bluuebunny/crossref_metadata_2025 huggingface dataset:
P‐glycoprotein and cytochrome P450 3A act together in restricting the oral bioavailability of paclitaxel
Authors: Hendrikx Jeroen J.M.A. , Lagas Jurjen S. , Rosing Hilde , Schellens Jan H.M. , Beijnen Jos H. , Schinkel Alfred H.
Published: October 2012

Paclitaxel is avidly transported by P‐glycoprotein (P‐gp/MDR1/ABCB1). This results in low oral bioavailability, which can be boosted by coadministration of P‐gp inhibitors. Unlike paclitaxel, docetaxel is extensively metabolized by CYP3A4 and its oral bioavailability can be enhanced in mice and humans by coadministration of the potent CYP3A inhibitor ritonavir. Unexpectedly, ritonavir also enhances the oral bioavailability of paclitaxel in humans. We aimed to resolve the mechanism underlying this enhancement. Using mice lacking Cyp3a and/or P‐gp, we investigated the combined and separate restricting roles of Cyp3a and P‐gp in the oral bioavailability of paclitaxel, and the boosting effect of ritonavir. CYP3A4‐humanized mice were used for translation to the human situation. P‐gp had a dominant effect (11.6‐fold, p < 0.001) over Cyp3a (<1.5‐fold, n.s.) in limiting plasma concentrations of oral paclitaxel. However, in the absence of P‐gp, Cyp3a decreased paclitaxel plasma concentrations twofold (p < 0.001). Coadministered ritonavir inhibited Cyp3a‐mediated metabolism, but not P‐gp‐mediated transport of paclitaxel. Owing to the dominant effect of P‐gp, ritonavir enhanced only paclitaxel plasma concentrations in P‐gp‐deficient mice. Mouse liver microsomes metabolized paclitaxel far less efficiently than human or CYP3A4‐transgenic liver microsomes, revealing much lower efficiency of paclitaxel metabolism by mouse than by human CYP3As. Accordingly, ritonavir could enhance the oral bioavailability of paclitaxel in CYP3A4‐humanized mice, despite the fact that these mice are P‐gp‐proficient. Our results show that CYP3A4 inhibition most likely underlies the boosting effect of ritonavir on oral paclitaxel bioavailability in humans. Furthermore, CYP3A4‐humanized mice allow improved understanding of CYP3A4‐mediated paclitaxel metabolism in humans.
Where Are They? A Multilens Examination of the Distribution of Full‐Time Faculty by Institutional Type, Race/Ethnicity, Gender, and Citizenship
Authors: Smith Daryl G. , Tovar Esau , García Hugo A.
Published: October 2012

This introduction chapter presents descriptive statistics on the postsecondary faculty population in the United States and highlights the progressing diversity and growing number of minority, women, and international faculty
Lessons from the Past and Directions for the Future
Authors: Xu Yonghong Jade
Published: October 2012

Four themes that have emerged from the previous chapters are discussed; changes and improvements are suggested for future data collection and institutional research on faculty diversity.
Acceptance and commitment therapy for fibromyalgia: A randomized controlled trial
Authors: Wicksell R. K. , Kemani M. , Jensen K. , Kosek E. , Kadetoff D. , Sorjonen K. , Ingvar M. , Olsson G. L.
Published: October 2012

Background

Fibromyalgia (FM) is characterized by widespread pain and co‐morbid symptoms such as fatigue and depression. For FM, medical treatments alone appear insufficient. Recent meta‐analyses point to the utility of cognitive behaviour therapy (CBT), but effects are moderate. Within the continuous development of CBT, the empirical support for acceptance and commitment therapy (ACT) has increased rapidly. ACT focuses on improving functioning by increasing the patient's ability to act in accordance with personal values also in the presence of pain and distress (i.e., psychological flexibility). However, no study has yet explored the utility of ACT in FM.

Objectives

To evaluate the efficacy of ACT for FM and the role of psychological inflexibility as a mediator of improvement.

Methods

In this randomized controlled trial, ACT was evaluated in comparison to a waiting list control condition. Forty women diagnosed with FM participated in the study. Assessments were made pre‐ and post‐treatment and at 3 months of follow‐up. The ACT intervention consisted of 12 weekly group sessions.

Results

Significant differences in favour of ACT were seen in pain‐related functioning, FM impact, mental health‐related quality of life, self‐efficacy, depression, anxiety and psychological inflexibility. Changes in psychological inflexibility during the course of treatment were found to mediate pre‐ to follow‐up improvements in outcome variables.

Conclusions

The results correspond with previous studies on ACT for chronic pain and suggest the utility of ACT for FM as well as the role of psychological inflexibility as a mediator of improvement.
Effect of BDNF–plasma–collagen matrix controlled delivery system on the behavior of adult rats neural stem cells
Authors: Yang Zhaoyang , Qiao Hui , Sun Zhiwei , Li Xiaoguang
Published: October 2012

The neurogenesis amount in central nervous system (CNS) stimulated by the injury or diseases is so small that neural stem cells (NSCs) cannot specifically differentiate into the ideal phenotypes to repair the injured CNS. The transplanted exogenous NSCs also have such problems as poor survival and insufficient neuronal differentiation. In this study, the behavior of NSCs from the spinal cord of adult rats was compared at the neurosphere level after the respective addition of the brain‐derived neurotrophic factor (BDNF) daily, the BDNF‐loaded plasma–collagen matrix, the plasma–collagen matrix alone, or the defined medium alone. The results suggested that the BDNF, either in the control release form or in the soluble form, initiated NSCs proliferation and differentiation by activating receptors Trk B and p75NTR. BDNF also increased the differentiation percentage of adult NSCs into neurons and supported the long‐term cell survival and growth. The BDNF was stably released by the plasma‐collagen matrix for up to 21 days. The plasma–collagen matrix alone showed its biocompatibility with cells by facilitating the adhesion, survival, and differentiation of NSCs. The NSCs in the defined medium alone group showed poor survival and a very low level of neuronal differentiation and proliferation abilities than above three groups. This study suggested that the BDNF‐loaded plasma–collagen matrix may provide a promising means to resolve either the poor survival and insufficient neuronal differentiation of transplanted exogenous NSCs, or stimulating the intrinsic NSCs to proliferate and differentiate into neurons so as to repair the injured adult CNS. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013.
Mechanisms underlying the inhibition of murine sperm capacitation by the seminal protein, SPINKL
Authors: Tseng Huan‐Chin , Lee Robert Kuo‐Kuang , Hwu Yuh‐Ming , Lu Chung‐Hao , Lin Ming‐Huei , Li Sheng‐Hsiang
Published: October 2012

SPINKL, a serine protease inhibitor kazal‐type‐like protein initially found in mouse seminal vesicle secretions, possesses structurally conserved six‐cysteine residues of the kazal‐type serine protease inhibitor family. However, it has no inhibitory activity against serine proteases. Previously, it was found to have the ability to suppress murine sperm capacitation in vitro. Herein, we investigated the mechanisms underlying the suppressive effect of SPINKL on sperm capacitation. Three in vitro capacitation‐enhancing agents, including bovine serum albumin (BSA), methyl‐beta‐cyclodextrin (MBCD), and dibutyryl cyclic AMP (dbcAMP), coupled with 3‐isobutyl‐1‐methylxanthine (IBMX), were used to evaluate the influence of SPINKL on capacitation signaling. Preincubation of sperm with SPINKL suppressed BSA‐ and MBCD‐induced sperm capacitation by blocking three upstream signals of capacitation that is the cholesterol efflux from sperm plasma membranes, extracellular calcium ion influx into sperm, and increases in intracellular cAMP. Moreover, SPINKL also inhibited downstream signal transduction of capacitation since it suppressed dbcAMP/IBMX and N6‐phenyl cAMP (6‐Phe‐cAMP)‐activated cAMP‐dependent protein kinase‐associated protein tyrosine phosphorylation. Such inhibition is probably mediated by attenuation of SRC tyrosine kinase activity. Furthermore, SPINKL could not reverse capacitation once sperm had been capacitated by capacitation‐enhancing agents or capacitated in vivo in the oviduct. SPINKL bound to sperm existed in the uterus but had disappeared from sperm in the oviduct during the sperm's transit through the female reproductive tract. Therefore, SPINKL may serve as an uncapacitation factor in the uterus to prevent sperm from precocious capacitation and the subsequent acrosome reaction and thus preserve the fertilization ability of sperm. J. Cell. Biochem. 114: 888–898, 2013. © 2012 Wiley Periodicals, Inc.
Spodoptera frugiperda FKBP‐46 is a consensus p53 motif binding protein
Authors: Mohareer Krishnaveni , Sahdev Sudhir , Hasnain Seyed E.
Published: October 2012

p53 protein, the central molecule of the apoptosis pathway, is mutated in 50% of the human cancers. Of late, p53 homologues have been identified from different invertebrates including Drosophila melanogaster, Caenorhabditis elegans, Squid, and Clams. We report the identification of a p53‐like protein in Spodoptera frugiperda (Sf9) insect cells, which is activated during oxidative stress, caused by exposure to UV‐B or H2O2, and binds to p53 consensus DNA binding motifs as well as other p53 cognate motifs. Sf9 p53 motif‐binding protein is similar to murine and Drosophila p53 in terms of molecular size, which is around 50–60 kDa, as evident from UV cross‐linking, and displays DNA binding characteristics similar to both insect and vertebrate p53 as seen from electrophoretic mobility shift assays. The N‐terminal sequencing of the purified Sf9 p53 motif‐binding protein reveals extensive homology to the pro‐apoptotic FK‐506 binding protein (FKBP‐46), earlier identified in Sf9 cells as a factor which interacts with murine casein kinase. FKBP, an evolutionarily conserved protein of mammalian origin functions as a pro‐apoptotic factor. Identification of FKBP‐46 as a novel p53 motif‐binding protein in insect cells adds a new facet to our understanding of the mechanisms of apoptosis under oxidative stress in the absence of a typical p53 homologue. J. Cell. Biochem. 114: 899–907, 2013. © 2012 Wiley Periodicals, Inc.
Characterization of Oct4‐GFP spermatogonial stem cell line and its application in the reprogramming studies
Authors: Youn Haesun , Kim Song‐Hee , Choi Kyung Ah , Kim Sungtae
Published: October 2012

Establishment of mouse spermatogonial stem cell (SSC) culture systems offers a useful stem cell model for studies of proliferation and self‐renewal of mammalian germline stem cells. In addition, spontaneous development of pluripotent stem cells from cultured SSCs emphasizes their possible applications in regenerative medicine as a substitute for embryonic stem cells (ESCs). These pluripotent stem cells termed multipotent germline stem cells (mGSCs) or germline‐derived pluripotent stem cells (gPSCs) exhibit almost identical properties in terms of morphology and gene expression patterns to mouse ESCs (mESCs). In this study, to help understand mechanisms underlying reprogramming of SSCs into pluripotent stem cells, we established a culture system of SSCs derived from mice harboring green fluorescence protein (GFP) transgene whose expression is modulated by Oct4 regulatory sequences. Our results indicated that GFP intensity faithfully reflected cellular states upon reprogramming of SSCs or treatment with a selective extracellular signal‐regulated kinase (ERK) inhibitor PD0325901. Moreover, in contrast to mESCs, regulation of Nanog expression did not appear to couple to the Oct4 level in SSCs. Further analysis of Oct4‐GFP SSCs demonstrated that a posttranscriptional control of pluripotency marker genes such as Oct4 and Sox2 might play an important role as an inhibitory mechanism preventing the acquisition of pluripotency. J. Cell. Biochem. 114: 920–928, 2013. © 2012 Wiley Periodicals, Inc.
Dual‐source parallel RF transmission for diffusion‐weighted imaging of the abdomen using different b values: Image quality and apparent diffusion coefficient comparison with conventional single‐source transmission
Authors: Guo Lijun , Liu Cheng , Chen Weibo , Chan Queenie , Wang Guangbin
Published: October 2012

Purpose:

To prospectively and intraindividually evaluate what effects dual‐source parallel radiofrequency (RF) transmission have on image quality and apparent diffusion coefficient (ADC) of abdomen diffusion‐weighted imaging (DWI) using different b values, compared with the single‐source RF transmission.

Materials and Methods:

Eighteen healthy male volunteers were enrolled in this Health Insurance Portability and Accountability Act (HIPAA)‐compliant Institutional Review Board (IRB)‐approved study. Abdominal DWI was performed with dual‐source and single‐source RF transmission at 3.0 T using a series of b‐value combinations: 0/100, 0/500, 0/800, and 0/100/800. RF field homogeneity, subjective image quality, and signal to noise ratio (SNR) of each abdominal organ were evaluated. ADC values were calculated for each abdominal organ. Wilcoxon test and repeated‐measures analysis of variance was used to calculate statistical significance.

Results:

The parallel RF transmission significantly improved homogeneity of the RF field (P = 0.0001–0.008) and subjective image quality (P < 0.0001) at each b value and also increased SNR. At lower and higher b value, the measured ADC of lateral left hepatic lobe and spleen between dual‐source and single‐source images were significantly different (P = 0.0001–0.047). At b = 0/500, there was no significant difference in ADC measurements between dual‐source and single‐source RF transmission for abdominal organs, except a slight statistically significant difference for spleen (P = 0.047).

Conclusion:

Parallel RF transmission significantly improved the image quality and homogeneity of the RF field. The RF transmission had a significant influence on measured ADC of lateral left hepatic lobe and spleen. At b = 0/500 the influence was minimum for all abdominal organs. J. Magn. Reson. Imaging 2013;37:875–885. © 2012 Wiley Periodicals, Inc.
Ferumoxytol in clinical practice: Implications for MRI
Authors: McCullough Brendan J. , Kolokythas Orpheus , Maki Jeffrey H. , Green Douglas E.
Published: October 2012

Ferumoxytol is an iron‐containing parenteral treatment for iron deficiency anemia that was recently approved by the Food and Drug Administration. The iron is in the form of a superparamagnetic iron oxide that causes T1, T2, and T2* shortening on magnetic resonance imaging (MRI). Furthermore, the drug has a long intravascular half‐life of 14–15 hours; a standard dose can affect MRI for days to months. We describe a case in which a patient underwent contrast‐enhanced MRI of the liver 2 days after receiving a dose of ferumoxytol, which was unknown to the radiology team. The blood pool and soft tissues were hyperintense on T1‐weighted images, concealing enhancement from the gadolinium‐based contrast agent that was administered during the exam and rendering the exam nondiagnostic. Radiologists must be aware of this potential effect in screening patients for MRI and interpreting exams. J. Magn. Reson. Imaging 2013;37:1476–1479. © 2012 Wiley Periodicals, Inc.
Evaluation of left atrial contraction contribution to left ventricular filling using cardiovascular magnetic resonance
Authors: Alhogbani Tariq , Strohm Oliver , Friedrich Matthias G.
Published: October 2012

Purpose:

To describe a new method to quantify the left atrial contraction contribution (ACC) to left ventricular (LV) filling using cardiovascular magnetic resonance (CMR).

Materials and Methods:

We assessed 120 normal subjects (50% female) using steady‐state free precession CMR volumetry. Volumes measurements were performed using short axis and rotational long axis views. The percentage of ACC was calculated by dividing the LV filling volume resulting from left atrial (LA) contraction by the LV stroke volume (LVSV).

Results:

The described method was well reproducible. The ACC in normal subjects was 15 ± 5% for ages <40 years, 28 ± 8% for ages 40 to 55 years, and 38 ± 5% for ages >55 years. When adjusted for age, ie, dividing the ACC percentage by age, a value between 0.4 and 0.7 was found to represent the normal range of ACC at any age.

Conclusion:

The study presents a new and accurate CMR volumetric method to quantify ACC to LV filling. ACC ranges from 10%–40%, depending on age. J. Magn. Reson. Imaging 2013;37:860–864. © 2012 Wiley Periodicals, Inc.
Evaluation of the tibial tunnel after intraoperatively administered platelet‐rich plasma gel during anterior cruciate ligament reconstruction using diffusion weighted and dynamic contrast‐enhanced MRI
Authors: Rupreht Mitja , Jevtič Vladimir , Serša Igor , Vogrin Matjaž , Jevšek Marko
Published: October 2012

Purpose:

To evaluate effect of platelet‐rich plasma gel (PRPG), locally administered during the anterior cruciate ligament (ACL) reconstruction, with two MRI methods. The proximal tibial tunnel was assessed with diffusion weighted imaging (DWI) and with dynamic contrast‐enhanced imaging (DCE‐MRI).

Materials and Methods:

In 50 patients, standard arthroscopic ACL reconstructions were performed. The patients in the PRPG group (n = 25) received a local application of PRPG. The proximal tibial tunnel was examined by DWI and DCE‐MRI, which were used to calculate apparent diffusion coefficient (ADC) values, as well as the contrast enhancement gradient (Genh) and enhancement factor (Fenh) values.

Results:

At 1 month, the calculated average ADC value in the PRPG group was significantly lower than in the control group. At 2.5 and at 6 months, Genh was significantly higher in the PRPG group. There were no significant differences in Fenh between the groups at any control examination.

Conclusion:

DWI and DCE‐MRI measurements indicate a reduced extent of edema during the first postoperative month as well as an increased vascular density and microvessel permeability in the proximal tibial tunnel at 1 and 2.5 postoperative months as the effect of the application of PRPG. J. Magn. Reson. Imaging 2013;37:928–935. © 2012 Wiley Periodicals, Inc.
Multidrug‐resistant hepatitis B virus resulting from sequential monotherapy with lamivudine, adefovir, and entecavir: Clonal evolution during lamivudine plus adefovir therapy
Authors: Kim Soon Sun , Cho Sung Won , Kim Soo‐Ok , Hong Sun Pyo , Cheong Jae Youn
Published: October 2012

Whether multidrug‐resistant (MDR) hepatitis B virus (HBV) harbors mutations co‐located in the same HBV clones that confer reduced sensitivity to antiviral therapy remains uncertain. This study investigated the evolution of MDR HBV strains developed from sequential monotherapy with lamivudine (LAM), adefovir (ADV), and entecavir (ETV) during LAM plus ADV salvage therapy. Sera were obtained from six patients who had developed sequential resistance to LAM, ADV, and ETV before and during LAM plus ADV therapy. The HBV genomes from each patient were amplified, cloned, and sequenced. Among 6 sets of 20 clones obtained before salvage therapy, all clones harbored the rtM204V mutation, and ETV‐resistant mutations were detected with the rtM204V in 108 clones. The rtA181 mutation was not detected at baseline, but emerged in five patients during therapy. Among 9 sets of 20 clones obtained during salvage therapy, 39 clones harbored rtA181T/V ± rtN236T mutations, which were detected in the absence of rtM204 and ETV‐resistant mutations in 37 clones (94.9%). Only two clones (5.1%) harbored both rtA181T/V and ETV‐resistant mutations. The rtA181T/V mutation emerged after reversion from ETV‐resistant mutants to wild‐type HBV. Five patients achieved a partial virologic response to LAM plus ADV therapy. In conclusion, the majority of MDR mutations existed in different genomes. Suboptimal response to LAM plus ADV therapy may not result from the co‐localization of MDR HBV mutations in the same genome, but instead the low antiviral potency of these drugs. Thus, more potent antiviral drug combinations may be an effective salvage therapy for patients infected with MDR HBV. J. Med. Virol. 85:55–64, 2012. © 2012 Wiley Periodicals, Inc.
BMP‐6 and BMPR‐1a are up‐regulated in the growth plate of the fractured tibia
Authors: Fischerauer Eva E. , Manninger Martin , Seles Maximilian , Janezic Gregor , Pichler Karin , Ebner Birgit , Weinberg Annelie M.
Published: October 2012

Bone overgrowth is a known phenomenon occurring after fracture of growing long bones with possible long‐term physical consequences for affected children. Here, the physeal expression of bone morphogenetic proteins (BMPs) was investigated in a fracture‐animal model to test the hypothesis that a diaphyseal fracture stimulates the physeal expression of these known key regulators of bone formation, thus stimulating bone overgrowth. Sprague–Dawley rats (male, 4 weeks old), were subjected to a unilateral mid‐diaphyseal tibial fracture. Kinetic expression of physeal BMP‐2, ‐4, ‐6, ‐7, and BMP receptor‐1a (BMPR‐1a) was analyzed in a monthly period by quantitative real time‐polymerase chain reaction and immunohistochemistry. On Days 1, 3, 10, and 14 post‐fracture, no changes in physeal BMPs gene‐expression were detected. Twenty‐nine days post‐fracture, when the fracture was consolidated, physeal expression of BMP‐6 and BMPR‐1a was significantly upregulated in the growth plate of the fractured and contra‐lateral intact bone compared to control (p < 0.005). This study demonstrates a late role of BMP‐6 and BMPR‐1a in fracture‐induced physeal growth alterations and furthermore, may have discovered the existence of a regulatory “cross‐talk” mechanism between the lower limbs whose function could be to limit leg‐length‐discrepancies following the breakage of growing bones. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 357–363, 2013
Optimization of the position of the acetabulum in a ganz periacetabular osteotomy by finite element analysis
Authors: Zou Zhenmin , Chávez‐Arreola Arturo , Mandal Parthasarathi , Board Tim N , Alonso‐Rasgado Teresa
Published: October 2012

Periacetabular osteotomy (PAO) is a surgical procedure to correct acetabular orientation in developmental dysplasia of the hip (DDH). It changes the position of the acetabulum to increase femoral head coverage and distribute the contact pressure over the cartilage surface. The success of PAO depends significantly on the surgeon's experience. Using computed tomography data from patients with DDH, we developed a 3D finite element (FE) model to investigate the optimal position of the acetabulum following PAO. A virtual PAO was performed with the acetabulum rotated in increments from the original center edge (CE) angle. Contact area, contact pressure, and Von Mises stress in the femoral and pelvic cartilage were analyzed. Five dysplastic hips from four patients were modeled. Contact area, contact pressure, and Von Mises stress in the cartilage all varied according to the change of CE angle through virtual PAO. An optimal position could be achieved for the acetabulum that maximizes the contact area while minimizing the contact pressure and von Mises stress in the pelvic and femoral cartilage. The optimal position of the acetabulum was patient dependent and did not always correspond to what would be considered a “normal” CE angle. We demonstrated for the first time the interrelation of correction angle, contact area, and contact pressure between the pelvic and femoral cartilage in PAO surgery. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 472–479, 2013
Micro‐Raman and GC/MS analysis to characterize the wall painting technique of Dicho Zograph in churches from Republic of Macedonia
Authors: Čukovska Lidija Robeva , Minčeva – Šukarova Biljana , Lluveras‐Tenorio Anna , Andreotti Alessia , Colombini Maria Perla , Nastova Irena
Published: October 2012

Micro‐Raman spectroscopy, pyrolysis/gas chromatography–mass spectrometry (Py/GC/MS) and gas chromatography‐mass spectrometry (CG/MS) were applied for the characterization of pigments and binders used in the wall paintings ascribed to the works of the prominent 19th century Macedonian iconographer, Dicho Zograph. Among numerous works attributed to him, wall paintings from three churches in the Western part of the Republic of Macedonia have been selected for pigment and binder analysis.

A rich palette of pigments, both natural/mineral and synthetic ones, were identified by micro‐Raman spectroscopy. Organic material analysis evidenced the use of mixtures of proteinaceous materials (mainly animal glue and egg) with linseed oil and pine resin, while saccharide materials were excluded.

A comparison between the pigments and binders identified in this study and those suggested in Dicho's Painter's Manual (from 1851) showed that some materials had not been mentioned in his written source. Copyright © 2012 John Wiley & Sons, Ltd.
Heterostereocomplex Crystallization and Homocrystallization From the Melt in Blends of Substituted and Unsubstituted Poly(lactide)s
Authors: Tsuji Hideto , Deguchi Fumiaki , Sakamoto Yuzuru , Shimizu Satoru
Published: October 2012

Poly(L‐2‐hydroxybutyrate) [P(L‐2HB)] and poly(D‐lactide) (PDLA) in their blends were phase separated to form P(L‐2HB)‐ and PDLA‐enriched domains, and heterostereocomplex (HTSC) crystallization occurred at the interface between these domains. In the blends, HTSC crystallites were formed at crystallization temperature (Tc) = 80–160 °C, and their exclusive formation without the formation of other crystalline species was observed at Tc of 150 or 160 °C. The effects of polymer blend ratio on the types of formed crystalline species were very small due to the phase separation of the blends. The presence of a small amount of P(L‐2HB) decreased the low limit of crystallizable Tc of PDLA homocrystallites from 80 to 60 °C. The equilibrium melting temperature of HTSC crystallites was 257.6 °C.
Influence of Comesogens on the Thermal and Actuation Properties of 2‐tert‐Butyl‐1,4‐bis[4‐(4‐pentenyloxy)benzoyl]hydroquinone Based Nematic Main‐Chain Liquid Crystalline Elastomers
Authors: Melchert Christian , Behl Marc , Nöchel Ulrich , Lendlein Andreas
Published: October 2012

Although the shape‐changing capabilities of LCEs hold great potential for applications ranging from micropumps to artificial muscles, customization of the LCE functionality to the applications' requirements is still a challenge. It is studied whether the orientation of NMC‐LCPs and NMC‐LCEs based on 2‐tert‐butyl‐1,4‐bis[4‐(4‐pentenyloxy)benzoyl]hydroquinone can be enhanced by copolymerization with 2‐methyl‐1,4‐bis[4‐(4‐pentenyloxy)benzoyl]hydroquinone or 2,6‐bis[4‐(4‐pentenyl‐oxy)‐benzoyl]anthracene. An increasing content of the comonomers stabilizes the nematic phase, which enables a tailoring ofTNIfor the NMC‐LCP between 45 and 68 °C, while for the NMC‐LCETNIranges between 69 and 76 °C. In addition, NMC‐LCE show an increased actuation performance.

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Postnatal longitudinal evaluation of children diagnosed with prenatal hydronephrosis: insights in natural history and referral pattern
Authors: Barbosa Joao A. B. A. , Chow Jeanne S. , Benson Carol B. , Yorioka Marco A. , Bull Alexandre S. , Retik Alan B. , Nguyen Hiep T.
Published: October 2012

Objectives

Clinical significance and management of prenatal hydronephrosis (PNH) are sources of debate. Existing studies are flawed with biased cohorts or inconsistent follow‐up. We aimed to evaluate the incidence of pathology in a large cohort of PNH and assess the biases and outcomes of this population.

Methods

We reviewed 1034 charts of fetuses with PNH. Records of delivered offspring were reviewed at a pediatric center and analyzed with respect to prenatal and postnatal pathology and management.

Results

Prenatal resolution of hydronephrosis occurred in 24.7% of pregnancies. On first postnatal ultrasound, some degree of dilatation was present in 80%, 88% and 95% of mild, moderate and severe PNH cases, respectively. At the end of follow‐up, hydronephrosis persisted in 10%, 25% and 72% of children, respectively. Incidence of vesicoureteral reflux did not correlate with severity of PNH. Children with postnatal workup had more severe PNH than those without.

Conclusions

Despite prenatal resolution totalizing 25%, pelvic dilatation persisted on first postnatal imaging in most cases, thus justifying postnatal ultrasound evaluation. Whereas most mild cases resolved spontaneously, a quarter of moderate and more than half of severe cases required surgery. Patients with postnatal imaging and referral had more severe PNH, which could result in overestimation of pathology. © 2012 John Wiley & Sons, Ltd.
Solid‐phase glycan isolation for glycomics analysis
Authors: Yang Shuang , Zhang Hui
Published: October 2012

Glycosylation is one of the most significant protein PTMs. The biological activities of proteins are dramatically changed by the glycans associated with them. Thus, structural analysis of the glycans of glycoproteins in complex biological or clinical samples is critical in correlation with the functions of glycans with diseases. Profiling of glycans by HPLC‐MS is a commonly used technique in analyzing glycan structures and quantifying their relative abundance in different biological systems. Methods relied on MS require isolation of glycans from negligible salts and other contaminant ions since salts and ions may interfere with the glycans, resulting in poor glycan ionization. To accomplish those objectives, glycan isolation and clean‐up methods including SPE, liquid‐phase extraction, chromatography, and electrophoresis have been developed. Traditionally, glycans are isolated from proteins or peptides using a combination of hydrophobic and hydrophilic columns: proteins and peptides remain on hydrophobic absorbent while glycans, salts, and other hydrophilic reagents are collected as flowthrough. The glycans in the flowthrough are then purified through graphite‐activated carbon column by hydrophilic interaction LC. Yet, the drawback in these affinity‐based approaches is nonspecific binding. As a result, chemical methods by hydrazide or oxime have been developed for solid‐phase isolation of glycans with high specificity and yield. Combined with high‐resolution MS, specific glycan isolation techniques provide tremendous potentials as useful tools for glycomics analysis.
Application of 2D‐DIGE to formalin‐fixed diseased tissue samples from hospital repositories: Results from four case studies
Authors: Tanca Alessandro , Pisanu Salvatore , Biosa Grazia , Pagnozzi Daniela , Antuofermo Elisabetta , Burrai Giovanni P. , Canzonieri Vincenzo , Cossu‐Rocca Paolo , Re Valli De , Eccher Albino , Fanciulli Giuseppe , Rocca Stefano , Uzzau Sergio , Addis Maria Filippa
Published: October 2012

Purpose

In the recent past, the potential suitability of fixed samples to 2D‐DIGE studies has been demonstrated on model tissues, but not on “real‐world” archival tissues. Therefore, this study was aimed to assess the quality of the results delivered by 2D‐DIGE on samples retrieved from hospital tissue repositories.

Experimental design

Diseased and normal tissue samples (namely, human gastric adenocarcinoma and normal gastric tissue, human lung neuroendocrine tumors, canine mammary tubulo‐papillary carcinoma and normal mammary tissue, sheep liver with cloudy swelling degeneration and normal liver tissue) were retrieved from human and veterinary biorepositories and subjected to full‐length protein extraction, cyanine labeling, 2D‐DIGE separation, image analysis, MS analysis, and protein identification.

Results

Archival samples could be successfully subjected to 2D‐DIGE, providing maps of satisfactory resolution, although with varying pattern complexity (possibly influenced by preanalytical variables). Moreover, differentially expressed protein identities were consistent with the disease biology.

Conclusions and clinical relevance

2D‐DIGE can support biomarker discovery and validation studies on large sample cohorts. In fact, although some information complexity is lost when compared to fresh‐frozen tissues, their vast availability and the associated patient information can considerably boost studies suffering limited sample availability or involving long‐distance exchange of samples.
SWCNT growth from C:Ni nanocomposites
Authors: Krause Matthias , Haluška Miro , Abrasonis Gintautas , Gemming Sibylle
Published: October 2012

Carbon:nickel (C:Ni) nanocomposite thin films deposited by ion beam co‐sputtering were used for catalytic chemical vapor deposition (CVD) growth of single‐walled carbon nanotubes (SWCNTs). The SWCNTs were characterized by scanning electron microscopy and Raman spectroscopy. The approach allows a precise and reproducible control of the catalyst diameter, while the embedding carbon matrix prevents the particles from coalescence during catalyst activation and nanotube growth. The SWCNTs obtained from Ni particles with ∼4 nm diameter have a radial breathing mode frequency distribution of 147.5 ± 32 cm−1 and a diameter distribution of 1.6 ± 0.4 nm. Small line widths of the radial breathing mode and ID/IG ratios of 0.05 indicate SWCNTs with a low defect concentration.

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Left: Scheme of C:Ni nanocomposite based SWCNT synthesis. The dark contrast image regions correspond to the Ni particles. Right: Radial breathing mode Raman spectrum of a structurally highly ordered SWCNT.
Geometry dependent performance of bucky gel actuators: Increasing operating frequency by miniaturization
Authors: Biso Maurizio , Ansaldo Alberto , Ricci Davide
Published: October 2012

Bucky gel actuators are one of the most promising type of electrochemical actuators based on carbon nanotubes (CNTs). They are lightweight, they are able to work in air without any liquid electrolyte and require just few volts to operate. In order to find real world applications where bucky gel actuators can outperform conventional motors, there are still some issues to be addressed. One key aspect in CNT‐based electrochemical actuators is that their actuation speed is limited by the ability of charging and discharging the device without exceeding the electrochemical stability window of the electrolyte. This speed is macroscopically related with the product of the resistance and the capacitance of the equivalent circuit (circuit time constant), and with the ion diffusion speed inside the active electrodes. To enhance the actuator performance it is necessary to increase the ion drift current in the electrolyte avoiding to significantly raise the voltage at the electrodes and shorten the ion path necessary to charge the bucky gel electrodes. By proper material processing, we have successfully addressed this issue. A reduced thickness of the actuators to one third of the original size results in a one order of magnitude increase both of the strain at higher frequencies and of the maximum operating frequency.
Studies on some exponential‐screened coulomb potentials
Authors: Roy Amlan K.
Published: October 2012

The generalized pseudospectral method is used to study the bound‐state spectra of some of the exponentially screened Coulomb potentials, namely, the exponential cosine screened Coulomb (ECSC) and general exponential screened Coulomb (GESC) potential, with special emphasis on higher states and stronger interaction. Eigenvalues accurate up to 11 significant figures are obtained through a nonuniform optimal spatial discretization of the radial Schrödinger equation. All the 55 eigenstates of ECSC potential with n ≤ 10 and 36 eigenstates of GESC potential with n ≤ 8 are considered for arbitrary values of the screening parameter, covering a wide range of interaction. Excited states as high as up to n = 18 have been computed with high accuracy for the first time. Excellent agreement with the literature data has been observed in all cases. All the GESC eigenstates are calculated with much greater accuracy than the existing methods available in literature. Many l ≠ 0 states of this potential are reported here. In both cases, a detailed variation of energies with respect to the parameters in potential is monitored. © 2012 Wiley Periodicals, Inc.
Emergency response to the nuclear accident at the Fukushima Daiichi Nuclear Power Plants using mobile rescue robots
Authors: Nagatani Keiji , Kiribayashi Seiga , Okada Yoshito , Otake Kazuki , Yoshida Kazuya , Tadokoro Satoshi , Nishimura Takeshi , Yoshida Tomoaki , Koyanagi Eiji , Fukushima Mineo , Kawatsuma Shinji
Published: October 2012

On March 11, 2011, a massive earthquake (magnitude 9.0) and accompanying tsunami hit the Tohoku region of eastern Japan. Since then, the Fukushima Daiichi Nuclear Power Plants have been facing a crisis due to the loss of all power that resulted from the meltdown accidents. Three buildings housing nuclear reactors were seriously damaged from hydrogen explosions, and, in one building, the nuclear reactions became out of control. It was too dangerous for humans to enter the buildings to inspect the damage because radioactive materials were also being released. In response to this crisis, it was decided that mobile rescue robots would be used to carry out surveillance missions. The mobile rescue robots needed could not be delivered to the Tokyo Electric Power Company (TEPCO) until various technical issues were resolved. Those issues involved hardware reliability, communication functions, and the ability of the robots' electronic components to withstand radiation. Additional sensors and functionality that would enable the robots to respond effectively to the crisis were also needed. Available robots were therefore retrofitted for the disaster reponse missions. First, the radiation tolerance of the electronic componenets was checked by means of gamma ray irradiation tests, which were conducted using the facilities of the Japan Atomic Energy Agency (JAEA). The commercial electronic devices used in the original robot systems operated long enough (more than 100 h at a 10% safety margin) in the assumed environment (100 mGy/h). Next, the usability of wireless communication in the target environment was assessed. Such tests were not possible in the target environment itself, so they were performed at the Hamaoka Daiichi Nuclear Power Plants, which are similar to the target environment. As previously predicted, the test results indicated that robust wireless communication would not be possible in the reactor buildings. It was therefore determined that a wired communication device would need to be installed. After TEPCO's official urgent mission proposal was received, the team mounted additional devices to facilitate the installation of a water gauge in the basement of the reactor buildings to determine flooding levels. While these preparations were taking place, prospective robot operators from TEPCO trained in a laboratory environment. Finally, one of the robots was delivered to the Fukushima Daiichi Nuclear Power Plants on June 20, 2011, where it performed a number of important missions inside the buildings. In this paper, the requirements for the exploration mission in the Fukushima Daiichi Nuclear Power Plants are presented, the implementation is discussed, and the results of the mission are reported.
Co‐evolutionary analysis: a policy exploration method for system dynamics models
Authors: Liu Hongliang , Howley Enda , Duggan Jim
Published: October 2012

In system dynamics (SD), complex nonlinear systems can generate a wide range of possible behaviours that frequently require search and optimization algorithms in order to explore optimal policies. Within the SD literature, the conventional approach to optimization is the formulation of a single objective function, with a targeted parameter list, and the entire model is simulated repeatedly in order to arrive at optimum values. However, many sector‐based SD models contain heuristics of “intended rationality”, and a desired outcome for modellers to be able to explore the policy implications of locally rational behaviours. This can now be achieved through a method known as coevolution, which allows modellers to divide an unsolved problem into constituent parts, where each part can be solved with respect to its own fitness function. In this paper, we specify a solution for evolving locally rational strategies across a multi‐sector SD structure. Using the beer distribution game (BDG) as an illustration, we demonstrate the utility of this approach in terms of the impact of two different order management strategies on the policy space of the BDG. Copyright © 2012 System Dynamics Society.
Cell Autonomous and Nonautonomous Mechanisms Drive Hematopoietic Stem/progenitor Cell Loss in the Absence of DNA Repair
Authors: Cho Joon Seok , Kook Sung Ho , Robinson Andria Rasile , Niedernhofer Laura J. , Lee Byeong-Chel
Published: October 2012

Daily, cells incur tens of thousands of DNA lesions caused by endogenous processes. Due to their long-lived nature, adult stem cells may be particularly susceptible to the negative impact of this constant genotoxic stress. Indeed, in murine models of DNA repair deficiencies, there is accumulation of DNA damage in hematopoietic stem cells and premature loss of function. Herein, we demonstrate that mice expressing reduced levels of ERCC1-XPF DNA repair endonuclease (Ercc1−/Δ mice) spontaneously display a progressive decline in the number and function of hematopoietic stem/progenitor cells (HSPCs). This was accompanied by increased cell death, expression of senescence markers, reactive oxygen species, and DNA damage in HSPC populations, illustrating cell autonomous mechanisms that contribute to loss of function. In addition, the bone marrow microenvironment of Ercc1−/Δ mice was not permissive for the engraftment of transplanted normal stem cells. Bones from Ercc1−/Δ mice displayed excessive osteoclastic activity, which alters the microenvironment in a way that is unfavorable to HSPC maintenance. This was accompanied by increased proinflammatory cytokines in the bone marrow of Ercc1−/Δ mice. These data provide novel evidence that spontaneous, endogenous DNA damage, if not repaired, promotes progressive attrition of adult stem cells via both cell autonomous and nonautonomous mechanisms.
Brief Report: The Potential Role of Epigenetics on Multipotent Cell Differentiation Capacity of Mesenchymal Stromal Cells
Authors: Yannarelli Gustavo , Pacienza Natalia , Cuniberti Luis , Medin Jeffrey , Davies John , Keating Armand
Published: October 2012

Human umbilical cord perivascular cells (HUCPVCs) are a readily available source of mesenchymal stromal cells (MSCs) for cell therapy. We were interested in understanding how differences from human bone marrow (BM)-derived MSCs might yield insights into MSC biology. We found that HUCPVCs exhibited increased telomerase activity and longer telomeres compared with BM-MSCs. We also observed enhanced expression of the pluripotency factors OCT4, SOX2, and NANOG in HUCPVCs. The methylation of OCT4 and NANOG promoters was similar in both cell types, indicating that differences in the expression of pluripotency factors between the MSCs were not associated with epigenetic changes. MSC methylation at these loci is greater than reported for embryonic stem cells but less than in dermal fibroblasts, suggesting that multipotentiality of MSCs is epigenetically restricted. These results are consistent with the notion that the MSC population (whether BM- or HUCPV-derived) exhibits higher proliferative capacity and contains more progenitor cells than do dermal fibroblasts.
Systems requirements engineering—State of the methodology
Authors: Bijan Yvonne , Yu Junfang , Stracener Jerrell , Woods Timothy
Published: October 2012

There are many references about the characteristics of a good requirement. But what is the process for developing clear, unambiguous requirements, and how do we know when we have defined the requirements successfully? This paper investigates the current state of the methodology for developing complex system requirements. Significant work has been accomplished over the last several years to describe requirements development and systems engineering. This paper identifies and investigates requirements development methodologies and techniques. ©2012 Wiley Periodicals, Inc. Syst Eng 16
Global Performance Management in MNEs—Conceptualization and Profiles of Country–Specific Characteristics in China, Germany, and the United States
Authors: Festing Marion , Knappert Lena , Dowling Peter J. , Engle Allen D.
Published: October 2012

While multinational enterprises (MNEs) need to balance the global and local requirements of their global performance management (GPM) practices, GPM research lacks conceptual and encompassing comprehension of country‐specific peculiarities. First, this article suggests a conceptualization of the elements of GPM (criteria, actors, methods, purposes, feedback). Then, an encompassing literature review provides evidence for the peculiarities of the identified elements of GPM and their underlying explanations in different contexts. On this basis, the authors analyze the GPM elements in three culturally and institutionally diverse major economies (Germany, United States, and China). They suggest country‐specific GPM profiles that consistently and comprehensively capture the particularities present in various national contexts. Testable propositions are suggested as a basis for further empirical research. © 2012 Wiley Periodicals, Inc.
Training and Development Roles and Structures in European Call Centers: The Influence of Strategic Choice, Institutional and Coevolutionary Processes
Authors: Garavan Thomas N. , Cross Christine , Wilson John , Carbery Ronan
Published: October 2012

The global call center sector has emerged as a vibrant and economically successful industry in recent decades. Training and development of employees is acknowledged as a key component of call center strategy in facilitating the utilization of new technologies, enhanced customer service, and profitability. Relatively little is, however, known concerning how training roles and structures are configured in call centers. Here, we explore competitive, institutional, and coevolutionary drivers of training and development roles and structures in European call centers. Drawing on qualitative data gathered from 20 call centers and multiple respondents located across Europe we found greater evidence of variation than similarity, indicating the importance of strategic choice and coevolutionary influences. The findings highlight the importance of institutional processes in understanding the similarities observed. The interaction of institutional, strategic choice, and coevolutionary factors is, however, extremely complex and requires further investigation. © 2012 Wiley Periodicals, Inc.
Tensile properties, degradation behavior, and water absorption of sago starch plastic films
Authors: Ismail Hanafi , Zaaba Nor Fasihah
Published: October 2012

Sago starch plastic films were prepared by a blending and casting method using various amounts of additives. The additives were glycerol (GLY), polyethylene glycol (PEG), and glutaraldehyde (GLU). Results indicated that the films had an optimum tensile strength of about 2.6 MPa and an optimum elongation at break of 74%. Meanwhile, a GLU content of five parts by weight gave the best tensile properties. Elongation at break of the films increased while tensile strength decreased upon increasing the level of plasticizer (GLY and PEG). The addition of plasticizer also increased the water absorption and soil burial degradation rate. However, the addition of GLU gave opposite results. J. VINYL ADDIT. TECHNOL., 2012. © 2012 Society of Plastics Engineers