bluuebunny/crossref_metadata_2025 huggingface dataset:
Hyperpolarized 13C NMR studies of glucose metabolism in living breast cancer cell cultures
Authors: Harris T. , Degani H. , Frydman L.
Published: October 2013

The recent development of dissolution dynamic nuclear polarization (DNP) gives NMR the sensitivity to follow metabolic processes in living systems with high temporal resolution. In this article, we apply dissolution DNP to study the metabolism of hyperpolarized U‐13C,2H7‐glucose in living, perfused human breast cancer cells. Spectrally selective pulses were used to maximize the signal of the main product, lactate, whilst preserving the glucose polarization; in this way, both C1‐lactate and C3‐lactate could be observed with high temporal resolution. The production of lactate by T47D breast cancer cells can be characterized by Michaelis–Menten‐like kinetics, with Km = 3.5 ± 1.5 mm and Vmax = 34 ± 4 fmol/cell/min. The high sensitivity of this method also allowed us to observe and quantify the glycolytic intermediates dihydroxyacetone phosphate and 3‐phosphoglycerate. Even with the enhanced DNP signal, many other glycolytic intermediates could not be detected directly. Nevertheless, by applying saturation transfer methods, the glycolytic intermediates glucose‐6‐phosphate, fructose‐6‐phosphate, fructose‐1,6‐bisphosphate, glyceraldehyde‐3‐phosphate, phosphoenolpyruvate and pyruvate could be observed indirectly. This method shows great promise for the elucidation of the distinctive metabolism and metabolic control of cancer cells, suggesting multiple ways whereby hyperpolarized U‐13C,2H7‐glucose NMR could aid in the diagnosis and characterization of cancer in vivo. Copyright © 2013 John Wiley & Sons, Ltd.
High‐resolution MRI of uveal melanoma using a microcoil phased array at 7 T
Authors: Beenakker J. W. M. , van Rijn G. A. , Luyten G. P. M. , Webb A. G.
Published: October 2013

High‐field MRI is a promising technique for the characterisation of ocular tumours, both in vivo and after enucleation. For in vivo imaging at 7 T, a dedicated three‐element microcoil array was constructed as a high‐sensitivity receive‐only device. Using a dedicated blink/fixation protocol, high‐resolution in vivo images could be acquired within 3 min in volunteers and patients with no requirement for post‐acquisition image registration. Quantitative measures of axial length, aqueous depth and lens thickness in a healthy volunteer were found to agree well with standard ocular biometric techniques. In a patient with uveal melanoma, in vivo MRI gave excellent tumour/aqueous body contrast. Ex vivo imaging of the enucleated eye showed significant heterogeneity within the tumour. Copyright © 2013 John Wiley & Sons, Ltd.
Glutamate and glutamine: a review of in vivo MRS in the human brain
Authors: Ramadan Saadallah , Lin Alexander , Stanwell Peter
Published: October 2013

Our understanding of the roles that the amino acids glutamate (Glu) and glutamine (Gln) play in the mammalian central nervous system has increased rapidly in recent times. Many conditions are known to exhibit a disturbance in Glu–Gln equilibrium, and the exact relationships between these changed conditions and these amino acids are not fully understood. This has led to increased interest in Glu/Gln quantitation in the human brain in an array of conditions (e.g. mental illness, tumor, neuro‐degeneration) as well as in normal brain function.

Accordingly, this review has been undertaken to describe the increasing number of in vivo techniques available to study Glu and Gln separately, or pooled as ‘Glx’. The present MRS methods used to assess Glu and Gln vary in approach, complexity, and outcome, thus the focus of this review is on a description of MRS acquisition approaches, and an indication of relative utility of each technique rather than brain pathologies associated with Glu and/or Gln perturbation. Consequently, this review focuses particularly on (1) one‐dimensional 1H MRS, (2) two‐dimensional 1H MRS, and (3) one‐dimensional 13C MRS techniques. Copyright © 2013 John Wiley & Sons, Ltd.
Nonexistence of optimal graphs for all terminal reliability
Authors: Brown J. I. , Cox D.
Published: October 2013

Suppose that every edge of a graph G (finite and undirected) is independently operational with probability . The all terminal reliability of G is the probability that all vertices can communicate. It was conjectured that among all graphs with n vertices and m edges there always exists a most optimal graph, that is, one whose all terminal reliability is at least as large as any other such graph, no matter what the value of p. For each , a single value of m was found for which the restriction of the conjecture to simple graphs failed, but it remained open as to whether most optimal graphs exist when multiple edges are allowed. We show that in fact for a given , there are several values of m for which a most optimal simple graph does not exist. Moreover, we prove that including multiple edges still does not introduce a most optimal graph, disproving for the first time the conjecture for general graphs. In contrast, it will be shown that for a given n and m, there always exists a least optimal graph. © 2013 Wiley Periodicals, Inc. NETWORKS, Vol. 63(2), 146–153 2014
A two‐scale failure model for heterogeneous materials: numerical implementation based on the finite element method
Authors: Toro S. , Sánchez P.J. , Huespe A.E. , Giusti S.M. , Blanco P.J. , Feijóo R.A.
Published: October 2013

In the first part of this contribution, a brief theoretical revision of the mechanical and variational foundations of a Failure‐Oriented Multiscale Formulation devised for modeling failure in heterogeneous materials is described.

The proposed model considers two well separated physical length scales, namely: (i) the macroscale where nucleation and evolution of a cohesive surface is considered as a medium to characterize the degradation phenomenon occurring at the lower length scale, and (ii) the microscale where some mechanical processes that lead to the material failure are taking place, such as strain localization, damage, shear band formation, and so on. These processes are modeled using the concept of Representative Volume Element (RVE). On the macroscale, the traction separation response, characterizing the mechanical behavior of the cohesive interface, is a result of the failure processes simulated in the microscale. The traction separation response is obtained by a particular homogenization technique applied on specific RVE sub‐domains. Standard, as well as, Non‐Standard boundary conditions are consistently derived in order to preserve objectivity of the homogenized response with respect to the micro‐cell size.

In the second part of the paper, and as an original contribution, the detailed numerical implementation of the two‐scale model based on the finite element method is presented. Special attention is devoted to the topics, which are distinctive of the Failure‐Oriented Multiscale Formulation, such as: (i) the finite element technologies adopted in each scale along with their corresponding algorithmic expressions, (ii) the generalized treatment given to the kinematical boundary conditions in the RVE, and (iii) how these kinematical restrictions affect the capturing of macroscopic material instability modes and the posterior evolution of failure at the RVE level.

Finally, a set of numerical simulations is performed in order to show the potentialities of the proposed methodology, as well as, to compare and validate the numerical solutions furnished by the two‐scale model with respect to a direct numerical simulation approach. Copyright © 2013 John Wiley & Sons, Ltd.
A Koiter‐Newton approach for nonlinear structural analysis
Authors: Liang Ke , Abdalla Mostafa , Gürdal Zafer
Published: October 2013

A new approach termed the Koiter‐Newton is presented for the numerical solution of a class of elastic nonlinear structural response problems. It is a combination of a reduction method inspired by Koiter's post‐buckling analysis and Newton arc‐length method so that it is accurate over the entire equilibrium path and also computationally efficient in the presence of buckling. Finite element implementation based on element independent co‐rotational formulation is used. Various numerical examples of buckling sensitive structures are presented to evaluate the performance of the method. The examples demonstrate that the method is robust and completely automatic and that it outperforms traditional path‐following techniques. This improved efficiency will open the door for the direct use of detailed nonlinear finite element models in the design optimization of next generation flight and launch vehicles. Copyright © 2013 John Wiley & Sons, Ltd.
Corporate Volunteering: Benefits and Challenges for Nonprofits
Authors: Samuel Olga , Wolf Patricia , Schilling Axel
Published: October 2013

In the frame of corporate social responsibility, corporate volunteering is almost exclusively studied from the point of view of companies, while the perspectives of nonprofit organizations are neglected. Hence, this article focuses on the perspective of managers of nonprofit organizations on volunteer partnership projects with for‐profit companies. In the center of this article lie nonprofit managers' strategy and motivation for participating in corporate volunteering, conception of corporate volunteer activities, and the often‐cited win‐win‐win aspect. Key findings suggest that a majority of the questioned nonprofits lack strategic behavior and management tools for undertaking volunteer partnership projects with companies. Nevertheless, corporate volunteering is widely perceived as an opportunity and a promising method of raising donations for nonprofit organizations. This article suggests that the key to successful future cooperation between nonprofits and profit‐oriented organizations lies in the processes of internal evaluation and subsequent strategy development.
Palliative Care Communication: Linking Patients' Prognoses, Values, and Goals of Care
Authors: Norton Sally A. , Metzger Maureen , DeLuca Jane , Alexander Stewart C. , Quill Timothy E. , Gramling Robert
Published: October 2013

Prognostic communication is a primary component of goals of care conversations in palliative care (PC) practice. Little is known about these conversations in the natural setting. This study's aim was to describe the processes of prognostic communication in PC goals of care consultations. Using line‐by‐line qualitative analysis, we examined prognostic conversation in 66 audio‐taped PC consultations. We identified five processes by which clinicians link prognoses, values, and goals of care: (1) signposting the crossroads; (2) closing off a goal; (3) clarifying current path; (4) linking paths and patients' values; and (5) choosing among paths. The findings add to our understanding of PC consultation by describing how prognoses link with patients' values and choices in goals of care conversations. © 2013 Wiley Periodicals, Inc. Res Nurs Health 36: 582–590, 2013
Modifying effect of obesity on the association between sitting and incident diabetes in post‐menopausal women
Authors: Manini Todd M. , LaMonte Michael J. , Seguin Rebecca A. , Manson JoAnn E. , Hingle Melanie , Garcia Lorena , Stefanick Marcia L. , Rodriguez Beatriz , Sims Stacy , Song Yiqing , Limacher Marian
Published: October 2013

Objective

To evaluate the association between self‐reported daily sitting time and the incidence of type 2 diabetes in a cohort of postmenopausal women.

Methods

Women (N=88,829) without diagnosed diabetes reported the number of hours spent sitting over a typical day. Incident cases of diabetes were identified annually by self‐reported initiation of using oral medications or insulin for diabetes > 14.4 years follow‐up.

Results

Each hour of sitting time was positively associated with increased risk of diabetes [risk ratio (RR): 1.05; 95% confidence interval (CI): 1.02–1.08]. However, sitting time was only positively associated with incident diabetes in obese women. Obese women reporting sitting 8–11 (RR: 1.08; 95% CI 1.0–1.1), 12–15 (OR: 1.13; 95% CI 1.0–1.2), and ≥16 hours (OR: 1.25; 95% CI 1.0–1.5) hours per day had an increased risk of diabetes compared to women sitting ≤7 hours per day. These associations were adjusted for demographics, health conditions, behaviors (smoking, diet, and alcohol intake), and family history of diabetes. Time performing moderate to vigorous intensity physical activity did not modify these associations.

Conclusions

Time spent sitting was independently associated with increased risk of diabetes diagnosis among obese women—a population already at high risk of the disease.
Effects of dietary interventions on liver volume in humans
Authors: Bian Hua , Hakkarainen Antti , Lundbom Nina , Yki‐Järvinen Hannele
Published: October 2013

Objective

To compare effects of similar weight loss induced either by a short‐term low‐carbohydrate or by a long‐term hypocaloric diet, and to determine effects of high carbohydrate overfeeding on liver total, lean, and fat volumes.

Methods

Liver total, lean, and fat volumes were measured before and after (i) a 6‐day low‐carbohydrate diet (n = 17), (ii) a 7‐month standard hypocaloric diet (n = 26), and (iii) a 3‐week high‐carbohydrate diet (n = 17), by combining magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (1H‐MRS) techniques.

Results

At baseline, three groups were comparable with respect to age, body mass index, liver volumes and the liver fat content. Body weight decreased similarly by the short‐term and long‐term hypocaloric diets. Liver total volume decreased significantly more during the short‐term low‐carbohydrate (−22 ± 2%) than the long‐term (−7 ± 2%) hypocaloric diet (P < 0.001). This was due to a greater decrease in liver lean volume in the short‐term (−20 ± 2%) than the long‐term (−4 ± 2%) weight loss group (P < 0.001). Decreases in liver fat were comparable. Liver volume increased by 9 ± 3% due to overfeeding (P< 0.02 for before vs. after).

Conclusions

These data support the use of a short‐term low‐carbohydrate diet whenever a reduction in liver volume is desirable. Overeating carbohydrate is harmful because it increases liver volume.
Dinner rituals that correlate with child and adult BMI
Authors: Wansink Brian , van Kleef Ellen
Published: October 2013

Objective

What predicts whether a child will be at risk for obesity? Whereas past research has focused on foods, eating habits, feeding styles, and family meal patterns, this study departs from a food‐centric approach to examine how various dinner rituals might influence the BMIs of children and adults.

Methods

In this study of 190 parents (BMI = 29.1 ± 7.2) and 148 children (BMI = 20.3 ± 4.4), the relationship between their BMIs and everyday family dinner rituals was examined using both correlation and regression analysis (controlled for educational level of parents).

Results

Families who frequently ate dinner in the kitchen or dining room had significantly lower BMIs for both adults (r = −0.31) and children (r = −0.24) compared to families who ate elsewhere. Additionally, helping cook dinner was associated with higher BMI for girls (r = 0.26), and remaining at the table until everyone is finished with eating was associated with lower BMI for boys (r = −0.31).

Conclusions

Dinner tables may be one place where social support and family involvement meet—both of which relate to the BMI of children as well as parents. Family meals and their rituals might be an underappreciated battleground to fight obesity.
Fasting plasma adropin concentrations correlate with fat consumption in human females
Authors: St‐Onge Marie‐Pierre , Shechter Ari , Shlisky Julie , Tam Charmaine S. , Gao Su , Ravussin Eric , Butler Andrew A.
Published: October 2013

Objective

This study investigated whether plasma adropin concentrations are influenced by sleep restriction and correlate with dietary preferences.

Methods

Plasma adropin concentrations were measured by ELISA using samples from a study that investigated feeding behavior in sleep deprived lean (body mass index 22‐26 kg/m2) men and women aged 30‐45 y. Sleep (habitual or restricted to 4h/night) and diet were controlled during a 4‐day inpatient period. On day 5, food was self‐selected (FS). Adropin was measured on day 4 in samples collected throughout the day, and then after an overnight fast at 0730 on days 5 (Pre‐FS) and 6 (Post‐FS).

Results

Plasma adropin concentrations were not affected by sleep restriction. However, circulating adropin concentrations correlated with food selection preferences in women, irrespective of sleep status. Pre‐FS adropin correlated positively with fat intake (total fat, r = 0.867, P < 0.05; saturated fat, r = 0.959, P < 0.01) and negatively with carbohydrate intake (r = ‐0.894, P < 0.05) as a percent total energy. Post‐FS adropin correlated with total (r = 0.797, P < 0.05) and saturated fat intake (r = 0.945, P < 0.01), and negative with total carbohydrate intake (r = ‐0.929, P < 0.01). Pre‐FS adropin also correlated with fat intake in kcal adjusted for body size (total fat, r = 0.852, P < 0.05; saturated fat, r = 0.927, P < 0.01).

Conclusions

Plasma adropin concentrations correlate with fat consumption in women.
Examining behavioral processes through which lifestyle interventions promote weight loss: Results from PREMIER
Authors: Fitzpatrick Stephanie L. , Bandeen‐Roche Karen , Stevens Victor J. , Coughlin Janelle W. , Rubin Richard R. , Brantley Phillip J. , Funk Kristine L. , Svetkey Laura P. , Jerome Gerald J. , Dalcin Arlene , Charleston Jeanne , Appel Lawrence J.
Published: October 2013

Objective

To examine the behavioral processes through which lifestyle interventions impacted weight loss.

Methods

The analyses were limited to overweight and obese Black and White adults randomized to a PREMIER lifestyle intervention (N = 501). Structural equation modeling was conducted to test the direct and indirect relationships of session attendance, days of self‐monitoring diet and exercise, change in diet composition and exercise, and 6‐month weight change.

Results

Greater session attendance was associated with increased self‐monitoring, which was in turn significantly related to reduction in percent energy from total fat consumed. Change in percent energy from fat and self‐monitoring was associated with 6‐month percent change in weight. Both a decrease in fat intake and increase in self‐monitoring are potential mediators of the relationship between attendance and weight change.

Conclusions

The findings provide a reasonable model that suggests regular session attendance and use of behavioral strategies like self‐monitoring are associated with improved behavioral outcomes that are associated with weight loss.
Insulin Sensitivity and Insulin Clearance Are Heritable and Have Strong Genetic Correlation in Mexican Americans
Authors: Goodarzi Mark O. , Langefeld Carl D. , Xiang Anny H. , Chen Yii‐Der I. , Guo Xiuqing , Hanley Anthony J. G. , Raffel Leslie J. , Kandeel Fouad , Nadler Jerry L. , Buchanan Thomas A. , Norris Jill M. , Fingerlin Tasha E. , Lorenzo Carlos , Rewers Marian J. , Haffner Steven M. , Bowden Donald W. , Rich Stephen S. , Bergman Richard N. , Rotter Jerome I. , Watanabe Richard M. , Wagenknecht Lynne E.
Published: October 2013

Objective

The GUARDIAN (Genetics UndeRlying DIAbetes in HispaNics) consortium is described, along with heritability estimates and genetic and environmental correlations of insulin sensitivity and metabolic clearance rate of insulin (MCRI).

Methods

GUARDIAN is comprised of seven cohorts, consisting of 4,336 Mexican‐American individuals in 1,346 pedigrees. Insulin sensitivity (SI), MCRI, and acute insulin response (AIRg) were measured by frequently sampled intravenous glucose tolerance test in four cohorts. Insulin sensitivity (M, M/I) and MCRI were measured by hyperinsulinemic‐euglycemic clamp in three cohorts. Heritability and genetic and environmental correlations were estimated within the family cohorts (totaling 3,925 individuals) using variance components.

Results

Across studies, age, and gender‐adjusted heritability of insulin sensitivity (SI, M, M/I) ranged from 0.23 to 0.48 and of MCRI from 0.35 to 0.73. The ranges for the genetic correlations were 0.91 to 0.93 between SI and MCRI; and −0.57 to −0.59 for AIRg and MCRI (all P < 0.0001). The ranges for the environmental correlations were 0.54 to 0.74 for SI and MCRI (all P < 0.0001); and −0.16 to −0.36 for AIRg and MCRI (P < 0.0001‐0.06).

Conclusions

These data support a strong familial basis for insulin sensitivity and MCRI in Mexican Americans. The strong genetic correlations between MCRI and SI suggest common genetic determinants.
An Application of Unconditional Quantile Regression to Cigarette Taxes
Authors: Maclean Johanna Catherine , Webber Douglas A. , Marti Joachim
Published: October 2013

This study investigates heterogeneous response to state cigarette tax increases using unconditional quantile regression (UQR). We make two contributions to the empirical policy analysis literature. First, we argue that UQR provides more policy‐relevant information than conventional quantile regression in most empirical state policy analyses. Second, we document cigarette tax elasticity across a sample of adult smokers in the Current Population Survey Tobacco Use Supplements between 1992 and 2011. Our ordinary least squares regression show an imprecise negative relationship between taxes and cigarettes smoked in the past 30 days, while UQR reveals a U‐shaped relationship: Only moderate smokers reduce their smoking following a cigarette tax increase, and the magnitude of the effect is small. A $1.00 (135 percent) increase in the cigarette tax leads to a 3.5 percent reduction in the number of cigarettes smoked in the past 30 days among the most responsive smokers (implied tax elasticity = −0.03).
Preparation of high damping elastomer with broad temperature and frequency ranges based on ternary rubber blends
Authors: Lu Xun , Li Xujun , Tian Min
Published: October 2013

Based on the blends of chlorinated butyl rubber (CIIR), nitrile butadiene rubber (NBR) and chloroprene rubber (CR), a kind of high damping elastomer with broad temperature and frequency ranges is prepared. CIIR/NBR binary blend is prepared to take advantage of the immiscibility and the large difference in cross‐link density of the different phases caused by the curatives and accelerators migration. The dynamic mechanical analysis reveals that the binary blend was immiscible and its loss factor (tanδ) versus temperature curves show two separated and expanded loss peaks when compared with those of pure cured CIIR and NBR. In order to improve its damping properties at room temperature, the third component CR with the polarity between CIIR and NBR was blended into the binary blend. The resulted CIIR/NBR/CR ternary blend has gained effective damping properties (tanδ > 0.3) in the temperature range of −86.4 to 74.6°C and the frequency range of 10−2 to more than 109 Hz. Other effects on the damping properties of the ternary rubber were also studied. Copyright © 2013 John Wiley & Sons, Ltd.
Preparation of microcapsulated ammonium polyphosphate, pentaerythritol with glycidyl methacrylate, butyl methacrylate and their synergistic flame‐ retardancy for ethylene vinyl acetate copolymer
Authors: Tang Qinbo , Wang Bibo , Tang Gang , Shi Yongqian , Qian Xiaodong , Yu Bin , Song Lei , Hu Yuan
Published: October 2013

A new series of microcapsules containing pentaerythritol (PER) and ammonium polyphosphate (APP) with glycidyl methacrylate and butyl methacrylate as shell materials were synthesized by in situ polymerization. The structure and performance of the microencapsulated APP and microencapsulated PER were characterized by Fourier transform infrared spectroscopy, X‐ray photoelectron spectroscopy, scanning electron microscopy, and water contact angle. The flame retarded ethylene‐vinyl acetate copolymer (EVA) composites were studied by limiting oxygen index, UL‐94 test, and cone calorimeter. It was found that the microencapsulation of flame retardants (FRs) with the glycidyl methacrylate and butyl methacrylate lead to a decrease in the particle's water solubility and an improvement of the hydrophobicity. Results also demonstrated that the FR properties of EVA/microencapsulated APP/microencapsulated PER composites were better than those of the EVA/APP/PER composites at the same loading of FRs. The thermogravimetric analysis results reflected that the microencapsulated EVA composites had better thermal stability because of the forming of stable char during the combustion. Copyright © 2013 John Wiley & Sons, Ltd.
The evolving genomic classification of lung cancer
Authors: Shames David S , Wistuba Ignacio I
Published: October 2013

EGFR gene mutations and ALK gene fusions are well‐characterized molecular targets in NSCLC. Activating alterations in a variety of potential oncogenic driver genes have also been identified in NSCLC, including ROS1, RET, MET, HER2, and BRAF. Together with EGFR and ALK, these mutations account for ∼20% of NSCLCs. The identification of these oncogenic drivers has led to the design of rationally targeted therapies that have produced superior clinical outcomes in tumours harbouring these mutations. Many patients, however, have de novo or acquired resistance to these therapies. In addition, most NSCLCs are genetically complex tumours harbouring multiple potential activating events. For these patients, disease subsets are likely to be defined by combination strategies involving a number of targeted agents. These targets include FGFR1, PTEN, MET, MEK, PD‐1/PD‐L1, and NaPi2b. In light of the myriad new biomarkers and targeted agents, multiplex testing strategies will be invaluable in identifying the appropriate patients for each therapy and enabling targeted agents to be channelled to the patients most likely to gain benefit. The challenge now is how best to interpret the results of these genomic tests, in the context of other clinical data, to optimize treatment choices in NSCLC. © 2013 The Authors. Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
Carcinoma‐associated fibroblasts derive from mesothelial cells via mesothelial‐to‐mesenchymal transition in peritoneal metastasis
Authors: Sandoval Pilar , Jiménez‐Heffernan Jose Antonio , Rynne‐Vidal Ángela , Pérez‐Lozano María Luisa , Gilsanz Álvaro , Ruiz‐Carpio Vicente , Reyes Raquel , García‐Bordas Julio , Stamatakis Konstantinos , Dotor Javier , Majano Pedro L , Fresno Manuel , Cabañas Carlos , López‐Cabrera Manuel
Published: October 2013

Peritoneal dissemination is a frequent metastatic route for cancers of the ovary and gastrointestinal tract. Tumour cells metastasize by attaching to and invading through the mesothelial cell (MC) monolayer that lines the peritoneal cavity. Metastases are influenced by carcinoma‐associated fibroblasts (CAFs), a cell population that derives from different sources. Hence, we investigated whether MCs, through mesothelial–mesenchymal transition (MMT), were a source of CAFs during peritoneal carcinomatosis and whether MMT affected the adhesion and invasion of tumour cells. Biopsies from patients with peritoneal dissemination revealed the presence of myofibroblasts expressing mesothelial markers in the proximity of carcinoma implants. Prominent new vessel formation was observed in the peritoneal areas harbouring tumour cells when compared with tumour‐free regions. The use of a mouse model of peritoneal dissemination confirmed the myofibroblast conversion of MCs and the increase in angiogenesis at places of tumour implants. Treatment of omentum MCs with conditioned media from carcinoma cell cultures resulted in phenotype changes reminiscent of MMT. Adhesion experiments demonstrated that MMT enhanced the binding of cancer cells to MCs in a β1‐integrin‐dependent manner. Scanning electron microscopy imaging showed that the enhanced adhesion was mostly due to increased cell–cell interaction and not to a mere matrix exposure. Invasion assays suggested a reciprocal stimulation of the invasive capacity of tumour cells and MCs. Our results demonstrate that CAFs can derive from mesothelial cells during peritoneal metastasis. We suggest that MMT renders the peritoneum more receptive for tumour cell attachment/invasion and contributes to secondary tumour growth by promoting its vascularization. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Amplification and over‐expression of MAP3K3 gene in human breast cancer promotes formation and survival of breast cancer cells
Authors: Fan Yihui , Ge Ningling , Wang Xiaosong , Sun Wenjing , Mao Renfang , Bu Wen , Creighton Chad J , Zheng Pingju , Vasudevan Sanjeev , An Lei , Yang Jinshu , Zhao Yi‐Jue , Zhang Huiyuan , Li Xiao‐Nan , Rao Pulivarthi H , Leung Eastwood , Lu Yong‐Jie , Gray Joe W , Schiff Rachel , Hilsenbeck Susan G , Osborne C Kent , Yang Jianhua , Zhang Hong
Published: October 2013

Gene amplifications in the 17q chromosomal region are observed frequently in breast cancers. An integrative bioinformatics analysis of this region nominated the MAP3K3 gene as a potential therapeutic target in breast cancer. This gene encodes mitogen‐activated protein kinase kinase kinase 3 (MAP3K3/MEKK3), which has not yet been reported to be associated with cancer‐causing genetic aberrations. We found that MAP3K3 was amplified in approximately 8–20% of breast cancers. Knockdown of MAP3K3 expression significantly inhibited cell proliferation and colony formation in MAP3K3‐amplified breast cancer cell lines MCF‐7 and MDA‐MB‐361 but not in MAP3K3 non‐amplified breast cancer cells. Knockdown of MAP3K3 expression in MAP3K3‐amplified breast cancer cells sensitized breast cancer cells to apoptotic induction by TNFα and TRAIL, as well as doxorubicin, VP‐16 and fluorouracil, three commonly used chemotherapeutic drugs for treating breast cancer. In addition, ectopic expression of MAP3K3, in collaboration with Ras, induced colony formation in both primary mouse embryonic fibroblasts and immortalized human breast epithelial cells (MCF‐10A). Combined, these results suggest that MAP3K3 contributes to breast carcinogenesis and may endow resistance of breast cancer cells to cytotoxic chemotherapy. Therefore, MAP3K3 may be a valuable therapeutic target in patients with MAP3K3‐amplified breast cancers, and blocking MAP3K3 kinase activity with a small molecule inhibitor may sensitize MAP3K3‐amplified breast cancer cells to chemotherapy. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Mouse tumour models to guide drug development and identify resistance mechanisms
Authors: Das Thakur Meghna , Pryer Nancy K , Singh Mallika
Published: October 2013

We need improved, translatable and predictive tumour models for the evaluation of response and the evolution of resistance to targeted therapeutics. We provide a review of the use of different types of preclinical tumour models to evaluate novel anticancer agents, and model the rapidly evolving landscape of resistance to targeted therapy. We focus on describing the various preclinical models available for candidate drug development and design considerations for preclinical experiments, depending on the aspect of drug action being interrogated. We discuss selected examples of how experimental findings have translated into clinical outcomes for targeted agents, predicted mechanisms that drive resistance and strategies to overcome the evolution thereof. We discuss challenges in preclinical experimental design and interpretation and possible improvements in animal models of therapeutic response and resistance, with an emphasis on improved translation of experimental research into clinical practice. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Towards the introduction of the ‘Immunoscore’ in the classification of malignant tumours
Authors: Galon Jérôme , Mlecnik Bernhard , Bindea Gabriela , Angell Helen K , Berger Anne , Lagorce Christine , Lugli Alessandro , Zlobec Inti , Hartmann Arndt , Bifulco Carlo , Nagtegaal Iris D , Palmqvist Richard , Masucci Giuseppe V , Botti Gerardo , Tatangelo Fabiana , Delrio Paolo , Maio Michele , Laghi Luigi , Grizzi Fabio , Asslaber Martin , D'Arrigo Corrado , Vidal‐Vanaclocha Fernando , Zavadova Eva , Chouchane Lotfi , Ohashi Pamela S , Hafezi‐Bakhtiari Sara , Wouters Bradly G , Roehrl Michael , Nguyen Linh , Kawakami Yutaka , Hazama Shoichi , Okuno Kiyotaka , Ogino Shuji , Gibbs Peter , Waring Paul , Sato Noriyuki , Torigoe Toshihiko , Itoh Kyogo , Patel Prabhu S , Shukla Shilin N , Wang Yili , Kopetz Scott , Sinicrope Frank A , Scripcariu Viorel , Ascierto Paolo A , Marincola Francesco M , Fox Bernard A , Pagès Franck
Published: October 2013

The American Joint Committee on Cancer/Union Internationale Contre le Cancer (AJCC/UICC) TNM staging system provides the most reliable guidelines for the routine prognostication and treatment of colorectal carcinoma. This traditional tumour staging summarizes data on tumour burden (T), the presence of cancer cells in draining and regional lymph nodes (N) and evidence for distant metastases (M). However, it is now recognized that the clinical outcome can vary significantly among patients within the same stage. The current classification provides limited prognostic information and does not predict response to therapy. Multiple ways to classify cancer and to distinguish different subtypes of colorectal cancer have been proposed, including morphology, cell origin, molecular pathways, mutation status and gene expression‐based stratification. These parameters rely on tumour‐cell characteristics. Extensive literature has investigated the host immune response against cancer and demonstrated the prognostic impact of the in situ immune cell infiltrate in tumours. A methodology named ‘Immunoscore’ has been defined to quantify the in situ immune infiltrate. In colorectal cancer, the Immunoscore may add to the significance of the current AJCC/UICC TNM classification, since it has been demonstrated to be a prognostic factor superior to the AJCC/UICC TNM classification. An international consortium has been initiated to validate and promote the Immunoscore in routine clinical settings. The results of this international consortium may result in the implementation of the Immunoscore as a new component for the classification of cancer, designated TNM‐I (TNM‐Immune). © 2013 The Authors. Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
In Brief: Notch signalling in health and disease
Authors: Aster Jon C
Published: October 2013

The Notch pathway controls many aspects of development and is mutated in various human cancers. Remarkably, Notch function changes during the development of cellular hierarchies and can be either oncogenic or tumour‐suppressive, depending on cellular context. Notch dysregulation is also important in cardiovascular disease and disorders of immunity. This mini‐review outlines key features of the Notch signalling pathway and emerging data linking it to human diseases. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Favorable outcome of patients affected by rhabdoid tumors due to rhabdoid tumor predisposition syndrome (RTPS)
Authors: Kordes Uwe , Bartelheim Kerstin , Modena Piergiorgio , Massimino Maura , Biassoni Veronica , Reinhard Harald , Hasselblatt Martin , Schneppenheim Reinhard , Frühwald Michael C.
Published: October 2013

Rhabdoid tumor predisposition syndrome is usually associated with shorter survival in patients with malignant rhabdoid tumors regardless of anatomical origin. Here we present four children harboring truncating heterozygous SMARCB1/INI1 germline mutations with favorable outcome. All four patients received multi‐modality treatment, three according to therapeutic recommendations by the EU‐RHAB registry, two without radiotherapy, and mean event‐free survival accounts for 7 years. In conclusion, intensive treatment with curative intent is justified for children with rhabdoid tumors even if an underlying rhabdoid predisposition syndrome is demonstrated. Pediatr Blood Cancer 2014;61:919–921. © 2013 Wiley Periodicals, Inc.
Improvement in interfacial shear strength and fracture toughness for carbon fiber reinforced epoxy composite by fiber sizing
Authors: Liu WenBo , Zhang Shu , Li Bichen , Yang Fan , Jiao WeiCheng , Hao LiFeng , Wang RongGuo
Published: October 2013

Carbon fiber was sized by a thermoplastic polymer solution mixed with a compatible amine monomer. The effect of sizing agent on tensile strength was studied by single fiber strength testing. Interfacial properties of re‐sized carbon fiber/epoxy composite were investigated, with special emphasis on the improvement in both interfacial shear strength and interfacial fracture toughness. The interfacial fracture toughness of composites was characterized by calculating the effective interphase fracture energy rate through the information obtained from the force–displacement curve in the micro‐bond test. Fracture topography of micro‐bond specimen was observed to discuss the interfacial fracture mechanism. POLYM. COMPOS., 35:482–488, 2014. © 2013 Society of Plastics Engineers
Preparation and characterization of 2‐hydroxyethyl methacrylate–chitosan functionalized multiwall carbon nanotubes nanocomposites
Authors: Mahmoodian Hossein , Moradi Omid
Published: October 2013

Surface of chitosan (CS) functionalized multiwall carbon nanotubes (MWCNTs) was modified by using 2‐hydroxyethyl methacrylate (HEMA) monomers and the composites were synthesized under microwave irradiation. In this approach, multiwalled carbon nanotubes were functionalized with HEMA and CS in two steps. Firstly, CS was grafted onto the surface and side wall of carbon nanotubes by using microwave irradiation. At the second step, HEMA monomers were grafted onto the polymeric matrix surface. The modified surface of CS functionalized multi‐walled carbon nanotube composites are confirmed by Fourier transform infrared spectroscopy. Moreover, Transmission electron microscopic and scanning electron microscopic images show the morphological changes of the carbon nanotubes. Thermal gravimetric analysis shows content of HEMA–CS functionalized MWCNTs in the composites. Dispersibility of pristine MWCNTs was compared with dispersibility of resultant composites in aqueous phase as well. Results show that composites have higher dispersibility in aqueous phase. Considering the biomedical importance of HEMA monomers and CS polymer, in future, these materials are expected to be useful in the pharmaceutical industry as novel biomaterials composites with potential applications in drug delivery. POLYM. COMPOS., 35:495–500, 2014. © 2013 Society of Plastics Engineers
“Binary salt” of hexane‐1,6‐diaminium adipate and “carbon nanotubate” as a synthetic precursor of carbon nanotube/Nylon‐6,6 hybrid materials
Authors: Boncel Slawomir , Górka Jacek , Shaffer Milo S.P. , Koziol Krzysztof K.K.
Published: October 2013

A novel chemical approach was established to produce carbon nanotube/Nylon‐6,6 hybrid materials from readily available substrates, that is, Nylon‐6,6 salt and oxidized multiwall carbon nanotubes (O‐MWCNTs). The key synthetic precursor hexane‐1,6‐diaminium adipate and “carbon nanotubate”—“Binary nanotube salt”—was obtained and isolated as stable and easy‐to‐handle solid in over 80% yield and with no nanotube losses. The final hybrid materials of various nanotube loadings were synthesized at 270°C and were easily purified from the homopolymer. Purified hybrids were comprehensively analyzed (yields and grafting ratios, SEM, TEM, FT‐IR) revealing a two‐phase characteristics—individually grafted nanotubes and cross‐linked nanotube material. Isothermal TGA kinetic studies showed that in the “binary salts” diamine and diacid molecules were anchored to the nanotube outer shells and then held electrostatically enabling growth of polymer immobilized on O‐MWCNTs (“grafting‐from” mechanism). Depending on the density and type of nanotube functionalities and filler concentration in the “binary salt,” the O‐MWCNT/Nylon‐6,6 hybrids can be treated as hybrid material of a proportion of aliphatic polyamide and polyaramide properties. POLYM. COMPOS., 35:523–529, 2014. © 2013 Society of Plastics Engineers
Preparation and characterization of thermally conductive thermoplastic polyurethane/h‐BN nanocomposites
Authors: Çakmakçı Emrah , Koçyiğit Çiler , Çakır Selma , Durmus Ali , Kahraman M. Vezir
Published: October 2013

Polyurethane nanocomposites are versatile engineering polymers with unique properties. In this study, nano hexagonal boron nitride containing thermoplastic polyurethane elastomers were prepared via melt blending and hot‐pressing techniques. The nanocomposites were characterized using Fourier transform infrared, differential scanning calorimetry, thermal gravimetric analysis, tensile tests, and thermal conductivity measurements. The surface morphology of the TPU/h‐BN composites was characterized by scanning electron microscopy. The optical properties of the composites were determined by UV transmittance measurements and as the amount of h‐BN increased, optical transparencies decreased dramatically. Nanocomposites displayed higher E‐modulus values and lower elongation at break values than the pure TPU elastomer. Char yields of TPUs increased with increasing h‐BN percentage. Moreover, thermal conductivity of the composite materials improved with the incorporation of h‐BN. POLYM. COMPOS., 35:530–538, 2014. © 2013 Society of Plastics Engineers
Identification of Nuclear Factor‐κB Inhibitors and β2 Adrenergic Receptor Agonists in Chinese Medicinal Preparation Fuzilizhong Pills Using UPLC with Quadrupole Time‐of‐flight MS
Authors: Dong Linyi , Cheng Binfeng , Luo Yi , Zhang Ning , Duan Hongquan , Jiang Min , Wang Yiming , Bai Gang , Luo Guoan
Published: October 2013

Introduction

Fuzilizhong Pills (FZLZ), a modified form of a famous traditional Chinese medicine (TCM) Lizhong Wan in Treatise on Febrile Diseases and consisting of Panax ginseng C.A.Mey. (Ren Shen), Aconitum carmichaelii Debx. (Fu Zi, Zhi), Glycyrrhiza uralensis Fisch., Glycyrrhiza inflata Bat. or Glycyrrhiza glabra L. (Gan Cao), Atractylodes macrocephala Koidz. (Bai Zhu) and Zingiber offcinale Rosc. (Gan Jiang), show strong clinical therapeutic effects for dyspnea and pulmonary oedema. However, the bioactive compounds are still unclear. In this study, FZLZ was analysed using a rapid detection method to identify its anti‐inflammatory and spasmolytic constituents.

Objective

To develop a simple screening method to detect the anti‐inflammatory and spasmolytic constituents of FZLZ.

Methods

Ultra‐performance liquid chromatography with quadrupole time‐of‐flight mass spectrometry combined with dual‐bioactive (NF‐κB and β2‐adrenergic receptor) luciferase reporter assay systems was employed.

Results

Two β2‐adrenergic receptor agonists (salsolinol and higeramine) and three terpenoidal analogues of NF‐κB inhibitors such as ginsenosides derivatives, triperpenoids derivatives and diester‐diterpenoid aconitum alkaloid derivatives were characterised. Mesaconitine, flaconitine, ginsenosides Rb2, Rf, Rg2, F1 and Ro were considered to be new NF‐κB inhibitors. Furthermore, IL‐8 detection by enzyme linked immunosorbent assay confirmed the anti‐inflammatory effects of the potential NF‐κB inhibitors.

Conclusion

Compared with conventional fingerprints, activity‐integrated fingerprints that contain both chemical and bioactive details offer a more comprehensive understanding of the chemical composition of plant materials. This strategy clearly demonstrated that dual bioactivity‐integrated fingerprinting is a powerful tool for the improved screening and identification of potential dual‐target lead compounds in complex herbal medicines. Copyright © 2013 John Wiley & Sons, Ltd.
First trimester maternal serum placental growth factor levels in twin pregnancies
Authors: Cowans Nicholas J. , Spencer Kevin
Published: October 2013

Background

An understanding of the normal behavior of biochemical markers in twin pregnancies is necessary in order to offer prenatal screening to this subgroup. This study investigates the levels of first trimester maternal serum placental growth factor (PlGF) in twin and singleton pregnancies.

Methods

The PlGF concentrations were measured by an automated assay in the first trimester maternal serum of 440 dichorionic twin, 116 monochorionic twin, and 607 singleton pregnancy samples thawed from frozen storage.

Results

The PlGF concentrations in singleton levels were predicted by gestational age, maternal ethnicity, and smoking status. Following the correction for these variables, PlGF levels were, on average, 41% higher in dichorionics, but only 16% higher in monochorionics, compared to singleton pregnancies.

Conclusions

First trimester maternal serum PlGF levels are increased in twin pregnancies compared with singleton pregnancies, but to less of an extent than is common with other screening markers, especially in monochorionic twins. © 2013 John Wiley & Sons, Ltd.
Prescribing of antipsychotic drugs in patients with dementia: a comparison with age‐matched and sex‐matched non‐demented controls
Authors: Schulze Jana , Glaeske Gerd , van den Bussche Hendrik , Kaduszkiewicz Hanna , Koller Daniela , Wiese Birgitt , Hoffmann Falk
Published: October 2013

Purpose

Since the beginning of the 21st century, serious adverse events and an increased risk of mortality have been documented in patients with dementia treated with antipsychotics. The aim of this study was to assess antipsychotic prescribing in patients with incident dementia compared with a non‐demented control group.

Methods

We analysed the claims data of a German health insurance company for incident dementia patients and age‐matched and sex‐matched non‐demented controls aged 65 years and older in 2004 to 2006. The data were used to analyse the prescribing patterns of antipsychotics in the year of dementia incidence. We estimated odds ratios stratified by age, sex, care setting and care dependence and in a multivariate logistic regression.

Results

The 1848 patients with and 7385 persons without dementia were on average 78.8 years old (standard deviation: 7.4), and 47.6% were women. A total of 25.4% of the dementia patients received antipsychotics compared with 4.3% of the controls (ORcrude: 7.61; 95%CI: 6.52–8.87). An increase in care level, age, female gender and living in a nursing home is associated with a considerably higher prevalence of at least one prescription for antipsychotics. After adjusting for all these variables, a significant influence of age could no longer be found.

Conclusions

The results show that antipsychotics play an important role in dementia care—despite the risk of adverse events. Further research is needed with regard to safe pharmacological and non‐pharmacological approaches for the behavioural and psychological symptoms of dementia in this vulnerable group. Copyright © 2013 John Wiley & Sons, Ltd.