bluuebunny/crossref_metadata_2025 huggingface dataset:
A novel injectable and in situ crosslinked hydrogel based on hyaluronic acid and α,β‐polyaspartylhydrazide
Authors: Zhang Rui , Xue Mingyuan , Yang Jing , Tan Tianwei
Published: December 2011

A new injectable and in situ crosslinked hydrogel, based on a hyaluronic acid (HA) derivative and α,β‐polyaspartylhydrazide (PAHy), was produced during the research. This biodegradable and high molecular weight hydrogel can be in situ crosslinked in 15 s by the condensation reaction between aldehyde and amine groups. The HA derivative carrying aldehyde (HAALD) was oxidized from HA by sodium periodate, while the synthesis of hydrogel was performed in a phosphate‐buffered saline solution (PBS) using HAALD and PAHy without addition of crosslinker or catalyst. The pH and concentration of the reaction solution, considered as the important factors of the amine‐aldehyde reaction, were changed to reveal the crosslinking rule. Thereafter, crosslinked hydrogels were characterized by gelation time, gel content, swelling ratio, and in vitro degradation. Furthermore, the modified polymers were characterized by Fourier transformed infrared (FTIR) spectroscopy to examine their structures. Results from scanning electron microscope (SEM) observations confirmed that a freeze‐dried sample revealed a porous hydrogel structure with interconnected pores. The measurement of the cell adhesion confirmed the application potential of HAALD‐PAHy hydrogels. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012
Application of IVIVE and PBPK modeling in prospective prediction of clinical pharmacokinetics: strategy and approach during the drug discovery phase with four case studies
Authors: Chen Yuan , Jin Jin Y. , Mukadam Sophie , Malhi Vikram , Kenny Jane R.
Published: January 2012

Prospective simulations of human pharmacokinetic (PK) parameters and plasma concentration–time curves using in vitro in vivo extrapolation (IVIVE) and physiologically based pharmacokinetic (PBPK) models are becoming a vital part of the drug discovery and development process. This paper presents a strategy to deliver prospective simulations in support of clinical candidate nomination. A three stage approach of input parameter evaluation, model selection and multiple scenario simulation is utilized to predict the key components influencing human PK; absorption, distribution and clearance. The Simcyp® simulator is used to illustrate the approach and four compounds are presented as case studies. In general, the prospective predictions captured the observed clinical data well. Predicted Cmax was within 2‐fold of observed data for all compounds and AUC was within 2‐fold for all compounds following a single dose and three out of four compounds following multiple doses. Similarly, tmax was within 2‐fold of observed data for all compounds. However, Clast was less accurately captured with two of the four compounds predicting Clast within 2‐fold of observed data following a single dose. The trend in results was towards overestimation of AUC and Clast, this was particularly apparent for compound 2 for which clearance was likely underestimated via IVIVE. The prospective approach to simulating human PK using IVIVE and PBPK modeling outlined here attempts to utilize all available in silico, in vitro and in vivo preclinical data in order to determine the most appropriate assumptions to use in prospective predictions of absorption, distribution and clearance to aid clinical candidate nomination. Copyright © 2012 John Wiley & Sons, Ltd.
Application of Polyelectrolyte‐Enhanced Ultrafiltration for Rhenium Recovery from Aqueous Solutions
Authors: Zeng J. , Li S. , Sun X. , Chen X.
Published: January 2012

Polyelectrolyte‐enhanced ultrafiltration was investigated for rhenium(VII) recovery from aqueous solutions by using polyquaternium‐6 (PQ6) as a complexing agent. The effects of the operating parameters on the permeate flux (J) and the rhenium rejection coefficient (R) were studied. In the process of concentration, J declines slowly and R is about 1. The concentrated solution was used for the decomplexation. It takes 10 min to achieve the decomplexation equilibrium at a chloride ion concentration of 100 mg L–1. The decomplexation percentage reaches 45.6 %. In the diafiltration process, rhenium is extracted effectively, and the purification of the regenerated PQ6 is satisfactory. The regenerated PQ6 was used to bind rhenium(VII). The binding capacity of the regenerated PQ6 is close to that of fresh PQ6.
tBu or not tBu?
Authors: Nilsson Lill Sten O. , Ryberg Per , Rein Tobias , Bennström Evelina , Norrby Per‐Ola
Published: January 2012

The regioselectivity in the palladium‐catalyzed Heck coupling reaction between an aryl halide and ethyl vinyl ether with four different phosphine ligands: PPhntBum (n=0–3, m=3−n) has been investigated both experimentally and computationally. A zigzag selectivity pattern was experimentally observed upon consecutive replacement of Ph by tBu in the phosphine ligand. Use of a standard DFT method (B3LYP) was shown to give a correct prediction of product preference. However, the trend in relative selectivity among the different ligands could not be correctly described. The use of a more recent DFT functional (M06) parameterized to reproduce dispersion interactions resulted in an improved description. For the sterically most demanding ligands, PtBu3 and PPhtBu2, unexpectedly large deviations between experimental and M06 calculated selectivities raised the question of an alternative mechanism for these ligands. In the case of PtBu3 it was found, in agreement with literature data, that the phosphine ligand could be replaced by a second halide ligand, resulting in an anionic mechanism, with a calculated selectivity in excellent agreement with experimental data. For the PPhtBu2 ligand, two mechanisms are suggested to operate in parallel, as demonstrated both by computational studies and experimental observation of halide‐dependent selectivity. A Halpern effect is observed for all phosphine ligands investigated, that is, the least stable pre‐complex results in the most abundant product.
ChemInform Abstract: Solvent‐Free Synthesis of Enamines from Alkyl Esters of Propiolic or But‐2‐yne Dicarboxylic Acid in a Ball Mill.
Authors: Thorwirth Rico , Stolle Achim
Published: January 2012

In most cases, the (E) isomers are produced nearly exclusively.
Phase transition for potentials of high‐dimensional wells
Authors: Lin Fanghua , Pan Xing‐Bin , Wang Changyou
Published: January 2012

For a potential function
$\font\open=msbm10 at 10pt\def\R{\hbox{\open R}}F:\R^k \to\R _ +$
that attains its global minimum value at two disjoint compact connected submanifolds N± in $\font\open=msbm10 at 10pt\def\R{\hbox{\open R}}\R^k$, we discuss the asymptotics, as ϵ → 0, of minimizers uϵ of the singular perturbed functional ${\bf E}_\varepsilon (u) = \int_\Omega {(|\nabla u|^2 + {1 \over {\varepsilon ^2 }}F(u))} dx$
under suitable Dirichlet boundary data $\font\open=msbm10 at 10pt\def\R{\hbox{\open R}}g_\varepsilon :\partial \Omega \to\R ^k$. In the expansion of Eϵ (uϵ) with respect to ${1 \over \varepsilon }$, we identify the first‐order term by the area of the sharp interface between the two phases, an area‐minimizing hypersurface Γ, and the energy c of minimal connecting orbits between N+ and N−, and the zeroth‐order term by the energy of minimizing harmonic maps into N± both under the Dirichlet boundary condition on ∂Ω and a very interesting partially constrained boundary condition on the sharp interface Γ. © 2012 Wiley Periodicals, Inc.
Effect of Ionic Liquid on Diffusion in P123 Gel: Fluorescence Correlation Spectroscopy
Authors: Mandal Amit Kumar , Sen Mojumdar Supratik , Das Atanu Kumar , Bhattacharyya Kankan
Published: January 2012

The effect of two room‐temperature ionic liquids (RTILs) on the diffusion of three fluorescent dyes in the gel phase of a triblock copolymer, (PEO)20‐(PPO)70‐(PEO)20 [Pluronic P123; poly ethylene oxide (PEO), poly propylene oxide (PPO)], was studied by using fluorescence correlation spectroscopy (FCS). We used three dyes, 4‐(dicyanomethylene)‐2‐methyl‐6‐(4‐dimethylaminostyryl)‐4H‐pyran (DCM), coumarin 480 (C480), and coumarin 343 (C343). By field‐emission scanning electron microscopy (FESEM), it was observed that the macroscopic structure of the P123 gel remained unaffected upon addition of RTIL. In the absence of RTIL, the diffusion coefficient (Dt) of the hydrophobic dye DCM (1 μm2 s−1 at the core) is smaller than that of the other two hydrophilic dyes (7 μm2 s−1 for C480 and C343). On addition of RTIL, the Dt values of all of the dyes increase, indicating a decrease in local viscosity (ηeff). The ηeff of the core of the RTIL–P123 gel estimated from the Dt of DCM is lower than that of both the P123 gel (at the core η=90 cP) and RTIL (η=110 cP). It is shown that the RTIL affects the structure of the gel by modifying the size of the micellar aggregates and by penetrating the core.
An opportunity not to be missed – how do we improve postpartum screening rates for women with gestational diabetes?
Authors: Keely Erin
Published: January 2012

The ability to detect postpartum dysglycaemia, intervene and prevent type 2 diabetes in this high‐risk population may be the most compelling reason to diagnose gestational diabetes. However, most studies show that less than 50% of women receive any glucose screening in the postpartum period and are thus denied this opportunity. Although many have advocated for simpler testing, the 75‐g oral glucose tolerance test remains the gold standard as fasting glucose level will miss 30–40% of cases of type 2 diabetes and will not detect isolated impaired glucose tolerance. Haemoglobin A1c as a screening test has not been adequately studied.

To improve postpartum screening rates, we need to increase awareness of the very high risk of type 2 diabetes, improve communication between providers, reduce fragmentation of care and introduce system factors that facilitate screening adherence. Copyright © 2012 John Wiley & Sons, Ltd.
Optical coherence tomography captures rapid hemodynamic responses to acute hypoxia in the cardiovascular system of early embryos
Authors: Gu Shi , Jenkins Michael W. , Peterson Lindsy M. , Doughman Yong‐Qiu , Rollins Andrew M. , Watanabe Michiko
Published: January 2012

Background: The trajectory to heart defects may start in tubular and looping heart stages when detailed analysis of form and function is difficult by currently available methods. We used a novel method, Doppler optical coherence tomography (OCT), to follow changes in cardiovascular function in quail embryos during acute hypoxic stress. Chronic fetal hypoxia is a known risk factor for congenital heart diseases (CHDs). Decreased fetal heart rates during maternal obstructive sleep apnea suggest that studying fetal heart responses under acute hypoxia is warranted. Results: We captured responses to hypoxia at the critical looping heart stages. Doppler OCT revealed detailed vitelline arterial pulsed Doppler waveforms. Embryos tolerated 1 hr of hypoxia (5%, 10%, or 15% O2), but exhibited changes including decreased systolic and increased diastolic duration in 5 min. After 5 min, slower heart rates, arrhythmic events and an increase in retrograde blood flow were observed. These changes suggested slower filling of the heart, which was confirmed by four‐dimensional Doppler imaging of the heart itself. Conclusions: Doppler OCT is well suited for rapid noninvasive screening for functional changes in avian embryos under near physiological conditions. Analysis of the accessible vitelline artery sensitively reflected changes in heart function and can be used for rapid screening. Acute hypoxia caused rapid hemodynamic changes in looping hearts and may be a concern for increased CHD risk. Developmental Dynamics 241:534–544, 2012. © 2012 Wiley Periodicals, Inc.
Gold nanoparticle‐coated capillaries for protein and peptide analysis on open‐tubular capillary electrochromatography
Authors: Hamer Mariana , Yone Angel , Rezzano Irene
Published: January 2012

We report a new method of immobilization of gold nanoparticles (AuNPs) on a fused‐silica capillary through covalent binding. The resulting modified capillary was applied to electrophoretic systems to improve the efficiency of separation and the selectivity of selected solutes. The immobilization of AuNPs on the capillary wall was performed in a very simple and fast way without requiring heating. The surface features of an AuNP‐coated capillary column were determined using the scanning electron microscopy. The chromatographic properties of AuNP‐coated capillaries were investigated through variation of the buffer pH and separation voltage. Effective separations of synthetic peptides mixture were obtained on the AuNP‐coated capillaries. The method shows a remarkable stability since it was reused about 900 times. The capacity factor was duplicated. Therefore, this modification is stable and can be applied to different separation purposes. A complex mixture of tryptic peptide fragments of HSA was analyzed in both the bare‐ and the AuNP‐coated capillaries. Better electrophoretic peptide profile was observed when using the AuNP‐coated capillary.
Effects of aging and sensory loss on glial cells in mouse visual and auditory cortices
Authors: Tremblay Marie‐Ève , Zettel Martha L. , Ison James R. , Allen Paul D. , Majewska Ania K.
Published: January 2012

Normal aging is often accompanied by a progressive loss of receptor sensitivity in hearing and vision, whose consequences on cellular function in cortical sensory areas have remained largely unknown. By examining the primary auditory (A1) and visual (V1) cortices in two inbred strains of mice undergoing either age‐related loss of audition (C57BL/6J) or vision (CBA/CaJ), we were able to describe cellular and subcellular changes that were associated with normal aging (occurring in A1 and V1 of both strains) or specifically with age‐related sensory loss (only in A1 of C57BL/6J or V1 of CBA/CaJ), using immunocytochemical electron microscopy and light microscopy. While the changes were subtle in neurons, glial cells and especially microglia were transformed in aged animals. Microglia became more numerous and irregularly distributed, displayed more variable cell body and process morphologies, occupied smaller territories, and accumulated phagocytic inclusions that often displayed ultrastructural features of synaptic elements. Additionally, evidence of myelination defects were observed, and aged oligodendrocytes became more numerous and were more often encountered in contiguous pairs. Most of these effects were profoundly exacerbated by age‐related sensory loss. Together, our results suggest that the age‐related alteration of glial cells in sensory cortical areas can be accelerated by activity‐driven central mechanisms that result from an age‐related loss of peripheral sensitivity. In light of our observations, these age‐related changes in sensory function should be considered when investigating cellular, cortical, and behavioral functions throughout the lifespan in these commonly used C57BL/6J and CBA/CaJ mouse models. © 2012 Wiley Periodicals, Inc.
B‐cells and IL‐4 promote methylcholanthrene‐induced carcinogenesis but there is no evidence for a role of T/NKT‐cells and their effector molecules (Fas‐ligand, TNF‐α, perforin)
Authors: Kammertoens Thomas , Qin Zhihai , Briesemeister Dana , Bendelac Albert , Blankenstein Thomas
Published: December 2011

Mice deficient either in subtypes of immune cells, cytokines or lytic pathways have been subjected to chemical carcinogenesis by methylcholanthrene to evaluate whether these components of the immune system affect tumor development. Inbred mice of the same genotype but from different sources differed in tumor development in magnitude comparable to that previously attributed to differences in immunocompetence. This suggested that genetic drift between separate inbred colonies of mice and/or environmental factors (e.g., transport of the animals) influenced carcinogenesis. Therefore, littermates were used as control in subsequent experiments. Although deficiency of T‐cells, NKT‐cells, perforin, Fas‐ligand, TNF‐α‐receptor failed to reveal significant differences in tumor development, the presence of B‐cells and IL‐4 enhanced tumor development under similar experimental conditions.
PEA15 impairs cell migration and correlates with clinical features predicting good prognosis in neuroblastoma
Authors: Gawecka Joanna E. , Geerts Dirk , Koster Jan , Caliva Maisel J. , Sulzmaier Florian J. , Opoku‐Ansah John , Wada Randal K. , Bachmann André S. , Ramos Joe W.
Published: December 2011

ERK and RSK2 drive proliferation and invasion of many cancers. Phosphoprotein enriched in astrocytes 15 (PEA15) binds ERK and RSK2 and high PEA15 levels can impair ERK‐ and RSK2‐dependent transcription. PEA15 expression also inversely correlates with cell motility and invasiveness. We therefore tested PEA15 effects on neuroblastoma cells in vitro. We further analyzed PEA15 expression in the context of clinical and genetic features of neuroblastoma in tumor samples to determine its correlation with disease progression. Affymetrix microarray analysis was performed using 24 different neuroblastoma cell lines. Cell lines expressing low to intermediate levels of PEA15 were chosen for in vitro functional studies. The cell line results were verified by Affymetrix analysis of three different neuroblastic tumor types (total of 110 samples) PEA15 overexpression inhibited neuroblastoma migration in vitro. We verified that inhibition of motility required PEA15 interaction with its binding partners ERK and RSK2. Additionally, synthetic inhibitors of RSK2 suppressed integrin‐dependent migration. PEA15 expression correlates with clinical parameters and a 25% increase in patient survival rate. The highest PEA15 levels were found in low stage, more differentiated and less metastatic neuroblastic tumors, and correlated with lack of MYCN amplification. PEA15 blocks neuroblastoma migration through inhibition of ERK/RSK2 signaling. PEA15 expression levels correlate with favorable clinical features suggesting that PEA15 limits metastatic progression of neuroblastoma. Thus, PEA15 and its partners ERK and RSK2 are potential targets for the development of new therapeutics to impede progression of minimal residual disease in patients with high‐risk neuroblastoma.
Fine‐mapping of a region of chromosome 5p15.33 (TERT‐CLPTM1L) suggests a novel locus in TERT and a CLPTM1L haplotype are associated with glioma susceptibility in a Chinese population
Authors: Zhao Yingjie , Chen Gong , Zhao Yao , Song Xiao , Chen Hongyan , Mao Ying , Lu Daru
Published: December 2011

Two genome‐wide association studies (GWAS) have identified 5p15.33 (TERT‐CLPTM1L) as one of the susceptible regions for glioma in European background. A replication research of our group highlighted the association signals in the TERT gene of this region in a Chinese Han population. To comprehensively explore the region of glioma association at 5p15.33 and to refine the potential causal variants to a smaller critical region, we conducted a fine‐mapping association study among 983 cases and 1,024 controls in a Chinese Han population. Using Hapmap3 datasets as a reference, we genotyped 16 tag SNPs across this 87.9‐kb region encompassing TERT. Significant association with glioma risk was observed for rs2853677 [GG vs. GA: adjusted OR = 1.46, p = 5.51 × 10−6, GG vs. AA: adjusted OR = 1.72, p = 7.64 × 10−6, GG vs. GA and AA: adjusted OR = 1.96, p = 6.8 × 10−6] in TERT and an uncommon CLPTM1L haplotype G–T–A of rs4635969, rs6554759 and rs414965 (haplotype frequency = 0.07) was associated with higher glioma risk compared with the most common G–C–G haplotype (adjusted OR = 1.44, simulated p = 6.00 × 10−3 under additive model). Our results indicate that sequence variants in the region flanking rs2853677 may account for the GWAS and replication signals identified in 5p15.33 for glioma susceptibility in Chinese population; besides, haplotype G–T–A in CLPTM1L also confers a risk to glioma suggesting CLPTM1L is also involved in the etiology of glioma. Additional studies especially those taking advantage of sequencing platforms are warranted to further confirm the conclusions and go deeper with our findings.
CD31, EDNRB and TSPAN7 are promising prognostic markers in clear‐cell renal cell carcinoma revealed by genome‐wide expression analyses of primary tumors and metastases
Authors: Wuttig Daniela , Zastrow Stefan , Füssel Susanne , Toma Marieta I. , Meinhardt Matthias , Kalman Kristin , Junker Kerstin , Sanjmyatav Jimsgene , Boll Kerstin , Hackermüller Jörg , Rolle Axel , Grimm Marc‐Oliver , Wirth Manfred P.
Published: December 2011

Currently used clinicopathological parameters are insufficient for a reliable prediction of metastatic risk and disease‐free survival (DFS) of patients with clear‐cell renal cell carcinoma (ccRCC). To identify prognostic genes, the expression profiles of primary ccRCC obtained from patients with different DFS — eight synchronously, nine metachronously and seven not metastasized tumors — were determined by genome‐wide expression analyses. Synchronously and metachronously metastasized primary ccRCC differed in the expression of 167 genes. Thirty‐six of these genes were also differentially expressed in synchronously vs. metachronously developed pulmonary metastases analyzed in a previous study. Because of their DFS‐associated deregulation that is concordant in metastases and primary ccRCC, these genes are potentially functionally involved in metastatic tumor growth and are also prognostically useful. A prognostic impact was confirmed for the genes CD31,
EDNRB and TSPAN7 at the mRNA level (n = 86), and for TSPAN7 at the protein level (n = 106). Patients with a higher gene expression of EDNRB or TSPAN7, or with TSPAN7‐positive vessels in both cores investigated on tissue microarrays had a significantly longer DFS and tumor‐specific survival (TSS). Patients with a higher CD31 gene expression showed a significantly longer TSS. EDNRB was an independent prognostic marker for the DFS. CD31, EDNRB and TSPAN7 had an independent impact on the TSS. In summary, comparative analysis of primary tumors and metastases is appropriate to identify independent prognostic markers in ccRCC. Gene expression of CD31 and EDNRB, and endothelial TSPAN7 protein level are potentially useful to improve outcome prediction because of their independent prognostic impact.
The influence of prediagnostic demographic and lifestyle factors on esophageal squamous cell carcinoma survival
Authors: Thrift Aaron P. , Nagle Christina M. , Fahey Paul P. , Russell Anne , Smithers Bernard M. , Watson David I. , Whiteman David C. ,   for the Australian Cancer Study Clinical Follow‐Up Study
Published: December 2011

Demographic and lifestyle factors, in particular tobacco smoking and alcohol, are well established causes of esophageal squamous cell carcinoma (ESCC); however, little is known about the effect of these factors on survival. We included all 301 patients with incident ESCC, recruited into a population‐based case–control study of esophageal cancer in Australia. Detailed information about demographic and lifestyle factors was obtained at diagnosis, and deaths were identified using the National Death Index. Median follow‐up for all‐cause mortality was 6.4 years. Hazard ratios (HRs) and 95% confidence intervals (95% CI) were calculated from Cox proportional hazards models, adjusted for age, sex, pretreatment AJCC tumor stage, treatment and presence of comorbidities. Two hundred and thirteen patients (71%) died during follow‐up. High lifetime alcohol consumption was independently associated with poor survival. Relative to life‐long nondrinkers and those consuming <1 drink/week, the HRs for those with average consumption of 7–20 drinks/week or ≥21 drinks/week were 2.21 (95% CI = 1.27–3.84) and 2.08 (95% CI = 1.18–3.69), respectively. There was a suggestion of worse survival among current smokers (HR = 1.42, 95% CI = 0.89–2.28); however, the risk of early death was greatest among current smokers who reported regularly (≥7 drinks/week) consuming alcohol (HR = 3.84, 95% CI = 2.02–7.32). Other lifestyle factors putatively associated with risk of developing ESCC were not associated with survival. In addition to increasing disease risk, heavy alcohol consumption may be independently associated with worse survival among patients with ESCC. Future clinical follow‐up studies should consider alcohol as a potential prognosticator, in addition to known clinicopathologic factors.
DNA methylation of the CYP1A1 enhancer is associated with smoking‐induced genetic alterations in human lung
Authors: Tekpli Xavier , Zienolddiny Shanbeh , Skaug Vidar , Stangeland Lodve , Haugen Aage , Mollerup Steen
Published: December 2011

CYP1A1 (cytochrome P4501A1) catalyze the conversion of polycyclic aromatic hydrocarbons into reactive metabolites, which may induce DNA damage. We hypothesized that DNA methylation of the CYP1A1 enhancer could be involved in inter‐individual differences in mRNA levels of CYP1A1 or affect the smoking‐induced DNA damage in human lung. Using DNA bisulfite conversion and pyrosequencing, we show that DNA methylation of the CYP1A1 enhancer is affected by smoking. In adjacent histologically normal lung from lung cancer patients (n = 120), low levels of DNA methylation of the CYP1A1 enhancer were related to high levels of smoking‐induced hydrophobic DNA adduct (p < 0.03), and to the presence of TP53 or K‐ras mutations in the corresponding lung tumors (p < 0.03). We found an inverse correlation between DNA methylation of the CYP1A1 enhancer and mRNA levels in vivo (Spearman r = −0.54; p < 0.0001). Thus, in lung tumor tissues, the CYP1A1 enhancer hypermethylation was associated with lower mRNA levels compared to adjacent histologically normal tissue (p < 0.0001). In vitro, using a panel of cultured human lung cells, we found hypermethylation of the CYP1A1 enhancer in cancer cell lines and an inverse correlation between DNA methylation and mRNA levels (Spearman r = −0.53; p = 0.003). Altogether, our results indicated that low levels of DNA methylation of the CYP1A1 enhancer in histologically normal human lung were associated with high CYP1A1 mRNA levels and with smoking‐induced genetic alterations; thus, it may play a role in the initiation of lung carcinogenesis.
Effects of cold ischemia and inflammatory tumor microenvironment on detection of PI3K/AKT and MAPK pathway activation patterns in clinical cancer samples
Authors: Bonnas Christel , Specht Katja , Spleiss Olivia , Froehner Stefanie , Dietmann Gabriele , Krüger Juliane M. , Arbogast Susanne , Feuerhake Friedrich
Published: December 2011

The accuracy of common markers for PI3K/AKT and MAPK pathway activation in preclinical and clinical cancer biomarker studies depends on phosphoepitope stability and changes of phosphorylation under ischemia. Herein, we define conditions under which phosphoepitope‐specific duplex immunohistochemistry (IHC) on formalin‐fixed, paraffin‐embedded tumor tissues reflects pathway activation in situ as accurately as possible, and identify activation patterns linked to mutational status, pathway dependency and tumor microenvironment in clinical tumor samples, cell culture and xenograft tissues. Systematically assessing robustness of pAKT, pERK1/2, pMEK1/2 and pmTOR detection and related markers in xenograft tissues exposed to ischemia, we show that control of preprocessing and ischemia times allows accurate interpretation of staining results. Phosphorylation patterns were then analyzed in 33 xenograft models and in 58 cases with breast cancer, including 21 paired samples of core‐needle biopsies with corresponding mastectomy specimens, and 37 mastectomy samples obtained under rigorously controlled conditions minimizing ischemia time. Patterns of pAKT and pERK1/2 staining (predominant PI3K/AKT, predominant MAPK and concomitant activation) were associated with sensitivity to pathway inhibition and partially with the mutational status in cell lines and corresponding xenograft tumors. In contrast, no clear correlation between mutational status and staining patterns was observed in clinical breast cancer samples, suggesting that interaction with the human tumor microenvironment may interfere with the use of phosphoepitope‐specific IHC as potential markers for pathway dependency. In contrast to core needle biopsies, surgically resected breast cancer samples showed evidence of severe signal changes comparable to those effects observed in xenograft tumors exposed to controlled ischemia.
Oxidative stress and apoptosis induced by hydroxyapatite nanoparticles in C6 cells
Authors: Xu Jing , Xu Pengjuan , Li Zhigui , Huang Jie , Yang Zhuo
Published: December 2011

Hydroxyapatite (HA) nanoparticles have been reported to exhibit anti‐tumor effects on various human cancers, but the effects of HA on glioma cells remain unclear. The aim of this study was to explore whether HA can inhibit the proliferation and induce the apoptosis of C6 cells. Use of the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay indicated that HA induced C6 cell death in a concentration‐dependent and time‐dependent manner. Results from hoechst 33342 staining and flow cytometry assay showed that HA induced C6 cell apoptosis significantly. Meanwhile, the flow cytometric assay gave clear indication that HA induced intracellular accumulation of reactive oxygen species (ROS). The measurement of superoxide dismutase (SOD) generation showed that HA decreased the total SOD of cellular levels. Interestingly, pretreatment of N‐(mercaptopropionyl)‐glycine (N‐MPG), known as a type of ROS scavenger formulations, could somehow inhibit C6 cell apoptosis induced by HA. These results may provide potential anti‐glioma treatment in the future. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2012.
Simultaneous treatment of methane and swine slurry by biofiltration
Authors: Girard Matthieu , Viens Pascal , Ramirez Antonio Avalos , Brzezinski Ryszard , Buelna Gerardo , Heitz Michèle
Published: January 2012

BACKGROUND: The piggery industry is important both worldwide and in Canada, but localized production of large quantities of swine slurry causes severe environmental problems such as aquatic pollution and greenhouse gas emissions. The main objective of this study was to determine whether it is possible to simultaneously treat methane (CH4) and swine slurry using an inorganic biofilter.

RESULTS: A novel biofilter was designed to overcome the inhibition of CH4 biodegradation by swine slurry. The CH4 elimination capacity increased with the inlet load and a maximum value of 18.8 ± 1.0 g m−3 h−1 was obtained at an inlet load of 46.7 ± 0.9 g m−3 h−1 and a CH4 concentration of 3.3 g m−3. Four pure strains of fungi were used in an attempt to improve the removal of CH4, but no significant effect was observed. Between 0.35 and 3.4 g m−3, the CH4 concentration had no effect on swine slurry treatment with removal efficiencies of 67 ± 10% for organic carbon and 70 ± 7% for ammonium. The influence of the slurry supply was analyzed and the best results were obtained with a supply method of six doses of 50 mL per day.

CONCLUSION: Even though the results were lower than those obtained for the biofiltration of CH4 alone, this study demonstrated the feasibility of treating CH4 and swine slurry with the same biofilter using a novel design. Copyright © 2012 Society of Chemical Industry
Morphology, ultrastructure, and probable functions of the sense organs on the ovipositor stylets of the hymenoptran parasitoid, Venturia canescens (Gravenhorst)
Authors: Shah Zahid Ali
Published: January 2012

To help understand the mechanism of host discrimination during oviposition of a parasitoid wasp, Venturia canescens (Gravenhorst) (Hymenoptera: Ichneumonidae), the ultrastructure and morphology of the sense organs on the dorsal and ventral stylets of the ovipositor were examined using scanning and transmission electron microscopy. Ovipositor stylets were scanned for sense organs, because only unsheathed ovipositors are used for probing, stabbing, and host discrimination. Five types of sensilla and secretary pores were identified. Based on their pattern of innervation, the surface‐dome and pitted‐dome sensilla were thought to have a gustatory function and, thus, are the best candidates for host‐discrimination. The arrangements of dendrites of type I and type II campaniform sensilla suggested that these acted as pressure‐ and mechano‐receptors, respectively. Coeloconic sensilla might act as thermo‐hygroreceptors, whilst secretary pores might provide lubrication during the process of stabbing for oviposition. Surface‐dome sensilla were the most numerous type found followed by secretary pores, pitted‐dome sensilla, and coeloconic sensilla. Almost all the sensilla and secretary pores were more numerous on the dorsal than on the ventral stylets, and the maximum number of these sensilla and secretary pores occurred on the distal end of the ovipositor stylets and decreased toward the proximal end. The surface‐dome sensilla and secretary pores occurred in alternate rows while the pitted‐dome sensilla were scattered all over the surface of the ovipositor stylets, especially on the sides of the stylets. Microsc. Res. Tech. 2012. © 2012 Wiley Periodicals, Inc.
Mineralization pattern of vertebral bone material following fragility fracture of the spine
Authors: Hofstaetter Jochen G. , Hofstaetter Stefan G. , Nawrot‐Wawrzyniak Kamilla , Hiertz Helmut , Grohs Josef G. , Trieb Klemens , Windhager Reinhard , Klaushofer Klaus , Roschger Paul
Published: January 2012

Little is known whether trabecular bone matrix mineralization is altered at the site of osteoporotic vertebral fractures. Bone mineralization density distribution (BMDD) was assessed in trabecular bone of acute, single‐level compression fractures of the spine at various stages of fracture repair using quantitative backscattered electron imaging (qBEI). The grading of the repair stage was performed by histological methods. From 20 patients, who underwent either kyphoplasty (n = 18) or vertebroplasty (n = 2), a vertebral bone biopsy was taken prior to cement augmentation. Six patients took bisphosphonates (BP) prior to fracture. Three study groups were formed: N1 = early‐, N2 = late‐healing and B = BP treatment at late healing stage. In general, all groups had an altered BMDD when compared to historical normative reference data. Mean matrix mineralization (CaMean) was significantly (p < 0.001) lower in all groups (N1: −5%, N2: −16%, and B2: −16%). In N2, CaMean was −13.1% (p < 0.001) lower than N1. At this stage, deposition of new bone matrix and/or formation of woven bone are seen, which also explains the more heterogeneous matrix mineralization (CaWidth). Moreover, BP treatment (B2) led to a significant reduction in CaWidth (−28.5%, p < 0.001), when compared to N2. Bone tissue from vertebrae with acute compression fractures reveals a large variation in matrix mineralization depending on the stage of repair. Bisphosphonate treatment does affect the mineralization pattern of tissue repair. The low mineralization values found in early stage of repair suggest that altered bone material properties may play a role in the occurrence of fragility fractures of the spine. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:1089–1094, 2012
Footprint‐based estimates of arch structure are confounded by body composition in adults
Authors: Wearing Scott C. , Grigg Nicole L. , Lau Hin C. , Smeathers James E.
Published: January 2012

Previous research employing indirect measures of arch structure, such as those derived from footprints, have indicated that obesity results in a “flatter” foot type. In the absence of radiographic measures, however, definitive conclusions regarding the osseous alignment of the foot cannot be made. We determined the effect of body mass index (BMI) on radiographic and footprint‐based measures of arch structure. The research was a cross‐sectional study in which radiographic and footprint‐based measures of foot structure were made in 30 subjects (10 males, 20 female) in addition to standard anthropometric measures of height, weight, and BMI. Multiple (univariate) regression analysis demonstrated that both BMI (β = 0.39, t26 = 2.12, p = 0.04) and radiographic arch alignment (β = 0.51, t26 = 3.32, p < 0.01) were significant predictors of footprint‐based measures of arch height after controlling for all variables in the model (R2 = 0.59, F3,26 = 12.3, p < 0.01). In contrast, radiographic arch alignment was not significantly associated with BMI (β = −0.03, t26 = −0.13, p = 0.89) when Arch Index and age were held constant (R2 = 0.52, F3,26 = 9.3, p < 0.01). Adult obesity does not influence osseous alignment of the medial longitudinal arch, but selectively distorts footprint‐based measures of arch structure. Footprint‐based measures of arch structure should be interpreted with caution when comparing groups of varying body composition. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:1351–1354, 2012
Fatty acid profiles, antioxidant compounds and antiradical properties ofPinus halepensisMill. cones and seeds
Authors: Dhibi Madiha , Mechri Beligh , Brahmi Faten , Skhiri Fathia , Alsaif Mohammed A , Hammami Mohamed
Published: January 2012

BACKGROUND:Pinus halepensis(Aleppo pine) is a widespread tree that can be found in both natural and urban environments. A discrimination study based on the antioxidant compounds, antioxidant capacity and fatty acid (FA) profile ofP. halepensiscones (PHC) and seeds (PHS) was performed.

RESULTS:The total amount of phenols was about 72‐fold higher in PHC extract than in PHS extract (P< 0.001). Anthocyanin and carotenoid contents were 10‐ and 12‐fold higher respectively in PHC extract. PHC and PHS extracts at a concentration of 1 mg mL−1differed significantly in free radical‐scavenging activity on 2,2‐diphenyl‐1‐picrylhydrazyl radical (DPPH•) (86.65vs16.97%). PHC had higher antioxidant ability on 2,2′‐azino‐bis(3‐ethylbenzothialozine‐6‐sulfonic acid) radical cation (ABTS•+) than PHS (EC500.368vs2.345 mg mL−1). The FA profile of PHC oil revealed its richness in saturated FAs (41.5%) and high levels oftransFA isomers, with a predominance oftrans,trans‐linoleic acid (4.74%). However, polyunsaturated FAs in PHS oil represented more than 64% of total FAs.

CONCLUSION:PHC showed important antioxidant activities as well as high levels of bioactive compounds. Thus PHC is a potential source of natural antioxidants that may afford several health benefits. However, the lipid extract of PHS seems to have more nutritional value as a polyunsaturated oil than that of PHC, which is high in saturated andtransFAs. Copyright © 2011 Society of Chemical Industry
Genetic susceptibility to otitis media in childhood
Authors: Rye Marie S. , Blackwell Jenefer M. , Jamieson Sarra E.
Published: January 2012

Otitis media (OM) is a common disease in early childhood characterized by inflammation of the middle ear cavity. Heritability studies suggest that there is a substantial genetic component (40%–70%) to the risk of recurrent acute OM, defined as three or more episodes in 6 months or four or more episodes in a year, or chronic OM with effusion (COME), defined as middle ear fluid for ≥3 months. To date, only a handful of the regions/genes underlying this genetic susceptibility have been identified. These include several regions of linkage on chromosome 3p25, 10q22, 10q26, 17q12, and 19q13 identified by two genome‐wide linkage scans, which appear to harbor susceptibility loci. Fine mapping of these regions has yet to identify the causative genes. Several candidate genes studies have also been reported, with candidates selected on the basis of a plausible biological role in OM or through OM mouse models. Reviewed in this article, these studies have identified positive association at 21 genes, including FBXO11, TLR4, and TNF, with association at five of these replicated in independent populations. However, these studies have been based on small sample sizes, and it is only recently that well‐powered OM cohorts suitable for genome‐wide association studies (GWAS) have become available. Results from such GWAS will identify novel genes involved in this complex disease. Identification of the genes that contribute to OM susceptibility in childhood will provide important insights into the biological complexity of this disease that could ultimately contribute to improved preventative and therapeutic strategies to reduce the incidence of this disease.
Competition in the brewing industry: Does further concentration imply collusion?
Authors: Chalk Andrew J.
Published: January 2012

Earlier papers reach conflicting conclusions about the effect of concentration in the US brewing industry. This paper argues that stock market data on a more recent set of events, the intense merger activity of 1981–2, can help to resolve these differences. The results indicate that mergers between brewers, excluding the two industry leaders (Anheuser‐Busch and Miller Brewing), enhance industry performance by enabling smaller brewers to exploit the scale economies enjoyed by the large ones.
Investment performance of Canadian real estate stocks using sharpe's performance index: A comment
Authors: Cadsby Charles Bram
Published: January 2012

This comment corrects three typographical errors contained in Achour et al. (1984). It also takes issue with their use and interpretation of multivariate tests in the context of a bivariate null hypothesis.
Concentration ratios, strategy and performance: The case of the Norwegian telecommunications industry
Authors: Grønhaug Kjell , Fredriksen Tor
Published: January 2012

This article explores how changes in industry structure are reflected in changes in performance and strategy. A set of interrelated hypotheses is proposed and examined in one industry (the Norwegian telecommunications industry). Increasing competition was found to be positively related to increasing industry concentration but negatively related to new entries and performance as measured by value added. Large and small firms were found to vary in performance, and they are seemingly applying different strategies in coping with stagnating market opportunities.
Risk aversion, forward markets and the competitive labor‐managed firm under price uncertainty
Authors: Wang Leonard F. S. , Bowles David C.
Published: January 2012

This paper examines the behavior of a labor‐managed co‐operative firm which can sell its output in both spot and forward markets, where the random spot price varies between a price floor and a price ceiling but the forward price is a known parameter. We demonstrate that a risk‐averse labor‐managed firm will base its production decision on the forward market price, and that risk aversion is sufficient to give the direct relationship between a change in uncertainty and the amount hedged in the forward market.
Competition, regulation and bribery: A further note
Authors: Lien Da‐Hsiang Donald
Published: January 2012

In this note we extend the analysis of Beck and Maher (1989) concerning the effects of discriminatory anti‐bribery regulation. We argue that their approaches are challengeable due to an additional assumption that is most likely inconsistent with the benchmark model. Upon discarding the controversial assumption, we have an asymmetric bribery game. The corresponding Bayesian Nash equilibrium is nonetheless possessed with the properties described in Beck and Maher, despite the fact that their approaches may be incorrect.
25‐hydroxyvitamin D, vitamin D receptor gene polymorphisms, and severity of Parkinson's disease
Authors: Suzuki Masahiko , Yoshioka Masayuki , Hashimoto Masaya , Murakami Maiko , Kawasaki Keiichi , Noya Miki , Takahashi Daisuke , Urashima Mitsuyoshi
Published: December 2011

We aimed to examine associations among serum 25‐hydroxyvitamin D levels, 1,25‐dihyroxyvitamin D levels, vitamin D receptor polymorphisms, vitamin D binding protein gene polymorphisms, and the severity of Parkinson's disease. In 137 patients, the severity of Parkinson's disease was evaluated using Hoehn & Yahr stage and Unified Parkinson's Disease Rating Stage by neurologists and compared with 25‐hydroxyvitamin D, 1,25‐hydroxyvitamin D, vitamin D receptor polymorphisms, ie, FokI (rs10735810), BsmI (rs1544410), Cdx2 (rs11568820), ApaI (rs7976091), and TaqI (rs731236), and vitamin D binding protein gene polymorphisms GC1 (rs7041)/GC2 (rs4588) in a cross‐sectional study. Mean ± standard deviation levels of 25‐hydroxyvitamin D were 21.1 ± 9.0 ng/mL. Levels were deficient (<20 ng/mL) in 49% of patients. In contrast, 1,25‐hydroxyvitamin D levels were considered normal in all patients. Higher circulating 25‐hydroxyvitamin D levels were significantly associated with milder Parkinson's disease evaluated by Hoehn & Yahr stage (P = .002) and total Unified Parkinson's Disease Rating Stage (P = .004) even after multivariate adjustment for 8 covariates, including disease duration. However, significant associations were not observed in 1,25‐hydroxyvitamin D levels. Under multivariate analysis with 25‐hydroxyvitamin D as well as other 8 covariates including disease duration, carriers of vitamin D receptor FokICC genotype had a milder form of Parkinson's disease: odds ratio, 0.32; 95% confidence interval, 0.16 to 0.66, P = 0.002. These results suggest that higher 25‐hydroxyvitamin D levels and the vitamin D receptor FokICC genotype may be independently associated with milder forms of Parkinson's disease. However, significant associations were not observed in 1,25‐hydroxyvitamin D levels. © 2011 Movement Disorder Society
Subthalamic neuronal responses to cortical stimulation
Authors: Janssen Marcus L.F. , Zwartjes Daphne G.M. , Temel Yasin , van Kranen‐Mastenbroek Vivianne , Duits Annelien , Bour Lo J. , Veltink Peter H. , Heida Tjitske , Visser‐Vandewalle Veerle
Published: December 2011

Background:

Deep brain stimulation of the subthalamic nucleus alleviates motor symptoms in Parkinson's disease patients. However, some patients suffer from cognitive and emotional changes. These side effects are most likely caused by current spread to the cognitive and limbic territories in the subthalamic nucleus. The aim of this study was to identify the motor part of the subthalamic nucleus to reduce stimulation‐induced behavioral side effects, by using motor cortex stimulation.

Methods:

We describe the results of subthalamic nucleus neuronal responses to stimulation of the hand area of the motor cortex and evaluate the safety of this novel technique.

Results:

Responses differed between regions within the subthalamic nucleus. In the anterior and lateral electrode at dorsal levels of the subthalamic nucleus, an early excitation (∼5–45 ms) and subsequent inhibition (45–105 ms) were seen. The lateral electrode also showed a late excitation (∼125–160 ms). Focal seizures were observed following motor cortex stimulation.

Conclusions:

To prevent seizures the current density should be lowered, so that motor cortex stimulation‐evoked responses can be safely used during deep brain stimulation surgery. © 2011 Movement Disorder Society