cost preparation of bioactive FGF‐2 at bench‐scale and may be beneficial to the effective production of other cytokines.
Amphibians at risk? Susceptibility of terrestrial amphibian life stages to pesticides
Authors: Brühl Carsten A , Pieper Silvia , Weber Brigitte
Published: August 2011

Current pesticide risk assessment does not specifically consider amphibians. Amphibians in the aquatic environment (aquatic life stages or postmetamorphic aquatic amphibians) and terrestrial living juvenile or adult amphibians are assumed to be covered by the risk assessment for aquatic invertebrates and fish, or mammals and birds, respectively. This procedure has been evaluated as being sufficiently protective regarding the acute risk posed by a number of pesticides to aquatic amphibian life stages (eggs, larvae). However, it is unknown whether the exposure and sensitivity of terrestrial living amphibians are comparable to mammalian and avian exposure and sensitivity. We reviewed the literature on dermal pesticide absorption and toxicity studies for terrestrial life stages of amphibians, focusing on the dermal exposure pathway, that is, through treated soil or direct overspray. In vitro studies demonstrated that cutaneous absorption of chemicals is significant and that chemical percutaneous passage, P (cm/h), is higher in amphibians than in mammals. In vivo, the rapid and substantial uptake of the herbicide atrazine from treated soil by toads (Bufo americanus) has been described. Severe toxic effects on various amphibian species have been reported for field-relevant application rates of different pesticides. In general, exposure and toxicity studies for terrestrial amphibian life stages are scarce, and the reported data indicate the need for further research, especially in light of the global amphibian decline. Environ. Toxicol. Chem. 2011;30:2465–2472. © 2011 SETAC
Validation of a chronic dietary cadmium bioaccumulation and toxicity model for Hyalella azteca exposed to field-contaminated periphyton and lake water
Authors: Golding Lisa A , Borgmann Uwe , Dixon D. George
Published: August 2011

A model previously developed in the laboratory to predict chronic bioaccumulation and toxicity of cadmium to Hyalella azteca from a diet of periphyton was validated by comparing predictions with measurements of Cd in two exposure scenarios: laboratory-cultured H. azteca exposed for 28 d to field-contaminated water and periphyton, and Cd measured in field-collected H. azteca. In both exposure scenarios, model predictions of bioaccumulation were shown to be robust; however, effects on Cd bioaccumulation from complexation with dissolved organic carbon (DOC) and inhibition of Cd bioaccumulation by Ca2+ must be incorporated into the model to permit its wider application. The model predicted that 80 to 84% of Cd in H. azteca came from periphyton when H. azteca were chronically exposed to dissolved Cd in lake water at 2.63 to 3.01 nmol/L and periphyton at 1,880 to 2,630 nmol/g ash-free dry mass. Dietary Cd contributed markedly to the model-predicted decrease in 28-d survival to 74% at environmental Cd concentrations in food and water. In reality, survival decreased to 10%. The lower than predicted survival likely was due to the higher nutritional quality of periphyton used to develop the model in the laboratory compared with the field-collected periphyton. Overall, this research demonstrated that Cd in a periphyton diet at environmental concentrations can contribute to chronic toxicity in H. azteca. Environ. Toxicol. Chem. 2011;30:2628–2638. © 2011 SETAC
Mesh adaptivity for the transport equation led by variational multiscale error estimators
Authors: Hauke Guillermo , Doweidar Mohamed H. , Fuentes Sergio
Published: August 2011

Recently, we developed an explicit a posteriori error estimator especially suited for fluid dynamics problems solved with a stabilized method. The technology is based upon the theory that inspired stabilized methods, namely, the variational multiscale theory. The salient features of the formulation are that it can be readily implemented in existing codes, it is a very economical procedure, and it yields very accurate local error estimates uniformly from the diffusive to the advective regime.

In this work, the variational multiscale error estimator is applied to develop adaptive strategies for the advection–diffusion‐reaction equation. The performance of L1 and L2 local error norms combined with three strategies to adapt the mesh is investigated. Emphasis is placed on flows with sharp boundary and interior layers but also attention is given to diffusion‐dominated flows. Computational results show that the method generates meshes with a smooth transition of the element size, which capture all the flow features. Copyright © 2011 John Wiley & Sons, Ltd.
Differential genotoxicity of chemical properties and particle size of rare metal and metal oxide nanoparticles
Authors: Hasegawa Go , Shimonaka Motoyuki , Ishihara Yoko
Published: August 2011

Nanoparticles of rare metal compounds are used in various products. However, their carcinogenicity and genotoxicity have not been sufficiently evaluated. The tumor‐initiating and ‐promoting potentials of four rare metals, indium oxide (In2O3), dysprosium oxide (Dy2O3), tungsten oxide (WO3) and molybdenum (Mo), with a well‐defined particle diameter were evaluated. The mutagenicity of these rare metals was investigated by Ames test using five bacteria strains, and transformability of these rare metals was investigated by cell‐transformation assay using v‐Ha‐ras‐transfected BALB/c 3T3 cells (Bhas 42 cells). Nano‐sized Dy2O3 showed strong mutagenesis in all five bacteria strains tested with and without metabolic activation, while micro‐sized particles showed weak mutagenesis in two bacterial strains. Dy2O3 induced transformation colonies of Bhas 42 cell dose‐dependently, although there was no difference in the number of transformed foci between nano‐sized and micro‐sized particles. Nano‐sized In2O3 and WO3 showed positive mutagenic response in TA1537 and TA98, respectively, whereas the micro‐sized metal oxide particles showed no mutagenesis in the test bacterial strains. Both nano‐sized and micro‐sized In2O3 showed similar levels of transformability. However, nano‐sized and micro‐sized WO3 did not show any transformability. Both nano‐sized and micro‐sized Mo particles showed neither mutagenesis nor transformability. These results suggest that mutagenicity of rare metals depends on their particle size, although transformability depends on their chemical components but not on their particle size. Copyright © 2011 John Wiley & Sons, Ltd.
Beneficial effects of hydrocortisone or spironolactone coating on foreign body response to mesh biomaterial in a mouse model
Authors: Brandt Christopher J. , Kammer Daniel , Fiebeler Anette , Klinge Uwe
Published: August 2011

Prosthetic reinforcements markedly reduce the risk of hernia recurrence. However, the implantation of meshes is related to an inflammatory foreign body reaction (FBR) with serious complications (i.e., persistent seroma, wound infection, mesh migration, entrapment, chronic pain). Adrenal hormones profoundly modify inflammatory response. Their effects on FBR however, remain ill defined. We therefore studied the FBR to polyvinylidenfluoride (PVDF) mesh material that was coated with four different substances: hydrocortisone (COR) or mifepristone (MIF), which respectively stimulate and block the glucocorticoid receptor, and aldosterone (ALD) or spironolactone (SPI), which respectively stimulate and block the mineralocorticoid receptor. The coated substances were released from the meshes within 24 h. Seven, 21, and 90 days after implantation, the specimen was evaluated for collagen formation, granuloma size, inflammatory activity, and angiogenesis. COR and SPI coating protected from inflammatory response, while ALD and MIF coating showed little difference to the control group. The COR and SPI groups showed smaller granuloma sizes at all time points, as well as a reduced number of inflammatory cells (p < 0.001) at day 90, and decreased collagen formation starting after 21 days (p < 0.05). There was a negative correlation for angiogenesis with inflammation around foreign body structures. In summary, these results suggest that early and temporary stimulation of the glucocorticoid receptor or blockade of the mineralocorticoid receptor have beneficial effects on FBR in the long term. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 99A:335–335, 2011.
In vitroanalysis and mechanical properties of twin screw extruded single‐layered and coextruded multilayered poly(caprolactone) scaffolds seeded with human fetal osteoblasts for bone tissue engineering
Authors: Ergun Asli , Yu Xiaojun , Valdevit Antonio , Ritter Arthur , Kalyon Dilhan M.
Published: August 2011

In vitroculturing and mechanical properties of three types of three‐dimensional poly(caprolactone) scaffolds with interconnecting open‐foam networks are reported. The scaffolds targeted bone tissue regeneration and were fabricated using twin screw extrusion and coextrusion techniques, for continuous mixing/shaping and formation of single or multilayers with distinct and tailorable porosities and pore sizes. Human fetal preosteoblastic cells, hFOB, were cultured on the extruded and coextruded scaffolds under osteogenic supplements and the samples of the resulting tissue constructs were removed and characterized for cell viability and proliferation using the MTS assay, differentiation, and mineralized matrix synthesis via the alkaline phosphatase, ALP, activity and Alizarin Red staining and cell migration using confocal microscopy and scanning electron microscopy. The hFOB cells formed a confluent lining on scaffold surfaces, migrated to the interior and generated abundant extracellular matrix after 2 weeks of culturing, indicative of the promise of such scaffolds for utilization in tissue engineering. The scaffolds and tissue constructs exhibited compressive fatigue behavior that was similar to that of cancellous bone, suggesting the suitability of their use as bone graft substitutes especially for repair of critical‐sized defects or nonunion fractures. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2011.
Potential antiosteoporosis effect of biodegradable magnesium implanted in STZ‐induced diabetic rats
Authors: Yang Weili , Zhang Yu , Yang Jianhong , Tan Lili , Yang Ke
Published: August 2011

Pure magnesium (Mg) was implanted intramedullary into the femur of streptozotocin (STZ)‐induced diabetic rats to investigate its effect on bone growth after 6 weeks degradation. The experimental results showed that the femoral BMD in diabetic rats was significantly lower than that in controls (p < 0.01) but restored notably by Mg implantation. The contents of calcium (Ca), phosphorus (P), Mg, zinc (Zn), potassium (K), strontium (Sr), and sulfur (S) in bone of diabetic group were significantly lower than those in controls but remarkably increased with implantation of Mg. The residual weight calculation showed that 29.41% of Mg was degraded in vivo. The energy dispersive X‐ray spectroscopy (EDS) analysis showed that the reaction layer on the surface of the Mg implant mainly consisted of C, Ca, O, P, and Mg. Besides, serum Mg level was significantly decreased in diabetic group compared with the control group but increased by Mg treatment. Also, there were no significant differences in body weight and blood glucose, as well as blood glycosylated hemoglobin (HbAIc%), serum Ca, alanine aminitransperase (ALT), aspartate aminotransferase (AST), uric acid (UA), nonesterified fatty acid (NEFA), cholinesterase (CHE), and creatinine (CR) levels between diabetic and Mg‐implanted rats. The study indicated that Mg implant had no obvious toxicity in STZ‐induced diabetic rats and may act as a potential agent to treat osteoporosis. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2011.
A human‐like collagen/chitosan electrospun nanofibrous scaffold from aqueous solution: Electrospun mechanism and biocompatibility
Authors: Chen Lan , Zhu Chenhui , Fan Daidi , Liu Bowen , Ma Xiaoxuan , Duan Zhiguang , Zhou Yang
Published: August 2011

Novel human‐like collagen (HLC)/chitosan blended with poly(ethylene oxide) (PEO) nanofibrous meshes of different ratios were fabricated by electrospinning from aqueous solutions. Through studying the effects of the three composition on the solution rheological properties and the morphology of electrospun meshes, the mechanism of electrospinning was explored at the molecular level, and the ratio of PEO/(HLC & chitosan) (w/w) should be controlled below 1/4 as a plasticizer and HLC/chitosan maintained 4/3 w/w. Obtained meshes were treated by 0.2% glutaraldehyde solution (95% ethanol) for crosslinking and 0.2 M glycine solution for blocking unreacted aldehyde groups and became insoluble with fiber diameters of 151 ± 33 to 278 ± 46 nm, PEO was leached out after crosslinking and rinsing. HLC/chitosan scaffolds (4/3, w/w) could mimic native ECM in both chemical component and structure and support cellular in‐growth in vivo while exhibited proper degradation rate in vivo. Bone marrow stromal cells adopted a flattened shape with filopodia‐ and lamellipodia‐like extensions in the scaffolds and grew as a confluent layer after 7 days of culture in vitro. This study indicated the feasibility of electrospun nanofabrious HLC/chitosan scaffold from aqueous solution for tissue engineering application. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2011.
Microstructure and characteristics of the metal–ceramic composite (MgCa‐HA/TCP) fabricated by liquid metal infiltration
Authors: Gu X. N. , Wang X. , Li N. , Li L. , Zheng Y. F. , Miao Xigeng
Published: August 2011

In this article, a novel MgCa alloy‐hydroxyapatite‐tricalcium phosphate (HA/TCP) composite was fabricated using the liquid alloy infiltration technique. The feasibility of the composite for biomedical applications was studied through mechanical testing, electrochemical testing, immersion testing, and cell culture evaluation. It was shown that the composite had a strength about 200‐fold higher than that of the original porous HA/TCP scaffold but retained half of the strength of the bulk MgCa alloy. The corrosion test indicated that the resulting composite exhibited an average corrosion rate of 0.029 mL cm−2 h−1 in the Hank's solution at 37°C, which was slower than that of the bulk MgCa alloy alone. The indirect cytotoxicity evaluation revealed that 100% concentrated (i.e., undiluted or as‐collected) extract of the MgCa‐HA/TCP composite showed significant toxicity to L‐929 and MG63 cells (p < 0.05). In contrast, the diluted extracts with 50 and 10% concentrations of the MgCa‐HA/TCP composite exhibited a similar degree of cell viability (p > 0.05), equivalent to the grade I cytotoxicity of the standard ISO 10993‐5: 1999. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2011.
Lineage-committed osteoclast precursors circulate in blood and settle down into bone
Authors: Muto Akinori , Mizoguchi Toshihide , Udagawa Nobuyuki , Ito Susumu , Kawahara Ichiro , Abiko Yoshimitsu , Arai Atsushi , Harada Suguru , Kobayashi Yasuhiro , Nakamichi Yuko , Penninger Josef M , Noguchi Toshihide , Takahashi Naoyuki
Published: August 2011

Osteoclasts are derived from the monocyte/macrophage lineage, but little is known about osteoclast precursors in circulation. We previously showed that cell cycle–arrested quiescent osteoclast precursors (QOPs) were detected along bone surfaces as direct osteoclast precursors. Here we show that receptor activator of NF-κB (RANK)-positive cells isolated from bone marrow and peripheral blood possess characteristics of QOPs in mice. RANK-positive cells expressed c-Fms (receptors of macrophage colony-stimulating factor) at various levels, but scarcely expressed other monocyte/granulocyte markers. RANK-positive cells failed to exert phagocytic and proliferating activities, and differentiated into osteoclasts but not into dendritic cells. To identify circulating QOPs, collagen disks containing bone morphogenetic protein-2 (BMP disks) were implanted into mice, which were administered bromodeoxyuridine daily. Most nuclei of osteoclasts detected in BMP-2–induced ectopic bone were bromodeoxyuridine-negative. RANK-positive cells in peripheral blood proliferated more slowly and had a much longer lifespan than F4/80 (a macrophage marker)-positive macrophages. When BMP disks and control disks were implanted in RANK ligand-deficient mice, RANK-positive cells were observed in the BMP disks but not in the controls. F4/80-positive cells were distributed in both disks. Administration of FYT720, a sphingosine 1-phosphate agonist, promoted the egress of RANK-positive cells from hematopoietic tissues into bloodstream. These results suggest that lineage-determined QOPs circulate in the blood and settle in the bone. © 2011 American Society for Bone and Mineral Research