bluuebunny/crossref_metadata_2025 huggingface dataset:
Three‐color confocal Förster (or fluorescence) resonance energy transfer microscopy: Quantitative analysis of protein interactions in the nucleation of actin filaments in live cells
Authors: Wallrabe Horst , Sun Yuansheng , Fang Xiaolan , Periasamy Ammasi , Bloom George S.
Published: March 2015

Experiments using live cell 3‐color Förster (or fluorescence) resonance energy transfer (FRET) microscopy and corresponding in vitro biochemical reconstitution of the same proteins were conducted to evaluate actin filament nucleation. A novel application of 3‐color FRET data is demonstrated, extending the analysis beyond the customary energy‐transfer efficiency (E%) calculations. MDCK cells were transfected for coexpression of Teal‐N‐WASP/Venus‐IQGAP1/mRFP1‐Rac1, Teal‐N‐WASP/Venus‐IQGAP1/mRFP1‐Cdc42, CFP‐Rac1/Venus‐IQGAP1/mCherry‐actin, or CFP‐Cdc42/Venus‐IQGAP1/mCherry‐actin, and with single‐label equivalents for spectral bleedthrough correction. Using confirmed E% as an entry point, fluorescence levels and related ratios were correlated at discrete accumulating levels at cell peripheries. Rising ratios of CFP‐Rac1:Venus‐IQGAP1 were correlated with lower overall actin fluorescence, whereas the CFP‐Cdc42:Venus‐IQGAP1 ratio correlated with increased actin fluorescence at low ratios, but was neutral at higher ratios. The new FRET analyses also indicated that rising levels of mRFP1‐Cdc42 or mRFP1‐Rac1, respectively, promoted or suppressed the association of Teal‐N‐WASP with Venus‐IQGAP1. These 3‐color FRET assays further support our in vitro results about the role of IQGAP1, Rac1, and Cdc42 in actin nucleation, and the differential impact of Rac1 and Cdc42 on the association of N‐WASP with IQGAP1. In addition, this study emphasizes the power of 3‐color FRET as a systems biology strategy for simultaneous evaluation of multiple interacting proteins in individual live cells. © 2015 International Society for Advancement of Cytometry
Facilitated gate setting by sequential dot plot scanning
Authors: Günther Susanne , Müller Susann
Published: March 2015

Microbial communities comprising thousands of unknown organisms can be studied flow cytometrically by applying just one fluorescent parameter and using scatter characteristics of cells. Resulting 2D‐plots need to represent high numbers of cells to detect the many subcommunities, even rare ones that might be present in the sample. Evaluation of such data can be faulty and subjective due to the low number of parameters available for data discrimination and the high numbers of overlaying events. Here, we describe a procedure that helps to evaluate such data using facilitated gate setting by sequential dot‐plot scanning. © 2015 International Society for Advancement of Cytometry
Cardiac resynchronization therapy in mild heart failure should be reserved for true dyssynchronopathy
Authors: Maass Alexander H. , Westenbrink B. Daan
Published: March 2015

See Review by Hai O.Y et al
Human endogenous retrovirus envelope proteins target dendritic cells to suppress T‐cell activation
Authors: Hummel Jonas , Kämmerer Ulrike , Müller Nora , Avota Elita , Schneider‐Schaulies Sibylle
Published: March 2015

Though mostly defective, human endogenous retroviruses (HERV) can retain open reading frames, which are especially expressed in the placenta. There, the envelope (env) proteins of HERV‐W (Syncytin‐1), HERV‐FRD (Syncytin‐2), and HERV‐K (HML‐2) were implicated in tolerance against the semi‐allogenic fetus. Here, we show that the known HERV env‐binding receptors ASCT‐1 and ‐2 and MFSD2 are expressed by DCs and T‐cells. When used as effectors in coculture systems, CHO cells transfected to express Syncytin‐1, ‐2, or HML‐2 did not affect T‐cell expansion or overall LPS‐driven phenotypic DC maturation, however, promoted release of IL‐12 and TNF‐α rather than IL‐10. In contrast, HERV env expressing choriocarcinoma cell lines suppressed T‐cell proliferation and LPS‐induced TNF‐α and IL‐12 release, however, promoted IL‐10 accumulation, indicating that these effects might not rely on HERV env interactions. However, DCs conditioned by choriocarcinoma, but also transgenic CHO cells failed to promote allogenic T‐cell expansion. This was associated with a loss of DC/T‐cell conjugate frequencies, impaired Ca2+ mobilization, and aberrant patterning of f‐actin and tyrosine phosphorylated proteins in T‐cells. Altogether, these findings suggest that HERV env proteins target T‐cell activation indirectly by modulating the stimulatory activity of DCs.
ICOS is required for the generation of both central and effector CD4+ memory T‐cell populations following acute bacterial infection
Authors: Marriott Clare L. , Carlesso Gianluca , Herbst Ronald , Withers David R.
Published: March 2015

Interactions between ICOS and ICOS ligand (ICOSL) are essential for the development of T follicular helper (Tfh) cells and thus the formation and maintenance of GC reactions. Given the conflicting reports on the requirement of other CD4+ T‐cell populations for ICOS signals, we have employed a range of in vivo approaches to dissect requirements for ICOS signals in mice during an endogenous CD4+ T‐cell response and contrasted this with CD28 signals. Genetic absence of ICOSL only modestly reduced the total number of antigen‐specific CD4+ T cells at the peak of the primary response, but resulted in a severely diminished number of both T central memory and T effector memory cells. Treatment with blocking anti‐ICOS mAb during the primary response recapitulated these effects and caused a more substantial reduction than blocking CD28 signals with CTLA4Ig. During the memory phase of the response further signals through ICOS or CD28 were not required for survival. However, upon secondary challenge only Tfh cell expansion remained heavily ICOS‐dependent, while CD28 signals were required for optimal expansion of all subsets. These data demonstrate the importance of ICOS signals specifically for memory CD4+ T‐cell formation, while highlighting the potential of therapeutically targeting this pathway.
Synthesis, Structure, and Optical Properties of SiO2:Eu3+ Nanowires
Authors: Zhang Hui , Sheng Ye , Zhou Xiuqing , Chen Jie , Shi Zhan , Xu Xuechun , Zou Haifeng
Published: March 2015

SiO2:Eu3+ nanowires were prepared by a solvothermal method followed by subsequent calcination and acid washing processes. The structure, morphology, and properties of the products were characterized by X‐ray diffraction analysis (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared (FTIR) spectroscopy, thermogravimetric analysis (TGA), and photoluminescence (PL) spectroscopy. The results indicated that the obtained SiO2:Eu3+ nanowires exhibited red emission under ultraviolet light excitation and may have potential applications in optical and biological areas. In addition, a possible formation process for the SiO2:Eu3+ nanowires is proposed in detail.
Synthesis, Characterization, and Stereoselective Oxidations of the Dinuclear Copper(II) Complex Derived from a Chiral Diamino‐m‐xylenetetra(benzimidazole) Ligand
Authors: Perrone Maria Lucia , Lo Presti Eliana , Dell'Acqua Simone , Monzani Enrico , Santagostini Laura , Casella Luigi
Published: March 2015

Recent advances in dinuclear copper complexes as mimics of the catalytic centers of tyrosinase and catechol oxidase allowed the reproduction of the structural and mechanistic aspects of the enzymes. However, a challenging objective is the development of chiral complexes for bioinspired enantioselective oxidation reactions. Here, we report the synthesis and characterization of a dinuclear copper(II) complex with a new chiral diamino‐m‐xylenetetra(benzimidazole) ligand (L55Bu4), which has chiral centers at the four 2‐methylbutyl substituents of the benzimidazole rings. The spectral characteristics, ligand binding properties, and reactivity of [CuII2L55Bu4]4+ in the catalytic oxidations of several biogenic catechols (L‐/D‐dopa, L‐/D‐DopaOMe, and L‐/D‐norepinephrine) and thioanisole are reported. The best discriminating properties are displayed towards the DopaOMe derivatives, for which the oxidation rate of the L enantiomer is approximately one order of magnitude larger than that of the opposite D isomer.
Studies towards the Leucetta‐Derived Alkaloids Spirocalcaridine A and B – Possible Biosynthetic Implications
Authors: Koswatta Panduka B. , Das Jayanta , Yousufuddin Muhammed , Lovely Carl J.
Published: March 2015

An exploration of an abiotic approach to spirocalcaridines A and B is described centered on electrophile‐induced dearomatizing spirocyclization of aryl enyne derivatives. Elaboration of the α‐iodoenone through an Ullmann‐like, copper‐catalyzed amidation provided a formamide, which upon treatment with methylamine undergoes a dienol‐arene rearrangement to provide the corresponding kealiinine‐like framework. This observation suggests a possible biosynthetic links between the spirocalcaridine and naphthimidazole group of Leucetta alkaloids.
Synthesis of Functionalized MWCNTs Decorated with Copper Nanoparticles and Its Application as a Sensitive Sensor for Amperometric Detection of H2O2
Authors: Rezaei B. , Askarpour N. , Ghiaci M. , Niyazian F. , Ensafi A. A.
Published: March 2015

Functionalized‐multiwall carbon nanotubes decorated with redox active copper nanoparticles have been fabricated for sensitive enzyme‐less H2O2 detection. The new nanocomposite was characterized by Transmission electron microscopy, energy dispersive X‐ray analysis and cyclic voltammetry. The response of the modified electrode to H2O2 was examined using amperometry at −0.45 V vs. Ag/AgCl in a buffer solution at pH 10.0. The developed sensor displayed linear concentration ranges of 0.5–10.0 and 10.0–10000.0 µmol L−1 with a detection limit of 0.3 µmol L−1. The proposed sensor displayed good selectivity for H2O2 detection in the presence of common interferences such as ascorbic acid.
Galactose Oxidase/Prussian Blue Based Biosensors
Authors: Charmantray Franck , Touisni Nadia , Hecquet Laurence , Noguer Thierry , Mousty Christine
Published: March 2015

This paper describes the development of an amperometric biosensor based on galactose oxidase (GAOx) immobilization within a laponite clay film deposited on Carbon Screen‐Printed Electrodes modified by electrodeposited Prussian Blue and coated with poly‐(O‐phenylenediamine) (PPD/PB/CSPEs). Amperometric performances of GAOx@laponite/PPD/PB/CSPEs bioelectrodes were determined using several GAOx substrates. Using these modified electrodes the reduction of enzymatically generated hydrogen peroxide was performed at −0.2 V vs. Ag‐AgCl. In an initial attempt, E.Coli transketolase activity on its immobilized form was followed using a bienzymatic GAOx‐TK biosensor.
Micro‐injector for capillary electrophoresis
Authors: Sáiz Jorge , Koenka Israel Joel , García‐Ruiz Carmen , Müller Beat , Chwalek Thomas , Hauser Peter C.
Published: March 2015

A novel micro‐injector for capillary electrophoresis for the handling of samples with volumes down to as little as 300 nL was designed and built in our laboratory for analyses in which the available volume is a limitation. The sample is placed into a small cavity located directly in front of the separation capillary, and the injection is then carried out automatically by controlled pressurization of the chamber with compressed air. The system also allows automated flushing of the injection chamber as well as of the capillary. In a trial with a capillary electrophoresis system with contactless conductivity detector, employing a capillary of 25 μm diameter, the results showed good stability of migration times and peak areas. To illustrate the technique, the fast separation of five inorganic cations (Na+, K+, NH4+, Ca2+, and Mg2+) was set up. This could be achieved in less than 3 min, with good limits of detection (10 μM) and linear ranges (between about 10 and 1000 μM). The system was demonstrated for the determination of the inorganic cations in porewater samples of a lake sediment core.
Simultaneous analysis of Cr(III), Cr(VI), and chromium picolinate in foods using capillary electrophoresis‐inductively coupled plasma mass spectrometry
Authors: Chen YiQuan , Chen JinFa , Xi Zhiming , Yang Guidi , Wu Zujian , Li JianRong , Fu FengFu
Published: March 2015

We herein reported a method for the simultaneous detection of trace Cr(VI), Cr(III), and chromium(III) picolinate (CrPic) in foods using CE‐ICP‐MS together with ultrasonic‐assisted extraction. The Cr(III) (Cr3+) was chelated with trans‐1,2‐diaminocyclohexane‐N,N,N´,N´‐tetraacetic acid (DCTA) to form a single charged Cr‐DCTA− complex. Then, Cr(VI) (CrO42−), Cr‐DCTA−, and CrPic were separated by CE within 8 min under a separation voltage of –13 KV followed by their monitoring with ICP mass spectrometer (ICP‐MS). The proposed method is simple, effective, and sensitive. It has an instrument detection limit of 0.10, 0.18, and 0.20 ngCr/mL for Cr(VI), Cr(III), and CrPic, respectively. With the help of the methods, we have successfully determined Cr(VI), Cr(III), and CrPic in nutritional supplement (CrPic yeast tablet) with an RSD (n = 5) <6% and a recovery of 93–103%. The experimental results showed that CrPic was the main speciation of chromium in the nutritional supplement, with a concentration of 1514.6 μg Cr/g.
Strategies for permanent immobilization of enzymes on textile carriers
Authors: Kiehl Katharina , Straube Thomas , Opwis Klaus , Gutmann Jochen S.
Published: March 2015

The economical use of expensive enzymes in chemical synthesis can be improved by the immobilization of the catalyst on a suitable support material. Textile fabrics made of polyester, polyamide, or cotton represent comparatively inexpensive alternative carrier materials in contrast to conventional supports. Textile‐inherent advantages like its flexible and lightweight construction allow the use in reactors of arbitrary geometry, a quick separation from the reaction liquor, and the generation of residue‐free product. A low preparative and economical expense is needed to prepare fabrics with high enzyme loads (20–70 mg enzyme/g textile carrier), high relative activity (up to 20%) and excellent permanence against enzyme desorption as well. In this study, we present different strategies for the covalent fixation of enzymes on fiber forming polymers such as photochemical grafting, the use of bifunctional anchor molecules, monomeric, and polymeric cross‐linking agents or specific enzyme modification for direct immobilization. In addition, we compare the strategies in terms of load, catalytic activity, and reusability. All presented immobilization methods yield products, which exhibit a considerable activity even after twenty recycling steps. In conclusion, we have successfully identified textiles as alternative, new and promising low cost carrier materials for enzymes.
The Sensitivity of Interest Rate Options to Monetary Policy Decisions: A Regime‐Shift Pricing Approach
Authors: Ferland René , Gauthier Geneviève , Lalancette Simon
Published: March 2015

We look at whether monetary decisions constitute a significant macro‐finance risk for interest rate options and related implied volatilities. We devise an option‐pricing model based on the dynamics of the Federal Reserve's target rate via a regime‐shift approach modeled as discrete Markov chain capturing the timing of Federal Open Market Committee meetings. We find that the regime‐shift risk is significantly priced and that the downward and stable regimes of the target rate, associated with a decline in real activity, display higher probabilities of occurrence under the risk‐neutral measure. We also observe that implied volatilities display a counter‐cyclical behavior. © 2015 Wiley Periodicals, Inc. Jrl Fut Mark 36:66–87, 2016
Analyzing Oil Futures with a Dynamic Nelson‐Siegel Model
Authors: GrØnborg Niels S. , Lunde Asger
Published: March 2015

The dynamic Nelson–Siegel model is used to model the term structure of futures contracts on oil and obtain forecasts of prices of these contracts. Three factors are extracted and modelled in a very flexible framework. The outcome of this exercise is a class of models which describes the observed prices of futures contracts well and performs better than conventional benchmarks in realistic real‐time out‐of‐sample exercises. © 2015 Wiley Periodicals, Inc. Jrl Fut Mark 36:153–173, 2016
Reconciling Estimates of the Value to Firms of Reduced Regulatory Delay in the Marketing of Their New Drugs
Authors: Wilmoth Daniel R.
Published: March 2015

The prescription drug user fee program provides additional resources to the US Food and Drug Administration at the expense of regulated firms. Those resources accelerate the review of new drugs. Faster approvals allow firms to realize profits sooner, and the program is supported politically by industry. However, published estimates of the value to firms of reduced regulatory delay vary dramatically. It is shown here that this variation is driven largely by differences in methods that correspond to differences in implicit assumptions about the effects of reduced delay. Theoretical modeling is used to derive an equation describing the relationship between estimates generated using different methods. The method likely to yield the most accurate results is identified. A reconciliation of published estimates yields a value to a firm for a one‐year reduction in regulatory delay at the time of approval of about $60 million for a typical drug. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.
The Micro‐Dynamics of Intraorganizational and Individual Behavior and Their Role in Organizational Ambidexterity Boundaries
Authors: Stokes Peter , Moore Neil , Moss Danny , Mathews Martin , Smith Simon M. , Liu Yipeng
Published: March 2015

Organizational ambidexterity has emerged as a valuable contemporary lens on organizational design and action, examining the dynamic relationships between exploitative (extant) and explorative (evolving) resources within organizational contexts and environments. This article analyzes the literature pertaining to ambidexterity and underlines a number of recurrent preoccupations includingdefinitionof the nature, characteristics, and normative boundaries of organizational ambidexterity; a predilection toward consideringinterfirm/unitcomparisons oflarge‐scale corporate organizations;and a concentration on the significance of the managerialistic role of thesenior management team'sdisposition and action‐orientations. While a few calls have been made for a focus on the micro‐aspects, predominant attention has remained on the macro‐aspects of organizational ambidexterity.

The aim of the article, therefore, is to conduct a complementary study that considers the boundaries and transitions between exploitative and explorative modes at the intraorganizational, individual micro‐behavioral level. To facilitate this, the article surfaces and underscores the paradigmatic modernistic characterization of large areas of the current organizational ambidexterity literature and the implications of this. Moreover, it explores alternative potentially useful critical paradigms that assist in providing tools with which to examine the “micro.” The research conducts an ethnographic‐style study of a quasi‐public training and development organization to illustrate the above background contexts and the micro‐interface and boundary of explorative and exploitative modes of organizational ambidexterity in the intraorganizational situation. Within this, the study points up the significance of the role of sense‐making inoperational micro‐moment individual and small‐group situations, and their vital influence in ultimately underpinning, and contributing to, macro‐organizational ambidextrous contexts. © 2015 Wiley Periodicals, Inc.
Adoption of High‐Performance Work Systems by Local Subsidiaries of Developed Country and Turkish MNEs and Indigenous Firms in Turkey
Authors: Demirbag Mehmet , Tatoglu Ekrem , Wilkinson Adrian
Published: March 2015

High‐performance work systems (HPWSs) are seen as important in helping strengthen competitive strategies of developed‐country multinational enterprises (DC MNEs). Commensurate with global competitive pressures and internationalization strategies, emerging‐country MNEs (EC MNEs) and indigenous firms are also increasingly adopting HPWSs. HPWSs are not only seen as simply performance enhancing systems, but also as facilitators of internationalization. MNEs represent an important test bed for the HPWSs and their applicability in different national contexts. In this article, we contribute to the extant literature by focusing on HPWS adoption level within domestic subsidiaries of DC MNEs and EC MNEs along with stand‐alone indigenous firms in a single‐country setting by keeping the host‐country environment as constant. © 2015 Wiley Periodicals, Inc.
Varieties of Qualifications, Training, and Skills in Long‐Term Care: A German, Japanese, and UK Comparison
Authors: Gospel Howard
Published: March 2015

This article considers the systems of qualifications and training in the long‐term elderly care sector in Germany, Japan, and the United Kingdom. Each country faces similar challenges of coping with increasing demand and securing staff for quality and cost‐effective care. However, the three countries organize qualifications and training in very different ways. In the case of formal care workers, there is a hierarchy of training and skills, with Germany at the top, Japan in the middle, and the United Kingdom at the bottom. However, comparing the whole workforce, Germany has developed a dualistic structure with both highly and lowly trained workers; Japan has developed a relatively large proportion of moderately trained and qualified staff; and theUKworkforce consists of a relatively large proportion of lowly trained and unqualified workers. Explanations are considered and implications offered for human resource management. © 2015 Wiley Periodicals, Inc.
Factors affecting the spatial pattern of bedrock groundwater recharge at the hillslope scale
Authors: Appels Willemijn M. , Graham Chris B. , Freer Jim E. , McDonnell Jeffrey J.
Published: March 2015

The spatial patterns of groundwater recharge on hillslopes with a thin soil mantle overlying bedrock are poorly known. Complex interactions between vertical percolation of water through the soil, permeability contrasts between soil and bedrock and lateral redistribution of water result in large spatial variability of water moving into the bedrock. Here, we combine new measurements of saturated hydraulic conductivity of soil mantle and bedrock of the well‐studied Panola Mountain experimental hillslope with previously collected (sub)surface topography and soil depth data to quantify the factors affecting the spatial pattern of bedrock groundwater recharge.

We use geostatistical characteristics of the measured permeability to generate spatial fields of saturated hydraulic conductivity for the entire hillslope. We perform simulations with a new conceptual model with these random fields and evaluate the resulting spatial distribution of groundwater recharge during individual rainstorms and series of rainfall events. Our simulations show that unsaturated drainage from soil into bedrock is the prevailing recharge mechanism and accounts for 60% of annual groundwater recharge. Therefore, soil depth is a major control on the groundwater recharge pattern through available storage capacity and controlling the size of vertical flux. The other 40% of recharge occurs during storms that feature transient saturation at the soil‐bedrock interface. Under these conditions, locations that can sustain increased subsurface saturation because of their topographical characteristics or those with high bedrock permeability will act as hotspots of groundwater recharge when they receive lateral flow. Copyright © 2015 John Wiley & Sons, Ltd.
Reveromycin A‐Induced Apoptosis in Osteoclasts Is Not Accompanied by Necrosis
Authors: Mead Brittany , Morgan Heather , Mann‐Knowlton Alyssa , Tedeschi Laura , Sloan Chris , Lang Spenser , Hines Cory , Gragg Megan , Stofer Jonathan , Riemann Kaitlin , Derr Tyler , Heller Emily , Collins David , Landis Paul , Linna Nathan , Jones Daniel
Published: March 2015

Reveromycin A (RM‐A), a small natural product isolated from Streptomyces bacteria, is a potential osteoporosis therapeutic in that it specifically induces apoptosis in osteoclasts but not osteoblasts. The purpose of the study presented here was to further elucidate the intracellular mechanisms of RM‐A death effects in mature osteoclasts. A specific clone of RAW264.7 murine macrophages that was previously characterized for its ability to acquire an osteoclast nature on differentiation was differentiated in the presence of receptor activator of nuclear factor kappa B ligand (RANKL). Subsequent staining was performed for tartrate‐resistant acid phosphatase to confirm their osteoclast character. These osteoclasts were treated with ten micromolar RM‐A for 2, 4, 6, 24, and 48 h at a pH of 5.5. Peak apoptosis induction occurred at 4–6 h as measured by caspase 3 activity. Lactate dehydrogenase release assay revealed no significant RM‐A‐induced necrosis. Western blot analysis of cytoplasmic extracts demonstrated activation of caspase 9 (2.3‐fold at 2 h and 2.6‐fold at 4 h, each P < 0.05) and no significant changes in Bcl‐XL. In nuclear extracts, NFκB levels significantly increased on differentiation with RANKL but then remained constant through RM‐A treatment. Over the extended time course studied, RM‐A‐induced apoptosis in osteoclasts was not accompanied by necrosis, suggesting that RM‐A would likely have limited effects on immediate, neighboring bone cell types. This specific cell death profile is promising for potential clinical investigations of RM‐A as a bone antiresorptive. J. Cell. Biochem. 116: 1646–1657, 2015. © 2015 Wiley Periodicals, Inc.
Introduction of periodic boundary conditions into UNRES force field
Authors: Sieradzan Adam K.
Published: March 2015

In this article, implementation of periodic boundary conditions (PBC) into physics‐based coarse‐grained UNited RESidue (UNRES) force field is presented, which replaces droplet‐like restraints previously used. Droplet‐like restraints are necessary to keep multichain systems together and prevent them from dissolving to infinitely low concentration. As an alternative for droplet‐like restrains cuboid PBCs with imaging of the molecules were introduced. Owing to this modification, artificial forces which arose from restraints keeping a droplet together were eliminated what leads to more realistic trajectories. Due to computational reasons cutoff and smoothing functions were introduced on the long range interactions. The UNRES force field with PBC was tested by performing microcanonical simulations. Moreover, to asses the behavior of the thermostat in PBCs Langevin and Berendsen thermostats were studied. The influence of PBCs on association pattern was compared with droplet‐like restraints on the ββα hetero tetramer 1 protein system. © 2015 Wiley Periodicals, Inc.
p14ARF Prevents Proliferation of Aneuploid Cells by Inducing p53‐Dependent Apoptosis
Authors: Veneziano Lorena , Barra Viviana , Lentini Laura , Spatafora Sergio , Di Leonardo Aldo
Published: March 2015

Weakening the Spindle Assembly Checkpoint by reduced expression of its components induces chromosome instability and aneuploidy that are hallmarks of cancer cells. The tumor suppressor p14ARF is overexpressed in response to oncogenic stimuli to stabilize p53 halting cell progression. Previously, we found that lack or reduced expression of p14ARF is involved in the maintenance of aneuploid cells in primary human cells, suggesting that it could be part of a pathway controlling their proliferation. To investigate this aspect further, p14ARF was ectopically expressed in HCT116 cells after depletion of the Spindle Assembly Checkpoint MAD2 protein that was used as a trigger for aneuploidy. p14ARF Re‐expression reduced the number of aneuploid cells in MAD2 post‐transcriptionally silenced cells. Also aberrant mitoses, frequently displayed in MAD2‐depleted cells, were decreased when p14ARF was expressed at the same time. In addition, p14ARF ectopic expression in MAD2‐depleted cells induced apoptosis associated with increased p53 protein levels. Conversely, p14ARF ectopic expression did not induce apoptosis in HCT116 p53KO cells. Collectively, our results suggest that the tumor suppressor p14ARF may have an important role in counteracting proliferation of aneuploid cells by activating p53‐dependent apoptosis. J. Cell. Physiol. 231: 336–344, 2016. © 2015 Wiley Periodicals, Inc.
Portal vein reconstruction in adult living donor liver transplantation for patients with portal vein thrombosis in single center experience
Authors: Mori Akira , Iida Taku , Iwasaki Junji , Ogawa Kohei , Fujimoto Yasuhiro , Uemura Tadahiro , Hatano Etsuro , Okajima Hideaki , Kaido Toshimi , Uemoto Shinji
Published: March 2015

Background

Liver transplantation (LT) used to be contraindicated in patients with portal vein thrombosis (PVT). In comparison to deceased donor LT, living donor LT (LDLT) still presents additional difficulties in determining appropriate vein grafts and overcoming small‐for‐size syndrome. Here, we introduce our LDLT strategies and assess their outcomes in adult patients with pre‐existing PVT.

Methods

We performed 282 consecutive adult LDLTs between April 2006 and December 2011. Forty‐eight patients (17%) had pre‐existing PVT (grade I; 15, II; 20, III; 12, IV; 1).

Results

Our preferred treatments for PVT were thrombectomies/thromboendovenectomies in 30 patients, replaced grafts in seven, jump grafts in seven, renoportal anastomosis in one and no surgical intervention owing to minimal thrombosis in three. Post‐transplant portal vein complications occurred in eight of 48 (17%) cases, which were treated by surgery, anticoagulation therapy, and/or interventional radiology. Post‐transplant survival rates of patients with preexisting PVT at 1 year and 5 years were comparable to a PVT‐free cohort (1 year; 81% vs. 77%, 5 years; 81% vs. 73%).

Conclusions

The excellent survival rates in patients with PVT who underwent LDLT could be attributed to our strategies, which included surgical techniques and timely treatment of postoperative complications.
Technology of friction stir welding of aluminium alloy 6082 T‐joints and their behaviour under static and dynamic loads
Authors: Krasnowski K.
Published: March 2015

The paper deals with an investigation of technological possibilities to produce T‐joints of Al 6082 by friction stir welding technique and mechanical properties of the joints. It was indicated the importance of preparation proper welding stand by showing joints quality, presented on macrostructures, obtained with and without specially designed equipment for welding T‐joints. Different ways of base metal preparation prior to welding (T‐joints welded as two pieces and as three pieces), as well as two various shapes of steel dies directly forming the shape of tee connections, were used in experiments. It was shown how welding conditions influence structure and static properties of friction stir welding joints. Results show that for specified tool speeds significant imperfections, like voids, were formed. The best experimentally defined welding parameters, ensures lack of voids, were used to produce test joints for fatigue test. For the tested friction stir welding T‐joints the fatigue category FAT were determined and compared to FAT categories of equivalent T‐joints welded by conventional fusion welding. The study reveals also metallographic macroscopic and microscopic examination results, indicated typical imperfections arising during friction stir welding process of T‐joints, as well as results of hardness measurement of joints cross section.
The antifungal plant defensin AhPDF1.1b is a beneficial factor involved in adaptive response to zinc overload when it is expressed in yeast cells
Authors: Mith Oriane , Benhamdi Asma , Castillo Teddy , Bergé Muriel , MacDiarmid Colin W. , Steffen Janet , Eide David J. , Perrier Véronique , Subileau Maeva , Gosti Françoise , Berthomieu Pierre , Marquès Laurence
Published: March 2015

Antimicrobial peptides represent an expanding family of peptides involved in innate immunity of many living organisms. They show an amazing diversity in their sequence, structure, and mechanism of action. Among them, plant defensins are renowned for their antifungal activity but various side activities have also been described. Usually, a new biological role is reported along with the discovery of a new defensin and it is thus not clear if this multifunctionality exists at the family level or at the peptide level. We previously showed that the plant defensin AhPDF1.1b exhibits an unexpected role by conferring zinc tolerance to yeast and plant cells. In this paper, we further explored this activity using different yeast genetic backgrounds: especially the zrc1 mutant and an UPRE‐GFP reporter yeast strain. We showed that AhPDF1.1b interferes with adaptive cell response in the endoplasmic reticulum to confer cellular zinc tolerance. We thus highlighted that, depending on its cellular localization, AhPDF1.1b exerts quite separate activities: when it is applied exogenously, it is a toxin against fungal and also root cells, but when it is expressed in yeast cells, it is a peptide that modulates the cellular adaptive response to zinc overload.
Thermal stresses in borehole heat exchangers
Authors: Erol Selçuk , François Bertrand
Published: March 2015

The backfilling materials of borehole heat exchangers (BHE), particularly the grout material, must provide a suitable thermal contact and ensure durability to the induced thermal stresses because of the heat loading. In this paper, the thermal stresses that occurred in BHEs because of heat injection or extraction is investigated with an analytical solution of a hollow cylinder model that is adapted for time‐dependent heat loading, the geometry of a BHE, and the thermo‐mechanical properties of surrounding ground conditions. Firstly, the hollow cylinder model is solved with the considered boundary conditions in 2D plane stress. Secondly, the temperature differences at the inner and outer circles of the cylinder are evaluated with the heat line source models for continuous and discontinuous loading to observe the impact of the heat loading schedule. The developed analytical solution for thermal stress investigation is validated with numerical models. It is demonstrated that the analytical solutions agree well with numerical results for two types of BHE configurations (co‐axial and single U‐shaped pipes). Furthermore, the calculated maximum stresses are compared with the tensile strength of grout materials obtained from Brazilian tests. It is predicted that the thermal contraction of the grout, partially constrained by the surrounding rock, generates tensile stresses that may lead to cracking in the BHE. According to the results, the stiffness of rock has a primary role on the developed tensile stresses, and the relationship between the thermal conductivity of the ground and of the grout induces a proportional impact on the magnitude of thermal stresses. Copyright © 2015 John Wiley & Sons, Ltd.
Alkalinized lidocaine versus lidocaine gel as local anesthesia prior to intra‐vesical botulinum toxin (BoNTA) injections: A prospective, single center, randomized, double‐blind, parallel group trial of efficacy and morbidity
Authors: Nambiar Arjun K. , Younis Ayman , Khan Zainab A. , Hildrup Iona , Emery Simon J. , Lucas Malcolm G.
Published: March 2015

Aims

To assess the efficacy and morbidity of alkalinized lidocaine solution compared to lidocaine gel for intra‐vesical anesthesia during botulinum toxin (BoNTA) injections in a statistically powered, prospective, parallel group, double‐blind randomized controlled trial.

Methods

Fifty‐four patients of either sex were randomized to receive either alkalinized lidocaine (AL) solution (10 ml 8.4% sodium bicarbonate + 20 ml 2% lidocaine solution + 22 ml sterile Aquagel®) or lidocaine gel (LG) (22 ml standard 2% lidocaine gel Instillagel® + 30 ml 0.9% normal saline solution). Primary outcome was average pain (assessed by 100 mm visual analog score) felt during intra‐vesical BoNTA injections performed at least 20 min after instillation. Secondary outcome was the rate of adverse events.

Results

Of 60 randomized patients 54 received the allocated intervention and were analyzed. Mean pain score in the AL group was 17.11 mm (95%CI 8.65–25.57 mm) and in the LG group was 19.53 mm (95%CI 13.03–26.03mm) with no significant difference between the groups. Cost of interventional medication in the AL group was almost double that of the LG group. No adverse events were attributable to local anesthetic instillation in either group.

Conclusions

Alkalinized lidocaine solution is not superior to lidocaine gel for anesthesia during intra‐vesical BoNTA injections, and the higher cost precludes its use over lidocaine gel at our centre. We have used the results of this study to adapt our local protocol for BoNTA injections and continue to use lidocaine gel as the local anesthetic of choice. Neurourol. Urodynam. 35:522–527, 2016. © 2015 Wiley Periodicals, Inc.
Group IIE secretory phospholipase A2 regulates lipolysis in adipocytes
Authors: Zhi Hui , Qu Linbing , Wu Fang , Chen Ling , Tao Jun
Published: March 2015

Objective

To examine the function of group IIE secretory phospholipase A2 (sPLA2‐IIE) in adipocytes and to explore the possible signaling mechanism involved.

Methods

The expression of sPLA2‐IIE was demonstrated using real‐time PCR and Western blot analysis. Lipid accumulation was evaluated via the measurement of cellular triglycerides (TG). Lipolysis was quantified by measuring the release of free glycerol. The expressions of M‐type sPLA2 receptor (PLA2R1) and the genes encoding adipogenic proteins were measured using real‐time PCR. The activities of the Janus kinase 2 (JAK2), extracellular regulated protein kinase (ERK), and hormone‐sensitive lipase (HSL) were determined using Western blot.

Results

sPLA2‐IIE‐/‐ mice gained significantly more epididymal fat than wild‐type (WT) mice. When treated with adipogenic stimuli ex vivo, stromal vascular cells isolated from the adipose tissue of sPLA2‐IIE‐/‐ mice accumulated significantly more TG than those from WT mice. Conversely, a significant reduction in lipid accumulation and an increase of free glycerol were observed in OP9 cells overexpressing sPLA2‐IIE and in 3T3‐L1 cells treated with sPLA2‐IIE protein. Moreover, sPLA2‐IIE significantly induced adipocyte glycerol release and HSL activity, which was inhibited by PD98059, an ERK inhibitor.

Conclusions

sPLA2‐IIE regulates lipolysis in adipocytes, likely through the ERK/HSL signaling pathway.
Computational Exploration of the Photoprotective Potential of Gadusol
Authors: Losantos Raúl , Churio M. Sandra , Sampedro Diego
Published: March 2015

Gadusol shows one of the simplest structures among a series of natural UV‐absorbing compounds that have been related to the photoprotective and antioxidant functions in aquatic organisms. CASPT2//CASSCF methodology was used to carry out a theoretical study on this basic structure in order to describe the underlying features responsible for the photoprotective capacity of the molecule. The influence of the enol–enolate equilibrium on the photophysical properties was explored. The results confirm that both forms undergo a rapid deactivation, which very efficiently dissipates light energy as heat. This work highlights the potential of molecular‐level studies to provide an understanding of natural photoprotective mechanisms and gives support to the future design of structurally related new synthetic sunscreens.
Synthesis, characterization and X‐ray shielding properties of polypyrrole/lead nanocomposites
Authors: Hosseini Seyed Hossein , Noushin Ezzati S. , Askari M.
Published: March 2015

Novel radiation shielding nanocomposites based on a conducting polymer were fabricated and investigated to determine their abilities in attenuation of X‐rays. Polypyrrole/Pb nanocomposites were prepared through chemical reduction of lead salt by a facile solution‐phase method using t‐BuOLi‐activated LiH and in situ chemical polymerization of pyrrole in the presence of dodecyl benzene sulfonic acid as dopant and surfactant and iron chloride as the oxidant. The morphology, composition, and electrical conductivity of resulting products were characterized by scanning electron microscopy, transmission electron microscopy, X‐ray diffraction analysis, energy‐dispersive X‐ray spectroscopy, fourier transform infrared spectroscopy, and standard four‐wire technique, respectively. In order to evaluate capability of nanocomposites in radiation shielding, X‐ray photon interaction parameters such as linear attenuation coefficient, attenuation percentage, and half‐value thickness were determined for the samples with different Pb loadings and thicknesses, at photon energies of 13.95, 17.74, 20.08, 26.34, and 59.50 keV. The investigation was carried out to explore the potential of polypyrrole/Pb nanocomposites as thin and light‐weight radiation shielding materials. Copyright © 2015 John Wiley & Sons, Ltd.
In vitro analysis of overall particulate contamination exposure during multidrug IV therapy: Impact of infusion sets
Authors: Perez Maxime , Décaudin Bertrand , Abou Chahla Wadih , Nelken Brigitte , Barthélémy Christine , Lebuffe Gilles , Odou Pascal
Published: March 2015

Background

Drug incompatibilities, recognizable through precipitate, may have clinical consequences for patients, especially during multidrug IV therapies, where vancomycin and piperacillin are present. Drug concentration and infusion set influence the overall particulate contamination of pediatric infusion protocols. The use of multi‐lumen infusion sets could prevent such incompatibilities. Our goal was to define and assess a new way to infuse these drugs during leukemia treatment in children.

Procedures

This in vitro study focused on a pediatric multidrug protocol for patients diagnosed with lymphoblastic leukemia and receiving allogeneic transplantation. Different vancomycin concentrations were tested to infuse incompatible drugs simultaneously without any particle formation (optimized multidrug protocol). A dynamic particle count test was used over 24 hr to evaluate the overall particulate contamination of our standard and optimized multidrug protocols, using both a standard and a multi‐lumen infusion set.

Results

No visible particles were detected on a decreased vancomycin concentration compared to the standard dose. For the optimized multidrug protocol, the use of a multi‐lumen infusion set reduced overall particulate contamination by 68%, compared to the standard infusion set (P = 0.002). Large‐sized particles were significantly reduced when using the multi‐lumen infusion set approximately 60% (P = 0.027) and 90% (P = 0.009) for particle sizes ≥10 μm and 25 μm, respectively.

Conclusions

This study demonstrates that a large number of particles can be administered during parenteral multidrug infusion. The choice of drug concentration and/or the type of infusion set may reduce this. Further studies are required to evaluate adverse clinical effects. Pediatr Blood Cancer 2015;62:1042–1047. © 2015 Wiley Periodicals, Inc.
Detection of fetal chromosomal anomalies: does nuchal translucency measurement have added value in the era of non‐invasive prenatal testing?
Authors: Lichtenbelt K. D. , Diemel B. D. M. , Koster M. P. H. , Manten G. T. R. , Siljee J. , Schuring‐Blom G. H. , Page‐Christiaens G. C. M. L.
Published: March 2015

Objectives

The objective of this study is to determine what percentage of fetal chromosomal anomalies remains undetected when first trimester combined testing is replaced by non‐invasive prenatal testing for trisomies 13, 18, and 21. We focused on the added clinical value of nuchal translucency (NT) measurement.

Methods

Data on fetal karyotype, ultrasound findings, and pregnancy outcome of all pregnancies with an NT measurement ≥3.5 mm were retrospectively collected from a cohort of 25 057 singleton pregnancies in which first trimester combined testing was performed.

Results

Two hundred twenty‐five fetuses (0.9 %) had an NT ≥3.5 mm. In 24 of these pregnancies, a chromosomal anomaly other than trisomy 13, 18, or 21 was detected. Eleven resulted in fetal demise, and ten showed fetal ultrasound anomalies. In three fetuses with normal ultrasound findings, a chromosomal anomaly was detected, of which one was a triple X.

Conclusions

In three out of 25 057 pregnancies (0.01%), non‐invasive prenatal testing and fetal ultrasound would have missed a chromosomal anomaly that would have been identified by NT measurement. © 2015 John Wiley & Sons, Ltd.
Identification of novel biomarker candidates for immunohistochemical diagnosis to distinguish low‐grade chondrosarcoma from enchondroma
Authors: Lai Xianyin , Chen Shaoxiong
Published: March 2015

Chondrosarcoma is the third most common primary bone cancer, requiring surgical resection. However, differentiation of low‐grade chondrosarcoma (grade 1) from enchondroma that is benign and only requires regular follow‐up is one of the most frequent diagnostic dilemmas facing orthopedic oncologists in clinical management. Although multiple techniques are applied to make the distinction, immunohistochemistry is an important ancillary technique, especially when a histopathological stain of specimen must be obtained in order to guarantee an accurate confirmation. Currently, no adequate immunohistochemical diagnostic protein biomarkers are available to distinguish low‐grade chondrosarcoma from enchondroma. To discover novel protein biomarker candidates, an LC‐MS/MS approach was applied to directly compare formalin‐fixed, paraffin‐embedded low‐grade chondrosarcoma with enchondroma tissue samples. The proteomics analysis revealed 17 protein biomarker candidates. A principle was developed to prioritize the candidates using category and ranking. An algorithm, prioritization index of biomarker candidates for immunohistochemistry on tissue specimens, was developed to rank the candidates inside each category. Using the proteomics data and bioinformatics results, the prioritization index of biomarker candidates for immunohistochemistry on tissue revealed periostin as a top candidate. Immunohistochemical staining of periostin in 23 low‐grade chondrosarcoma and 31 enchondroma tissue specimens disclosed 87% specificity and 70% sensitivity.
Concealment of lung cancer diagnosis: prevalence and correlates
Authors: Gonzalez Brian D. , Jim Heather S. L. , Cessna Julie M. , Small Brent J. , Sutton Steven K. , Jacobsen Paul B.
Published: March 2015

Background

Lung cancer has a commonly understood behavioral etiology. Thus, lung cancer patients are often blamed for their illness and may seek to avoid this blame by concealing their diagnosis from others. This study sought to determine the prevalence of concealment and identify demographic, clinical, and psychosocial correlates of concealment among lung cancer patients.

Methods

A sample of 117 lung cancer patients receiving chemotherapy for non‐small cell or small cell lung cancer was recruited and completed self‐report demographic questionnaires, a measure of diagnosis concealment designed and pilot tested for this study, and standard measures of psychosocial variables. Clinical factors were assessed via a medical chart review.

Results

Thirty participants (26%) reported concealing their diagnosis in the previous month, most frequently from casual friends and close friends. Reported reasons for concealment largely reflected concern for others. Univariate analyses indicated that those who concealed their lung cancer diagnosis reported more internalized shame related to their illness and use of positive reappraisal as a coping strategy (ps ≤ 0.02). In addition, those who concealed were more likely to have used alcohol in the previous month and have a more recent recurrence, among those who had a recurrence (ps ≤ 0.04). Multivariate analyses indicated that internalized shame and use of positive reappraisal accounted for significant unique variance in concealment above and beyond that accounted for by use of alcohol (ps < 0.05).

Conclusions

Future research should aim to replicate and extend these findings with longitudinal designs to elucidate the directionality of the associations observed in this study. Copyright © 2015 John Wiley & Sons, Ltd.