bluuebunny/crossref_metadata_2025 huggingface dataset:
Matrix Metalloproteinase 13 Expression in Response to Double‐Stranded RNA in Human Chondrocytes
Authors: Radwan Marta , Gavriilidis Christos , Robinson John H. , Davidson Rose , Clark Ian M. , Rowan Andrew D. , Young David A.
Published: January 2013

Objective

To investigate the mechanism of matrix metalloproteinase 13 (MMP‐13) expression in chondrocytes via pattern‐recognition receptors (PRRs) for double‐stranded RNA (dsRNA).

Methods

Differential expression of PRRs was determined by real‐time reverse transcription–polymerase chain reaction (RT‐PCR) of RNA from patients with osteoarthritis (OA) and patients with femoral neck fracture (as normal control). Isolated human articular chondrocytes and the chondrosarcoma cell line SW‐1353 were activated with poly(I‐C) of different molecular weights as a dsRNA mimic, and changes in gene and protein expression were monitored by real‐time RT‐PCR and immunoblotting, respectively.

Results

The dsRNA signaling moieties Toll‐like receptor 3 (TLR‐3), retinoic acid–inducible gene 1 (RIG‐1), and nucleotide‐binding oligomerization domain–like receptor X1 were all differentially expressed in OA cartilage compared to normal cartilage, as determined by gene expression screening. Depletion of the dsRNA‐sensing receptors TLR‐3, RIG‐1, or melanoma differentiation–associated gene 5 (MDA‐5) suppressed the induction of MMP13 messenger RNA (mRNA) expression by poly(I‐C), regardless of its mode of delivery. In addition, depletion of the downstream transcription factor interferon regulatory factor 3 resulted in reduced induction of MMP13 mRNA expression by poly(I‐C).

Conclusion

Signaling by dsRNA in chondrocytes requires a range of PRRs, including TLR‐3, RIG‐1, and MDA‐5, for the full‐induction of MMP13, thus providing tight regulation of a gene critical for maintenance of cartilage integrity. Our data add to the understanding of MMP13 regulation, which is essential before such mechanisms can be exploited to alleviate the cartilage destruction associated with OA.
Amelioration of Systemic Fibrosis in Mice by Angiotensin II Receptor Blockade
Authors: Marut Wioleta , Kavian Niloufar , Servettaz Amélie , Hua‐Huy Thong , Nicco Carole , Chéreau Christiane , Weill Bernard , Dinh‐Xuan Anh Tuan , Batteux Frédéric
Published: January 2013

Objective

Systemic sclerosis (SSc) is characterized by microvascular damage, fibrosis of skin and visceral organs, and autoimmunity. Previous studies have shown that angiotensin II is involved in the synthesis of type I collagen. We investigated whether the blockade of angiotensin II receptor type I (AT1) by irbesartan reduces skin and lung fibrosis in 2 murine models of SSc.

Methods

SSc was induced by daily intradermal injection of HOCl into the backs of BALB/c mice (HOCl‐induced SSc). Mice were treated daily with irbesartan by oral gavage.

Results

Irbesartan reduced dermal thickness, collagen concentration, Smad2/3, and α‐smooth muscle actin expression, as well as fibroblast proliferation and H‐Ras expression in the skin of mice with HOCl‐induced SSc. Mice treated with irbesartan also displayed less lung fibrosis, less inflammation, and a lower concentration of collagen in the lungs than untreated mice. Exhaled nitric oxide, inducible nitric oxide synthase, and 3‐nitrotyrosine expression in the lungs were decreased following irbesartan treatment. Moreover, irbesartan reduced the number and the proliferation of splenic B and T cells and the serum levels of anti–DNA topoisomerase I autoantibodies.

Conclusion

Irbesartan, an AT1 antagonist, prevents fibrosis and inflammation and inhibits nitric oxide production in HOCl‐induced models of systemic fibrosis. Our findings extend the indication of an AT1 antagonist to SSc patients with diffuse fibrosis, especially those with lung involvement.
Utilization of biogenic residues and wastes in thermochemical systems for the production of fuels: current status of the project
Authors: Tröger Nicole , Kröger Michael , Richter Daniel , Förster Sascha , Schröder Jörg , Zech Konstantin , Liemen Franziska , Stahl Ralph , Müller‐Langer Franziska
Published: January 2013

For the production of alternative fuels, biogenic residues and waste materials were thermochemically converted by fast pyrolysis in a joint project between the Deutsches Biomasseforschungszentrum (DBFZ) and the Karlsruhe Institute of Technology (KIT). Biogenic residues and wastes which are not used so far or which could be utilized more efficiently were studied to add to the line of feedstock for future thermochemical applications. Project work includes the investigation and selection of possible residual feedstock and its potential, conversion of several feedstocks (e.g. different varieties of straw, hay, waste wood, bark, driftwood) by fast pyrolysis, and energetic use of the products to generate electricity and heat. An ecological and economic evaluation was conducted for an integral view of the process and feedstock utilized. Besides research and experimental activities of the project, a database on biomass pyrolysis tests has been established for public use. © 2013 Society of Chemical Industry and John Wiley & Sons, Ltd
A techno‐economic review of hydroprocessed renewable esters and fatty acids for jet fuel production
Authors: Pearlson Matthew , Wollersheim Christoph , Hileman James
Published: January 2013

Jet fuels produced from sources other than petroleum are receiving considerable attention because they offer the potential to diversify energy supplies while mitigating the net environmental impacts of aviation. The hydroprocessed esters and fatty acids (HEFA) process is a commercially deployed technology that converts vegetable oils and animal fats from triglycerides into hydrocarbons suitable for use in diesel and jet fuels. The technical means of producing alternative fuels from renewable oils, and the resulting carbon intensity has been documented in previous work. However, the cost of production is not available in the literature. This work reviews HEFA fuel production, and estimates the gate price of fuel for several plant sizes and operating conditions. Aspen Plus was used to model biorefinery material and energy balances for unit operations and supporting utilities. A discounted‐cash‐flow‐rate‐of‐return (DCFROR) economic model was used for sensitivity analysis. The gate price was found to range between $1.00 L–1 for a 378 MML yr–1 HEFA facility, and $1.16 L–1 for a 116 MML yr–1 facility. Maximizing jet fuel production ranged between $0.07 and $0.08 L–1 due to increased hydrogen use and decreased diesel and jet fuel yield. While feedstock cost is the most significant portion of fuel cost, facility size, financing, and capacity utilization also influence production costs. © 2013 Society of Chemical Industry and John Wiley & Sons, Ltd
Expression of functionally active sialylated human erythropoietin in plants
Authors: Jez Jakub , Castilho Alexandra , Grass Josephine , Vorauer‐Uhl Karola , Sterovsky Thomas , Altmann Friedrich , Steinkellner Herta
Published: January 2013

Recombinant human erythropoietin (rhEPO), a glycohormone, is one of the leading biopharmaceutical products. The production of rhEPO is currently restricted to mammalian cell expression systems because of rhEPO's highly complex glycosylation pattern, which is a major determinant for drug‐efficacy. Here we evaluate the ability of plants to produce different glycoforms of rhEPO. cDNA constructs were delivered to Nicotiana benthamiana (N. benthamiana) and transiently expressed by a viral based expression system. Expression levels up to 85 mg rhEPO/kg fresh leaf material were achieved. Moreover, co‐expression of rhEPO with six mammalian genes required for in planta protein sialylation resulted in the synthesis of rhEPO decorated mainly with bisialylated N‐glycans (NaNa), the most abundant glycoform of circulating hEPO in patients with anemia. A newly established peptide tag (ELDKWA) fused to hEPO was particularly well‐suited for purification of the recombinant hormone based on immunoaffinity. Subsequent lectin chromatography allowed enrichment of exclusively sialylated rhEPO. All plant‐derived glycoforms exhibited high biological activity as determined by a cell‐based receptor‐binding assay. The generation of rhEPO carrying largely homogeneous glycosylation profiles (GnGnXF, GnGn, and NaNa) will facilitate further investigation of functionalities with potential implications for medical applications.
Domain organization of membrane‐bound factor VIII
Authors: Stoilova‐McPhie Svetla , Lynch Gillian C. , Ludtke Steven , Pettitt B. Montgomery
Published: January 2013

Factor VIII (FVIII) is the blood coagulation protein which when defective or deficient causes for hemophilia A, a severe hereditary bleeding disorder. Activated FVIII (FVIIIa) is the cofactor to the serine protease factor IXa (FIXa) within the membrane‐bound Tenase complex, responsible for amplifying its proteolytic activity more than 100,000 times, necessary for normal clot formation. FVIII is composed of two noncovalently linked peptide chains: a light chain (LC) holding the membrane interaction sites and a heavy chain (HC) holding the main FIXa interaction sites. The interplay between the light and heavy chains (HCs) in the membrane‐bound state is critical for the biological efficiency of FVIII. Here, we present our cryo‐electron microscopy (EM) and structure analysis studies of human FVIII‐LC, when helically assembled onto negatively charged single lipid bilayer nanotubes. The resolved FVIII‐LC membrane‐bound structure supports aspects of our previously proposed FVIII structure from membrane‐bound two‐dimensional (2D) crystals, such as only the C2 domain interacts directly with the membrane. The LC is oriented differently in the FVIII membrane‐bound helical and 2D crystal structures based on EM data, and the existing X‐ray structures. This flexibility of the FVIII‐LC domain organization in different states is discussed in the light of the FVIIIa–FIXa complex assembly and function. © 2013 Wiley Periodicals, Inc. Biopolymers 99: 448–459, 2013.
Affinity and kinetic modulation of polyamide–DNA interactions byN‐modification of the heterocycles
Authors: Ramos Joseph P. , Babu Balaji , Chavda Sameer , Liu Yang , Plaunt Adam , Ferguson Amanda , Savagian Mia , Lee Megan , Tzou Samuel , Lin Shicai , Kiakos Konstantinos , Wang Shuo , Lee Moses , Hartley John A. , Wilson W. David
Published: January 2013

Synthetic N‐methyl imidazole and N‐pyrrole containing polyamides (PAs) that can form “stacked” dimers can be programmed to target and bind to specific DNA sequences and control gene expression. To accomplish this goal, the development of PAs with lower molecular mass which allows for the molecules to rapidly penetrate cells and localize in the nucleus, along with increased water solubility, while maintaining DNA binding sequence specificity and high binding affinity is key. To meet these challenges, six novel f‐ImPy*Im PA derivatives that contain different orthogonally positioned moieties were designed to target 5′‐ACGCGT‐3′. The synthesis and biophysical characterization of six f‐ImPy*Im were determined by CD, ΔTM, DNase I footprinting, SPR, and ITC studies, and were compared with those of their parent compound, f‐ImPyIm. The results gave evidence for the minor groove binding and selectivity of PAs1and6for the cognate sequence 5′‐ACGCGT‐3′, and with strong affinity, Keq= 2.8 × 108M−1and Keq= 6.2 × 107M−1, respectively. The six novel PAs presented in this study demonstrated increased water solubility, while maintaining low molecular mass, sequence specificity, and binding affinity, addressing key issues in therapeutic development. © 2013 Wiley Periodicals, Inc. Biopolymers 99: 497–507, 2013.
Acetone–butanol–ethanol production with high productivity using Clostridium acetobutylicum BKM19
Authors: Jang Yu‐Sin , Malaviya Alok , Lee Sang Yup
Published: January 2013

Conventional acetone–butanol–ethanol (ABE) fermentation is severely limited by low solvent titer and productivities. Thus, this study aims at developing an improved Clostridium acetobutylicum strain possessing enhanced ABE production capability followed by process optimization for high ABE productivity. Random mutagenesis of C. acetobutylicum PJC4BK was performed by screening cells on fluoroacetate plates to isolate a mutant strain, BKM19, which exhibited the total solvent production capability 30.5% higher than the parent strain. The BKM19 produced 32.5 g L−1 of ABE (17.6 g L−1 butanol, 10.5 g L−1 ethanol, and 4.4 g L−1 acetone) from 85.2 g L−1 glucose in batch fermentation. A high cell density continuous ABE fermentation of the BKM19 in membrane cell‐recycle bioreactor was studied and optimized for improved solvent volumetric productivity. Different dilution rates were examined to find the optimal condition giving highest butanol and ABE productivities. The maximum butanol and ABE productivities of 9.6 and 20.0 g L−1 h−1, respectively, could be achieved at the dilution rate of 0.85 h−1. Further cell recycling experiments were carried out with controlled cell‐bleeding at two different bleeding rates. The maximum solvent productivities were obtained when the fermenter was operated at a dilution rate of 0.86 h−1 with the bleeding rate of 0.04 h−1. Under the optimal operational condition, butanol and ABE could be produced with the volumetric productivities of 10.7 and 21.1 g L−1 h−1, and the yields of 0.17 and 0.34 g g−1, respectively. The obtained butanol and ABE volumetric productivities are the highest reported productivities obtained from all known‐processes. Biotechnol. Bioeng. 2013; 110: 1646–1653. © 2013 Wiley Periodicals, Inc.
A quantitative analysis of microalgal lipids for optimization of biodiesel and omega‐3 production
Authors: Olmstead Ian L.D. , Hill David R.A. , Dias Daniel A. , Jayasinghe Nirupama S. , Callahan Damien L. , Kentish Sandra E. , Scales Peter J. , Martin Gregory J.O.
Published: January 2013

The lipid characteristics of microalgae are known to differ between species and change with growth conditions. This work provides a methodology for lipid characterization that enables selection of the optimal strain, cultivation conditions, and processing pathway for commercial biodiesel production from microalgae. Two different microalgal species, Nannochloropsis sp. and Chlorella sp., were cultivated under both nitrogen replete and nitrogen depleted conditions. Lipids were extracted and fractionated into three major classes and quantified gravimetrically. The fatty acid profile of each fraction was analyzed using GC–MS. The resulting quantitative lipid data for each of the cultures is discussed in the context of biodiesel and omega‐3 production. This approach illustrates how the growth conditions greatly affect the distribution of fatty acid present in the major lipid classes and therefore the suitability of the lipid extracts for biodiesel and other secondary products. Biotechnol. Bioeng. 2013; 110: 2096–2104. © 2013 Wiley Periodicals, Inc.
Protein crystallization in stirred systems—scale‐up via the maximum local energy dissipation
Authors: Smejkal Benjamin , Helk Bernhard , Rondeau Jean‐Michel , Anton Sabine , Wilke Angelika , Scheyerer Peter , Fries Jacqueline , Hekmat Dariusch , Weuster‐Botz Dirk
Published: January 2013

Macromolecular bioproducts like therapeutic proteins have usually been crystallized with µL‐scale vapor diffusion experiments for structure determination by X‐ray diffraction. Little systematic know‐how exists for technical‐scale protein crystallization in stirred vessels. In this study, the Fab‐fragment of the therapeutic antibody Canakinumab was successfully crystallized in a stirred‐tank reactor on a 6 mL‐scale. A four times faster onset of crystallization of the Fab‐fragment was observed compared to the non‐agitated 10 µL‐scale. Further studies on a liter‐scale with lysozyme confirmed this effect. A 10 times faster onset of crystallization was observed in this case at an optimum stirrer speed. Commonly suggested scale‐up criteria (i.e., minimum stirrer speed to keep the protein crystals in suspension or constant impeller tip speed) were shown not to be successful. Therefore, the criterion of constant maximum local energy dissipation was applied for scale‐up of the stirred crystallization process for the first time. The maximum local energy dissipation was estimated by measuring the drop size distribution of an oil/surfactant/water emulsion in stirred‐tank reactors on a 6 mL‐, 100 mL‐, and 1 L‐scale. A comparable crystallization behavior was achieved in all stirred‐tank reactors when the maximum local energy dissipation was kept constant for scale‐up. A maximum local energy dissipation of 2.2 W kg−1 was identified to be the optimum for lysozyme crystallization at all scales under study. Biotechnol. Bioeng. 2013; 110: 1956–1963. © 2013 Wiley Periodicals, Inc.
Knockout of pgdS and ggt genes improves γ‐PGA yield in B. subtilis
Authors: Scoffone Viola , Dondi Daniele , Biino Ginevra , Borghese Giovanni , Pasini Dario , Galizzi Alessandro , Calvio Cinzia
Published: January 2013

One of the emerging biopolymers that are currently under active investigation is bacterial poly(γ‐glutamic acid) (γ‐PGA). However, before its full industrial exploitation, a substantial increase in microbial productivity is required. γ‐PGA obtained from the Bacillus subtilis laboratory strain 168 offers the advantage of a producer characterized by a well defined genetic framework and simple manipulation techniques. In this strain, the knockout of genes for the major γ‐PGA degrading enzymes, pgdS and ggt, leads to a considerable improvement in polymer yield, which attains levels analogous to the top wild γ‐PGA producer strains. This study highlights the convenience of using the laboratory strain of B. subtilis over wild isolates in designing strain improvement strategies aimed at increasing γ‐PGA productivity. Biotechnol. Bioeng. 2013; 110: 2006–2012. © 2013 Wiley Periodicals, Inc.
Identifying analytics for high throughput bioprocess development studies
Authors: Konstantinidis Spyridon , Kong Simyee , Titchener‐Hooker Nigel
Published: January 2013

In recent years, high throughput screening (HTS) studies have been increasingly employed as an integral element of bioprocess development activities. These studies are often limited by an analytical bottleneck; they generate multiple samples for analysis and the available analytical methods cannot always cope with the added analytical burden. A potential solution to this challenge is offered by the deployment of appropriate analytics. This article outlines features of analytical methods that affect their fit to high throughput (HT) applications. These are discussed for a range of analytics frequently used in bioprocess development studies of monoclonal antibodies. It then outlines how these features need to be considered in order to classify analytical methods in terms of their particular application in high throughput scenarios. Biotechnol. Bioeng. 2013; 110: 1924–1935. © 2013 Wiley Periodicals, Inc.
Is Serum Uric Acid Level an Independent Predictor of Heart Failure Among Patients With Coronary Artery Disease?
Authors: Eisen Alon , Benderly Michal , Goldbourt Uri , Haim Moti
Published: January 2013

Background:

Uric acid (UA) is elevated in patients with the metabolic syndrome, and there is a possible association with coronary events. Its association with future risk of heart failure (HF) is not clear. Our objective was to evaluate the association between levels of UA and risk of HF in patients with stable coronary artery disease (CAD).

Hypothesis:

Serum UA is associated with HF in CAD patients.

Methods:

A retrospective cohort analysis among 2939 participants of the bezafibrate infarction prevention study, assessing long‐term risk of HF incidence over an 8‐year of follow‐up in relation to baseline UA.

Results:

Among patients with high levels of UA, there was a larger proportion of men, systolic hypertension, diabetes mellitus, metabolic syndrome, elevated total cholesterol, chronic renal failure, and previous coronary revascularization procedures. The rate of myocardial infarction during the follow‐up was 10.9%, 10.3%, and 11.6% in the 1st, 2nd and 3rd tertiles of UA, respectively (P = 0.68). Age‐adjusted hazard ratios for HF were 1.16 (95% confidence interval [CI]: 0.94–1.45) and 1.28 (95% CI: 1.04–1.59) in the 2nd and 3rd tertiles, respectively, as compared to the 1st tertile. After adjusting for multiple confounders and myocardial infarction, the hazard ratio for developing HF was 1.18 (95% CI: 0.95–1.47) and 1.25 (95% CI: 1.00–1.56) in the 2nd and 3rd tertiles of UA levels, respectively.

Conclusions:

UA levels are associated with future risk of HF in patients with stable CAD, but this association is attenuated after adjusting for traditional CAD risk factors.

The authors have no funding, financial relationships, or conflicts of interest to disclose.
Partial depletion of gamma‐actin suppresses microtubule dynamics
Authors: Po'uha Sela T. , Honore Stephane , Braguer Diane , Kavallaris Maria
Published: January 2013

Actin and microtubule interactions are important for many cellular events, however these interactions are poorly described. Alterations in γ‐actin are associated with diseases such as hearing loss and cancer. Functional investigations demonstrated that partial depletion of γ‐actin affects cell polarity and induces resistance to microtubule‐targeted agents. To determine whether γ‐actin alterations directly affect microtubule dynamics, microtubule dynamic instability was analyzed in living cells following partial siRNA depletion of γ‐actin. Partial depletion of γ‐actin suppresses interphase microtubule dynamics by 17.5% due to a decrease in microtubule shortening rates and an increase in microtubule attenuation. γ‐Actin partial depletion also increased distance‐based microtubule catastrophe and rescue frequencies. In addition, knockdown of γ‐actin delayed mitotic progression, partially blocking metaphase–anaphase transition and inhibiting cell proliferation. Interestingly, in the presence of paclitaxel, interphase microtubule dynamics were further suppressed by 24.4% in the γ‐actin knockdown cells, which is comparable to 28.8% suppression observed in the control siRNA treated cells. Paclitaxel blocked metaphase–anaphase transition in both the γ‐actin knockdown cells and the control siRNA cells. However, the extent of mitotic arrest was much higher in the control cells (28.4%), compared to the γ‐actin depleted cells (8.5%). Therefore, suppression of microtubule dynamics by partial depletion of γ‐actin is associated with marked delays in metaphase‐anaphase transition and not mitotic arrest. This is the first demonstration that γ‐actin can modulate microtubule dynamics by reducing the microtubule shortening rate, promoting paused/attenuated microtubules, and increasing transition frequencies suggesting a mechanistic link between γ‐actin and microtubules. © 2013 Wiley Periodicals, Inc
Highly Sensitive Platinum‐Black Coated Platinum Electrodes for Electrochemical Detection of Hydrogen Peroxide and Nitrite in Microchannel
Authors: Li Yun , Sella Catherine , Lemaître Fredéric , Guille Collignon Manon , Thouin Laurent , Amatore Christian
Published: January 2013

The electrochemical detection of hydrogen peroxide and nitrite, as important representatives of cytotoxic reactive oxygen/nitrogen (ROS, RNS) species released during cellular oxidative bursts, is reported in microfluidic devices. Platinum‐black coated platinum (Pt/Pt‐black) electrodes were microfabricated and optimized to achieve optimal detection performances. In parallel, oxidation mechanisms of hydrogen peroxide and nitrite at these microelectrodes were investigated and electrode responses were compared to theoretical predictions based on convective mass transport at microchannel electrodes. In both cases, the active surface area of Pt/Pt‐black electrodes allowed to avoid inhibition effect leading to long term stability in contrast to bare Pt electrodes. Such highly sensitive Pt/Pt‐black electrodes allowed almost five decades of concentration range and detection limits down to 10 nM, a range suitable for detection of ROS and RNS released by a few cells.
Landform‐oriented flow‐routing algorithm for the dual‐structure loess terrain based on digital elevation models
Authors: Xiong Liyang , Tang Guoan , Yan Shijiang , Zhu Shijie , Sun Yiying
Published: January 2013

The loess landform in the Loess Plateau of China is with typical dual structure, namely, the upper smooth positive terrain and the lower cliffy negative terrain (P–N terrain for short). Obvious differences in their morphological feature, geomorphological mechanism, and hydrological process could be found in the both areas. Based on the differences, a flow‐routing algorithm that separately addresses the dual‐structure terrain would be necessary to encompass this spatial variation in their hydrological behaviour. This paper proposes a mixed flow‐routing algorithm to address aforementioned problems. First, the loess landform surface is divided into P–N terrains based on digital elevation models. Then, specific catchment area is calculated with the new algorithm to simulate the water flows in both positive and negative terrain areas. The mixed algorithm consists of the multiple flow‐routing algorithm (multiple‐flow direction) for positive areas and the D8 algorithm for negative areas, respectively. The approach is validated in two typical geomorphologic areas with low hills and dense gullies in the northern Shaanxi Loess Plateau. Four indices are used to examine the results, which show that the new algorithm is more suitable for loess terrain in simulating the spatial distribution of water accumulation, as well as in modeling the flow characteristics of the true surface by considering the morphological structures of the terrain. Copyright © 2013 John Wiley & Sons, Ltd.
N‐acetylcysteine increases susceptibility of HeLa cells to bacterial invasion
Authors: Bozhokina Ekaterina , Vakhromova Ekaterina , Gamaley Irina , Khaitlina Sofia
Published: January 2013

Serratia grimesii are non‐pathogenic bacteria capable, however, to invade eukaryotic cells provided that they synthesize intracellular metalloprotease grimelysin (Bozhokina et al. [2011] Cell. Biol. Int. 35: 111–118). To elucidate how invasion of grimelysin containing bacteria depends on physiological state of host cells, we studied the effect of N‐acetylcysteine (NAC) on susceptibility of HeLa cells to invasion by the wild‐type S. grimesii and recombinant E. coli expressing grimelysin gene. Incubation of HeLa cells with 10 mM NAC resulted in changes of cell morphology and disassembly of actin cytoskeleton that were reversed when NAC was removed from the culture medium. Both in the presence of NAC and upon its removal, the entry of grimelysin producing bacteria increased by a factor of 1.5–2 and 3–3.5 for wild‐type S. grimesii and recombinant E. coli, respectively. This effect does not correlate with cytoskeleton rearrangements but may be due to the NAC‐induced up‐regulation of cell surface receptors playing a role in cell adhesion and cell–cell junctions. A twofold difference in the efficiency of S. grimesii and recombinant E. coli to enter the NAC‐treated cells suggests that the entry of the wild‐type and recombinant bacteria occurs via different receptors which activity is differently affected by NAC. J. Cell. Biochem. 114: 1568–1574, 2013. © 2013 Wiley Periodicals, Inc.
Overexpression of microRNA‐122 enhances in vitro hepatic differentiation of fetal liver‐derived stem/progenitor cells
Authors: Doddapaneni Ravi , Chawla Yogesh K. , Das Ashim , Kalra Jasvinder Kaur , Ghosh Sujata , Chakraborti Anuradha
Published: January 2013

MicroRNAs (miRNAs) are a versatile class of tiny non‐coding RNAs involved in regulation of various biological processes. miRNA‐122 (miR‐122) is specifically and abundantly expressed in human liver. However, the role of miR‐122 in differentiation of fetal liver stem/progenitor cells into hepatocytes remains unclear. In this study, dual positive CD34+/CD117+ expressing human fetal liver stem/progenitor cells was enriched by magnetic cell sorting and cultured in vitro. The level of miR‐122 was found to be increased at specific time intervals. Interestingly, during the differentiation process of hepatocyte‐like cells, the increase in expression of miR‐122 was positively correlated with expression of hepatocyte‐specific genes. The status of differentiation process was improved by transfection of miR‐122 into enriched stem/progenitor cells. The expression level of hepatic‐specific genes as well as liver‐enriched transcription factors (LETFs) was significantly increased by overexpression of miR‐122 in fetal liver stem/progenitor cells. Thus, the study delineated the role of hepato‐specific miR‐122 in differentiation of fetal liver stem/progenitor cells into hepatocyte‐like cells which could be used as a therapeutic target molecule to generate abundant hepatocytes. J. Cell. Biochem. 114: 1575–1583, 2013. © 2013 Wiley Periodicals, Inc.
Heterogeneous Photocatalytic Degradation of Disulfoton in Aqueous TiO2 Suspensions: Parameter and Reaction Pathway Investigations
Authors: Chen Ming‐Hung , Chen Chiing‐Chang , Wu Ren‐Jang , Lu Chung‐Shin
Published: January 2013

The photocatalytic degradation of organophosphorus insecticide disulfoton is investigated by having titanium dioxide (TiO2) as a photocatalyst. About 99% of disulfoton is degraded after UV irradiation for 90 min. The effects of the solution pH, catalyst dosage, light intensity, and inorganic ions on the photocatalytic degradation of disulfoton are also investigated, as well as the reaction intermediates which are formed during the treatment. Eight intermediates have been identified and characterized through a mass spectra analysis, giving insight into the early steps of the degradation process. To the best of our knowledge, this is the first study reporting the degradation pathways of disulfoton. The results suggest that possible transformation pathways may involve in either direct electron or hole transfer to the organic substrate. The photodegradation of disulfoton by UV/TiO2 exhibits pseudo‐first‐order reaction kinetics and a reaction quantum yield of 0.267. The electrical energy consumption per order of magnitude for photocatalytic degradation of disulfoton is 85 kWh/(m3 order).
Reproducibility of fetal renal pelvis volume assessed by three‐dimensional ultrasonography with two different measurement techniques
Authors: Duin L.K. , Willekes C. , Vossen M. , Offermans J. , Nijhuis J.G.
Published: January 2013

Purpose:

To evaluate reproducibility of fetal renal pelvis volume as assessed by the Virtual Organ Computer Aided AnaLysis (VOCAL) imaging program and by Automatic Volume Calculation (SonoAVC). In addition, the intra‐ and interobserver reliability of fetal renal pelvis volume measurements with SonoAVC were established.

Methods:

In this study, the fetal renal pelvis volume was measured using 3D ultrasonography in 76 kidneys of 66 fetuses with renal pelvis dilatation in the second or third trimester of pregnancy. After volume acquisition by one observer, the reproducibility of volume calculation was assessed using VOCAL imaging program and SonoAVC by two observers. Intra‐ and interobserver reproducibility was evaluated by calculating intraclass correlation coefficients (ICC), coefficient of variation (CV) and repeatability coefficient (r). Bland‐Altman plots were generated to explore agreement.

Results:

A high degree of reproducibility was observed between VOCAL and SonoAVC, ICC of 0.989; 95% CI 0.983–0.993, respectively.

Intraobserver reproducibility of volume measurements performed by SonoAVC demonstrated a high degree of reliability with ICC of 0.995 (95% CI 0.993–0.997), CV 6.05% and r of 0.75.

The interobserver reproducibility with ICC of 0.995 (95% CI 0.992–0.997), CV 10.14% and r 1.21 was also indicative of good reliability.

Conclusion:

Volume measurements of fetal renal pelvis performed by SonoAVC renders reproducible measurements in comparison with the VOCAL imaging program. There is no significant difference between VOCAL imaging program and SonoAVC. The intra‐ and interobserver reliability of the fetal renal pelvis measurements made by SonoAVC were considered to be very good. SonoAVC, however, needs post processing in the majority of cases but is less time consuming than VOCAL. © 2013 Wiley Periodicals, Inc. J Clin Ultrasound, 2013
Cementation of a dual‐mobility acetabular component into a well‐fixed metal shell during revision total hip arthroplasty: A biomechanical validation
Authors: Wegrzyn Julien , Thoreson Andrew R. , Guyen Olivier , Lewallen David G. , An Kai‐Nan
Published: January 2013

Cementation of polyethylene (PE) liners into well‐fixed metal shells has become a popular option during revision total hip arthroplasty (THA) particularly for older and frail patients. Although dramatic results were reported with dual‐mobility acetabular components to manage hip instability during revision THA, no study evaluated the fixation strength of the cementation of dual‐mobility components into well‐fixed metal shells. Eight dual‐mobility and eight all‐PE components were cemented into a metal shell with a uniform 2‐ to 3‐mm cement mantle. The cemented fixation strength was evaluated using lever‐out and torsion testing. The interface at which failure occurred was determined. Lever‐out testing showed that dual‐mobility components failed at significantly higher maximum moment than the all‐PE components. No direct comparison could be performed with torsion testing due to early failure of the all‐PE component itself before failure of the cement fixation. However, the maximum moments measured were dramatically higher than the in vivo frictional moments classically reported in THA. In addition, failure was always observed at the metal shell/cement interface whenever it did occur. In conclusion, a dual‐mobility acetabular component cemented into a well‐fixed metal shell could constitute a biomechanically acceptable alternative to acetabular shell removal or PE liner cementation while simultaneously preventing instability of the THA revision. Clinical studies are warranted. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 991–997, 2013
Systematic Investigation of a Novel Low‐Bandgap Terpolymer Library via Inkjet Printing: Influence of Ink Properties and Processing Conditions
Authors: Teichler Anke , Perelaer Jolke , Kretschmer Florian , Hager Martin D. , Schubert Ulrich S.
Published: January 2013

The thin‐film properties of a polymer library consisting of novel conjugated low‐bandgap poly(diketopyrrolopyrrole‐co‐benzothiadiazole‐co‐fluorene) (poly(DPP‐co‐BTD‐co‐F)) polymers are investigated. The content of the monomer units in the copolymers is systematically varied. Structure–property relationships are obtained for the ink characteristics, the film formation qualities, and their optical properties. Toluene/o‐DCB in a ratio 90/10 and a concentration of 5 mg mL−1 is found to be a suitable solvent system for all polymers. The polymer compositions and the choice of solvent have a significant influence on the film properties. Inkjet printing is shown to be a suitable technique for the preparation of thin‐film libraries that subsequently can be characterized by combinatorial screening tools.
Liquid‐Crystalline Nano‐optomechanical Actuator
Authors: Tsoi Stanislav , Zhou Jing , Spillmann Christopher , Naciri Jawad , Ikeda Tomiki , Ratna Banahalli
Published: January 2013

The synthesis and characterization of organic nanoparticles composed of a polymer network of azobenzene moieties and capable of reproducible, photoinduced mechanical actuation are reported. The molecules within the nanoparticles undergo co‐ordinated, reversible isomerization between cis‐ and trans‐conformations in response to ultraviolet and visible electromagnetic radiation, resulting in a reversible 20% height contraction of nanoparticles adsorbed on a substrate. The kinetics of the actuation response as a function of light intensity and duration are reported and closely match the molecular kinetics of azobenzene photoisomerization. The results support the proposed mechanism of co‐ordinated molecular conformational changes resulting in observable nanoscale actuation.
Mechanical Properties and UV Curing Behavior of Poly(N‐Isopropylacrylamide) in Phosphonium‐Based Ionic Liquids
Authors: Ziółkowski Bartosz , Ates Zeliha , Gallagher Simon , Byrne Robert , Heise Andreas , Fraser Kevin J , Diamond Dermot
Published: January 2013

N‐isopropylacrylamide (NIPAM) is photopolymerized in a range of phosphonium‐based ionic liquids (ILs). The curing behaviour of polymer‐IL solutions (linear pNIPAM) and ionogels (crosslinked pNIPAM) is studied using rheometry, DSC, and GPC. It is found that the IL influences the mechanical properties, the rate of polymerization, and the LCST of the resulting pNIPAM ionogels. Ionogels made in trihexyl‐tetradecyl phosphonium dicyanamide show an order of magnitude smaller ratio of loss/storage moduli compared to that of trihexyl‐tetradecyl phosphonium chloride, and a doubling of the UV polymerization rate. Temperature‐ramp rheology scans of the water‐swollen ionogels show that upon LCST transition the moduli of the polymer network exhibit anion dependent increases.

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Statistical Conjugated Polymers Comprising Optoelectronically Distinct Units
Authors: Hollinger Jon , Sun J. , Gao D. , Karl D. , Seferos D. S.
Published: January 2013

Poly(3‐heptylselenophene)‐stat‐poly(3‐hexylthiophene) is synthesized and characterized in terms of its crystallinity and performance in an organic photovoltaic (OPV) cell. Despite the random distribution of units along the polymer main chain, the material is semi‐crystalline, as demonstrated by differential scanning calorimetry and wide‐angle X‐ray diffraction. Thin‐film absorption suggests an increased compatibility than seen with 3‐hexylselenophene monomer. Optoelectronic properties are an average of the two homopolymers, and OPV performance is enhanced by a broadened absorption profile and a favorable morphology.
Effectiveness of nursing interventions to increase pap smear test screening
Authors: Guvenc Gulten , Akyuz Aygul , Yenen Mufit Cemal
Published: January 2013

The purpose of this study was to determine the effect of a three‐stage nursing intervention to increase Turkish women's participation in Pap smear testing. Knowledge and beliefs about cervical cancer screening and barriers to Pap smears also were explored. In a quasi‐experimental study in a target population of 2,500 women, 237 completed pre‐test measures to inform the intervention, and an educational brochure was distributed to all 2,500. As a result, 510 women (20.4%) accepted free Pap smears. Of the remaining 1,990 women, 417 were randomly selected for telephone interviews, 302 participated, and 158 of these (52.3%) participated in free Pap smear testing. Of the 144 who did not have Pap smears after participating in telephone interviews, 54 were then interviewed face‐to‐face, and 20 (37.0%) decided to accept free Pap smears. A total of 668 women had accepted free Pap smears by the end of the intervention period. © 2013 Wiley Periodicals, Inc. Res Nurs Health 36:146–157, 2013
Enteroviruses and the pathogenesis of type 1 diabetes revisited: cross‐reactivity of enterovirus capsid protein (VP1) antibodies with human mitochondrial proteins
Authors: Hansson Sara F , Korsgren Stella , Pontén Fredrik , Korsgren Olle
Published: January 2013

Current or recent enteroviral infections show an association with type 1 diabetes. However, evidence for this has mainly been generated using a particular mouse monoclonal antibody (clone 5‐D8/1) which binds the viral capsid protein VP1. Difficulty in confirming these findings using other independent methods has led to the concern that this might be artefactual. To address this, we examined the potential cross‐reactivity of clone 5‐D8/1 with normal islet proteins. Western blotting, two‐dimensional gel electrophoresis, and mass spectrometry were used to identify human islet proteins bound by the clone 5‐D8/1. We found a distinct reactivity with two mitochondrial proteins, creatine kinase B‐type and ATP synthase beta subunit. Immunohistochemistry using the clone 5‐D8/1 revealed a granular cytoplasmic staining pattern in mitochondria‐rich cells, ie hepatocytes, ductal epithelial cells, vascular endothelial cells, skeletal muscle cells, and the neoplastic salivary gland oncocytoma cells, whereas connective tissue and infiltrating immune cells were negative. Staining on islets of Langerhans from subjects with recent‐onset type 1 diabetes, but not on isolated human islets infected in vitro with enteroviruses, could be blocked after mixing the clone 5‐D8/1 with the mitochondrial proteins. Collectively, our data show that the clone 5‐D8/1 detects two human mitochondrial enzymes in addition to enteroviral VP1. The notion that the previously reported VP1 positivity in islets of recent‐onset type 1 diabetes patients could reflect cross‐reactivity to native islet proteins and not the presence of EV is supported by difficulties in demonstrating EV infection by independent techniques such as PCR or in situ hybridization. These findings call for revisiting the presence of enteroviruses in pancreatic islets of patients with type 1 diabetes. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Initial testing (stage 1) of temozolomide by the pediatric preclinical testing program
Authors: Keir Stephen T. , Maris John M. , Reynolds C. Patrick , Kang Min H. , Kolb E. Anders , Gorlick Richard , Lock Richard , Carol Hernan , Morton Christopher L. , Wu Jianrong , Kurmasheva Raushan T. , Houghton Peter J. , Smith Malcolm A.
Published: January 2013

Background

The DNA methylating agent temozolomide was developed primarily for treatment of glioblastoma. However, preclinical data have suggested a broader application for treatment of childhood cancer. Temozolomide was tested against the PPTP solid tumor and ALL models.

Procedures

Temozolomide was tested against the PPTP in vitro panel at concentrations ranging from 0.1 to 1,000 µM and was tested against the PPTP in vivo panels at doses from 22 to 100 mg/kg administered orally daily for 5 days, repeated at day 21.

Results

In vitro temozolomide showed cytotoxicity with a median relative IC50 (rIC50) value of 380 µM against the PPTP cell lines (range 1 to > 1,000 µM). The three lines with rIC50 values lesser than 10 µM had low MGMT expression compared to the remaining cell lines. In vivo temozolomide demonstrated significant toxicity at 100 mg/kg, but induced tumor regressions in 15 of 23 evaluable solid tumor models (13 maintained CR [MCR], 2 CR) and 5 of 8 ALL models (3 MCR, 2 CR). There was a steep dose response curve, with lower activity at 66 mg/kg temozolomide and with tumor regressions at 22 and 44 mg/kg restricted to models with low MGMT expression.

Conclusions

Temozolomide demonstrated high level antitumor activity against both solid tumor and leukemia models, but also elicited significant toxicity at the highest dose level. Lowering the dose of TMZ to more closely match clinical exposures markedly reduced the antitumor activity for many xenograft lines with responsiveness at lower doses closely related to low MGMT expression. Pediatr Blood Cancer 2013; 60: 783–790. © 2013 Wiley Periodicals, Inc.
A family with Hoyeraal–Hreidarsson syndrome and four variants in two genes of the telomerase core complex
Authors: Vogiatzi Paraskevi , Perdigones Nieves , Mason Philip J. , Wilson David B. , Bessler Monica
Published: January 2013

We describe an African American family with Hoyeraal–Hreidarrson syndrome (HHS) in which 2 TERT mutations (causing P530L and A880T amino acid changes) and two in the DKC1 variants (G486R and A487A) were segregating. Both genes are associated with dyskeratosis congenita and HHS. It was important to determine the importance of these mutations in disease pathogenesis to counsel family members. From genetic analysis of family members, telomere length and X‐inactivation studies we concluded that compound heterozygosity for the TERT mutations was the major cause of HHS and the DKC1 G486R variant is a rare African variant unlikely to cause disease. Pediatr Blood Cancer 2013; 60: E4–E6. © 2013 Wiley Periodicals, Inc.
A phase I study of oxaliplatin and doxorubicin in pediatric patients with relapsed or refractory extracranial non‐hematopoietic solid tumors
Authors: Mascarenhas Leo , Malogolowkin Marcio , Armenian Saro H. , Sposto Richard , Venkatramani Rajkumar
Published: January 2013

Background

The combination of a platinum agent and anthracycline has shown activity in pediatric solid tumors. This trial evaluated the maximum tolerated dose (MTD) and dose limiting toxicities (DLT) of oxaliplatin combined with doxorubicin in pediatric patients with recurrent solid tumors.

Methods

Oxaliplatin was administered on day 1 and Doxorubicin on days 1–3 of each 21 day course. The study utilized a standard 3 + 3 dose escalation design. Three dose levels were evaluated: (1) oxaliplatin 105 mg/m2 and doxorubicin 20 mg/m2; (2) oxaliplatin 130 mg/m2 and doxorubicin 20 mg/m2; and (3) oxaliplatin 130 mg/m2 and doxorubicin 25 mg/m2. Dexrazoxane was administered at 10 times the doxorubicin dose prior to doxorubicin infusion.

Results

Seventeen patients were enrolled. Dose level 1 was the determined MTD. Grade 2 cardiac DLT was seen in one of six patients on dose level 1, grade 4 thrombocytopenia in two of five patients on dose level 2, and one each of grade 2 cardiac and grade 4 thrombocytopenia in five patients on dose level 3. Cardiac DLT was only noted in patients with prior exposure to both anthracycline and chest radiation. No grade 3 or 4 neurotoxicity or mucositis was seen. Objective responses were noted in two patients with neuroblastoma and one each of mixed germ cell tumor, thymic neuroendocrine carcinoma, and nasopharyngeal carcinoma.

Conclusions

Oxaliplatin 105 mg/m2 on day 1 combined with doxorubicin 20 mg/m2 days 1–3 was the MTD. This combination shows sufficient activity to justify further studies in select pediatric tumors. Pediatr Blood Cancer 2013; 60: 1103–1107. © 2013 Wiley Periodicals, Inc.
Dosing, efficacy, and safety of recombinant factor VIIa (rFVIIa) in pediatric versus adult patients: The experience of the Hemostasis and Thrombosis Research Society (HTRS) Registry (2004–2008)
Authors: Neufeld Ellis J. , Saxena Kapil , Kessler Craig M. , Cooper David L. ,   on behalf of the HTRS Investigators
Published: January 2013

Background

The longitudinal registry of the Hemostasis and Thrombosis Research Society (HTRS) provided data on treatment of bleeding episodes for pediatric and adult patients with congenital hemophilia complicated by inhibitors to factor VIII or IX.

Procedure

Data from 2,041 recombinant factor VIIa (rFVIIa)‐treated episodes were recorded in the HTRS Registry between January 2004 and November 2008 and included in this retrospective analysis. The authors compared dosing, efficacy, and safety in 1,712 episodes in 284 children (age ≤18 years) and 329 episodes in 145 adults (>18 years).

Results

Patients were predominantly non‐Hispanic white (52% of children, 68% of adults) with hemophilia A (91%). The majority of bleeds were spontaneous (55% pediatric, 69% adult) and occurred in the joint (55% pediatric, 65% adult). rFVIIa was used first line in most episodes (90% pediatric, 93% adult); 27% of episodes in both age groups were treated with a single dose. Children and adults received comparable median number of doses (three) and duration of therapy (1 day); adults had lower median [range] initial doses (90 [46–400] µg/kg vs. 120 [37–400] µg/kg) and median [range] total doses (270 [46–21,392] µg/kg vs. 480 [50–43,200] µg/kg) than children. Effectiveness was comparable between the groups. No thromboembolic complications were reported.

Conclusions

Dosing of rFVIIa was somewhat higher in pediatric than adult patients in the HTRS registry population, with similar effectiveness. Safety assessment, demonstrating lack of thromboembolic events associated with treatment of bleeding episodes, was similar between the children and adults in this retrospective registry. Pediatr Blood Cancer 2013; 60: 1178–1183. © 2013 Wiley Periodicals, Inc.