bluuebunny/crossref_metadata_2025 huggingface dataset:
An Electron‐Density‐Based Study on the Ionic Reactivity of 1,3‐Azoles
Authors: Otero Nicolás , Estévez Laura , Mandado Marcos , Mosquera Ricardo A.
Published: March 2012

Basic processes for the ionic chemistry of 1,3‐azoles (protonation, nitration, hydride addition, and deprotonation) have been studied by analyzing B3LYP/6‐311++G(2d,2p) 6d electron densities using the Quantum Theory of Atoms in Molecules (QTAIM) and delocalization indices in the gas phase and in aqueous solution modeled with the Polarizable Continuum Model (PCM) method. The most stable protonation site is N3 in all cases, and this takes place without a significant change in electron delocalization, whereas C5 is the preferred site for electrophilic substitution. Activating and deactivating effects on the carbon atoms of the imidazole ring were tested by analyzing the variation of atomic properties introduced by amino and nitro substituents, respectively. The largest activation was observed for C5 in 4‐aminoimidazole. C2 is the most favored site for hydridation in all 1,3‐azoles, which always results in loss of ring planarity and reduced electron delocalization in the ring. PCM calculations allow the experimentally observed preferred deprotonation C‐site in water for these compounds to be modeled and reproduced. In all anions, QTAIM charges do not keep in line with the resonance forms; whereas QTAIM describes deprotonated carbon atoms as positive or nearly neutral in the gas phase, they should display negative charge according to the resonance model.
Androgen pathway stimulates MicroRNA-216a transcription to suppress the tumor suppressor in lung cancer-1 gene in early hepatocarcinogenesis
Authors: Chen Po-Jen , Yeh Shiou-Hwei , Liu Wan-Hsin , Lin Chen-Ching , Huang Hsuan-Cheng , Chen Chi-Ling , Chen Ding-Shinn , Chen Pei-Jer
Published: March 2012

Deregulation of microRNAs (miRNAs) is common in advanced human hepatocellular carcinoma (HCC); however, the ones involved in early carcinogenesis have not yet been investigated. By examining the expression of 22 HCC-related miRNAs between precancerous and cancerous liver tissues, we found miR-216a and miR-224 were significantly up-regulated, starting from the precancerous stage. Furthermore, the elevation of miR-216a was mainly identified in male patients. To study this gender difference, we demonstrated that pri-miR-216a is activated transcriptionally by the androgen pathway in a ligand-dependent manner and is further enhanced by the hepatitis B virus X protein. The transcription initiation site for pri-miR-216a was delineated, and one putative androgen-responsive element site was identified within its promoter region. Mutation of this site abolished the elevation of pri-miR-216a by the androgen pathway. One target of miR-216a was shown to be the tumor suppressor in lung cancer-1 gene (

TSLC1

) messenger RNA (mRNA) through the three target sites at its 3′ untranslated region. Finally, the androgen receptor level increased in male liver tissues during hepatocarcinogenesis, starting from the precancerous stage, with a concomitant elevation of miR-216a but a decrease of TSLC1.

Conclusion:

The current study discovered the up-regulation of miRNA-216a by the androgen pathway and a subsequent suppression of TSLC1 as a new mechanism for the androgen pathway in early hepatocarcinogenesis. (HEPATOLOGY 2012)
Explaining the stress‐inducing effects of nicotine to cigarette smokers
Authors: Parrott Andrew C. , Murphy Rachel S.
Published: March 2012

Aims

To explain how nicotine dependency causes mood fluctuation and increases daily stress.

Methods

Prospective studies show that taking‐up smoking leads to higher stress and depression. Cross‐sectional studies show that adult smokers report more irritability, stress and depression than non‐smokers. Prospective studies show that smoking cessation leads to enduring mood gains. The adverse mood effects of nicotine dependency are explained by the deprivation reversal model. In between cigarettes, most smokers experience subtle abstinence symptoms, and cumulatively these can increase everyday stress. Hence, adolescents who take up smoking become more stressed, and quitting reduces stress. An explanatory leaflet to explain this model was empirically assessed with tobacco smokers.

Results

In a cohort study of 82 cigarette smokers, knowledge levels were significantly enhanced by the explanatory leaflet, and this understanding was maintained 1 week later. Hence, normal cigarette smokers can understand the adverse mood consequences of nicotine addiction. The information leaflet could prove useful for tobacco‐education packages in schools, and smoking‐cessation packages with adults.

Conclusions

The deprivation reversal model can be easily described using a simple leaflet. It explains how nicotine dependency can cause mood fluctuation, and outlines the psychological benefits of quitting. Copyright © 2012 John Wiley & Sons, Ltd.
Epigallocatechin gallate, cerebral blood flow parameters, cognitive performance and mood in healthy humans: a double‐blind, placebo‐controlled, crossover investigation
Authors: Wightman Emma L. , Haskell Crystal F. , Forster Joanne S. , Veasey Rachel C. , Kennedy David O.
Published: March 2012

Objective

The aim of the study was to assess the effects of oral ingestion of the ‘green tea’ polyphenol epigallocatechin gallate (EGCG) on cognitive performance, mood and localised cerebral blood flow (CBF) parameters in healthy human adults.

Method

In this double‐blind, placebo‐controlled, crossover study, 27 healthy adults received placebo and two doses (135 and 270 mg) of EGCG in counterbalanced order on separate days. Following a 45‐min resting absorption period, participants performed a selection of computerised cognitive tasks that activate the frontal cortex for a further 42 min. CBF and haemodynamics, as indexed by concentration changes in oxygenated and deoxygenated haemoglobin, were assessed in the frontal cortex throughout the post‐treatment period using Near‐infrared spectroscopy (NIRS).

Results

During the post‐dose task performance period, the administration of 135 mg EGCG resulted in reduced CBF in the frontal cortex, as indexed by significantly lower concentrations of both oxygenated and total haemoglobin, in comparison with placebo. Heart rate was significantly reduced from pre dose to post dose across all treatments. No significant differences were observed for the level of deoxygenated haemoglobin or on any of the cognitive performance/mood measures.

Conclusions

These results demonstrate that a single dose of orally administered EGCG can modulate CBF parameters in healthy humans but that this is not associated with changes in cognitive performance or mood. Copyright © 2012 John Wiley & Sons, Ltd.
The effects of heavy social drinking on executive function: a systematic review and meta‐analytic study of existing literature and new empirical findings
Authors: Montgomery Catharine , Fisk John E. , Murphy Philip N. , Ryland Ida , Hilton Joanne
Published: March 2012

Background

Previous investigations of executive function in alcohol dependent and in social drinkers have not always produced consistent results and have not utilised key indicators of recent theoretical models of Executive Function (EF). The present paper reports the results of two studies that seek to address these limitations.

Method

Study 1 took the form of a systematic review and meta‐analysis of studies examining EF in social drinkers. In Study 2, 41 participants completed an alcohol use inventory and were assigned to either light or heavy alcohol use via median split of average weekly dose. Participants completed measures of the fractionated executive processes of updating, shifting, inhibition and access to semantic memory.

Results

Study 1 only identified seven studies of EF in social drinkers, and the mean effect size was non‐significant. In study 2, the heavy alcohol use group performed worse on all measures of executive functioning except memory updating.

Conclusions

To our knowledge, this is the first systematic investigation of executive functioning in social drinkers. Given that the participants were non‐treatment seeking social drinking students, the EF deficit in the heavy user group is particularly worrying and could increase the likelihood of developing an alcohol use disorder. Copyright © 2012 John Wiley & Sons, Ltd.
Snow surface energy exchanges and snowmelt in a shrub‐covered bog in eastern Ontario, Canada
Authors: Knox Sara H. , Carey Sean K. , Humphreys Elyn R.
Published: March 2012

The objectives of this study were to measure and evaluate the energy balance of a snowpack in a northern peatland, with a particular emphasis on the ground heat flux (G), and to evaluate the performance of a point energy and mass balance snowmelt model (SNOBAL) in peatland ecosystems. G is typically considered a small component of the snowpack energy balance (EB) when compared with radiative and turbulent fluxes. However, in environments where the soil temperature remains above freezing throughout the winter, G may be an important energy input to the snowpack. For direct assessment of the role of G in the snow energy budget of such an environment, the EB components of the snowpack at the Mer Bleue bog, a northern peatland, were directly measured and modelled using SNOBAL during the 2009–2010 winter. When integrated over the pre‐melt period, simulated and measured G proved to be a large contributor to the EB (25%). Net radiation and G were somewhat under‐predicted by SNOBAL, whereas turbulent fluxes (especially latent heat fluxes LE) were considerably over‐predicted. G calculated by SNOBAL was found to be sensitive to the temperature gradient between the soil and the lower layer of the snowpack, whereas simulated turbulent fluxes were sensitive to the parameterization chosen to estimate roughness lengths for heat and water vapour. Copyright © 2012 John Wiley & Sons, Ltd.
Exploring uptake mechanisms of oral nanomedicines using multimodal nonlinear optical microscopy
Authors: Garrett Natalie Laura , Lalatsa Aikaterini , Uchegbu Ijeoma , Schätzlein Andreas , Moger Julian
Published: March 2012

Advances in pharmaceutical nanotechnology have yielded ever increasingly sophisticated nanoparticles for medicine delivery. When administered via oral, intravenous, ocular and transcutaneous delivery routes, these nanoparticles can elicit enhanced drug performance. In spite of this, little is known about the mechanistic processes underlying interactions between nanoparticles and tissues, or how these correlate with improved pharmaceutical effects. These mechanisms must be fully understood before nanomedicines can be rationally engineered to optimise their performance. Methods to directly visualise these particulates within tissue samples have traditionally involved imaging modalities requiring covalent labelling of fluorescent or radioisotope contrast agents. We present CARS, second harmonic generation and two photon fluorescence microscopy combined as a multi‐modal label‐free method for pinpointing polymeric nanoparticles within the stomach, intestine, gall bladder and liver. We demonstrate for the first time that orally administered chitosan nanoparticles follow a recirculation pathway from the GI tract via enterocytes, to the liver hepatocytes and intercellular spaces and then to the gall bladder, before being re‐released into the gut together with bile. (© 2012 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Production and utilization of acellular lung scaffolds in tissue engineering
Authors: Nichols Joan E. , Niles Jean A. , Cortiella Joaquin
Published: March 2012

Pulmonary disease is a worldwide public health problem that reduces the quality of life and increases the need for hospital admissions as well as the risk for premature death for those affected. For many patients, lung transplantation is the only chance for survival. Unfortunately, there is a significant shortage of lungs for transplantation and since the lung is the most likely organ to be damaged during procurement many lungs deemed unacceptable for transplantation are simply discarded. Rather than discarding these lungs they can be used to produce three‐dimensional acellular (AC) natural lung scaffolds for the generation of engineered lung tissue. AC scaffolds are lungs whose original cells have been destroyed by exposure to detergents and physical methods of removing cells and cell debris. This creates a lung scaffold from the skeleton of the lungs themselves. The scaffolds are then used to support adult, stem or progenitor cells which can be grown into functional lung tissue. Recent studies show that engineered lung tissues are capable of surviving after in vivo transplantation and support limited gas exchange. In the future engineered lung tissue has the potential to be used in clinical applications to replace lung functions lost following injury or disease. This manuscript discusses recent advances in development and use of AC scaffolds to support engineering of lung tissues. J. Cell. Biochem. 113: 2185–2192, 2012. © 2012 Wiley Periodicals, Inc.
On the moments of Cochran's Q statistic under the null hypothesis, with application to the meta‐analysis of risk difference
Authors: Kulinskaya Elena , Dollinger Michael B. , Bjørkestøl Kirsten
Published: March 2012

W. G. Cochran's Q statistic was introduced in 1937 to test for equality of means under heteroscedasticity. Today, the use of Q is widespread in tests for homogeneity of effects in meta‐analysis, but often these effects (such as risk differences and odds ratios) are not normally distributed. It is common to assume that Q follows a chi‐square distribution, but it has long been known that this asymptotic distribution for Q is not accurate for moderate sample sizes. In this paper, the effect and weight for an individual study may depend on two parameters: the effect and a nuisance parameter. We present expansions for the first two moments of Q without any normality assumptions. Our expansions will have wide applicability in testing for homogeneity in meta‐analysis. As an important example, we present a homogeneity test when the effects are the differences of risks between treatment and control arms of the several studies—a test which is substantially more accurate than that currently used. In this situation, we approximate the distribution of Q with a gamma distribution. We provide the results of simulations to verify the accuracy of our proposal and an example of a meta‐analysis of medical data. Copyright © 2012 John Wiley & Sons, Ltd.
Novel Radiation‐Induced Properties of Graphene and Related Materials
Authors: Kumar Prashant , Das Barun , Chitara Basant , Subrahmanyam K. S. , Gopalakrishnan K. , Krupanidhi S. B. , Rao C. N. R.
Published: March 2012

Interaction of graphene, graphene oxide, and related nanocarbons with radiation gives rise to many novel properties and phenomena. Irradiation of graphene oxide in solid state or in solution by sunlight, UV radiation, or excimer laser radiation reduces it to graphene with negligible oxygen functionalities on the surface. This transformation can be exploited for nanopatterning and for large scale production of reduced graphene oxide (RGO). Laser‐induced dehydrogenation of hydrogenated graphene can also be used for this purpose. All such laser‐induced transformations are associated with thermal effects. RGO emits blue light on UV excitation, a feature that can be used to generate white light in combination with a yellow emitter. RGO as well as graphene nanoribbons are excellent detectors of infra‐red radiation while RGO is a good UV detector.
Microwave‐Assisted Ring‐Opening Polymerization of D,L‐Lactide: A Probe for the Nonexistence of Nonthermal Microwave Effects
Authors: Ramier Julien , Renard Estelle , Grande Daniel
Published: March 2012

Ring‐opening polymerization of D,L‐lactide is critically reevaluated under both microwave dielectric heating and conventional conduction/convection heating in order to probe the nonexistence of “nonthermal” microwave effects. All experiments are conducted in toluene by resorting to a fiber‐optic sensor that allows for accurate internal reaction temperature measurements. For a given temperature, the results obtained either with a “temperature control” microwave heating mode or with a “power control” procedure can well be reproduced through conventional thermal heating. Microwave irradiation does not induce any alteration of the polymerization kinetics or “livingness”, clearly demonstrating the absence of any specific “nonthermal” effect in the microwave‐assisted process.
GSTM1 and GSTT1 copy numbers and mRNA expression in lung cancer
Authors: Rotunno Melissa , Lam Tram K. , Vogt Aurelie , Bertazzi Pier Alberto , Lubin Jay H. , Caporaso Neil E. , Landi Maria Teresa
Published: March 2012

Large fractions of the human population do not express GSTM1 and GSTT1 (GSTM1/T1) enzymes because of deletions in these genes. These variations affect xenobiotic metabolism and have been evaluated in relation to lung cancer risk, mostly based on null/present gene models. We measured GSTM1/T1 heterozygous deletions, not tested in genome‐wide association studies, in 2,120 controls and 2,100 cases from the Environment And Genetics in Lung cancer Etiology (EAGLE) study. We evaluated their effect on mRNA expression on lung tissue and peripheral blood samples and their association with lung cancer risk overall and by histology types. We tested the null/present, dominant, and additive models using logistic regression. Cigarette smoking and gender were studied as possible modifiers. Gene expression from blood and lung tissue cells was strongly down regulated in subjects carrying GSTM1/T1 deletions by both trend and dominant models (P < 0.001). In contrast to the null/present model, analyses distinguishing subjects with 0, 1, or 2 GSTM1/T1 deletions revealed several associations. There was a decreased lung cancer risk in never‐smokers (OR = 0.44; 95%CI = 0.23–0.82; P = 0.01) and women (OR = 0.50; 95%CI = 0.28–0.90; P = 0.02) carrying 1 or 2 GSTM1 deletions. Analogously, male smokers had an increased risk (OR = 1.13; 95%CI = 1.0–1.28; P = 0.05) and women a decreased risk (OR = 0.78; 95%CI = 0.63–0.97; P = 0.02) for increasing GSTT1 deletions. The corresponding gene smoking and gene–gender interactions were significant (P < 0.05). Our results suggest that decreased activity of GSTM1/T1 enzymes elevates lung cancer risk in male smokers, likely due to impaired carcinogens' detoxification. A protective effect of the same mutations may be operative in never‐smokers and women, possibly because of reduced activity of other genotoxic chemicals. © 2012 Wiley Periodicals, Inc.
Numerical analysis of heat and moisture transport with a finite difference method
Authors: Li Buyang , Sun Weiwei
Published: March 2012

In this article, we study a system of nonlinear parabolic partial differential equations arising from the heat and moisture transport through textile materials with phase change. A splitting finite difference method with semi‐implicit Euler scheme in time direction is proposed for solving the system of equations. We prove the existence and uniqueness of a classical positive solution to the parabolic system as well as the existence and uniqueness of a positive solution to the splitting finite difference system. We provide optimal error estimates for the splitting finite difference system under the condition that the mesh size and time step size are smaller than a positive constant which solely depends upon the physical parameters involved. Numerical results are presented to confirm our theoretical analysis. © 2012 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq 2013
Intense and Energetic Atmospheric Pressure Plasma Jet Arrays
Authors: Kim Jae Young , Ballato John , Kim Sung‐O
Published: March 2012

Intense and energetic atmospheric plasma emissions were achieved by direct jet‐to‐jet coupling using honeycomb‐structured quartz tube arrays. Two plasma modes were found to exist in the same plasma array structure under a change of gas flow conditions: an intense plasma mode and the well‐collimated plasma mode. In order to describe the direct jet‐to‐jet coupling by electrical coupling of charged particles in the plasma, the optical emission of the plasma array was compared with that of a single tube plasma jet. Under identical electrical driving and gas conditions, the optical intensity from the intense plasma jet was approximately four times larger in the coupled array than in the single plasma jet structure. Additionally, the electron energy in the intense plasma was larger than that of the well‐collimated plasma jets in the same device. This intense and energetic plasma jet, arising through direct jet‐to‐jet coupling, may provide novel applications requiring strong discharge processes using simplified structures and accompanying instrumentation when compared with the present vacuum plasma systems.

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Localized Growth of Silicon Oxide Nanowires by Micro‐Afterglow Oxidation
Authors: Arnoult Grégory , Gries Thomas , Henrion Gérard , Migot Sylvie , Fournée Vincent , Belmonte Thierry
Published: March 2012

Silicon oxide nanowires are synthesised below 523 K by a non‐VLS mechanism on different substrates: Fe‐0.5 wt.‐%Si and Fe‐1.5 wt.‐%Si alloys and silicon wafers coated or not by 30‐nm thick coatings of iron. An Ar‐O2 micro‐afterglow is used to feed the substrate with oxidising species over an area of ≈2 mm2. In this area, circular bundles of nanowires appear after 15 min and are randomly distributed. Each bundle diameter increases with time and reaches 50 µm. After several hours, bundles overlap and give a continuous carpet of nanowires. TEM analyses show that no iron is found in the nanowires, whatever the substrate. A growth mechanism, based on the emergence of a surface defect is proposed.

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A tale of two plants: Using LOPA for SIL assignment
Authors: Schmidt Michael S. , Kilpatrick Dan
Published: March 2012

Two plants operated by the same company have “identical” ammonium nitrate (AN) solution pump installations. Yet the teams performing the layer of protection analysis (LOPA) concluded that the safety instrumented functions (SIFs) to protect those pumps needed different safety integrity levels (SILs). Despite the similarity of the installations, the teams discovered legitimate differences that warranted different conclusions about what SIL assignment should be. For those with a specific interest in AN, this article reviews the consequences of AN pump hazards, their initiating causes, and the types of independent layers of protection (IPLs) that can be brought to bear. Of more general interest will be the discussion of the impact of risk tolerance criteria, frequency modifiers, and IPLs on final SIL assignment, and why dictating a fixed SIL assignment to certain types of hazards or installations is inappropriate, especially in the development of industry standards or government regulations. © 2012 American Institute of Chemical Engineers Process Saf Prog, 2012
X‐ray photoelectron spectroscopy of pulsed laser deposited Pb(Zr,Ti)O3−δ
Authors: Dragoi Cristina , Gheorghe Nicoleta G. , Lungu George A. , Trupina Lucian , Ibanescu Andra G. , Teodorescu Cristian M.
Published: March 2012

High quality pulsed laser deposited lead zirconate titanate (PZT) films are obtained by pulsed laser deposition on SrRuO3(111) single crystal layers and characterized by X‐ray photoelectron spectroscopy (XPS), to determine the surface composition. It is found that a minor amount of Pb forms PbO2 at the surface and also some Pb is included into the contamination layer, in form of a Pb(CO3)2 layer of about 1 nm thickness, occupying about one quarter of the PZT surface. The stoichiometry of the outermost 4–5 nm layers yielded as PbZr0.25Ti0.80O2.5, which suggest the formation of an oxygen depleted, Brownmillerite‐like layer at the surface, of at least 5 nm thickness.
Anticancer Drugs from Traditional Toxic Chinese Medicines
Authors: Man Shuli , Gao Wenyuan , Wei Changlong , Liu Changxiao
Published: March 2012

Many anticancer drugs are obtained from natural sources. Nature produces a variety of toxic compounds, which are often used as anticancer drugs. Up to now, there are at least 120 species of poisonous botanicals, animals and minerals, of which more than half have been found to possess significant anticancer properties. In spite of their clinical toxicity, they exhibit pharmacological effects and have been used as important traditional Chinese medicines for the different stages of cancer. The article reviews many structures such as alkaloids of Camptotheca acuminata, Catharanthus roseus and Cephalotaxus fortunei, lignans of Dysosma versipellis and Podophyllum emodi, ketones of Garcinia hanburyi, terpenoids of Mylabris and Ginkgo biloba, diterpenoids of Tripterygium wilfordii, Euphorbia fischeriana, Euphorbia lathyris, Euphorbia kansui, Daphne genkwa, Pseudolarix kaempferi and Brucea javanica, triterpenoids of Melia toosendan, steroids of Periploca sepium, Paris polyphylla and Venenum Bufonis, and arsenic compounds including Arsenicum and Realgar. By comparing their related phytochemistry, toxic effects and the recent advances in understanding the mechanisms of action, this review puts forward some ideals and examples about how to increase antitumour activity and/or reduce the side effects experienced with Chinese medicine. Copyright © 2012 John Wiley & Sons, Ltd.
Extract of Fermented Brown Rice Induces Apoptosis of Human Colorectal Tumor Cells by Activating Mitochondrial Pathway
Authors: Itoh Mari , Nishibori Naoyoshi , Sagara Takefumi , Horie Yukiko , Motojima Aya , Morita Kyoji
Published: March 2012

Brown rice fermented with Aspergillus oryzae, designated as FBRA, is a dietary fiber‐rich food, and fully appreciated as one of the prebiotics, which are generally considered to be beneficial to the health of the body, because of stimulating the growth and/or the activity of bacteria in the digestive system. To assess the effectiveness of FBRA as a functional food, the direct effect of FBRA extract on human colorectal tumor cells was examined. The exposure of HCT116 cells to FBRA extract reduced their viabilities in a concentration‐dependent manner, and the reduction of the cell viability might be attributed to the induction of apoptosis probably through the oxidative damage to the cells. Further studies showed that FBRA extract caused a significant elevation of Bax protein and a slight reduction of Bcl2 protein levels, and furthermore caused the activation of caspase‐3 in the cells. Thus, it seems reasonable to conclude that FBRA extract can exert oxidative damage to the cells, resulting in apoptotic cell death by activating the mitochondrial pathway in human colorectal tumor cells. Therefore, daily intake of FBRA can be expected to be beneficial for preventing carcinogenesis and/or suppressing tumor growth in the digestive tract. Copyright © 2012 John Wiley & Sons, Ltd.
Quercetin Up‐regulates LDL Receptor Expression in HepG2 Cells
Authors: Moon Jiyoung , Lee Seung‐Min , Do Hyun Ju , Cho Yoonsu , Chung Ji Hyung , Shin Min‐Jeong
Published: March 2012

Quercetin, an abundant flavonol found in fruits and vegetable, has been implicated in lowering the risk of cardiovascular disease that is often associated with high plasma levels of low density lipoprotein (LDL) cholesterol. Here we investigated whether quercetin could modulate the expression of LDL receptors (LDLR) in HepG2 cells and the possible underlying mechanisms to exert quercetin's effects. We found that quercetin was able to induce LDLR expression with at least a 75 µ m concentration, which was accompanied by an increase in nuclear sterol regulatory element binding protein 2 (SREBP2). This effect was mediated by activation of c‐jun‐N‐terminal kinase (JNK) and extracellular signal‐regulated kinase (ERK) signalling pathways as implicated by experiments using chemical inhibitors of each pathway. When cells were challenged with protein synthesis inhibitors in quercetin‐activated LDLR transcription, LDL mRNA levels were not significantly affected by cycloheximide but puromycin abolished quercetin‐induced LDLR transcription. Taken together, we conclude that quercetin can initiate LDLR transcription by enhancing SREBP2 processing, but new protein synthesis might be necessary to exert a maximum effect of quercetin in the up‐regulation of the LDLR gene. Our findings demonstrate that quercetin strongly up‐regulated LDLR gene expression, which might elicit hypolipidemic effects by increasing the clearance of circulating LDL cholesterol levels from the blood. Copyright © 2012 John Wiley & Sons, Ltd.
Novel sonomicrometry of ex vivo diaphragm after phrenic nerve injury: Role of matrix metalloproteinases
Authors: Wang Huan , Imamura Yukio , Matsumoto Naoya , Wang Hong , Ogura Hiroshi , Shimazu Takeshi , Seiyama Akitoshi
Published: March 2012

Extracellular matrix (ECM) proteins and their proteolytic enzymes, matrix metalloproteinases (MMPs), implicate in neuromuscular junctions (NMJs) function during development. However, their pathophysiological mechanisms in the diaphragm remain obscure, because a well‐characterized ex vivo experimental system has still been lacking. In the study, we aim to develop a novel ex vivo method of sonomicrometry and evaluate validity of the method with a mouse diaphragm twitch after phrenic nerve injury. In an ex vivo experiment using phrenic nerve‐injured mice, diaphragm twitch during electrical pulse stimulation of phrenic nerve was transiently suppressed on day 1. Recombinant MMPs administered in recording solution exerted dose‐responsive suppression on the diaphragm twitch in normal mice tissue. Furthermore, gelatinolytic and immunoblot experiments were performed to evaluate MMPs' involvement and NMJs' insults. After nerve injury, (1) in vivo levels of MMPs were transiently upregulated at day 1 and (2) expressions of ECM proteins, agrin (nicotinic acetylcholine receptor stabilizer) and laminin, were transiently reduced at day 1 in the diaphragm. These alterations were cancelled by preinjection of the MMP inhibitor. In conclusion, MMPs hamper NMJ synaptic function in association with the impairment of ECM milieu. Our novel experimental method using ex vivo sonomicrometry is necessary for examining the molecular pathophysiolgy for the dysfunction of NMJs in the diaphragm. Synapse, 2012. © 2012 Wiley Periodicals, Inc.
Quantitative hippocampal structural changes following electroconvulsive seizure treatment in a rat model of depression
Authors: Kaae Susanne S. , Chen Fenghua , Wegener Gregers , Madsen Torsten M. , Nyengaard Jens R.
Published: March 2012

Objective: The pathophysiology of depression and the effects of antidepressant treatment are hypothesized to be related to hippocampal structural changes. This study aims to investigate the effect of electroconvulsive seizures on behavior and hippocampal structure in a rat model of depression. Methods: Flinders Sensitive Line (FSL) and Flinders Resistant Line (FRL) rats were treated daily for 10 days with either electroconvulsive seizures or sham treatment. The behavior was evaluated using the forced swim test. Design‐based stereological methods were used to quantify the hippocampal volume and the numbers of neurons and glial cells in specific hippocampal subregions. Results: The basal level of hippocampal volume and neuron number differed significantly between the two rat strains, and a trend toward the FSL strain having more glial cells was found. The structural differences found between the sham‐treated animals were counteracted by electroconvulsive seizure (ECS) treatment, which also normalized the behavior. ECS treatment increased the number of glial cells in hilus significantly in the FRL rats and with the same tendency for the FSL rats. Conclusion: Our results indicate that along with hippocampal neurogenesis, gliogenesis may also be involved in the pathophysiology of depression and in the effect of antidepressant treatment. The underlying mechanisms remain unknown, and further investigations are required to clarify whether the structural changes are necessary to induce a therapeutic effect of antidepressant treatment or if they rather represent an epiphenomenon. Synapse, 2012. © 2012 Wiley Periodicals, Inc.
Nomifensine alters sex differences in striatal dopaminergic function
Authors: Poth Luke S. , O'connell Bryan P. , Mcdermott Janet L. , Dluzen Dean E.
Published: March 2012

A series of three experiments are presented in which the acute effects of the catecholamine reuptake inhibitor, nomifensine, upon striatal dopaminergic function are compared in female and male mice. In Experiment 1, treatment with nomifensine (5 mg kg−1), at 30 min prior to injection of methamphetamine (40 mg kg−1) significantly decreased the amount of striatal dopamine depletion in male, but not female, mice, thereby abolishing the sex difference in methamphetamine‐induced neurotoxicity (males > females). In Experiment 2, the methamphetamine‐evoked sex differences in dopamine and DOPAC output from superfused striatal tissue (males > females) were abolished in mice treated with nomifensine at 30 min prior to tissue removal. In Experiment 3, the potassium chloride‐evoked sex differences in dopamine and DOPAC output from superfused striatal tissue (females > males) were reversed in mice treated with nomifensine at 30 min prior to tissue removal. Taken together these results demonstrate the critical role played by catecholamine transporters in sex differences of dopaminergic function and suggest that this may involve the dopamine transporter, due to its high concentrations within the striatum. Such findings highlight the need for gender‐specific considerations in use of treatments that target reuptake transporters function. Synapse, 2012. © 2012 Wiley Periodicals, Inc.
Putting Life in Literacy
Authors: Boucher Barbara A.
Published: March 2012

View From the Chalkboard essays share readers’ reflections on teaching experiences, advice for new teachers, and perspectives on current issues.
No evidence for mevalonate shunting in moderately affected children with Smith‐Lemli‐Opitz syndrome
Authors: Roullet Jean‐Baptiste , Merkens Louise S. , Pappu Anuradha S. , Jacobs Megan D. , Winter Rolf , Connor William E. , Steiner Robert D.
Published: March 2012

Smith‐Lemli‐Opitz syndrome (SLOS) is caused by a genetic deficiency in 7‐dehydrocholesterol (7‐DHC) reductase (EC 1.3.1.21), the last enzyme of the cholesterol synthetic pathway. In SLOS, plasma cholesterol concentration is reduced and immediate precursor concentration (7‐DHC) is elevated. Surprisingly, total sterol synthesis is reduced but HMG‐CoA reductase activity, a rate‐limiting enzyme in cholesterol synthesis is unaltered as judged by normal urinary excretion of mevalonic acid (MVA) (Pappu et al. J Lipid Res 43:1661–1669, 2002). These findings raise the possibility of increased diversion of MVA into the MVA shunt pathway away from sterol synthesis, by activation of the shunt pathway enzymes. To test this hypothesis, we measured the urinary excretion of 3‐methylglutaconic acid (U‐3MGC), a by‐product of the shunt pathway, in 19 mildly to moderately severely affected SLOS subjects (ten males, nine females) receiving either a cholesterol‐free or a high cholesterol diet, and in 20 age‐ and sex‐matched controls. U‐3MGC was similar in SLOS and controls, and was unaffected by dietary cholesterol intake. Further, no change in U‐3MGC was observed in a subset of SLOS subjects (n = 9) receiving simvastatin. In contrast, U‐MVA was reduced by cholesterol supplementation (~54%, p < 0.05) and by simvastatin (~50%, p < 0.04). There was no correlation between U‐3MGC and either plasma sterol concentrations, urinary isoprenoids, or the subjects’ clinical severity score. However U‐3MGC was inversely correlated with age (p < 0.04) and body weight (p < 0.02), and higher in females than in males (~65%, p < 0.025). The data show that DHCR7 deficiency does not result in 3MGC accumulation in SLOS and suggest that the MVA shunt pathway is not activated in patients with the condition.
A comprehensive outcome comparison of surgical and Ponseti clubfoot treatments with reference to pediatric norms
Authors: Church Chris , Coplan Julie A. , Poljak Dijana , Thabet Ahmed M. , Kowtharapu Durga , Lennon Nancy , Marchesi Stephanie , Henley John , Starr Roland , Mason Dan , Belthur Mohan V. , Herzenberg John E. , Miller Freeman
Published: March 2012

Purpose

Isolated congenital clubfoot can be treated either operatively (posteromedial release) or conservatively (Ponseti method). This study retrospectively compared mid-term outcomes after surgical and Ponseti treatments to a normal sample and used multiple evaluation techniques, such as detailed gait analysis and foot kinematics.

Methods

Twenty-six children with clubfoot treated surgically and 22 children with clubfoot treated with the Ponseti technique were evaluated retrospectively and compared to 34 children with normal feet. Comprehensive evaluation included a full gait analysis with multi-segment and single-segment foot kinematics, pedobarograph, physical examination, validated outcome questionnaires, and radiographic measurements.

Results

The Ponseti group had significantly better plantarflexion and dorsiflexion range of motion during gait and had greater push-off power. Residual varus was present in both treatment groups, but more so in the operative group. Gait analysis also showed that the operative group had residual in-toeing, which appeared well corrected in the Ponseti group. Pedobarograph results showed that the operative group had significantly increased varus and significantly decreased medial foot pressure. The physical examination demonstrated significantly greater stiffness in the operative group in dorsiflexion, plantarflexion, ankle inversion, and midfoot abduction and adduction. Surveys showed that the Ponseti group had significantly more normal pediatric outcome data collection instrument results, disease-specific indices, and Dimeglio scores. The radiographic results suggested greater equinus and cavus and increased foot internal rotation profile in the operative group compared with the Ponseti group.

Conclusions

Ponseti treatment provides superior outcome to posteromedial release surgery, but residual deformity still persists.
Oriented, Multimeric Biointerfaces of the L1 Cell Adhesion Molecule: An Approach to Enhance Neuronal and Neural Stem Cell Functions on 2-D and 3-D Polymer Substrates
Authors: Cherry Jocie F. , Carlson Aaron L. , Benarba Farah L. , Sommerfeld Sven D. , Verma Devendra , Loers Gabriele , Kohn Joachim , Schachner Melitta , Moghe Prabhas V.
Published: March 2012

This article focuses on elucidating the key presentation features of neurotrophic ligands at polymer interfaces. Different biointerfacial configurations of the human neural cell adhesion molecule L1 were established on two-dimensional films and three-dimensional fibrous scaffolds of synthetic tyrosine-derived polycarbonate polymers and probed for surface concentrations, microscale organization, and effects on cultured primary neurons and neural stem cells. Underlying polymer substrates were modified with varying combinations of protein A and poly-d-lysine to modulate the immobilization and presentation of the Fc fusion fragment of the extracellular domain of L1 (L1-Fc). When presented as an oriented and multimeric configuration from protein A-pretreated polymers, L1-Fc significantly increased neurite outgrowth of rodent spinal cord neurons and cerebellar neurons as early as 24 h compared to the traditional presentation via adsorption onto surfaces treated with poly-d-lysine. Cultures of human neural progenitor cells screened on the L1-Fc/polymer biointerfaces showed significantly enhanced neuronal differentiation and neuritogenesis on all protein A oriented substrates. Notably, the highest degree of βIII-tubulin expression for cells in 3-D fibrous scaffolds were observed in protein A oriented substrates with PDL pretreatment, suggesting combined effects of cell attachment to polycationic charged substrates with subcellular topography along with L1-mediated adhesion mediating neuronal differentiation. Together, these findings highlight the promise of displays of multimeric neural adhesion ligands via biointerfacially engineered substrates to “cooperatively” enhance neuronal phenotypes on polymers of relevance to tissue engineering.
“Brands as Intentional Agents”: Questions and extensions
Authors: MacInnis Deborah J.
Published: March 2012

The notion that consumers' relationships with brands can be characterized in ways that resemble their relationships with people is gaining considerable ground in the areas of consumer behavior and branding. Kervyn, Fiske and Malone's “Brands as Intentional Agents” offers additional support for this basic proposition. The authors argue that the ability to translate research on human social interaction relationships with brand relationships provides useful insights into brand positioning and brand communications. This author, while raising a few general questions about the SCM and BIAF models, identifies additional research questions in the consumer behavior and branding domains that might be informed by the basic components of the SCM model.
Family and Social Change
Authors: Janssens Angelique
Published: March 2012

This book is a quantitative study into the influence of the process of industrialisation on the nature and strength of family relationships in a Dutch community between 1850 and 1920. The study makes use of the unique and unusually rich source of Dutch population registers, which enables the author to trace the history of individual households. The study closely relates aspects of family and household with the social processes characteristic of an industrialising society, such as increasing rates of social and geographical mobility and the shift of production from the home into the factory. Results reveal a striking continuity in the strength of nineteenth-century family relations despite the gradual but profound process of social change surrounding these families. Changes in behavioural patterns did occur, however, under the influence of changes in demographic rates, regional geographical mobility systems and local developments in the housing market. Nevertheless, these changes cannot be taken as a weakening of family relationships.
The Secret Drama of Shakespeare's Sonnets
Authors: Massey Gerald
Published: March 2012

Gerald Massey's work of 1888 presented a strong argument against the many theorists who viewed Shakespeare's Sonnets as autobiographical – 'a permanent reply to Shakespeare's misinterpreters'. Beginning by outlining the known background and context of the Sonnets, Massey proceeds to wage what he terms his 'battle against fictions, fallacies, forgeries, and groundless assumptions'. Who were the Sonnets addressed to, if anyone, and what is the significance of the inscription in the edition of 1609? What is the correct arrangement of the Sonnets, and why did Shakespeare himself give personal testimony to their 'purity'? Following detailed descriptions of the many different theories, Massey provides close readings and analysis of the Sonnets themselves to dispute the autobiographical claims, and to demonstrate that the Sonnets are 'partly personal and partly dramatic'.
Specimens of Printing Types and Ornaments
Authors: Clark John Willis
Published: March 2012

First published in 1901, this is a rich repository of typefaces (including English, Greek, Latin, Sanskrit, Arabic, Hebrew and Cyrillic), ornaments, borders and various decorative devices used in books printed at the University Press, Cambridge, until 1900. Highlights of the compilation include a wide range of historical typefaces (including Caslon, Marr, Figgins, Blake, and Miller and Richards), stylish borders, corners and head and tail pieces, university and college shields, and a detailed catalogue of Egyptian hieroglyphs. It also contains sections on accented letters and signs, 'poster founts' and ornately styled initial letters. Prefaced with a brief 'Historical Sketch' by J. W. Clark, a noted Cambridge academic and antiquarian, Specimens is a valuable archive of the craft of lettering and design before the advent of the digital age that will delight bibliophiles, typographers and collectors.
The Works of Thomas Carlyle
Authors: Carlyle Thomas
Published: March 2012

Thomas Carlyle (1795–1881) was one of the most influential authors of the nineteenth century. Eagerly studied at the highest level of intellectual society, his satirical essays and perceptive historical biographies caused him to be regarded for much of the Victorian period as a literary genius and eminent social philosopher. After graduating from Edinburgh University in 1814, he published his first scholarly work on German literature in 1824, before finding literary success with his ground-breaking history of the French Revolution in 1837. After falling from favour during the first part of the twentieth century, his work has more recently become the subject of scholarly re-examination. His introduction of German literature and philosophy into the British intellectual milieu profoundly influenced later philosophical ideas and literary studies. These volumes are reproduced from the 1896 Centenary Edition of his collected works. Volume 2 contains the first volume of The French Revolution.
The Works of Thomas Carlyle
Authors: Carlyle Thomas , Cromwell Oliver
Published: March 2012

Thomas Carlyle (1795–1881) was one of the most influential authors of the nineteenth century. Eagerly studied at the highest level of intellectual society, his satirical essays and perceptive historical biographies caused him to be regarded for much of the Victorian period as a literary genius and eminent social philosopher. After graduating from Edinburgh University in 1814, he published his first scholarly work on German literature in 1824, before finding literary success with his history of the French Revolution in 1837. After falling from favour during the first part of the twentieth century, his work has more recently become the subject of scholarly re-examination. His introduction of German literature and philosophy into the British intellectual milieu profoundly influenced later philosophical ideas and literary studies. These volumes are reproduced from the 1896 Centenary Edition of his collected works. Volume 8 contains the third volume of Oliver Cromwell's Letters and Speeches.
The Revised Latin Primer
Authors: Kennedy Benjamin Hall
Published: March 2012

Described by Mary Beard in The Independent as 'the Rolls Royce of textbooks', Kennedy's classic 1888 guide has remained the pre-eminent Latin reference grammar in schools and universities for well over a century. This is a reissue of the first edition, which appeared the year before the author's death. Benjamin Hall Kennedy (1804–1889), headmaster of Shrewsbury School for thirty years before becoming Regius Professor of Greek at Cambridge, was probably assisted by his daughters in producing this completely revised version of an earlier, unsuccessful publication. From tables of nouns and verbs to obscure nuances of style, the book covered all the key points of Latin grammar and was detailed, well-organised and easy to use. This original Victorian edition will fascinate present-day students and teachers of Latin and historians of education.
Vollständige Anleitung zur Niedern und Höhern Algebra
Authors: Euler Leonhard
Published: March 2012

In 1770, one of the founders of pure mathematics, the Swiss-born mathematician Leonard Euler (1707–1783), published an algebra textbook for students. It was soon translated into French, with notes and additions by Joseph-Louis Lagrange, another giant of eighteenth-century mathematics, and the French edition was used as the basis of this three-volume 1790s German edition. Volume 3 consists of the German translation of Lagrange's additional material, which the German publisher printed in a separate volume to enable those who already owned Euler's Algebra to obtain the supplementary material 'without incurring unnecessary expenditure'. The translator (the tutor to the sons of the Duke of Württemberg) added notes and further appendices of his own. This book provides tangible evidence of the lively international mathematical community that flourished despite the political uncertainties of the late eighteenth century.