bluuebunny/crossref_metadata_2025 huggingface dataset:
What Patients with Anorexia Nervosa Should Wear When They Are Being Weighed: Report of Two Pilot Surveys
Authors: Jaffa Tony , Davies Sarah , Sardesai Anagha
Published: March 2011

Aim

Weighing patients with anorexia nervosa tends to be an integral part of their treatment, yet there is variability in the detail of how this is conducted. The aim of this study was to carry out preliminary exploration of one aspect of this, namely what patients wear when being weighed.

Method

Two Web‐based surveys were conducted accessing the views of ex‐patients (20 respondents) and professionals (98 respondents).

Results

Responses confirmed the variability in arrangements for weighing patients. Both patients and professionals were more concerned with accuracy than with privacy, and the patients stated a preference for being weighed in underwear. Between 30 and 57% of patients reported having falsified their weight during treatment.

Discussion

These surveys provide a reminder of the high frequency of falsification of weight and some support for a policy of weighing in underwear. The strength of the findings is limited by the methodology with small number of ex‐patients all of whom had been through the same treatment programme. Given the paucity of literature on this clinically relevant topic, this does seem to be an area that warrants further investigation. Copyright © 2011 John Wiley & Sons, Ltd and Eating Disorders Association.
Linear combination‐based energy detection algorithm in low signal‐to‐noise ratio for cognitive radios
Authors: Zhang Shibing , Bao Zhihua
Published: March 2011

This paper considers the spectrum sensing technique for cognitive radio‐based on energy detection. It proposes an improved spectrum sensing algorithm by linearly combining the criteria of the probability of detection and the probability of false alarm. Then, the optimal decision threshold is derived for energy detection in the proposed linear combination (LC) algorithm. The performance of primal user detection is significantly improved by using the proposed LC algorithm, especially under low signal‐to‐noise ratios. Simulation results verify the effectiveness of the proposed algorithm with different kinds of primary user signals. Copyright © 2011 John Wiley & Sons, Ltd.
Steigerung der Effizienz von Erdwärmesonden durch Luftinjektion an Standorten ohne Grundwasserströmung
Authors: Ma Xiaolong , Grabe Jürgen
Published: March 2011

Zur Nutzung der oberflächennahen Geothermie stehen geschlossene und offene Systeme zur Verfügung. In geschlossenen Systemen wird bei Fehlen einer Grundwasserströmung die Wärme im Boden durch Wärmeleitung transportiert. Dieses ist ein langsamer Vorgang und schränkt die Entzugsleistung von Erdwärmeanlagen ein. Es wird eine patentierte Methode vorgestellt, in der ein geschlossenes Erdwärmesystem mit Grundwasserzirkulationsverfahren kombiniert wird. Dadurch wird eine Zirkulationsströmung künstlich in Gang gesetzt, die zur Erhöhung des konvektiven Wärmetransports und der Leistung der Erdwärmeanlage führt. In diesem Beitrag wird eine mit Luftinjektionsbrunnen kombinierte Erdwärmesonde dreidimensional numerisch abgebildet. Die durch Luftinjektion erzeugte Grundwasserzirkulation sowie die Wärmeausbreitung im Boden werden sequenziell simuliert. Die Entzugsleistung dieser Anlage wird mit der einer üblichen Erdwärmeanlage verglichen. Weiterhin werden Variationsberechnungen durchgeführt, um den Einfluss der Dichte des Wasser‐ Luft‐Gemisches im Brunnen, der Wärmeleitfähigkeit und der Durchlässigkeit des Bodens zu untersuchen. Eine Wirtschaftlichkeitsanalyse vervollständigt diesen Beitrag.

Increasing the efficiency of downhole heat exchangers by air sparging in locations without groundwater flow. Closed and open systems are available for the exploitation of shallow geothermal energy. If there is no groundwater flow, heat in closed systems can only be transferred by conduction. Unfortunately, heat conduction is a relatively slow heat transfer mechanism, which limits the heating capacity of geothermal systems. A patented method is presented, in which a closed system is combined with groundwater circulation technology. In this system, a groundwater circulation is created artificially, which increases the convective heat transfer in the soil and therefore the heat capacity of the geothermal system. In this paper a downhole heat exchanger combined with an air sparging well is numerically simulated. The groundwater circulation induced by air sparging and the heat propagation are calculated sequentially. The heat capacity of this system is compared with a normal downhole heat exchanger. Furthermore, variation calculations are performed to investigate the influence of the density of the water‐air mixture in the well, permeability and conductivity of the soil. A profitability analysis rounds off the paper.
Speech perception in the child brain: Cortical timing and its relevance to literacy acquisition
Authors: Parviainen Tiina , Helenius Päivi , Poskiparta Elisa , Niemi Pekka , Salmelin Riitta
Published: March 2011

Speech processing skills go through intensive development during mid‐childhood, providing basis also for literacy acquisition. The sequence of auditory cortical processing of speech has been characterized in adults, but very little is known about the neural representation of speech sound perception in the developing brain. We used whole‐head magnetoencephalography (MEG) to record neural responses to speech and nonspeech sounds in first‐graders (7‐8‐year‐old) and compared the activation sequence to that in adults. In children, the general location of neural activity in the superior temporal cortex was similar to that in adults, but in the time domain the sequence of activation was strikingly different. Cortical differentiation between sound types emerged in a prolonged response pattern at about 250 ms after sound onset, in both hemispheres, clearly later than the corresponding effect at about 100 ms in adults that was detected specifically in the left hemisphere. Better reading skills were linked with shorter‐lasting neural activation, speaking for interdependence of the maturing neural processes of auditory perception and developing linguistic skills. This study uniquely utilized the potential of MEG in comparing both spatial and temporal characteristics of neural activation between adults and children. Besides depicting the group‐typical features in cortical auditory processing, the results revealed marked interindividual variability in children. Hum Brain Mapp, 2011. © 2011 Wiley Periodicals, Inc.
Head injury or head motion? Assessment and quantification of motion artifacts in diffusion tensor imaging studies
Authors: Ling Josef , Merideth Flannery , Caprihan Arvind , Pena Amanda , Teshiba Terri , Mayer Andrew R.
Published: March 2011

The relationship between head motion and diffusion values such as fractional anisotropy (FA) and mean diffusivity (MD) is currently not well understood. Simulation studies suggest that head motion may introduce either a positive or negative bias, but this has not been quantified in clinical studies. Moreover, alternative measures for removing bias as result of head motion, such as the removal of problematic gradients, has been suggested but not carefully evaluated. The current study examined the impact of head motion on FA and MD across three common pipelines (tract‐based spatial statistics, voxelwise, and region of interest analyses) and determined the impact of removing diffusion weighted images. Our findings from a large cohort of healthy controls indicate that while head motion was associated with a positive bias for both FA and MD, the effect was greater for MD. The positive bias was observed across all three analysis pipelines and was present following established protocols for data processing, suggesting that current techniques (i.e., correction of both image and gradient table) for removing motion bias are likely insufficient. However, the removal of images with gross artifacts did not fundamentally change the relationship between motion and DTI scalar values. In addition, Monte Carlo simulations suggested that the random removal of images increases the bias and reduces the precision of both FA and MD. Finally, we provide an example of how head motion can be quantified across different neuropsychiatric populations, which should be implemented as part of any diffusion tensor imaging quality assurance protocol. Hum Brain Mapp, 2012. © 2011 Wiley Periodicals, Inc.
Dissociation between anterior and posterior cortical regions during self‐specificity and familiarity: A combined fMRI–meta‐analytic study
Authors: Qin Pengmin , Liu Yijun , Shi Jinfu , Wang Yuzhi , Duncan Niall , Gong Qiyong , Weng Xuchu , Northoff Georg
Published: March 2011

The familiarity to the subject of any potential stimuli presents one of the major difficulties for the investigation of the self; the separation of effects resulting from familiarity from self‐effects being extremely problematic. The aim of this study was thus to investigate the neural distinction between self and familiarity by combining two sets of fMRI data with a meta‐analysis. In the first fMRI experiment, regions responding to self/familiarity were investigated using the subject's own name and names of familiar others. These effects were confirmed and extended in a second fMRI experiment using the subject's own name and a stranger's name, as spoken by familiar and unfamiliar voices. Finally, a meta‐analysis of self‐ and familiarity‐related studies was conducted. Neural activity in the anterior brain regions, such as the anterior cingulate (ACC) and anterior insula (AI), was found to be specific for self‐specific stimuli. In contrast, posterior brain regions, such as the posterior cingulate, were activated by familiar stimuli. Finally, the distinction between anterior and posterior regions for self and familiarity was confirmed by meta‐analytic data. This study demonstrates a clear anterior–posterior cortical partition between self‐specificity and familiarity. Hum Brain Mapp, 2012. © 2010 Wiley Periodicals, Inc.
Frontal parietal control network regulates the anti‐correlated default and dorsal attention networks
Authors: Gao Wei , Lin Weili
Published: March 2011

Recent reports demonstrate the anti‐correlated behaviors between the default (DF) and the dorsal attention (DA) networks. We aimed to investigate the roles of the frontal parietal control (FPC) network in regulating the two anti‐correlated networks through three experimental conditions, including resting, continuous self‐paced/attended sequential finger tapping (FT), and natural movie watching (MW), respectively. The two goal‐directed tasks were chosen to engage either one of the two competing networks—FT for DA whereas MW for default. We hypothesized that FPC will selectively augment/suppress either network depending on how the task targets the specific network; FPC will positively correlate with the target network, but negatively correlate with the network anti‐correlated with the target network. We further hypothesized that significant causal links from FPC to both DA and DF are present during all three experimental conditions, supporting the initiative regulating role of FPC over the two opposing systems. Consistent with our hypotheses, FPC exhibited a significantly higher positive correlation with DA (P = 0.0095) whereas significantly more negative correlation with default (P = 0.0025) during FT when compared to resting. Completely opposite to that observed during FT, the FPC was significantly anti‐correlated with DA (P = 2.1e‐6) whereas positively correlated with default (P = 0.0035) during MW. Furthermore, extensive causal links from FPC to both DA and DF were observed across all three experimental states. Together, our results strongly support the notion that the FPC regulates the anti‐correlated default and DA networks. Hum Brain Mapp, 2012. © 2011 Wiley Periodicals, Inc.
Neural basis of single‐word reading in Spanish–English bilinguals
Authors: Jamal Nasheed I. , Piche Ashley W. , Napoliello Eileen M. , Perfetti Charles A. , Eden Guinevere F.
Published: March 2011

Brain imaging studies have identified a left‐lateralized network of regions that are engaged when monolinguals read. However, for individuals who are native speakers of two languages, it is unclear whether this pattern of activity is maintained across both languages or if it deviates according to language‐specific properties. We used functional magnetic resonance imaging to investigate single‐word processing in Spanish and in English in 12 proficient early Spanish–English bilinguals matched in skill level in both languages. Word processing in Spanish engaged the left inferior frontal and left middle temporal gyri. Word processing in English activated the left inferior frontal, middle frontal, and fusiform gyri extending to inferior temporal gyrus and the right middle temporal gyrus extending into superior temporal sulcus. The comparison of reading in Spanish greater than reading in English revealed involvement of the left middle temporal gyrus extending into the superior temporal sulcus. English greater than Spanish, however, demonstrated greater engagement of the left middle frontal gyrus extending into the superior frontal gyrus. We conclude that although word processing in either language activates classical areas associated with reading, there are language‐specific differences, which can be attributed to the disparity in orthographic transparency. English, an orthographically deep language, may require greater engagement of the frontal regions for phonological coding, whereas Spanish allows increased access to semantic processing via the left middle temporal areas. Together, these results suggest that bilinguals will show adjustments to the typical neural representation of reading as necessitated by the demands of the orthography. Hum Brain Mapp, 2012. © 2010 Wiley Periodicals, Inc.
Nonlinear estimation of neural processing time from BOLD signal with application to decision‐making
Authors: Biazoli Claudinei Eduardo , Sato João Ricardo , Cardoso Ellison Fernando , Brammer Michael John , Amaro Edson
Published: March 2011

The extraction of information about neural activity timing from BOLD signal is a challenging task as the shape of the BOLD curve does not directly reflect the temporal characteristics of electrical activity of neurons. In this work, we introduce the concept of neural processing time (NPT) as a parameter of the biophysical model of the hemodynamic response function (HRF). Through this new concept we aim to infer more accurately the duration of neuronal response from the highly nonlinear BOLD effect. The face validity and applicability of the concept of NPT are evaluated through simulations and analysis of experimental time series. The results of both simulation and application were compared with summary measures of HRF shape. The experiment that was analyzed consisted of a decision‐making paradigm with simultaneous emotional distracters. We hypothesize that the NPT in primary sensory areas, like the fusiform gyrus, is approximately the stimulus presentation duration. On the other hand, in areas related to processing of an emotional distracter, the NPT should depend on the experimental condition. As predicted, the NPT in fusiform gyrus is close to the stimulus duration and the NPT in dorsal anterior cingulate gyrus depends on the presence of an emotional distracter. Interestingly, the NPT in right but not left dorsal lateral prefrontal cortex depends on the stimulus emotional content. The summary measures of HRF obtained by a standard approach did not detect the variations observed in the NPT. Hum Brain Mapp, 2012. © 2010 Wiley Periodicals, Inc.
Sensitive period for white‐matter connectivity of superior temporal cortex in deaf people
Authors: Li Yanyan , Ding Guosheng , Booth James R. , Huang Ruiwang , Lv Yating , Zang Yufeng , He Yong , Peng Danling
Published: March 2011

Previous studies have shown that white matter in the deaf brain changes due to hearing loss. However, how white‐matter development is influenced by early hearing experience of deaf people is still unknown. Using diffusion tensor imaging and tract‐based spatial statistics, we compared white‐matter structures among three groups of subjects including 60 congenitally deaf individuals, 36 acquired deaf (AD) individuals, and 38 sex‐ and age‐matched hearing controls (HC). The result showed that the deaf individuals had significantly reduced fractional anisotropy (FA) values in bilateral superior temporal cortex and the splenium of corpus callosum compared to HC. The reduction of FA values in acquired deafness correlated with onset age of deafness, but not the duration of deafness. To explore the underlying mechanism of FA changes in the deaf groups, we further analyzed radial and axial diffusivities and found that (1) the reduced FA values in deaf individuals compared to HC is primarily driven by higher radial diffusivity values and (2) in the AD, higher radial diffusivity was correlated with earlier onset age of deafness, but not the duration of deafness. These findings imply that early sensory experience is critical for the growth of fiber myelination, and anatomical reorganization following auditory deprivation is sensitive to early plasticity in the brain. Hum Brain Mapp, 2012. © 2010 Wiley Periodicals, Inc.
Differential effects of intranasal insulin and caffeine on cerebral blood flow
Authors: Grichisch Yuko , Çavuşoğlu Mustafa , Preissl Hubert , Uludağ Kamil , Hallschmid Manfred , Birbaumer Niels , Häring Hans U. , Fritsche Andreas , Veit Ralf
Published: March 2011

Insulin is an important modulator of brain functions such as memory and appetite regulation. Besides the effect on neuronal activity, it is also possible that insulin has a direct vasodilatory effect on cerebral blood flow (CBF). We investigated the impact of increased insulin levels in the central nervous system on basal and task‐induced CBF as well as blood oxygenation level‐dependent (BOLD) response in the visual cortex using pulsed arterial spin‐labeling MRI. An intranasal insulin application was used to avoid peripheral hyperinsulinaemia, which would lead to a cascade of hormonal changes. In a control experiment, caffeine was applied due to its well‐known impact on the vasculature of the brain leading to a reliable reduction of CBF. Eight lean subjects were included in the study. On 2 separate days, intranasal human insulin or caffeine tablets were given to the subjects after fasting over night. On each day, basal CBF and task‐induced CBF were measured before and 30 min after application of insulin or caffeine in each subject. During the task condition, a flickering checkerboard was presented. Insulin had no effect on basal CBF and task‐induced CBF in comparison with drug‐free baseline measurement in the visual cortex and control regions. After caffeine application, however, there was a significant decrease of CBF during stimulation in the visual cortex. The BOLD response was not altered by insulin or caffeine between pre‐ and postdose measurements. In conclusion, we found no evidence for a direct vasodilatory effect of intranasal insulin on the cerebral vascular system in this study. Hum Brain Mapp, 2012. © 2011 Wiley Periodicals, Inc.
Seeing different objects in different ways: Measuring ventral visual tuning to sensory and semantic features with dynamically adaptive imaging
Authors: Cusack Rhodri , Veldsman Michele , Naci Lorina , Mitchell Daniel J. , Linke Annika C.
Published: March 2011

A key challenge of object recognition is achieving a balance between selectivity for relevant features and invariance to irrelevant ones. Computational and cognitive models predict that optimal selectivity for features will differ by object, and here we investigate whether this is reflected in visual representations in the human ventral stream. We describe a new real‐time neuroimaging method, dynamically adaptive imaging (DAI), that enabled measurement of neural selectivity along multiple feature dimensions in the neighborhood of single referent objects. The neural response evoked by a referent was compared to that evoked by 91 naturalistic objects using multi‐voxel pattern analysis. Iteratively, the objects evoking the most similar responses were selected and presented again, to converge upon a subset that characterizes the referent's “neural neighborhood.” This was used to derive the feature selectivity of the response. For three different referents, we found strikingly different selectivity, both in individual features and in the balance of tuning to sensory versus semantic features. Additional analyses placed a lower bound on the number of distinct activation patterns present. The results suggest that either the degree of specificity available for object representation in the ventral stream varies by class, or that different objects evoke different processing strategies. Hum Brain Mapp, 2012. © 2011 Wiley Periodicals, Inc.
Relationship between functional connectivity and sensory impairment: Red flag or red herring?
Authors: Dinomais Mickaël , Groeschel Samuel , Staudt Martin , Krägeloh‐Mann Ingeborg , Wilke Marko
Published: March 2011

Resting‐state functional magnetic resonance imaging (fMRI) can be used to study the functional connectivity in the somatosensory system. However, the relationship between sensory network connectivity, sensory deficits, and structural abnormality remains poorly understood. Previously, we investigated the motor network in children with congenital hemiparesis due to middle cerebral artery strokes (MCA, n = 6) or periventricular lesions (PL, n = 8). In the present study, we validate the use of interleaved resting‐state data from blocked fMRI designs to investigate the somatosensory network in these patients. The approach was validated by assessing the predicted “crossed‐over” connectivity between the cerebral cortex and the cerebellum. Furthermore, the impact on the volume of gray‐matter (GM) in primary (S1) and secondary (S2) somatosensory cortex on functional connectivity measures was investigated. We were able to replicate the well‐known “crossed‐over” pattern of functional connectivity between cerebral and cerebellar cortex. The MCA group displayed more sensory deficit and significantly reduced functional connectivity in the lesioned S2 (but not in lesioned S1) when compared with the PL group. However, when accounting for GM volume loss, this difference disappeared. This study demonstrates the applicability of analyzing resting‐state connectivity in patients with brain lesions. Reductions of functional connectivity within the somatosensory network were associated with sensory deficits, but were fully explained by the underlying GM damage. This underlines the influence of cortical GM volume on functional connectivity measures. Hum Brain Mapp, 2012. © 2011 Wiley Periodicals, Inc.
Yes-associated protein regulation of adaptive liver enlargement and hepatocellular carcinoma development in mice
Authors: Kowalik Marta A. , Saliba Christian , Pibiri Monica , Perra Andrea , Ledda-Columbano Giovanna M. , Sarotto Ivana , Ghiso Elena , Giordano Silvia , Columbano Amedeo
Published: March 2011

The Hippo kinase cascade, a growth-suppressive pathway that ultimately antagonizes the transcriptional coactivator Yes-associated protein (YAP), has been shown in transgenic animals to orchestrate organ size regulation. The purpose of this study was to determine whether in non–genetically modified mice (1) the Hippo pathway is involved in the regulation of adaptive liver enlargement caused by the mitogen 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP), an agonist of constitutive androstane receptor and (2) a dysregulation of this pathway occurs during the development of chemically induced hepatocellular carcinoma (HCC). We show that liver enlargement caused by TCPOBOP was associated with an increase of YAP protein levels that paralleled the increase in 2-bromodeoxyuridine incorporation. Interestingly, when a second dose of TCPOBOP was given to mice with enlarged livers, no further increases in liver mass or YAP protein levels were observed, suggesting that the Hippo pathway prevents further growth of the hyperplastic liver. Viral-mediated exogenous expression of active YAP in mouse livers was able to partially overcome the block of hepatocyte proliferation. We also show that HCCs developed in mice given diethylnitrosamine and then subjected to repeated treatments with TCPOBOP had increased levels of YAP that were associated with down-regulation of microRNA 375, which is known to control YAP expression, and with enhanced levels of alpha-fetoprotein and connective tissue growth factor, two target genes of YAP.

Conclusion:

These results suggest that the Hippo pathway regulates adaptive liver enlargement and is probably inactivated in initiated cells that escape the suppressive constrain exerted on the surrounding normal tissue, thus allowing clonal expansion to HCC (HEPATOLOGY 2011;)
A classification of ductal plate malformations based on distinct pathogenic mechanisms of biliary dysmorphogenesis
Authors: Raynaud Peggy , Tate Joshua , Callens Céline , Cordi Sabine , Vandersmissen Patrick , Carpentier Rodolphe , Sempoux Christine , Devuyst Olivier , Pierreux Christophe E. , Courtoy Pierre , Dahan Karin , Delbecque Katty , Lepreux Sébastien , Pontoglio Marco , Guay-Woodford Lisa M. , Lemaigre Frédéric P.
Published: March 2011

Ductal plate malformations (DPMs) are developmental anomalies considered to result from lack of ductal plate remodeling during bile duct morphogenesis. In mice, bile duct development is initiated by the formation of primitive ductal structures lined by two cell types, namely ductal plate cells and hepatoblasts. During ductal plate remodeling, the primitive ductal structures mature to ducts as a result from differentiation of the ductal plate cells and hepatoblasts to cholangiocytes. Here, we report this process is conserved in human fetal liver. These findings prompted us to evaluate how DPMs develop in three mouse models, namely mice with livers deficient in hepatocyte nuclear factor 6 (HNF6), HNF1β, or cystin-1 ( cpk [congenital polycystic kidney] mice). Human liver from a patient with a HNF1B/TCF2 mutation, and from fetuses affected with autosomal recessive polycystic kidney disease (ARPKD) were also analyzed. Despite the epistatic relationship between HNF6, HNF1β, and cystin-1, the three mouse models displayed distinct morphogenic mechanisms of DPM. They all developed biliary cysts lined by cells with abnormal apicobasal polarity. However, the absence of HNF6 led to an early defect in ductal plate cell differentiation. In HNF1β-deficient liver, maturation of the primitive ductal structures was impaired. Normal differentiation and maturation but abnormal duct expansion was apparent in cpk mouse livers and in human fetal ARPKD.

Conclusion:

DPM is the common endpoint of distinct defects initiated at distinct stages of bile duct morphogenesis. Our observations provide a new pathogenic classification of DPM. (HEPATOLOGY 2011;)
Antitumor effects of OSU-2S, a nonimmunosuppressive analogue of FTY720, in hepatocellular carcinoma
Authors: Omar Hany A. , Chou Chih-Chien , Berman-Booty Lisa D. , Ma Yihui , Hung Jui-Hsiang , Wang Dasheng , Kogure Takayuki , Patel Tushar , Terracciano Luigi , Muthusamy Natarajan , Byrd John C. , Kulp Samuel K. , Chen Ching-Shih
Published: March 2011

Accumulating evidence suggests the therapeutic potential of the immunosuppressive agent FTY720 (fingolimod) in hepatocellular carcinoma (HCC). Based on our previous finding that FTY720 mediates apoptosis in HCC cells by activating reactive oxygen species (ROS)–protein kinase Cδ (PKCδ) signaling independent of effects on sphingosine-1-phosphate (S1P) receptors, we embarked on the pharmacological exploitation of FTY720 to develop a nonimmunosuppressive analogue with antitumor activity. This effort led to the development of OSU-2S, which exhibits higher potency than FTY720 in suppressing HCC cell growth through PKCδ activation. In contrast to FTY720, OSU-2S was not phosphorylated by sphingosine kinase 2 (SphK2) in vitro, and did not cause S1P1 receptor internalization in HCC cells or T lymphocyte homing in immunocompetent mice. Although devoid of S1P1 receptor activity, OSU-2S exhibited higher in vitro antiproliferative efficacy relative to FTY720 against HCC cells without cytotoxicity in normal hepatocytes. Several lines of pharmacological and molecular genetic evidence indicate that ROS–PKCδ–caspase-3 signaling underlies OSU-2S–mediated antitumor effects, and that differences in the antitumor activity between FTY720 and OSU-2S were attributable to SphK2-mediated phosphorylation of FTY720, which represents a metabolic inactivation of its antitumor activity. Finally, OSU-2S exhibited high in vivo potency in suppressing xenograft tumor growth in both ectopic and orthotopic models without overt toxicity.

Conclusion:

Using the molecular platform of FTY720, we developed OSU-2S, a novel PKCδ-targeted antitumor agent, which is devoid of S1P1 receptor activity and is highly effective in suppressing HCC tumor growth in vivo. These findings suggest that OSU-2S has clinical value in therapeutic strategies for HCC and warrants continued investigation in this regard. (HEPATOLOGY 2011;)
Novel roles of galectin-1 in hepatocellular carcinoma cell adhesion, polarization, and in vivo tumor growth
Authors: Espelt María V. , Croci Diego O. , Bacigalupo María L. , Carabias Pablo , Manzi Malena , Elola María T. , Muñoz Marina C. , Dominici Fernando P. , Wolfenstein-Todel Carlota , Rabinovich Gabriel A. , Troncoso María F.
Published: March 2011

Galectin-1 (Gal-1), a widely expressed β-galactoside–binding protein, exerts pleiotropic biological functions. Gal-1 is up-regulated in hepatocarcinoma cells, although its role in liver pathophysiology remains uncertain. We investigated the effects of Gal-1 on HepG2 hepatocellular carcinoma (HCC) cell adhesion and polarization. Soluble and immobilized recombinant Gal-1 (rGal-1) promoted HepG2 cell adhesion to uncoated plates and also increased adhesion to laminin. Antibody-mediated blockade experiments revealed the involvement of different integrins as critical mediators of these biological effects. In addition, exposure to rGal-1 markedly accelerated the development of apical bile canaliculi as shown by TRITC-phalloidin labeling and immunostaining for multidrug resistance associated-protein 2 (MRP2). Notably, rGal-1 did not interfere with multidrug resistance protein 1/P-glycoprotein or MRP2 apical localization, neither with transfer nor secretion of 5-chloromethylfluorescein diacetate through MRP2. Stimulation of cell adhesion and polarization by rGal-1 was abrogated in the presence of thiodigalactoside, a galectin-specific sugar, suggesting the involvement of protein–carbohydrate interactions in these effects. Additionally, Gal-1 effects were abrogated in the presence of wortmmanin, PD98059 or H89, suggesting involvement of phosphoinositide 3-kinase (PI3K), mitogen-activated protein kinase and cyclic adenosine monophosphate–dependent protein kinase signaling pathways in these functions. Finally, expression levels of this endogenous lectin correlated with HCC cell adhesion and polarization and up-regulation of Gal-1–favored growth of hepatocarcinoma in vivo. Conclusion: Our results provide the first evidence of a role of Gal-1 in modulating HCC cell adhesion, polarization, and in vivo tumor growth, with critical implications in liver pathophysiology. (HEPATOLOGY 2011;)
Comparative study on toxic effects induced by oral or intravascular administration of commonly used disinfectants and surfactants in rats
Authors: Xue Yuying , Zhang Shanshan , Tang Meng , Zhang Ting , Wang Yiqing , Hieda Yoko , Takeshita Haruo
Published: March 2011

Accidental ingestion or injection of household products sometimes occurs due to their accessibility, but the toxic manifestations have not been well characterized when they are internally administered. The aim of this study was to investigate the toxic effects induced by ingestion or injection of different ionic surfactants and disinfectants in rats. The test drugs involved benzalkonium and benzethonium (BZK and BZT, both cationic surfactants used as disinfectants), alkyldiaminoethylglycine (AEG, an amphoteric surfactant used as a disinfectant), linear alkylbenzenesulfonate (LAS, an anionic surfactant), polyoxyethylene cetylether (PEC, a nonionic surfactant), chlorhexidine (CHX, not a surfactant but a disinfectant) and saline (control). Male Sprague–Dawley rats were administered one of the test drugs orally (p.o.), intravenously (i.v.) or intraarterially (i.a.). The fatal effects appeared rapidly (<30 min) in i.v.‐administered rats, while taking hours (>5 h) in i.a./p.o.‐administered rats after a dose of around LD50, although the progress and degree of toxic effects varied among the drugs tested. In intravascular administration, BZK and BZT were fatal at doses of 15–20 mg kg−1. Higher concentrations in lung and kidney than in blood were determined. CHX showed a high toxic effect compared with cationic surfactants. The rats administered anionic (LAS) or amphoteric (AEG) surfactant died in less than 24 h at doses over 100 mg kg−1. In p.o. administration, the toxic effects were concentration/dose‐dependent, and all rats administered high doses of surfactants except for PEC died at 5–20 h. The overall toxic ranks could be: cationic surfactant/CHX> anionic/amphoteric surfactant > nonionic surfactant. Copyright © 2011 John Wiley & Sons, Ltd.
Administration of the insulin into the scaffold atelocollagen for tissue‐engineered cartilage
Authors: Ko Edward Chengchuan , Fujihara Yuko , Ogasawara Toru , Asawa Yukiyo , Nishizawa Satoru , Nagata Satoru , Takato Tsuyoshi , Hoshi Kazuto
Published: March 2011

Three‐dimensional culture of the tissue‐engineered cartilage constructs may increase the matrix production, but central necrosis must occur if the construct becomes large. To increase the cell viability in the middle part of constructs and to enhance thein vivocartilage regeneration, we attempted to administer the insulin into the scaffold. Insulin is known to strongly enhance the matrix production in the chondrocytes. The pellets of human auricular chondrocytes with atelocollagen hydrogel were 3D‐cultured in the medium. The comparison among three groups (insulin mixed in the atelocollagen, insulin added to the medium, and control group, i.e.; insulin in neither atelocollagen nor medium) revealed that both insulin mixed in the atelocollagen and that in the medium could effectively promoted the cell viability and matrix synthesis of the chondrocytes. The daily assay also showed the gradual release of insulin from the atelocollagen hydrogel, suggesting that this material may work as a control release of insulin. We actually transplanted the poly‐L‐lactide porous scaffolds carrying the chondrocytes and the atelocollagen mixed with or without insulin, into the nude mice, showing that glycosaminoglycan accumulation was evident in the group with insulin although less without insulin. We thus showed the possibility to enhance thein vivocartilage regeneration, when administered insulin into the atelocollagen hydrogel. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 2011.
Osteoblast‐like cell adhesion on porous silicon‐incorporated TiO2 coating prepared by micro‐arc oxidation
Authors: Zhang Zhenxiang , Sun Junying , Hu Hongjie , Wang Quanming , Liu Xuanyong
Published: March 2011

Silicon‐incorporated TiO2 coating (Si‐TiO2) was prepared on titanium (Ti) by micro‐arc oxidation (MAO) technique in the Ca, P, Si‐containing electrolyte. The surface topography, phase, and element composition of the coatings were characterized by scanning electron microscopy (SEM), X‐ray diffraction (XRD), and energy‐dispersive X‐ray spectrometry (EDS), respectively. Osteoblast‐like MC3T3‐E1 cells were cultured on the surface of the coatings to evaluate their adhesion behavior. The obtained results showed that Si element was successfully incorporated into the porous TiO2 coating, which did not alter apparently the surface topography and phase composition of the coating. The adhesion of the MC3T3‐E1 cells on Si‐incorporated TiO2 coating was significantly enhanced compared with the Si‐free TiO2 coating and pure Ti plates. In addition, the enhanced cell adhesion may at least partly be mediated by integrin β1‐FAK signal transduction pathway. The present work suggests that the Si‐TiO2 coating is worth further consideration for orthopedic implant applications. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2011.
Characterization of bionanocomposite scaffolds comprised of amine‐functionalized gold nanoparticles and silicon carbide nanowires crosslinked to an acellular porcine tendon
Authors: Deeken Corey R. , Fox Derek B. , Bachman Sharon L. , Ramshaw Bruce J. , Grant Sheila A.
Published: March 2011

As one of the most common proteins found in the human body, collagen is regarded as biocompatible and has many properties making it ideal for soft‐tissue repair applications. However, collagen matrices fabricated from purified forms of collagen are notoriously weak and easily degraded by the body. The extracellular matrix of many tissues including human dermis, porcine dermis, and porcine small intestine submucosa are often utilized instead, and several of these scaffolds are crosslinked. Crosslinking has been shown to improve the mechanical properties of collagenous tissues and increase their resistance to degradation. In this study we investigated two novel “bionanocomposite” materials in which either gold nanoparticles or silicon carbide nanowires were crosslinked to a porcine tendon. Scanning electron micrographs confirmed that the nanomaterials were successfully crosslinked to the tissues. A collagenase assay, tensile testing, flow cytometry, and bioreactor studies were also performed to further characterize the properties of these novel materials. The results of these studies indicated that crosslinking porcine diaphragm tissues with nanomaterials resulted in scaffolds with improved resistance to enzymatic degradation and appropriate biocompatibility characteristics, thus warranting further study of these materials for soft tissue repair and tissue engineering applications. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2011.
Profiling signalling pathways in formalin‐fixed and paraffin‐embedded breast cancer tissues reveals cross‐talk between EGFR, HER2, HER3 and uPAR
Authors: Berg Daniela , Wolff Claudia , Malinowsky Katharina , Tran Kai , Walch Axel , Bronger Holger , Schuster Tibor , Höfler Heinz , Becker Karl‐Friedrich
Published: March 2011

In the last few years, new approaches and developments in patient‐tailored cancer therapies have raised the need to select, more precisely, those patients who will respond to personalized treatments. Therefore, the most efficient way for optimal therapy and patient selection is to provide a tumour‐specific protein network portrait prior to treatment. The aim of our study was to monitor protein networks in formalin‐fixed and paraffin‐embedded (FFPE) breast cancer tissues, with special emphasis on epidermal growth factor receptor 2 (HER2)‐mediated signalling pathways, to identify and validate new disease markers. For this purpose we used a recently developed technology to extract full‐length proteins from FFPE tissues and analysed 23 molecules involved in HER2‐related signalling by reverse phase protein microarray (RPPA) in a series of 106 FFPE breast cancer tissue samples. We found a significant correlation of HER2 with human epidermal growth factor receptor 3 (HER3/erbB3), epidermal growth factor receptor 1 (EGFR/HER1/erbB1) and urokinase plasminogen receptor (uPAR) in routinely used FFPE breast cancer tissues. Thus, targeting HER2, EGFR, HER3 and uPAR together may offer a more efficient treatment option for patients with breast cancer. J. Cell. Physiol. 227: 204–212, 2012. © 2011 Wiley Periodicals, Inc.
Synergistic anti‐tumor activity of isochaihulactone and paclitaxel on human lung cancer cells
Authors: Yu Yung‐Luen , Su Kuo‐Jung , Chen Cheng‐Jueng , Wei Chyou‐Wei , Lin Ching‐Ju , Yiang Giou‐Teng , Lin Shinn‐Zong , Harn Horng‐Jyh , Chen Yi‐Lin Sophia
Published: March 2011

Drug resistance frequently develops in tumors during chemotherapy. Therefore, to improve the clinical outcome, more effective and tolerable combination treatment strategies are needed. Here, we show that isochaihulactone (K8) enhanced paclitaxel‐induced apoptotic death in human lung cancer cells, and the enhancing effect was related to increased NSAID‐activated gene‐1 (NAG‐1) expression. CalcuSyn software was used to evaluate the synergistic interaction of K8 and paclitaxel on human lung cancer cells; the synergistic effect of K8 in combination with paclitaxel was increased more than either of these drugs alone. Furthermore, the activity of ERK1/2 was enhanced by the combination of K8 and paclitaxel, and an ERK1/2 inhibitor dramatically inhibited NAG‐1 expression in human lung cancer cells. Therefore, this synergistic apoptotic effect in human lung cancer cells may be directly associated with K8‐induced NAG‐1 expression through ERK1/2 activation. Moreover, over‐expression of NAG‐1 enhanced K8/paclitaxel‐induced apoptosis in human lung cancer cells. In addition, treatment of nude mice with K8 combined with paclitaxel induced phospho‐ERK1/2 and NAG‐1 expression in vivo. Targeting of NAG‐1 signaling could enhance therapeutic efficacy in lung cancer. Our results reveal that activation of NAG‐1 by K8 enhanced the therapeutic efficacy of paclitaxel in human lung cancer cells via the ERK1/2 signaling pathway. J. Cell. Physiol. 227: 213–222, 2012. © 2011 Wiley Periodicals, Inc.
MALDI‐ToF analysis of polythiophene: use of trans‐2‐[3‐(4‐t‐butyl‐phenyl)‐2‐methyl‐ 2‐propenylidene]malononitrile—DCTB—as matrix
Authors: Winter Julien De , Deshayes Gaëlle , Boon Florian , Coulembier Olivier , Dubois Philippe , Gerbaux Pascal
Published: March 2011

Nowadays, numerous experimental and theoretical studies are devoted to the research field of polythiophenes and other electroconjugated polymers due to the huge potentialities of those conducting polymers. Synthetic procedures are now developed to reach the highest control over both polymerization and analytical methodologies allowing an in‐depth and straightforward characterization of the polymer samples without any required doubt. Mass spectrometry methodologies and in particular MALDI‐ToF measurements are definitively suitable to meet the characterization requirements. In the present study, trans‐2‐[3‐(4‐t‐butyl‐phenyl)‐2‐methyl‐2‐propenylidene]malononitrile (DCTB) was shown to afford better results than the reported terthiophene and dithranol matrices as far as sensitivity and signal‐to‐noise ratio are concerned. We tentatively proposed that the ionization of the P3HT molecules is performed by charge exchange in the condensed phase (clusters) with matrix molecule radical cations and subsequent neutral matrix molecule evaporation from the clusters. The putative key parameters to account for the really high efficiency of DCTB for the MALDI analysis of P3HT are (1) the highest ionization energy of DCTB amongst the three matrices, (2) the really high absorptivity of the matrix molecule at the laser wavelength and (3) the presence of the tertiobutyl group on the matrix molecule. The presence of this substituent is likely to decrease the intermolecular interactions in the condensed phase rendering the evaporation of the neutral matrix molecules less energy demanding. We also demonstrated for polymer samples presenting an average number molecular weight (Mn) below 10 000 g mol−1 that the systematic overestimation of the low mass oligomers upon MALDI measurements ends up with wrong Mn and polydispersity index (PDI) values. A systematic Soxhlet extraction against heptane was shown to allow the recording of absolute Mn and PDI. Copyright © 2011 John Wiley & Sons, Ltd.
IRMPD and ECD fragmentation of intermolecular cross‐linked peptides
Authors: Santos Luiz Fernando Arruda , Eberlin Marcos Nogueira , Gozzo Fábio Cesar
Published: March 2011

Despite the increasing number of studies using mass spectrometry for three dimensional analyses of proteins (MS3D), the identification of cross‐linked peptides remains a bottleneck of the method. One of the main reasons for this is the lack of knowledge about the fragmentation of these species. Intermolecular cross‐linked peptides are considered the most informative species present in MS3D experiment, since different peptides are connected by a cross‐linker, the peptides chain can be either from a single protein, providing information about protein folding, or from two different proteins in a complex, providing information about binding partners, complex topology and interaction sites. These species tend to be large and highly charged in ESI, making comprehensive fragmentation by CID MS/MS problematic. On the other hand, these highly charged peptides are very suitable for dissociation using both infrared multiphoton dissociation (IRMPD) and electron capture dissociation (ECD). Herein, we report the fragmentation study of intermolecular cross‐linked peptides using IRMPD and ECD. Using synthetic peptides and different commercial cross‐linkers, a series of intermolecular cross‐linked peptides were generate, and subsequently fragmented by IRMPD and ECD in a FT‐ICR‐MS instrument. Due to the high mass accuracy and resolution of the FT‐ICR, the fragment ions could be attributed with high confidence. The peptides sequence coverage and fragmentation features obtained from IRMPD and ECD were compared for all charge states. Copyright © 2011 John Wiley & Sons, Ltd.
Factors affecting detectability of river otters during sign surveys
Authors: Jeffress Mackenzie R. , Paukert Craig P. , Sandercock Brett K. , Gipson Philip S.
Published: March 2011

Sign surveys are commonly used to study and monitor wildlife species but may be flawed when surveys are conducted only once and cover short distances, which can lead to a lack of accountability for false absences. Multiple observers surveyed for river otter (Lontra canadensis) scat and tracks along stream and reservoir shorelines at 110 randomly selected sites in eastern Kansas from January to April 2008 and 2009 to determine if detection probability differed among substrates, sign types, observers, survey lengths, and near access points. We estimated detection probabilities (p) of river otters using occupancy models in Program PRESENCE. Mean detection probability for a 400‐m survey was highest in mud substrates (p = 0.60) and lowest in snow (p = 0.18) and leaf litter substrates (p = 0.27). Scat had a higher detection probability (p = 0.53) than tracks (p = 0.18), and experienced observers had higher detection probabilities (p > 0.71) than novice observers (p < 0.55). Detection probabilities increased almost 3‐fold as survey length increased from 200 m to 1,000 m, and otter sign was not concentrated near access points. After accounting for imperfect detection, our estimates of otter site occupancy based on a 400‐m survey increased >3‐fold, providing further evidence of the potential negative bias that can occur in estimates from sign surveys when imperfect detection is not addressed. Our study identifies areas for improvement in sign survey methodologies and results are applicable for sign surveys commonly used for many species across a range of habitats. © 2010 The Wildlife Society