bluuebunny/crossref_metadata_2025 huggingface dataset:
EGF stimulates müller glial proliferation via a BMP‐dependent mechanism
Authors: Ueki Yumi , Reh Thomas A.
Published: January 2013

Müller glia, the major type of glia in the retina, are mitotically quiescent under normal conditions, though they can be stimulated to proliferate in some pathological states. Among these stimuli, EGF is known to be a potent mitogen for Müller glia. However, the signaling pathways required for EGF‐mediated proliferation of Müller glia are not clearly understood. In this study, postnatal day 12 (P12) or adult trp53−/− mouse retinas were explanted and cultured in the presence of EGF to stimulate Müller glial proliferation. Treatment with signaling inhibitors showed that activation of both MEK/ERK1/2 and PI3K/AKT pathways is required for EGF‐induced proliferation of Müller glia. Interestingly, BMP/Smad1/5/8 activation downstream of PI3K/AKT signaling was also necessary for robust Müller glial proliferation, though activation of BMP/Smad1/5/8 signaling alone failed to stimulate their proliferation. In dissociated Müller glial culture, treatment with EGF induced the upregulation of Bmp7, and this upregulation was blocked significantly by co‐treatment with the BMP inhibitor dorsomorphin, suggesting that BMP/Smad1/5/8 activation is mediated at least in part by an autocrine mechanism in Müller glia. A better understanding of how BMP/Smad1/5/8 signaling is involved in glial proliferation may have important implications for proliferative disorders, as well as for retinal regeneration in mammalian retinas.
Associations between T1 white matter lesion volume and regional white matter microstructure in aging
Authors: Leritz Elizabeth C. , Shepel Juli , Williams Victoria J. , Lipsitz Lewis A. , McGlinchey Regina E. , Milberg William P. , Salat David H.
Published: January 2013

White matter lesions, typically manifesting as regions of signal intensity abnormality (WMSA) on MRI, increase in frequency with age. However, the role of this damage in cognitive decline and disease is still not clear, as lesion volume has only loosely been associated with clinical status. Diffusion tensor imaging (DTI) has been used to examine the quantitative microstructural integrity of white matter, and has applications in the examination of subtle changes to tissue that appear visually normal on conventional imaging. The primary goal of this study was to determine whether major macrostructural white matter damage, (total WMSA volume), is associated with microstructural integrity of normal appearing white matter, and if these macrostructural changes fully account for microstructural changes. Imaging was performed in 126 nondemented individuals, ages 43–85 years, with no history of cerebrovascular disease. Controlling for age, greater WMSA volume was associated with decreased fractional anisotropy (FA) in widespread brain regions. Patterns were similar for FA and radial diffusivity but in contrast, WMSA was associated with axial diffusivity in fewer areas. Age was associated with FA in several regions, and many of these effects remained even when controlling for WMSA volume, suggesting the etiology of WMSAs does not fully account for all age‐associated white matter deterioration. These results provide evidence that WMSA volume is associated with the integrity of normal‐appearing white matter. In addition, our results suggest that overt lesions may not account for the association of increasing age with decreased white matter tissue integrity. Hum Brain Mapp 35:1085–1100, 2014. © 2013 Wiley Periodicals, Inc.
Segregating cognitive functions within hippocampal formation: A quantitative meta‐analysis on spatial navigation and episodic memory
Authors: Kühn Simone , Gallinat Jürgen
Published: January 2013

The most important cognitive domains where hippocampal formation is crucially involved are navigation and memory. Some evidence suggests that different hippocampal subregions mediate these domains. However, a quantitative meta‐analysis on neuroimaging studies of spatial navigation versus memory is lacking. By means of activation likelihood estimation (ALE), we investigate concurrence of brain regions activated during spatial navigation encoding and retrieval as well as during episodic memory encoding and retrieval tasks in humans. During encoding in spatial navigation, activity was located in more posterior regions of the hippocampal formation, whereas episodic memory encoding was located in more anterior regions. Retrieval in spatial navigation was more strongly lateralized to the right compared to episodic memory retrieval. Within studies on spatial navigation retrieval, immediate recall was located more posterior and delayed recall more anterior. Overlap between concurrence of activation in spatial navigation and episodic memory was rather limited in comparison to uniquely involved regions. This argues in favor of two distinct networks, one for spatial navigation the other for episodic memory within the hippocampal formation. Hum Brain Mapp 35:1129–1142, 2014. © 2013 Wiley Periodicals, Inc.
Efficacy of Tenofovir Disoproxil Fumarate At 240 Weeks in Patients With Chronic Hepatitis B With High Baseline Viral Load
Authors: Gordon Stuart C. , Krastev Zahary , Horban Andrzej , Petersen Jörg , Sperl Jan , Dinh Phillip , Martins Eduardo B. , Yee Leland J. , Flaherty John F. , Kitrinos Kathryn M. , Rustgi Vinod K. , Marcellin Patrick
Published: January 2013

We evaluated the antiviral response of patients with chronic hepatitis B (CHB) who had baseline high viral load (HVL), defined as having hepatitis B virus (HBV) DNA ≥9 log10 copies/mL, after 240 weeks of tenofovir disoproxil fumarate (TDF) treatment. A total of 641 hepatitis B e antigen (HBeAg)-negative and HBeAg-positive patients (129 with HVL) received 48 weeks of TDF 300 mg (HVL n = 82) or adefovir dipivoxil (ADV) 10 mg (HVL n = 47), followed by open-label TDF for an additional 192 weeks. Patients with confirmed HBV DNA ≥400 copies/mL on or after week 72 had the option of adding emtricitabine (FTC). By week 240, 98.3% of HVL and 99.2% of non-HVL patients on treatment achieved HBV DNA <400 copies/mL. Both groups had similar rates of histologic regression between baseline and week 240. Patients with HVL generally took longer to achieve HBV DNA <400 copies/mL than non-HVL patients, but by week 96, the percentages of patients with HBV DNA <400 copies/mL were similar in both groups. Among HVL patients, time to achieving HBV DNA <400 copies/mL was shorter among those initially receiving TDF, compared to ADV. No patient with baseline HVL had persistent viremia at week 240 or amino acid substitutions associated with TDF resistance.

Conclusion

: CHB patients with HVL can achieve HBV DNA negativity with long-term TDF treatment, although time to HBV DNA <400 copies/mL may be longer, relative to patients with non-HVL. (Hepatology 2013;58:505–513)
Sensitivity of endoscopic screening for gastric cancer by the incidence method
Authors: Hamashima Chisato , Okamoto Mikizo , Shabana Michiko , Osaki Yoneatsu , Kishimoto Takuji
Published: January 2013

Although radiographic screening for gastric cancer has been conducted in Japan, it is anticipated that endoscopy will become a new screening method because of its high detection rate. The sensitivities of endoscopic and radiographic screening were calculated by the detection method and the incidence method based on the results of community‐based screening in Japan. There were 56,676 screenings for gastric cancer using endoscopy and radiography from April 2002 to March 2007 in Yonago, Japan. The target age group was from 40 to 79 years. Screen‐detected and interval cancers were investigated based on a screening database linked to the Tottori Cancer Registry. All gastric cancers diagnosed within 1 year after a negative screen were considered interval cancers. Based on the screening history, these were divided into prevalence screening and incidence screening. Prevalence screenings included 7,388 for endoscopic screening and 5,410 for radiographic screening, whereas incidence screenings included 18,021 for endoscopic screening and 11,417 for radiographic screening. The sensitivity of prevalence screening calculated by the incidence method was 0.886 (95% confidence interval [CI] = 0.698–0.976) for endoscopic screening and 0.831 (95% CI = 0.586–0.964) for radiographic screening; however, the difference was not significant (p = 0.626). The sensitivity of incidence screening calculated by the incidence method was 0.954 (95% CI = 0.842–0.994) for endoscopic screening and 0.855 (95% CI = 0.637–0.970) for radiographic screening (p = 0.177). Endoscopic screening for gastric cancer had a higher sensitivity than radiographic screening by the incidence method in both screening rounds. However, further study is needed to evaluate mortality reduction and to estimate overdiagnosis with endoscopic screening for gastric cancer.
Intercellular adhesion molecule‐1 (ICAM‐1) expression correlates with oral cancer progression and induces macrophage/cancer cell adhesion
Authors: Usami Yu , Ishida Ken , Sato Sunao , Kishino Mitsunobu , Kiryu Megumi , Ogawa Yuzo , Okura Masaya , Fukuda Yasuo , Toyosawa Satoru
Published: January 2013

Intercellular adhesion molecule‐1 (ICAM‐1) is a transmembrane glycoprotein in the immunoglobulin superfamily, which plays an important role in cell adhesion and signal transduction. Although ICAM‐1 is believed to play a role in several malignancies, it is still uncertain whether or not ICAM‐1 expression contributes to cancer progression. In this study, we performed clinicopathological and cell biological analyses of ICAM‐1 expression in oral squamous cell carcinoma (SCC). First, we examined the ICAM‐1 expression in tongue SCC immunohistochemically, and revealed that ICAM‐1 was expressed predominantly at the invasive front area of tongue SCC. ICAM‐1 expression at the invasive front area was correlated with invasion, lymph node metastasis and increased blood and lymphatic vessel density of the tongue SCC. The relationship between ICAM‐1 expression and clinicopathological factors were consistent with the increased proliferation, invasion and cytokine‐production activities of ICAM‐1‐transfected SCC cells. Second, we analyzed the relationship between macrophages and ICAM‐1‐expressing tongue SCC cells because ICAM‐1 is known to act as a ligand for adhesion of immune cells. Increased ICAM‐1 expression in tongue SCC was correlated with increased macrophage infiltration within SCC nests. Moreover, macrophage/SCC‐cell adhesion through ICAM‐1 molecule was revealed using an in vitro cell adhesion and blockade assay. These findings indicate that ICAM‐1 plays an important role in tongue SCC progression, which may result from the SCC‐cell activity, angiogenic activity, lymphangiogenic activity and macrophage/SCC‐cell adhesion.
Decreased muscle concentrations of ATP and PCR in the quadriceps muscle of fibromyalgia patients – A 31P‐MRS study
Authors: Gerdle B. , Forsgren M.F. , Bengtsson A. , Leinhard O. Dahlqvist , Sören B. , Karlsson A. , Brandejsky V. , Lund E. , Lundberg P.
Published: January 2013

Background and Methods

Fibromyalgia (FMS) has a prevalence of approximately 2% in the population. Central alterations have been described in FMS, but there is not consensus with respect to the role of peripheral factors for the maintenance of FMS. 31P Magnetic Resonance Spectroscopy (31P‐MRS) has been used to investigate the metabolism of phosphagens in muscles of FMS patients, but the results in the literature are not in consensus. The aim was to investigate the quantitative content of phosphagens and pH in resting quadriceps muscle of patients with FMS (n = 19) and in healthy controls (Controls; n = 14) using 31P‐MRS. It was also investigated whether the concentrations of these substances correlated with measures of pain and/or physical capacity.

Results

Significantly lower concentrations of adenosine triphosphate (ATP) and phosphocreatinine (PCr; 28–29% lower) were found in FMS. No significant group differences existed with respect to inorganic phosphate (Pi), Pi/PCr and pH. The quadriceps muscle fat content was significantly higher in FMS than in Controls [FMS: 9.0 ± 0.5% vs. Controls: 6.6 ± 0.6%; (mean ± standard error); P = 0.005]. FMS had significantly lower hand and leg capacity according to specific physical test, but there were no group differences in body mass index, subjective activity level and in aerobic fitness. In FMS, the specific physical capacity in the leg and the hand correlated positively with the concentrations of ATP and PCr; no significant correlations were found with pain intensities.

Conclusions

Alterations in intramuscular ATP, PCr and fat content in FMS probably reflect a combination of inactivity related to pain and dysfunction of muscle mitochondria.
Incorporation of bioactive glass in calcium phosphate cement: Material characterization and in vitro degradation
Authors: Renno A. C. M. , Nejadnik M. R. , van de Watering F. C. J. , Crovace M. C. , Zanotto E. D. , Hoefnagels J. P. M. , Wolke J. G. C. , Jansen J. A. , van den Beucken J. J. J. P.
Published: January 2013

Calcium phosphate cements (CPCs) have been widely used as an alternative to biological grafts due to their excellent osteoconductive properties. Although degradation has been improved by using poly(D,L‐lactic‐co‐glycolic) acid (PLGA) microspheres as porogens, the biological performance of CPC/PLGA composites is insufficient to stimulate bone healing in large bone defects. In this context, the aim of this study was to investigate the effect of incorporating osteopromotive bioactive glass (BG; up to 50 wt %) on setting properties, in vitro degradation behavior and morphological characteristics of CPC/BG and CPC/PLGA/BG. The results revealed that the initial and final setting time of the composites increased with increasing amounts of incorporated BG. The degradation test showed a BG‐dependent increasing effect on pH of CPC/BG and CPC/PLGA/BG pre‐set scaffolds immersed in PBS compared to CPC and CPC/PLGA equivalents. Whereas no effects on mass loss were observed for CPC and CPC/BG pre‐set scaffolds, CPC/PLGA/BG pre‐set scaffolds showed an accelerated mass loss compared with CPC/PLGA equivalents. Morphologically, no changes were observed for CPC and CPC/BG pre‐set scaffolds. In contrast, CPC/PLGA and CPC/PLGA/BG showed apparent degradation of PLGA microspheres and faster loss of integrity for CPC/PLGA/BG pre‐set scaffolds compared with CPC/PLGA equivalents. Based on the present in vitro results, it can be concluded that BG can be successfully introduced into CPC and CPC/PLGA without exceeding the setting time beyond clinically acceptable values. All injectable composites containing BG had suitable handling properties and specifically CPC/PLGA/BG showed an increased rate of mass loss. Future investigations should focus on translating these findings to in vivo applications. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013.
Graft copolymer polyelectrolyte complexes for delivery of cationic antimicrobial peptides
Authors: Niece Krista L. , Vaughan Asa D. , Devore David I.
Published: January 2013

Peptides have enormous potential as therapeutic agents for the treatment of infection, in immunomodulation and for other medical applications, but their hydrolytic degradation in biological fluids is a serious limitation to their in vivo performance. Here we demonstrate the potential utility of polyelectrolyte nanoparticle complexes of novel self‐assembling anionic graft copolymers for protecting peptides from degradation in human plasma. The anionic graft copolymers are synthesized by covalently attaching pendent polyetheramine chains to poly(alkylacrylic acid) backbones by carbodiimide coupling. The peptide:copolymer nanocomplexes' particle size, zeta‐potential, peptide binding, and controlled release of the peptide are shown to be dependent upon the pendent chain graft density, polymer backbone alkyl groups (propyl vs. methyl), and the nanocomplexes' electrostatic charge ratio. The nanocomplexes can provide substantial protection to the bound peptides from degradation in human plasma for at least 24 h and, in standard microbiological assays are shown to retain some or all of the peptide's antimicrobial activity against a clinically relevant strain of Staphylococcus aureus. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 101A: 2548–2558, 2013.
The effect of particle size on the osteointegration of injectable silicate‐substituted calcium phosphate bone substitute materials
Authors: Coathup Melanie J. , Cai Qian , Campion Charlie , Buckland Thomas , Blunn Gordon W
Published: January 2013

Calcium phosphate (CaP) particles as a carrier in an injectable bone filler allows less invasive treatment of bony defects. The effect of changing granule size within a poloxamer filler on the osteointegration of silicate‐substituted calcium phosphate (SiCaP) bone substitute materials was investigated in an ovine critical‐sized femoral condyle defect model. Treatment group (TG) 1 consisted of SiCaP granules sized 1000–2000 μm in diameter (100 vol %). TG2 investigated a granule size of 250–500 μm (75 vol %), TG3 a granule size of 90–125 μm (75 vol %) and TG4 a granule size of 90–125 μm (50 vol %). Following a 4 and 8 week in vivo period, bone area, bone‐implant contact, and remaining implant area were quantified within each defect. At 4 weeks, significantly increased bone formation was measured in TG2 (13.32% ± 1.38%) when compared with all other groups (p = 0.021 in all cases). Bone in contact with the bone substitute surface was also significantly higher in TG2. At 8 weeks most new bone was associated within defects containing the smallest granule size investigated (at the lower volume) (TG4) (42.78 ± 3.36%) however this group was also associated with higher amounts of fragmented SiCaP. These smaller particles were phagocytosed by macrophages and did not appear to have a negative influence on healing. In conclusion, SiCaP granules of 250–500 μm in size may be a more suitable scaffold when used as an injectable bone filler and may be a convenient method for treating bony defects. © 2013 The Authors. Journal of Biomedical Materials Research Part B: Applied Biomaterials Published by Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 101B: 902–910, 2013
Fibroblast growth factor, estrogen, and prolactin receptor features in different grades of prostatic adenocarcinoma in elderly men
Authors: Hetzl Amanda Cia , Montico Fabio , Misitieri Raisa , Kido Larissa , Cândido Eduardo , Billis Athanase , Ferreira Ubirajara , Cagnon Valeria Ha
Published: January 2013

The objective was to characterize and associate the receptor reactivities of fibroblastic growth factor (FGF)‐2, FGF‐7, FGF‐8, epidermal growth factor (EGF), α‐actin and vimentin in relation to the androgen receptor (AR), α and β estrogen receptors (ERα and ERβ), and prolactin receptor in the prostate of elderly men showing low‐ and high‐grade adenocarcinoma. Thirty prostatic samples were taken from 60‐ to 90‐year‐old patients without prostatic lesions and with low‐grade cancer and high‐grade cancer, from the University Hospital, School of Medicine, the State University of Campinas. The results showed that increased FGF‐2, FGF‐7, and FGF‐8 receptor reactivities and decreased AR reactivity were verified in both high‐ and low‐grade cancer. However, the FGF‐8 receptor showed greater involvement at the beginning of the malignancy alterations. Increased EGF receptor (EGFR) reactivity and diminished α‐actin immunohistochemistry were identified in both cancer groups. Also, increased ERα, PR, and vimentin receptors were verified in both cancer groups. To conclude, the ERα involvement in the reactive stroma activation led to a microenvironment, which was favorable to cancer progression, due to maximizing stromal imbalance. The prolactin could be related to cancer progression due to its interaction with ERα action, indicating that this hormone could be a relevant target to prevent the estrogenic effects in the prostatic lesions. Both FGF receptor (FGFR)‐2 and FGFR‐8 play a fundamental role in the early stages of prostate cancer, suggesting that these molecules could be a promising therapeutic target. The differential localization of the fibroblastic factors between the prostatic epithelium and stroma of elderly men, who presented prostate cancer, could indicate a favorable distinction for tumoral progression. Microsc. Res. Tech. 76:321–330, 2013. © 2013 Wiley Periodicals, Inc.
Ultrastructural characterization of surface‐induced platelet activation on artificial materials by transmission electron microscopy
Authors: Yoshimoto Yukihiro , Hasebe Terumitsu , Takahashi Kei , Amari Masao , Nagashima So , Kamijo Aki , Hotta Atsushi , Takahashi Koki , Suzuki Tetsuya
Published: January 2013

Platelet adhesion is one of the most pivotal events of blood clotting for artificial surfaces. However, the mechanisms of surface‐induced platelet activation have not been fully been elucidated or visualized so far. In this study, we attempted to observe the internal structures and adhesion interfaces of human platelets attached to artificial surfaces by transmission electron microscopy (TEM) during the platelet activation process. We prepared observation samples by a conventional embedding method using EPON 812 resin. The sectioning was sliced perpendicular to the a‐platelet/material interface. Observation by TEM indicates that internal granules coalesce in the center of the platelet accompanied by pseudopodial growth in the early stage of platelet activation. Pseudopodia from a platelet attach to the material interface not along a plane but at a point. In addition, along with the process of platelet activation, the gap between the platelet membrane and the material surface at the interface disappeared and a‐platelet/material adhesion became much tighter. In the fully activated platelet stage, the platelet becomes thinner and tightly adheres to the substrate. As a result of comparative observation of an adherent platelet on polycarbonate (PC) and on amorphous carbon (a‐C:H), it was found that internal granules release was inhibited more remarkably on a‐C:H coating rather than on PC. Despite numerous technical difficulties in preparing sectional samples, such a study might prove the essential mechanism of biomaterial‐related thrombosis, and it might become possible to modify the surfaces of materials to minimize material‐related thrombosis. Microsc. Res. Tech. 76:342–349, 2013. © 2013 Wiley Periodicals, Inc.
Efficacy of different final irrigant activation protocols on smear layer removal by EDTA and citric acid
Authors: Herrera Daniel R. , Santos Zarina T. , Tay Lidia Y. , Silva Emmanuel J. , Loguercio Alessandro D. , Gomes Brenda P.F.A.
Published: January 2013

The aim of this study was to evaluate the influence of different activation protocols for chelating agents used after chemo‐mechanical preparation (CMP), for smear layer (SL) removal. Forty‐five single‐rooted human premolars with straight canals and fully formed apex were selected. The specimens were randomly divided into three groups depending on the chelating agent used for smear layer removal: distilled water (DW, control group); 17% ethylenediaminetetraacetic acid (EDTA); and 10% citric acid (CA). Each group was further divided into three subgroups according to the activation protocol used: no‐activation (NA), manual dynamic activation (MDA), or sonic activation (SA). After CMP, all specimens were sectioned and processed for observation of the apical thirds by using scanning electron microscopy (SEM). Two calibrated evaluators attributed scores to each specimen. The differences between activation protocols were analyzed with Kruskal‐Wallis and Mann‐Whitney U tests. Friedman and Wilcoxon signed rank tests were used for comparison between each root canal third. When chelating agents were activated, either by MDA or SA, it was obtained the best cleaning results with no significant difference between EDTA and CA (P > 0.05). Sonic activation showed the best results when root canal thirds were analyzed, in comparison to MDA and NA groups (P < 0.05). The activation of chelating agents, independent of the protocol used, benefits smear layer removal from root canals. Microsc. Res. Tech. 76:364–369, 2013. © 2013 Wiley Periodicals, Inc.
A practical synthesis of [18F]FtRGD: an angiogenesis biomarker for PET
Authors: Bejot Romain , Goggi Julian , Moonshi Shebbrin S. , Robins Edward G.
Published: January 2013

Integrins have become increasingly attractive targets for molecular imaging of angiogenesis with positron emission tomography or single‐photon emission computed tomography, but the reliable production of radiopharmaceuticals remains challenging. A strategy for chemoselective labeling of the integrin ligand—c(RGDyK) peptide—has been developed on the basis of the Cu(I)‐catalyzed conjugation reaction. Recently, we reported a nucleophilic detagging and fluorous solid‐phase extraction method providing an easy way to implement an approach for obtaining 2‐[18F]fluoroethyl azide. In this work, we report the practical use of this method for the preparation of the 2‐[18F]fluoroethyl‐triazolyl conjugated c(RGDyK) peptide: [18F]FtRGD. The two‐step, two‐pot synthesis, HPLC purification, and reformulation could be readily performed with a standard nucleophilic radiofluorination synthesizer (GE TRACERlab FXFN), with minimal modifications. [18F]FtRGD was obtained in a solution for injection (>500 MBq/mL) in 10–30% nondecay‐corrected radiochemical yield, excellent radiochemical purity (>98%), and 28 ± 13 GBq/µmol specific activity. [18F]FtRGD (Ki = 54 ± 14 nM for αVβ3 and 1.7 ± 0.2 nM for αVβ5) was evaluated in mice and showed good stability in vivo, good tumor‐to‐background ratio (1.6 ± 0.3 %ID/g at 1.5 h post‐injection in U87‐MG tumors), and rapid urinary excretion. Therefore, [18F]FtRGD proved valuable for preclinical positron emission tomography imaging of integrin expression.
Preparation and stability of ethanol‐free solution of [18F]florbetapir ([18F]AV‐45) for positron emission tomography amyloid imaging
Authors: Hayashi Kazutaka , Tachibana Akiko , Tazawa Shusaku , Mizukawa Yosuke , Osaki Katsuhiko , Morimoto Yoko , Zochi Riyo , Kurahashi Masahiro , Aki Hatsumi , Takahashi Kazuhiro
Published: January 2013

We have developed an ethanol‐free formulation method of [18F]florbetapir ([18F]AV‐45) using a commercially available automated JFE multi‐purpose synthesizer. We have also evaluated the radiochemical stability in an ethanol‐free solution of [18F]AV‐45 under visible light irradiation and dark conditions by comparison with a conventional 10% ethanol solution of [18F]AV‐45. [18F]AV‐45 was obtained with a radiochemical yield of 55.1 ± 2.2% (decay‐corrected to end of bombardment), specific activity of 591.6 ± 90.3 GBq/µmol and radiochemical purity of >99% within a total synthesis time of about 73 min. The radiochemical purity of [18F]AV‐45 formulated by dissolving the ethanol‐free solution was found to decrease as a function of the period of exposure to visible light. In contrast, the visible light photolysis could be suppressed by adding 10% ethanol to the formulation or by avoiding exposure to visible light. In the radiosynthesis of [18F]AV‐45 formulated by dissolving the ethanol‐free solution, [18F]AV‐45 could be obtained with high radiochemical purity and high stability by avoiding exposure to visible light. Copyright © 2013 John Wiley & Sons, Ltd.
Formation of insulin fragments by insulin‐degrading enzyme: the role of zinc(II) and cystine bridges
Authors: Bellia Francesco , Pietropaolo Adriana , Grasso Giuseppe
Published: January 2013

Insulin is the hormone mainly involved in widespread diseases such as diabetes mellitus. It is widely recognized that metal ions such as zinc(II) as well as insulin degradation and insulin fragments are inexplicably linked to the hormone action. Insulin‐degrading enzyme (IDE) has been identified as the main factor of insulin degradation, but it is still unknown the exact way and location at which IDE action toward insulin occurs and how metal ions can modulate this interaction. Interestingly, some insulin fragments have different biological activity from the intact hormone, and it is not clear how they can be generated from insulin.

In this work, the role of zinc(II) and cystine bridges in the degradation of insulin by IDE are investigated by high‐performance liquid chromatography‐mass spectrometry (HPLC‐MS), and the experimental conditions at which peculiar insulin fragments having biological activity are formed by the action of IDE are found and discussed. Docking simulations of IDE/insulin A and B chains are in good accordance with the insulin fragments detected by HPLC‐MS. Copyright © 2013 John Wiley & Sons, Ltd.
Detection of layer‐by‐layer self‐assembly multilayer films by low‐temperature plasma mass spectrometry
Authors: Xu Xiangyu , Na Na , Wen Jiying , Ouyang Jin
Published: January 2013

The detection of layer‐by‐layer self‐assembly multilayer films was carried out using low‐temperature plasma (LTP) mass spectrometry (MS) under ambient conditions. These multilayer films have been prepared on quartz plates through the alternate assembling of oppositely charged 4‐aminothiophenol (4‐ATP) capped Au particles and thioglycolic acid (TGA) capped Ag particles. An LTP probe was used for direct desorption and ionization of chemical components on the films. Without the complicated sample preparation, the structure information of 4‐ATP and TGA on films was studied by LTP‐MS. Characteristic ions of 4‐ATP (M) and TGA (F), including [M]+•, [M‐NH2]+, [M‐HCN‐H]+, and [F + H]+, [F‐H]+, [F‐OH]+, [F‐COOH]+ were recorded by LTP‐MS on the films. However, [M‐CS‐H]+ and [F‐SH]+ could not be observed on the film, which were detected in the neat sample. In addition, the semi‐quantitative analysis of chemical components on monolayer film was carried out, and the amounts of 4‐ATP and TGA on monolayer surface were 45 ng/mm2 and 54 ng/mm2, respectively. This resulted the ionization efficiencies of 72% for 4‐ATP and 54% for TGA. In order to evaluate the reliability of present LTP‐MS, the correlations between this approach and some traditional methods, such as UV–vis spectroscopy, atomic force microscope and X‐ray photoelectron spectroscopy were studied, which resulted the correlation coefficients of higher than 0.9776. The results indicated that this technique can be used for analyzing the films without any pretreatment, which possesses great potential in the studies of self‐assembly multilayer films. Copyright © 2013 John Wiley & Sons, Ltd.
Reliable reduced cost modeling and design optimization of microwave filters using co‐kriging
Authors: Koziel Slawomir , Leifsson Leifur , Couckuyt Ivo , Dhaene Tom
Published: January 2013

A reliable methodology for accurate modeling of microwave filter is presented. Our approach exploits co‐kriging that utilizes low‐fidelity and high‐fidelity electromagnetic simulation data and combines them into a single surrogate model. Densely sampled low‐fidelity data determine a trend function, which is further corrected by sparsely sampled high‐fidelity simulations. Low‐fidelity electromagnetic data are also enhanced by using a frequency scaling to reduce its misalignment with the high‐fidelity model. With our method, accurate models can be obtained at a fraction of the cost required by conventional approximation models that are exclusively based on high‐fidelity simulations. Three examples of microstrip filters are considered for verification purposes. We also provide comparisons with conventional approximation models and include an application of co‐kriging models for filter design optimization. Copyright © 2013 John Wiley & Sons, Ltd.
Common trace elements alleviate pain in an experimental mouse model
Authors: Tamba Bogdan I. , Leon Maria‐Magdalena , Petreus Tudor
Published: January 2013

Trace elements represent a group of essential metals or metaloids necessary for life, present in minute amounts. Analgesic adjuvants can enhance the effect of other pain drugs or be used for pain control themselves. Previous studies on the effects of trace elements on nociception and their potential use as analgesic adjuvants have yielded conflicting results. In this study, we tested the hypothesis that three vital trace elements (Zn2+, Mg2+, Cu2+) have direct antinociceptive effects. Groups of eight Swiss mice were intraperitoneally (i.p) injected with incremental concentrations of Zn2+ sulfate (0.5, 2.0 mg/kg), Zn2+ citrate (0.125, 0.5 mg/kg), Mg2+ chloride (37.5, 75, 150 mg/kg), Cu2+ chloride (0.5, 1.0, 2.0 mg/kg), and Cu2+ sulfate (0.5, 1.0 mg/kg) or saline (control). Evaluations were made by hot plate (HP) and tail flick (TF) tests for central antinociceptive effect, writhing test (WT) for visceral antinociceptive effect, and activity cage (AC) test for spontaneous behavior. Zn2+ induced pain inhibition in HP/TF tests (up to 17%) and WT (up to 25%), with no significant differences among the salts used. Mg2+ salts induced pain inhibition for all performed tests (up to 85% in WT). Cu2+ salts showed antinociceptive effects for HP/TF (up to 28.6%) and WT (57.28%). Only Mg2+ and Cu2+ salts have displayed significant effects in AC (Mg2+ anxiolytic/depressant effect; Cu2+ anxiolytic effect). We interpret these data to mean that all tested trace elements induced antinociceptive effects in central and visceral pain tests. Our data indicate the potential use of these cheap adjuvants in pain therapy. © 2013 Wiley Periodicals, Inc.
Glycogen synthase kinase‐3 inhibition prevents learning deficits in diabetic mice
Authors: King Matthew R. , Anderson Nicholas J. , Guernsey Lucie S. , Jolivalt Corinne G.
Published: January 2013

There is an increasing awareness that diabetes has an impact on the central nervous system, with reports of impaired learning, memory, and mental flexibility being more common in diabetic subjects than in the general population. Insulin‐deficient diabetic mice also display learning deficits associated with defective insulin‐signaling in the brain and increased activity of GSK3. In the present study, AR‐A014418, a GSK3β inhibitor, and TX14(A), a neurotrophic factor with GSK3 inhibitory properties, were tested against the development of learning deficits in mice with insulin‐deficient diabetes. Treatments were started at onset of diabetes and continued for 10 weeks. Treatment with AR‐A014418 or TX14(A) prevented the development of learning deficits, assessed by the Barnes maze, but only AR‐A014418 prevented memory deficits, as assessed by the object recognition test. Diabetes‐induced increased levels of amyloid β protein and phosphorylated tau were not significantly affected by the treatments. However, the diabetes‐induced decrease in synaptophysin, a presynaptic protein marker of hippocampal plasticity, was partially prevented by both treatments. These results suggest a role for GSK3 and/or reduced neurotrophic support in the development of cognitive deficits in diabetic mice that are associated with synaptic damage. © 2013 Wiley Periodicals, Inc.
Hotel Innovation and Its Effect on Business Performance
Authors: Mattsson Jan , Orfila‐Sintes Francina
Published: January 2013

This paper explores the dynamics of hotel innovation and its impact on hotel performance with a representative sample of the whole hotel sector operating in the Balearic Islands, Spain. The managers of sampled hotels (N = 331) answered questions about innovations over a 6‐year period. On the basis of an earlier developed model of innovation types, we investigate the effect on performance of different types of innovation. We find that two combinations of innovation types impact hotel performance in a positive way, namely the combinations termed, Full and Service&Back‐Office innovation. We therefore suggest that these combinations are used to create synergies for hotel performance. Copyright © 2013 John Wiley & Sons, Ltd.
Dynamic Mechanical Analysis and Hydrolytic Degradation Behavior of Linear and Branched Poly(L‐lactide)s and Poly(L‐lactide‐co‐glycolide)s
Authors: Atkinson Jeffrey L. , Vyazovkin Sergey
Published: January 2013

Linear and branched poly(lactide)s and poly(lactide‐co‐glycolide)s are synthesized using stannous (II) 2‐ethylhexanoate and alcoholic co‐initators resulting in polymers with 1, 2, 25, or 51 arms. 1‐dodecanol is used to produce the 1‐arm polymer, poly(ethylene glycol) is used for the 2‐arm polymers, and poly(glycidol)s of appropriate molecular weights are used to initiate the 25‐ and 51‐arm branched polyesters. The polymers are evaluated by melt rheology and dynamic mechanical analysis. In vitro degradation is investigated in phosphate buffer pH 7.4 at 37 °C for 28 d for moisture uptake and mass loss. Degraded samples are analyzed by gravimetry, differential scanning calorimetry, dilute solution viscometry (Cannon‐Fenske), and gel‐permeation chromatography.

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Toward Photopatternable Thin Film Optical Sensors Utilizing Reactive Polyphenylacetylenes
Authors: Pauly Anja C. , Theato Patrick
Published: January 2013

Substituted polyphenylacetylenes featuring reactive pentafluorophenyl (PFP) ester moieties are synthesized. Parts of the reactive PFP groups are then converted with a mono ortho‐nitrobenzyl‐protected diamine in variable ratios. Thin films are prepared from these copolymers and irradiated with UV light (λ = 365 nm), resulting in crosslinking of the irradiated areas and hence enabling a photopatterning. We found that during the photocrosslinking process, the excess of PFP ester moieties is stable and remained intact, enabling a subsequent post‐polymerization modification step with amines. Noteworthy, this subsequent modification with amines results in a dramatically shift in the UV–vis absorption spectra, rendering these patterned conjugated polymer films ideal candidates for optical sensors.
Similar Problem in the Activities of Daily Living but Different Experience: A Qualitative Analysis in Six Rheumatic Conditions and Eight European Countries
Authors: Stamm Tanja , Hieblinger Robin , Boström Carina , Mihai Carina , Birrell Fraser , Thorstensson Carina , Fialka‐Moser Veronika , Meriaux‐Kratochvila Silvia , Smolen Josef , Coenen Michaela
Published: January 2013

Objective

The aim of the present study was to compare and contrast the concepts of functioning in daily life which were important to patients with different rheumatological conditions.

Method

The study comprised a qualitative analysis of 44 focus groups in eight European countries, in 229 patients with fibromyalgia, hand osteoarthritis, psoriatic arthritis, rheumatoid arthritis, systemic lupus erythematosus and systemic sclerosis, using the World Health Organization, 2001 International Classification of Functioning, Disability and Health as a framework. Concepts and – where necessary – also sub‐concepts and transcripts were combined and compared independently by two researchers who, in case of disagreement, achieved consensus through discussion.

Results

Twenty concepts out of 109 (e.g. body image, fatigue, emotional issues, mobility and hand function) were similarly described in all six diseases. However, even if the same concept was mentioned, patients' experiences were different, such as mental AND physical aspects limiting the ability to drive in patients with fibromyalgia compared with ONLY physical problems in all other diseases. Within body functions and structures, several concepts were relevant for certain conditions only.

Conclusion

A large number of similar problems are mentioned as ‘typical’ by patients with different rheumatic conditions. These could probably be targeted, using a disease‐specific approach, in interventions by non‐physician health professionals. Copyright © 2013 John Wiley & Sons, Ltd.
Women and Literacy in Tanzania
Authors: Bell Sharon Cramer
Published: January 2013

The question of whether or not women's concerns are being adequately addressed and incorporated into planning and materials for newly literate women is discussed within the framework of the Tanzanian national literacy campaign, a movement which has been a model for nations interested in using adult education as a basis for political, social, and economic development. The important role of women in development and the connection between education and development are well recognized, yet women continue to have a higher rate of illiteracy than men. Using first‐hand experience in producing literacy materials as well as reviewing the literature, the author finds that women, due to unequal division of labor, have less time than men to participate in literacy efforts. Most of the curricula are designed to maintain women's traditional, subservient roles. Many textbooks and popular literature contain gender biases and sex stereotyping, both of which hinder self‐growth and independence. Recommendations include reorienting teaching materials to promote change through joint decision making, assisting women to develop income generation skills, and focusing on the development of leadership skills and higher self‐esteem.
Model Building and Strategic Planning in Continuing Higher Education
Authors: Edelson Paul J.
Published: January 2013

The value of creating descriptive models for organizing continuing higher education is explored in this paper as a way of critically assessing previously unexamined assumptions. Limitations of the pervasive marketing model are explored and twelve alternatives are described including the omnibus, academic department, and facilitator.
Towards an Anti‐Racist, Feminist Teaching Method
Authors: DasGupta Tania
Published: January 2013

This paper presents contemporary ideas and writings about anti‐racist and feminist education and a corresponding teaching methodology. The article discusses the essential elements of anti‐racist, feminist education and the curricular implications of this teaching approach, emphasizing Canadian perspectives and literature. It concludes by making recommendations for creating an institutional climate and structure in which these alternative pedagogies can be practiced.
Planning for an Evaluation of a National Vocational Education Program in a Developing Nation
Authors: Farmer Edgar I. , Taylor Raymond G. , Kim Hyunyoung , Konate Yacouba
Published: January 2013

This paper describes the planning phase of an evaluation process used by the senior author during his tenure as a W. K. Kellogg Consultant for prospective grant recipients in Zimbabwe. Specifically, this paper presents an overview of the planning that was used in evaluating the vocational and technical education programs in Zimbabwe, southern Africa. The planning process used in this paper is designed to serve as a springboard to a more generic planning approach to be applied to any external evaluation of a vocational program in developing countries. Finally, this paper emphasizes planning as a precursor to logistical arrangements, implementation, analysis, and reporting.
Student Diversity and the Culture of Higher Education
Authors: Rohfeld Rae Wahl
Published: January 2013

Despite the tremendous growth of participation in higher education over the last century, for some groups colleges and universities have been highly resistent to change. This article considers the idea of cultural access, one of the five types of access in a model that Carol Aslanian developed, as a source of remaining barriers. Using this concept, it draws on the experience of Jane Addams and the Hull House College Extension Program to look at differences between the culture of the university and the culture of the working‐class neighborhood. Noting a recent pilot program to bridge such cultural differences, along with changes in academia emerging mainly from feminist and post‐modern thought, it invites readers to discuss whether the concept of cultural access and the current changes in the university can help us deal with some of the limits to access that still exist.
The Singing Heart of Highlander Folk School
Authors: Carter Vicki K.
Published: January 2013

From 1932 until 1961, the Highlander Folk School conducted informal adult education programs focused on the southern labor movement, citizenship, and civil rights. Beginning in 1935 until her death in 1956, Zilphia Horton, first wife of Highlander's founder Myles Horton, enhanced the cultural pluralism of the school by developing a curriculum which incorporated and elevated the importance of folk music, dance, and drama. This paper discusses the life and contributions of Zilphia Horton, Highlander's “singing heart,” and addresses the role of music in particular, and the arts in general, at Highlander. Two frequently neglected areas of adult education history (women and culture) are highlighted by examining Zilphia Horton's presence at Highlander.
Political Correctness, Post‐Modernism, and Academic Adult Education
Authors: Griffith William S.
Published: January 2013

Professors of adult education encounter hostility and opposition from some practicing adult educators who believe that since “truth” has been discovered regarding a number of politically sensitive issues, professors ought only deliver the “politically correct” version of the “truth”. Further, the editors of the ADULT EDUCATION QUARTERLY are confronted by individuals filled with “righteous indignation” regarding the practice of allowing any males to act as referees for manuscripts submitted by feminists who use a variety of non‐traditional research and reporting styles. This article addresses the steps professors might take to deal with the challenge of political correctness claims and the perceptions of post‐modernists.
Embracing Change: Evolving to the Campus of the Future
Authors: Hall James W. , Shiffman Paul H.
Published: January 2013

In this article the authors present their vision of the future direction that colleges and universities should pursue, so that they can serve the diverse population of learners who will continue to seek learning opportunities through higher education. They describe a pressing need to remodel the higher education infrastructure in order to meet the dramatic changes that colleges and universities are facing. A paradigm shift in the assumptions about the ways that teaching and learning can occur is called for, one that places the student, rather than the institution, at the center. The transformational capacity of applications of technology are discussed, along with strategies for moving toward the new “networked teaching and learning”.
Andragogy and Distance Education: Together in the New Millennium
Authors: Rossman Mark H.
Published: January 2013

Andragogy, as promulgated by the late Malcolm Knowles, is a set of assumptions designed to facilitate adult learning and program planning. Distance education is a process of delivering education used extensively by adult learners. Burge (1988) proposed that the implications of andragogy to distance education be examined. This article continues in that direction. Following a brief overview of andragogical development, the author presents andragogy as a framework for discussing distance education programs designed for the adult learner. Andragogically compatible processes, such as the “general to specific” approach for developing learning contracts and individualizing course projects, and the “group charter” concept for learner participation in asynchronous discussion forums, are presented and discussed as examples of applying andragogy to climate setting and learner involvement in distance education settings.
Old Planet, New Millennium, Same Excuses?: Taking Responsibility: The Need for Adult Environmental Education
Authors: Wright Tarah Sharon Alexandra
Published: January 2013

Education is recognized as an essential component to the advancement of humans living sustainably with the environment. While it is critical to instill an environmental ethic in school children, it is equally important for environmental education to be directed towards adults, as they make consumer, social and political decisions that affect our world. This brief paper explores adult environmental education and its importance within the environmental movement. The underlying argument is that the health of humanity and the planet can be improved through adult environmental education.