bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis, biophysical properties, and oxygenation potential of variable molecular weight glutaraldehyde‐polymerized bovine hemoglobins with low and high oxygen affinity
Authors: Zhou Yipin , Jia Yiping , Buehler Paul W. , Chen Guo , Cabrales Pedro , Palmer Andre F.
Published: April 2011

In a recent study, ultrahigh molecular weight (Mw) glutaraldehyde‐polymerized bovine hemoglobins (PolybHbs) were synthesized with low O2 affinity and exhibited no vasoactivity and a slight degree of hypertension in a 10% top‐load model.1 In this work, we systematically investigated the effect of varying the glutaraldehyde to hemoglobin (G:Hb) molar ratio on the biophysical properties of PolybHb polymerized in either the low or high O2 affinity state. Our results showed that the Mw of the resulting PolybHbs increased with increasing G:Hb molar ratio. For low O2 affinity PolybHbs, increasing the G:Hb molar ratio reduced the O2 affinity and CO association rate constants in comparison to bovine hemoglobin (bHb). In contrast for high O2 affinity PolybHbs, increasing the G:Hb molar ratio led to increased O2 affinity and significantly increased the CO association rate constants compared to unmodified bHb and low O2 affinity PolybHbs. The methemoglobin level and NO dioxygenation rate constants were insensitive to the G:Hb molar ratio. However, all PolybHbs displayed higher viscosities compared to unmodified bHb and whole blood, which also increased with increasing G:Hb molar ratio. In contrast, the colloid osmotic pressure of PolybHbs decreased with increasing G:Hb molar ratio. To preliminarily evaluate the ability of low and high O2 affinity PolybHbs to potentially oxygenate tissues in vivo, an O2 transport model was used to simulate O2 transport in a hepatic hollow fiber (HF) bioreactor. It was observed that low O2 affinity PolybHbs oxygenated the bioreactor better than high O2 affinity PolybHbs. This result points to the suitability of low O2 affinity PolybHbs for use in tissue engineering and transfusion medicine. Taken together, our results show the quantitative effect of varying the oxygen saturation of bHb and G:Hb molar ratio on the biophysical properties of PolybHbs and their ability to oxygenate a hepatic HF bioreactor. We suggest that the information gained from this study can be used to guide the design of the next generation of hemoglobin‐based oxygen carriers (HBOCs) for use in tissue engineering and transfusion medicine applications. © 2011 American Institute of Chemical Engineers Biotechnol. Prog., 2011
Automated live cell imaging systems reveal dynamic cell behavior
Authors: Chirieleison Steven M. , Bissell Taylor A. , Scelfo Christopher C. , Anderson Jordan E. , Li Yong , Koebler Doug J. , Deasy Bridget M.
Published: April 2011

Automated time‐lapsed microscopy provides unique research opportunities to visualize cells and subcellular components in experiments with time‐dependent parameters. As accessibility to these systems is increasing, we review here their use in cell science with a focus on stem cell research. Although the use of time‐lapsed imaging to answer biological questions dates back nearly 150 years, only recently have the use of an environmentally controlled chamber and robotic stage controllers allowed for high‐throughput continuous imaging over long periods at the cell and subcellular levels. Numerous automated imaging systems are now available from both companies that specialize in live cell imaging and from major microscope manufacturers. We discuss the key components of robots used for time‐lapsed live microscopic imaging, and the unique data that can be obtained from image analysis. We show how automated features enhance experimentation by providing examples of uniquely quantified proliferation and migration live cell imaging data. In addition to providing an efficient system that drastically reduces man‐hours and consumes fewer laboratory resources, this technology greatly enhances cell science by providing a unique dataset of temporal changes in cell activity. © 2011 American Institute of Chemical Engineers Biotechnol. Prog., 2011
Cell culture and gene transcription effects of copper sulfate on Chinese hamster ovary cells
Authors: Qian Yueming , Khattak Sarwat F. , Xing Zizhuo , He Aiqing , Kayne Paul S. , Qian Nan‐Xin , Pan Shih‐Hsie , Li Zheng Jian
Published: April 2011

This study reports the effects of varying concentrations of copper sulfate on the metabolic and gene transcriptional profile of a recombinant Chinese hamster ovary (CHO) cell line producing an immunoglobulin G (IgG)‐fusion protein (B0). Addition of 50 μM copper sulfate significantly decreased lactate accumulation in the cultures while increasing viable cell density and protein titer. These changes could be seen from day 6 and became increasingly evident with culture duration. Reducing the copper sulfate concentration to 5 μM retained all the above beneficial effects, but with the added benefit of reduced levels of the aggregated form of the B0 protein. To profile the cellular changes due to copper sulfate addition at the transcriptional level, Affymetrix® CHO microarrays were used to identify differentially expressed genes related to reduced cellular stresses and facilitated cell cycling. Based on the microarray results, down‐regulation of the transferrin receptor and lactate dehydrogenase, and up‐regulation of a cytochrome P450 family‐2 polypeptide were then confirmed by Western blotting. These results showed that copper played a critical role in cell metabolism and productivity on recombinant CHO cells and highlighted the usefulness of microarray data for better understanding biological responses on medium modification. © 2011 American Institute of Chemical Engineers Biotechnol. Prog., 2011
Does the Terminologia Anatomica really matter?
Authors: Hirsch Bruce Elliot
Published: April 2011

This article points out how the Terminologia Anatomica is often ignored and suggests ways that its acceptance can be improved. Clin. Anat. 24:503–504, 2011. © 2011 Wiley‐Liss, Inc.
A numerical simulation model to facilitate the understanding of the properties of a diffraction grating
Authors: Zurek Eduardo E. , Moreno Wilfrido A. , García‐Rubio Luis H.
Published: April 2011

This paper introduces a new tool to approach the effects of a diffraction grating and its interaction with other optical and electronic components in a light wavelength analysis system. The model's theoretical background is described. This model is intended for educational purposes and it is referred to a miniaturized spectrophotometer. © 2011 Wiley Periodicals, Inc. Comput Appl Eng Educ 22:187–194, 2014; View this article online at wileyonlinelibrary.com/journal/cae; DOI 10.1002/cae.20544
Membrane cholesterol modulates the cytolytic mechanism of myotoxin II, a Lys49 phospholipase A2 homologue from the venom of Bothrops asper
Authors: Rangel José , Quesada Orestes , Gutiérrez José María , Angulo Yamileth , Lomonte Bruno
Published: April 2011

Lys49 phospholipase A2 (PLA2) homologues present in crotalid snake venoms lack enzymatic activity, yet they induce skeletal muscle necrosis by a membrane permeabilizing mechanism whose details are only partially understood. The present study evaluated the effect of altering the membrane cholesterol content on the cytolytic activity of myotoxin II, a Lys49 PLA2 isolated from the venom of Bothrops asper, using the myogenic cell line C2C12 as a model target. Cell membrane cholesterol depletion by methyl‐β‐cyclodextrin (MβCD) treatment enhanced the cytolytic action of myotoxin II, as well as of its bioactive C‐terminal synthetic peptide p115‐129. Conversely, cell membrane cholesterol enrichment by preformed cholesterol‐MβCD complexes reduced the cytolytic effect of myotoxin II. The toxic actions of myotoxin I, a catalytically active PLA2 from the same venom, as well as of the cytolytic peptide melittin from bee venom, also increased in cholesterol‐depleted cells. Although physical and functional changes resulting from variations in membrane cholesterol are complex, these findings suggest that membrane fluidity could be a relevant parameter to explain the observed modulation of the cytolytic mechanism of myotoxin II, possibly influencing bilayer penetration. In concordance, the cytolytic effect of myotoxin II decreased in direct proportion to lower temperature, a physical factor that affects membrane fluidity. In conclusion, physicochemical properties that depend on membrane cholesterol content significantly influence the cytolytic mechanism of myotoxin II, reinforcing the concept that the primary site of action of Lys49 PLA2 myotoxins is the plasma membrane. Copyright © 2011 John Wiley & Sons, Ltd.
Effect of pH on Hydride Transfer by Escherichia coli Dihydrofolate Reductase
Authors: Loveridge E. Joel , Allemann Rudolf K.
Published: April 2011

The kinetic isotope effect (KIE) on hydride transfer in the reaction catalysed by dihydrofolate reductase from Escherichia coli (EcDHFR) is known to be temperature dependent at pH 7, but essentially independent of temperature at elevated pH. Here, we show that the transition from the temperature‐dependent regime to the temperature‐independent regime occurs sharply between pH 7.5 and 8. The activation energy for hydride transfer is independent of pH. The mechanism leading to the change in behaviour of the KIEs is not clear, but probably involves a conformational change in the enzyme brought about by deprotonation of a key residue (or residues) at high pH. The KIE on hydride transfer at low pH suggests that the rate constant for the reaction is not limited by a conformational change to the enzyme under these conditions. The effect of pH on the temperature dependence of the rate constants and KIEs for hydride transfer catalysed by EcDHFR suggests that enzyme motions and conformational changes do not directly influence the chemistry, but that the reaction conditions affect the conformational ensemble of the enzyme prior to reaction and control the reaction though this route.
Mechanism‐Based Inhibition of Quinone Reductase 2 (NQO2): Selectivity for NQO2 over NQO1 and Structural Basis for Flavoprotein Inhibition
Authors: Dufour Marine , Yan Chao , Siegel David , Colucci Marie A. , Jenner Matthew , Oldham Neil J. , Gomez Joe , Reigan Philip , Li Yazhuo , De Matteis Cristina I. , Ross David , Moody Christopher J.
Published: April 2011

A role for the flavoprotein NRH:quinone oxidoreductase 2 (NQO2, QR2) in human diseases such as malaria, leukemia and neurodegeneration has been proposed. In order to explore the potential of NQO2 as a therapeutic target, we have developed potent and selective mechanism‐based inhibitors centered on the indolequinone pharmacophore. The compounds show remarkable selectivity for NQO2 over the closely related flavoprotein NQO1, with small structural changes defining selectivity. Biochemical studies confirmed the mechanism‐based inhibition, whereas X‐ray crystallography and mass spectrometry revealed the nature of the inhibitor interaction with the protein. These indolequinones represent the first mechanism‐based inhibitors of NQO2, and their novel mode of action involving alkylation of the flavin cofactor, provides significant advantages over existing competitive inhibitors in terms of potency and irreversibility, and will open new opportunities to define the role of NQO2 in disease.
Diverse Clinical Compounds Alter the Quaternary Structure and Inhibit the Activity of an Essential Enzyme
Authors: Lawrence Sarah H. , Selwood Trevor , Jaffe Eileen K.
Published: April 2011

An in vitro evaluation of the Johns Hopkins Clinical Compound Library demonstrates that certain drugs can alter the quaternary structure of an essential human protein. Human porphobilinogen synthase (HsPBGS) is an essential enzyme involved in heme biosynthesis; it exists as an equilibrium of high‐activity octamers, low‐activity hexamers, and alternate dimer configurations that dictate the stoichiometry and architecture of further assembly. Decreased HsPBGS activity is implicated in toxicities associated with lead poisoning and 5‐aminolevulinate dehydratase (ALAD) porphyria, the latter of which involves hexamer‐favoring HsPBGS variants. A medium‐throughput native PAGE mobility‐shift screen coupled with evaluation of hits as HsPBGS inhibitors revealed 12 drugs that stabilize the HsPBGS hexamer and inhibit HsPBGS activity in vitro. A detailed characterization of these effects is presented. Drug inhibition of HsPBGS in vivo by inducing hexamer formation would constitute an unprecedented mechanism for side effects. We suggest that small‐molecule perturbation of quaternary structure equilibria be considered as a general mechanism for drug action and side effects.
Design and Stereoselective Synthesis of Retinoids with Ferrocene or N‐Butylcarbazole Pharmacophores that Induce Post‐Differentiation Apoptosis in Acute Promyelocytic Leukemia Cells
Authors: Ivanova Diana , Gronemeyer Hinrich , de Lera Angel R.
Published: April 2011

New ferrocene and N‐alkylcarbazole retinoids were designed and synthesized stereoselectively in good yields. A number of these synthesized ligands, in particular 2, 3, and 11, were found to exhibit a high RARα activation potential and to effectively induce post‐differentiation apoptosis in NB4 acute promyelocytic leukemia (APL) cells. Increasing the length of the side chain attached to the heterocycle of the carbazole arotinoids creates new opportunities for altered compound catabolism and for fine‐tuning of the apoptosis‐inducing potential of the ligand. In the carbazole series of new retinoids, maximal activity was established for N‐butylcarbazole analogue 11 in all assays (i.e., RARα activation, differentiation induction, and apoptosis induction). Study of the mechanism of apoptosis revealed an activation of initiator caspases‐8 and ‐9, followed by efficient cleavage of effector caspase‐3 on day 6 of treatment. Subsequent induction of a caspase cascade in NB4 cells triggered ultimate leukemic cell death. The selected ligands 2, 3, and 11 may provide alternate options for the treatment of APL in cases of life‐threatening ATRA syndrome, resistance, and high toxicity to conventionally used retinoids.
From critical values to critical diagnoses
Authors: Chapman Christopher N. , Otis Christopher N.
Published: April 2011

The concept of critical values in the medical laboratory found its roots in clinical pathology nearly 40 years ago. The goal of this review was to trace the evolution of the critical value concept from clinical into anatomic pathology with specific emphasis on cytopathology. Difficulties in the meaningful application of the critical value concept in the practice of cytopathology are reviewed along with ambiguities that have yet to be fully resolved. Suggestions that may enhance the operational success of critical value policies in cytopathology and a central role for the cytotechnologist are presented. Cooperation between key pathology and clinical organizations is essential for improvement in the critical value process. Cancer (Cancer Cytopathol) 2011;. © 2011 American Cancer Society.
Industrial Photoinitiators: A Technical Guide. by W. Arthur Green.
Authors: Liska Robert
Published: April 2011

CRC Press 2010, 302 pp., softcover, $ 80.96.—ISBN 978‐1‐4398274‐5‐1
Electrocatalysis of Direct Methanol Fuel Cells: From Fundamentals to Applications. Edited by Hansan Liu and Jiujun Zhang
Authors: Kunze Julia , Paschos Odysseas
Published: April 2011

Wiley‐VCH 2009, XXII+584 pp., hardcover, € 139.00—ISBN 978‐527‐32377‐7
The Reaction Microscope: Imaging and Pulse Shaping Control in Photodynamics
Authors: Vredenborg Arno , Lehmann C. Stefan , Irimia Daniel , Roeterdink Wim G. , Janssen Maurice H. M.
Published: April 2011

Herein, we review the current capabilities and potential of advanced single‐particle imaging techniques to study photodynamics in isolated molecules. These reaction microscopes are able to measure the full three‐dimensional energy and angular distribution of (correlated) particles such as electrons and molecular fragments ejected after photoexcitation of molecules. In particular, we discuss the performance and capabilities of a novel photoelectron–photoion coincidence imaging spectrometer constructed at LaserLaB Amsterdam. This microscope was developed for the study of nonadiabatic effects in ultrafast time‐resolved experiments. It is specifically targeted at optimal control studies of photodynamics to foster and advance our understanding of mechanisms in optimal control with shaped ultrafast laser pulses. We review a few recent experimental results illustrating the wealth of detailed information that can be obtained in such imaging experiments about the interplay between (shaped) laser fields, molecular dynamics, ionization processes and competing multichannel pathways. Furthermore, the recently developed photoelectron–circular‐dichroism imaging technique to detect enantiomers and to study chirality effects will be discussed, as a further illustration of the potential of modern reaction microscopes in stereochemistry.
Regulative patterning in limb bud transplants is induced by distalizing activity of apical ectodermal ridge signals on host limb cells
Authors: Roselló‐Díez Alberto , Torres Miguel
Published: April 2011

We have used the chick limb as a model to gain insight into the longstanding question of regulative vs. mosaic development. To test the influence of signals on limb proximodistal development, distal limb bud tips of several stages were grafted to regions of the embryo known to provide different signaling environments. Of interest, thin grafts (100‐micron thick) formed elements more proximal in character when grafted to the proximal limb region than when grafted to other regions. The extra elements were derived from host tissue, presumably distalized and recruited by the graft's apical ectodermal ridge signals. The results of classic and recent experiments have been reinterpreted in light of our conclusions. Developmental Dynamics 240:1203–1211, 2011. © 2011 Wiley‐Liss, Inc.
Cochrane Review: One dose per day compared to multiple doses per day of gentamicin for treatment of suspected or proven sepsis in neonates
Authors: Rao Shripada C , Srinivasjois Ravisha , Hagan Ronald , Ahmed Mohmed
Published: April 2011

Background

Animal studies and trials in older children and adults suggest that a one dose per day regimen of gentamicin is superior to a multiple doses per day regimen.

Objectives

To compare the efficacy and safety of one dose per day compared to multiple doses per day of gentamicin in suspected or proven sepsis in neonates.

Search strategy

Eligible studies were identified by searching MEDLINE (February 2010), EMBASE 1980 to 2009, Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2010) and CINAHL (December 1982 to October 2009). Abstracts of the Society for Pediatric Research were searched from 1980 to 2009 inclusive.

Selection criteria

All randomised or quasi randomised controlled trials comparing one dose per day ( 'once a day') compared to multiple doses per day ( 'multiple doses a day') of gentamicin to newborn infants < 28 days of life.

Data collection and analysis

Data collection and analysis was performed according to the standards of the Cochrane Neonatal Review Group.

Main results

Eighteen studies were excluded and eleven studies (N = 574) included.

All infants in both 'once a day' as well as 'multiple doses a day' regimen showed adequate clearance of sepsis [typical RD 0.00 (95% CI ‐ 0.19, 0.19); 3 trials; N = 36]. For the other primary outcome measures relating to gentamicin pharmacokinetics 'once a day' dosing of gentamicin was superior. 'Once a day' gentamicin regimen was associated with less failures to attain peak level of at least 5 µg/ml [Typical RR 0.22 (95% CI 0.11, 0.47); 9 trials; N = 422] and less failures to achieve trough levels of ≤ 2 µg/ml [Typical RR 0.38 (95% CI 0.27, 0.55); 11 trials N = 503] compared to 'multiple doses a day' regimen.

Ototoxicity and nephrotoxicity were not noted with either of the treatment regimens.

Authors' conclusions

There is insufficient evidence from the currently available RCTs to conclude whether 'once a day' or 'multiple doses a day' regimen of gentamicin is superior in treating proven neonatal sepsis. However data suggests that pharmacokinetic properties of 'once a day' gentamicin regimen are superior to 'multiple doses a day' regimen in that it achieves higher peak levels while avoiding toxic trough levels. There is no change in nephrotoxicity or auditory toxicity. Based on this assessment of pharmacokinetics, 'once a day regimen' may be superior in treating neonatal sepsis in neonates greater than 32 weeks gestation.

Plain Language Summary

Gentamicin dosage in neonates

Gentamicin is a commonly used antibiotic that is very effective in treating bacterial infections in neonates. However, gentamicin may cause adverse effects on auditory and renal functions that may be related to the dosage, interval and in turn the drug levels in plasma. Safer and potentially more effective levels of the drug were maintained using a one dose per day treatment schedule.
Summary of ‘One dose per day compared to multiple doses per day of gentamicin for treatment of suspected or proven sepsis in neonates’
Authors: Canadian Editorial Office Evidence‐Based Child Health
Published: April 2011

This is a summary of a Cochrane review, published in this issue of EBCH, first published as: Rao SC, Srinivasjois R, Hagan R, Ahmed M. One dose per day compared to multiple doses per day of gentamicin for treatment of suspected or proven sepsis in neonates. Cochrane Database of Systematic Reviews 2006, Issue 1. Art.No.: CD005091. DOI: 10.1002/14 651 858.CD005091.pub2. Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. The Cochrane Collaboration
WHO Calls for Targeted Research on the Pharmacological Treatment of Persisting Pain in Children with Medical Illnesses
Authors: Milani Barbara , Magrini Nicola , Gray Andy , Wiffen Phil , Scholten Willem
Published: April 2011

The WHO has undertaken an update of the 1998 WHO Cancer Pain Relief and Palliative Care in Children Guidelines, in extending the scope to persisting pain associated with other medical conditions. The new WHO Guidelines for Pharmacological Treatment of Persisting Pain in Children with Medical Illnesses, using the GRADE approach for evidence synthesis and grading of recommendations, are expected to help reduce the enormous treatment gap for pain in children. The WHO aims to update these guidelines within the next five years. Given the paucity of studies in the paediatric population with persisting pain, a meaningful revision of these guidelines will need the international scientific community to invest in research on the topics that were identified as evidence gaps during the development process For this reason, the WHO calls for a collaborative effort to cover the identified priority research areas and related systematic reviews of evidence. Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. The Cochrane Collaboration
Atrazine does not affect algal biomass or snail populations in microcosm communities at environmentally relevant concentrations
Authors: Baxter Leilan R , Moore Dana L , Sibley Paul K , Solomon Keith R , Hanson Mark L
Published: April 2011

The herbicide atrazine is a photosynthetic inhibitor used around the world in agricultural applications. Contamination of surface waters adjacent to treated areas can directly reduce growth of nontarget aquatic autotrophs, but the severity of impacts is highly dependent on species sensitivity and exposure concentration. Secondary effects resulting from macrophyte or phytoplankton decline may include an expansion of the more tolerant periphyton community. Recently, this shift in the autotrophic community has been proposed as a mechanism for increased rates of parasite infections in amphibians via augmented populations of aquatic snails which act as intermediate hosts to larval trematodes. To further clarify this relationship, an outdoor microcosm study was conducted to examine the effects of atrazine on primary production and snail populations over a range of environmentally relevant concentrations. In July 2009, 15 experimental ponds were treated to achieve initial concentrations of 0, 1, 10, 30, and 100 µg/L atrazine. Over a period of 73 d, measures were taken of macrophyte, phytoplankton, and periphyton biomass, growth, and fecundity of caged snails (Physella spp. and Stagnicola elodes) and free-living snails (Physella spp.). Except for declines in macrophyte biomass at the highest treatment level, no consistent relationships were found between atrazine concentration and any measured parameter. Comparison of these results with previous findings highlights the variability of responses to atrazine exposure between similarly constructed freshwater communities, even at concentrations up to 20 times higher than sustained environmental levels. Environ. Toxicol. Chem. 2011; 30:1689–1696. © 2011 SETAC
Selected pesticides adsorption and desorption in substrates from artificial wetland and forest buffer
Authors: Passeport Elodie , Benoit Pierre , Bergheaud Valérie , Coquet Yves , Tournebize Julien
Published: April 2011

Buffer zones such as artificial wetlands and forest buffers may help decrease non–point-source pesticide pollution from agricultural catchments. The present study focuses on understanding the role of the substrates mainly found in such buffer zones for pesticide adsorption and desorption. Radiolabeled [14C]isoproturon, [14C]metazachlor, and [14C]epoxiconazole were used to measure adsorption and desorption isotherms on wetland sediments and plants and forest soil and litter from two sites in France. Wetland sediments and forest soil exhibited the most important potential for pesticide adsorption. Wetland plants and forest litter also showed high adsorption coefficients and were associated with highly hysteretic desorption, particularly for the moderately mobile isoproturon and metazachlor. Adsorption of the highly hydrophobic epoxiconazole was strong and associated with weak desorption from all substrates. Calculated sorption coefficients were larger than those classically measured on soils. Isoproturon, metazachlor, and epoxiconazole KOC sorption coefficients ranged from 84 to 372, 131 to 255, and 1,356 to 3,939 L/kg, respectively. Therefore, specifically collecting buffer zone substrate sorption data is needed for modeling purposes. Results showed that forests and wetlands present potential for pesticide retention. This may be enhanced by planting vegetation and leaving dead vegetal material in buffer zone design. Environ. Toxicol. Chem. 2011; 30:1669–1676. © 2011 SETAC
A note on the performance of regime switching hedge strategy
Authors: Lien Donald
Published: April 2011

We characterize conditions under which the regime switching (RS) hedge strategy will perform better than the ordinary least squares (OLS) hedge strategy. The result can be extended to the case where the GARCH effects prevail. Specifically, these conditions would allow the RS‐GARCH hedge strategy to dominate both OLS and GARCH hedge strategies. © 2011 Wiley Periodicals, Inc. Jrl Fut Mark
Head direction cells in the postsubiculum do not show replay of prior waking sequences during sleep
Authors: Brandon Mark P. , Bogaard Andrew R. , Andrews Chris M. , Hasselmo Michael E.
Published: April 2011

During slow‐wave sleep (SWS) and rapid eye movement (REM) sleep, hippocampal place cells in the rat show replay of sequences previously observed during waking. We tested the hypothesis from computational modeling that the temporal structure of REM sleep replay could arise from an interplay of place cells with head direction cells in the postsubiculum. Physiological single‐unit recording was performed simultaneously from five or more head direction or place by head direction cells in the postsubiculum during running on a circular track allowing sampling of a full range of head directions, and during sleep periods before and after running on the circular track. Data analysis compared the spiking activity during individual REM periods with waking as in previous analysis procedures for REM sleep. We also used a new procedure comparing groups of similar runs during waking with REM sleep periods. There was no consistent evidence for a statistically significant correlation of the temporal structure of spiking during REM sleep with spiking during waking running periods. Thus, the spiking activity of head direction cells during REM sleep does not show replay of head direction cell activity occurring during a previous waking period of running on the task. In addition, we compared the spiking of postsubiculum neurons during hippocampal sharp wave ripple events. We show that head direction cells are not activated during sharp wave ripples, whereas neurons responsive to place in the postsubiculum show reliable spiking at ripple events. © 2011 Wiley Periodicals, Inc.
Folate‐conjugated amphiphilic star‐shaped block copolymers as targeted nanocarriers
Authors: Zhu Jundong , Zhou Zhichao , Yang Cuihong , Kong Deling , Wan Ying , Wang Zheng
Published: April 2011

Folate (FA)‐conjugated star‐shaped copolymer was prepared as a targeted carrier for anticancer drug delivery by ring‐opening polymerization of L‐lactide using pentaerythritol (PTL) as an initiator, followed by conjugation with methoxy poly(ethylene glycol) (MPEG) and FA‐poly(ethylene glycol) (FA‐PEG). The resulting amphiphilic star‐shaped copolymer was shaped into drug‐loaded micelles, and the achieved micelles had an average size of around 146 nm in diameter. It was found that the sustained release time of model drug (indomethacin, IMC) from some selected micelles could reach around 40 h. In comparison with linear poly(L‐lactic acid)‐block‐methoxy poly(ethylene glycol) copolymer (PLA‐MPEG), the stability of the star‐shaped pentaerythritol‐co‐poly(L‐lactic acid)‐block‐[methoxy poly(ethylene glycol) and FA‐poly(ethylene glycol)] (PTL‐PLA‐MPEG/PEG‐FA) micelle was significantly improved because of the lower critical micelle concentration (CMC). The specificity of PTL‐PLA‐MPEG/PEG‐FA targeting cancer cells was demonstrated by intracellular uptake of PTL‐PLA‐MPEG/PEG‐FA and PTL‐PLA‐MPEG using HeLa human cervical cancer cells. After 2 h in vitro incubation, a significant intracellular uptake for PTL‐PLA‐MPEG/PEG‐FA over PTL‐PLA‐MPEG was observed by using inverted fluorescence microscope and flow cytometry. These results suggested that PTL‐PLA‐MPEG/PEG‐FA polymeric micelle could be a potentially useful carrier for delivering selected drugs to FA‐receptor positive cancer cells. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2011.
Biological performance of a novel biodegradable polyamidoamine hydrogel as guide for peripheral nerve regeneration
Authors: Magnaghi Valerio , Conte Vincenzo , Procacci Patrizia , Pivato Giorgio , Cortese Paolo , Cavalli Erika , Pajardi Giorgio , Ranucci Elisabetta , Fenili Fabio , Manfredi Amedea , Ferruti Paolo
Published: April 2011

Polyamidoamines (PAAs) are a well‐known family of synthetic biocompatible and biodegradable polymers, which can be prepared as soft hydrogels characterized by low interfacial tension and tunable elasticity. For the first time we report here on the in vivo performance of a PAA hydrogel implant as scaffold for tissue engineering. In particular, an amphoteric agmatine‐deriving PAA hydrogel shaped as small tubing was obtained by radical polymerization of a soluble functional oligomeric precursor and used as conduit for nerve regeneration in a rat sciatic nerve cut model. The animals were analyzed at 30, 90, and 180 days post‐surgery. PAA tubing proved to facilitate nerve regeneration. Good surgical outcomes were achieved with no signs of inflammation or neuroma. Moreover, nerve regeneration was morphologically sound and the quality of functional recovery satisfactory. In conclusion, PAA hydrogel scaffolds may represent a novel and promising material for peripheral nerve regeneration. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2011.
Cancellous bone formation response to simulated resistance training during disuse is blunted by concurrent alendronate treatment
Authors: Swift Joshua M , Swift Sibyl N , Nilsson Mats I , Hogan Harry A , Bouse Scott D , Bloomfield Susan A
Published: April 2011

The purpose of this study was to assess the effectiveness of simulated resistance training (SRT) exercise combined with alendronate (ALEN) in mitigating or preventing disuse-associated losses in cancellous bone microarchitecture and formation. Sixty male Sprague-Dawley rats (6 months old) were randomly assigned to either cage control (CC), hind limb unloading (HU), HU plus either ALEN (HU + ALEN), SRT (HU + SRT), or a combination of ALEN and SRT (HU + SRT/ALEN) for 28 days. HU + SRT and HU + SRT/ALEN rats were anesthetized and subjected to muscle contractions once every 3 days during HU (four sets of five repetitions, 1000 ms isometric + 1000 ms eccentric). Additionally, HU + ALEN and HU + SRT/ALEN rats received 10 µg/kg of body weight of ALEN three times per week. HU reduced cancellous bone-formation rate (BFR) by 80%, with no effect of ALEN treatment (−85% versus CC). SRT during HU significantly increased cancellous BFR by 123% versus CC, whereas HU + SRT/ALEN inhibited the anabolic effect of SRT (−70% versus HU + SRT). SRT increased bone volume and trabecular thickness by 19% and 9%, respectively, compared with CC. Additionally, osteoid surface (OS/BS) was significantly greater in HU + SRT rats versus CC (+32%). Adding ALEN to SRT during HU reduced Oc.S/BS (−75%), Ob.S/BS (−72%), OS/BS (−61%), and serum TRACP5b (−36%) versus CC. SRT and ALEN each independently suppressed a nearly twofold increase in adipocyte number evidenced with HU and inhibited increases in osteocyte apoptosis. These results demonstrate the anabolic effect of a low volume of high-intensity muscle contractions during disuse and suggest that both bone resorption and bone formation are suppressed when SRT is combined with bisphosphonate treatment. © 2011 American Society for Bone and Mineral Research
Altered bone composition in children with vertebral fracture
Authors: Tamminen Inari S , Mäyränpää Mervi K , Turunen Mikael J , Isaksson Hanna , Mäkitie Outi , Jurvelin Jukka S , Kröger Heikki
Published: April 2011

Primary osteoporosis in children often leads to vertebral fractures, but it remains unknown whether these fractures associate with changes in bone composition. This study aimed to determine the differences in bone composition in fracture-prone children with and without vertebral fractures, as assessed by Fourier transform infrared spectroscopic imaging (FTIRI) and bone histomorphometry. Iliac crest bone biopsies (n = 24) were obtained from children who were suspected of primary osteoporosis based on evidence from the fracture history and/or low bone mineral density (BMD) by dual-energy X-ray absorptiometry. Vertebral morphology was determined by radiography. Bone biopsies were analyzed using histomorphometry and FTIRI. Phosphate-to-amide I, carbonate-to-phosphate, carbonate-to-amide I, and cross-link ratio (collagen maturity) were calculated. Children with (n = 14) and without (n = 10) vertebral fracture were compared. Low cancellous bone volume (BV/TV) was detected by histomorphometry in 36% of the children with vertebral fracture, and bone turnover rate was abnormal in 64% of them. Children with vertebral fractures had lower carbonate-to-phosphate ratios (p < .05) and higher collagen maturity (p < .05) than children without vertebral fracture. The children with low BV/TV in biopsy showed lower carbonate-to-amide I ratios (p < .05) than the children with normal bone volume. This study showed changes in bone composition among fracture-prone children who had sustained a vertebral fracture. The observed changes in bone composition in these children may contribute to their greater propensity to sustain vertebral fractures. © 2011 American Society for Bone and Mineral Research
Current financial reporting issues
Authors: Ciesielski Jack T. , Weirich Thomas R.
Published: April 2011

The main theme of the latest Securities and Exchange Commission (SEC) and Public Company Accounting Oversights Board (PCAOB) Developments Conference was restoring public trust and investor confidence in the capital markets. Various speakers also noted the need for more transparency and improved disclosures by companies. Although there was not much discussion of strictly auditing issues, the conference provided a number of “heads‐up” warnings for both auditors and preparers. What signals are the SEC and PCAOB sending right now? What's on regulators' minds? The authors report in detail about all of it. © 2011 Wiley Periodicals, Inc.
Local staging of rectal cancer: A review of imaging
Authors: Beets‐Tan Regina G.H. , Beets Geerard L.
Published: April 2011

During the past decades the management of patients with rectal cancer has substantially changed, with a significant reduction in local recurrence rates following the introduction of better imaging, better surgery, and more efficient neoadjuvant therapy. This review discusses the clinically relevant information radiologists should know on staging of rectal cancer patients. The crucial role of the radiologist in patient management is explained. Furthermore, the evidence for the use of magnetic resonance imaging (MRI) in staging and restaging of rectal cancer patients as well as the main features that need to be evaluated when interpreting rectal cancer MRI are given. New diagnostic challenges as a result of new treatment options are also discussed. J. Magn. Reson. Imaging 2011;33:1012–1019. © 2011 Wiley‐Liss, Inc.
Adaptive noise cancellation to suppress electrocardiography artifacts during real‐time interventional MRI
Authors: Wu Vincent , Barbash Israel M. , Ratnayaka Kanishka , Saikus Christina E. , Sonmez Merdim , Kocaturk Ozgur , Lederman Robert J. , Faranesh Anthony Z.
Published: April 2011

Purpose:

To develop a system for artifact suppression in electrocardiogram (ECG) recordings obtained during interventional real‐time magnetic resonance imaging (MRI).

Materials and Methods:

We characterized ECG artifacts due to radiofrequency pulses and gradient switching during MRI in terms of frequency content. A combination of analog filters and digital least mean squares adaptive filters were used to filter the ECG during in vivo experiments and the results were compared with those obtained with simple low‐pass filtering. The system performance was evaluated in terms of artifact suppression and ability to identify arrhythmias during real‐time MRI.

Results:

Analog filters were able to suppress artifacts from high‐frequency radiofrequency pulses and gradient switching. The remaining pulse artifacts caused by intermittent preparation sequences or spoiler gradients required adaptive filtering because their bandwidth overlapped with that of the ECG. Using analog and adaptive filtering, a mean improvement of 38 dB (n = 11, peak QRS signal to pulse artifact noise) was achieved. This filtering system was successful in removing pulse artifacts that obscured arrhythmias such as premature ventricular complexes and complete atrioventricular block.

Conclusion:

We have developed an online ECG monitoring system employing digital adaptive filters that enables the identification of cardiac arrhythmias during real‐time MRI‐guided interventions. J. Magn. Reson. Imaging 2011;33:1184–1193. © 2011 Wiley‐Liss, Inc.
Right ventricular outflow tract obstruction as a confounding factor in the assessment of the impact of pulmonary regurgitation on the right ventricular size and function in patients after repair of tetralogy of fallot
Authors: Śpiewak Mateusz , Biernacka Elżbieta K. , Małek Łukasz A. , Petryka Joanna , Kowalski Mirosław , Miłosz Barbara , Żabicka Magdalena , Miśko Jolanta , Rużyłło Witold
Published: April 2011

Purpose:

To compare right ventricular (RV) size and function between patients with combined pulmonary regurgitation (PR) plus RV outflow tract (RVOT) obstruction (RVOTO) and patients with isolated PR.

Materials and Methods:

Consecutive individuals with significant PR (PR fraction ≥20%) after tetralogy of Fallot (TOF) repair who underwent cardiovascular magnetic resonance (CMR) were included. Patients with additional hemodynamic abnormalities (residual ventricular septal defect, extracardiac shunt, and/or more than mild regurgitation at a valve other than the pulmonary valve) were excluded. Significant RVOTO was defined as peak gradient across RVOT ≥30 mmHg.

Results:

Significant differences between patients with combined PR+RVOTO (n = 9) and isolated PR (n = 33) were observed in RV end‐diastolic volume (138.6 ± 25.1 vs. 167.0 ± 34.6 mL/m2, P = 0.02, respectively), RV end‐systolic volume (65.0 ± 9.6 vs. 92.7 ± 26.2 mL/m2, P = 0.003), and RV ejection fraction (RVEF) (52.8 ± 3.7 vs. 45.0 ± 6.4%, P = 0.001). Both PR and peak RVOT gradient were independent predictors of RV size.

Conclusion:

Patients with combined PR+RVOTO had smaller RV volumes and higher RVEF when compared with patients with isolated PR. The confounding effect of RVOTO on RV size and function needs to be considered in CMR studies evaluating patients after TOF repair. J. Magn. Reson. Imaging 2011;33:1040–1046. © 2011 Wiley‐Liss, Inc.
New MR imaging methods for metallic implants in the knee: Artifact correction and clinical impact
Authors: Chen Christina A. , Chen Weitian , Goodman Stuart B. , Hargreaves Brian A. , Koch Kevin M. , Lu Wenmaio , Brau Anja C. , Draper Christine E. , Delp Scott L. , Gold Garry E.
Published: April 2011

Purpose:

To evaluate two magnetic resonance imaging (MRI) techniques, slice encoding for metal artifact correction (SEMAC) and multiacquisition variable‐resonance image combination (MAVRIC), for their ability to correct for artifacts in postoperative knees with metal.

Materials and Methods:

A total of 25 knees were imaged in this study. Fourteen total knee replacements (TKRs) in volunteers were scanned with SEMAC, MAVRIC, and 2D fast spin‐echo (FSE) to measure artifact extent and implant rotation. The ability of the sequences to measure implant rotation and dimensions was compared in a TKR knee model. Eleven patients with a variety of metallic hardware were imaged with SEMAC and FSE to compare artifact extent and subsequent patient management was recorded.

Results:

SEMAC and MAVRIC significantly reduced artifact extent compared to FSE (P < 0.0001) and were similar to each other (P = 0.58), allowing accurate measurement of implant dimensions and rotation. The TKRs were properly aligned in the volunteers. Clinical imaging with SEMAC in symptomatic knees significantly reduced artifact (P < 0.05) and showed findings that were on the majority confirmed by subsequent noninvasive or invasive patient studies.

Conclusion:

SEMAC and MAVRIC correct for metal artifact, noninvasively providing high‐resolution images with superb bone and soft tissue contrast. J. Magn. Reson. Imaging 2011;33:1121–1127. © 2011 Wiley‐Liss, Inc.
Longitudinal 3.0T MRI analysis of changes in lymph node volume and apparent diffusion coefficient in an experimental animal model of metastatic and hyperplastic lymph nodes
Authors: Klerkx Wenche M. , Geldof Albert A. , Heintz A. Peter , van Diest Paul J. , Visser Fredy , Mali Willem P. , Veldhuis Wouter B.
Published: April 2011

Purpose:

To perform a longitudinal analysis of changes in lymph node volume and apparent diffusion coefficient (ADC) in healthy, metastatic, and hyperplastic lymph nodes.

Materials and Methods:

Three groups of four female Copenhagen rats were studied. Metastasis was induced by injecting cells with a high metastatic potential in their left hind footpad. Reactive nodes were induced by injecting Complete Freund Adjuvant (CFA). Imaging was performed at baseline and at 2, 5, 8, 11, and 14 days after tumor cell injection. Finally, lymph nodes were examined histopathologically.

Results:

The model was highly efficient in inducing lymphadenopathy: subcutaneous cell or CFA inoculation resulted in ipsilateral metastatic or reactive popliteal lymph nodes in all rats. Metastatic nodal volumes increased exponentially from 5–7 mm3 at baseline to 25 mm3 at day 14, while the control node remained 5 mm3. The hyperplastic nodes showed a rapid volume increase reaching a plateau at day 6. The ADC of metastatic nodes significantly decreased (range 13%–32%), but this decrease was also seen in reactive nodes.

Conclusion:

Metastatic and hyperplastic lymph nodes differed in terms of enlargement patterns and ADC changes. Enlarged reactive or malignant nodes could not be differentiated based on their ADC values. J. Magn. Reson. Imaging 2011;33:1151–1159. © 2011 Wiley‐Liss, Inc.
Local specific absorption rate in high‐pass birdcage and transverse electromagnetic body coils for multiple human body models in clinical landmark positions at 3T
Authors: Yeo Desmond T.B. , Wang Zhangwei , Loew Wolfgang , Vogel Mika W. , Hancu Ileana
Published: April 2011

Purpose:

To use electromagnetic (EM) simulations to study the effects of body type, landmark position, and radiofrequency (RF) body coil type on peak local specific absorption rate (SAR) in 3T magnetic resonance imaging (MRI).

Materials and Methods:

Numerically computed peak local SAR for four human body models (HBMs) in three landmark positions (head, heart, pelvic) were compared for a high‐pass birdcage and a transverse electromagnetic 3T body coil. Local SAR values were normalized to the IEC whole‐body average SAR limit of 2.0 W/kg for normal scan mode.

Results:

Local SAR distributions were highly variable. Consistent with previous reports, the peak local SAR values generally occurred in the neck‐shoulder area, near rungs, or between tissues of greatly differing electrical properties. The HBM type significantly influenced the peak local SAR, with stockier HBMs, extending extremities towards rungs, displaying the highest SAR. There was also a trend for higher peak SAR in the head‐centric and heart‐centric positions. The impact of the coil types studied was not statistically significant.

Conclusion:

The large variability in peak local SAR indicates the need to include more than one HBM or landmark position when evaluating safety of body coils. It is recommended that an HBM with arms near the rungs be included to create physically realizable high‐SAR scenarios. J. Magn. Reson. Imaging 2011;33:1209–1217. © 2011 Wiley‐Liss, Inc.
Comparison of measurements of the transverse diameter and perimeter of the fetal thymus obtained by magnetic resonance and ultrasound imaging
Authors: De Leon‐Luis Juan , Ruiz Yolanda , Gamez Francisco , Pintado Pilar , Oyelese Yinka , Pereda Ana , Ortiz‐Quintana Luis , Santolaya‐Forgas Joaquin
Published: April 2011

Purpose:

To compare measurements of the fetal thymus obtained by magnetic resonance imaging (MRI) and ultrasound (US).

Materials and Methods:

Written informed consent was obtained from the patients that participated in this Institutional Review Board‐approved observational study. The study population consisted of 17 pregnant women carrying fetuses between 21 and 34 weeks of gestation with suspected abnormalities. The transverse diameter and perimeter of the thymus were measured in these fetuses at the level of an axial view of the thorax that includes the pulmonary, aorta, and superior vena cava. The degree of agreement between MRI and US measurements was determined using Lin's concordance correlation coefficient and Bland–Altman analysis.

Results:

The mean (standard deviation, SD) gestational age at the time of the prenatal evaluation was 28.4 weeks (3.6). The thymus was measured by MRI and US in all cases. Comparison of the measurements from these two imaging modalities demonstrated a relatively good reproducibility with no evidence of systematic error.

Conclusion:

MRI and US measurements of the fetal thymus during the second half of pregnancy are comparable. This finding suggests that MRI can become a useful adjuvant to US for assessment of the fetal thymus. J. Magn. Reson. Imaging 2011;33:1100–1105. © 2011 Wiley‐Liss, Inc.