bluuebunny/crossref_metadata_2025 huggingface dataset:
MEASURING AND CONTROLLING THE CHAOTIC MOTION OF PROFITS
Authors: JANUÁRIO CRISTINA , GRÁCIO CLARA , MENDES DIANA A. , DUARTE JORGE
Published: February 2010

The study of economic systems has generated deep interest in exploring the complexity of chaotic motions in economy. Due to important developments in nonlinear dynamics, the last two decades have witnessed strong revival of interest in nonlinear endogenous business chaotic models. The inability to predict the behavior of dynamical systems in the presence of chaos suggests the application of chaos control methods, when we are more interested in obtaining regular behavior. In the present article, we study a specific economic model from the literature. More precisely, a system of three ordinary differential equations gather the variables of profits, reinvestments and financial flow of borrowings in the structure of a firm. Firstly, using results of symbolic dynamics, we characterize the topological entropy and the parameter space ordering of kneading sequences, associated with one-dimensional maps that reproduce significant aspects of the model dynamics. The analysis of the variation of this numerical invariant, in some realistic system parameter region, allows us to quantify and to distinguish different chaotic regimes. Finally, we show that complicated behavior arising from the chaotic firm model can be controlled without changing its original properties and the dynamics can be turned into the desired attracting time periodic motion (a stable steady state or into a regular cycle). The orbit stabilization is illustrated by the application of a feedback control technique initially developed by Romeiras et al. [1992]. This work provides another illustration of how our understanding of economic models can be enhanced by the theoretical and numerical investigation of nonlinear dynamical systems modeled by ordinary differential equations.
MEMRISTOR CELLULAR AUTOMATA AND MEMRISTOR DISCRETE-TIME CELLULAR NEURAL NETWORKS
Authors: ITOH MAKOTO , CHUA LEON O.
Published: February 2010

In this paper, we design a cellular automaton and a discrete-time cellular neural network (DTCNN) using nonlinear passive memristors. They can perform a number of applications, such as logical operations, image processing operations, complex behaviors, higher brain functions, RSA algorithm, etc. By modifying the characteristics of nonlinear memristors, the memristor DTCNN can perform almost all functions of memristor cellular automaton. Furthermore, it can perform more than one function at the same time, that is, it allows multitasking.
A HYPERCHAOTIC CHUA SYSTEM
Authors: RECH PAULO C. , ALBUQUERQUE HOLOKX A.
Published: February 2010

In this paper, we report a new four-dimensional autonomous hyperchaotic system, constructed from a Chua system where the piecewise-linear function usually taken to describe the nonlinearity of the Chua diode has been replaced by a cubic polynomial. Analytical and numerical procedures are conducted to study the dynamical behavior of the proposed new hyperchaotic system.
VALUATIVE DOMAINS
Authors: CAHEN PAUL-JEAN , DOBBS DAVID E. , LUCAS THOMAS G.
Published: February 2010

A (commutative integral) domain R is said to be valuative if, for each nonzero element u in the quotient field of R, at least one of R ⊆ R[u] and R ⊆ R[u-1] has no proper intermediate rings. Such domains are closely related to valuation domains. If R is a valuative domain, then R has at most three maximal ideals, and at most two if R is not integrally closed. Also, if R is valuative, the set of nonmaximal prime ideals of R is linearly ordered, at most one maximal ideal of R does not contain each nonmaximal prime of R, and RPis a valuation domain for each prime P except for at most one maximal ideal. Any integrally closed valuative domain is a Bézout domain. Valuation domains are characterized as the quasilocal integrally closed valuative domains. Each one-dimensional Prüfer domain with at most three maximal ideals is valuative.
LOCAL DESCRIPTORS BASED ON COLOR IMAGES
Authors: CHENG D. , XIE S. Q. , HÄMMERLE E.
Published: February 2010

This paper investigates local descriptor methods utilizing color images instead of grayscale images to improve the uniqueness of the local descriptors. A color model was utilized in order to be invariant to illumination condition changes. Two local descriptor methods, namely color local descriptor and hybrid local descriptor methods, were developed. Results from the experiments conducted show that these methods are more robust against a variety of image transformation and illumination condition changes compared to existing methods.
Ghrelin and PYY in the regulation of energy balance and metabolism: lessons from mouse mutants
Authors: Kirchner Henriette , Tong Jenny , Tschöp Matthias H. , Pfluger Paul T.
Published: February 2010

Effective control of body weight and energy homeostasis requires stringent regulation of caloric intake and energy expenditure. Gut-brain interactions comprise a central axis for the control of energy homeostasis by integrating the intake of nutrients with an effective utilization of ingested calories either by storage or by expenditure as cellular fuel. Ghrelin, a stomach-derived peptide, is the only known circulating orexigenic hormone. It is acylated with a medium-chain fatty acid by the enzyme ghrelin O-acetyltransferase (GOAT) and displays a broad range of activity, from central control of food intake to peripheral functions such as gastric emptying and insulin secretion. PYY, a peptide produced by L cells of the small intestine and rectum, has been shown to inhibit gut motility and is proposed to stimulate a powerful central satiety response. In recent years, pharmacological studies in animals and clinical studies in humans have contributed to our knowledge of principal ghrelin and PYY actions. However, valuable findings from studies using ghrelin-deficient mice, ghrelin receptor [growth hormone secretagogue receptor-1a (GHSR1a)]-deficient mice, double-knockout mice (for ghrelin and GHSR), and GOAT-deficient or -overexpressor mice, as well as mice deficient for PYY or neuropeptide Y receptors have allowed better definition of the actual physiological functions of ghrelin and PYY. This review summarizes findings from mutant mouse studies with emphasis on respective gene knockout and transgenic animals and describes how these studies contribute to the current understanding of how endogenous ghrelin and PYY as two major representatives of endocrine gut-brain communications may regulate energy and glucose homeostasis.
Does respiratory sinus arrhythmia serve a buffering role for diastolic pressure fluctuations?
Authors: Tan Can Ozan , Taylor J. Andrew
Published: February 2010

Though many consider the magnitude of respiratory sinus arrhythmia as an index of cardiac vagal control, its physiological origins remain unclear. One influential model postulates that the systolic pressure rise within a given beat stimulates the baroreflex arc to adjust the following heart period such that diastolic pressure is “stabilized” and hence displays lesser fluctuation. Accordingly, the magnitude of diastolic pressure fluctuations with respiration should change reciprocally after augmentation or inhibition of respiratory sinus arrhythmia. To test this, we augmented and subsequently inhibited respiratory sinus arrhythmia with vagotonic and vagolytic atropine administration in 19 healthy young volunteers to assess the relation between respiratory R-R interval and diastolic pressure fluctuations. Respiratory diastolic pressure fluctuations showed parallel rather than inverse changes in relation to those in respiratory sinus arrhythmia: they increased with augmented respiratory sinus arrhythmia (138 and 190% of baseline in the frequency and time domains, both P < 0.05) and tended to decrease with inhibited respiratory sinus arrhythmia (82 and 93% of baseline in frequency and time domains, P = 0.20 and P = 0.07). Furthermore, >60% of the change in diastolic pressure fluctuations was explained by the change in respiratory sinus arrhythmia ( R2= 0.62; P < 0.001), that is, an ∼50-ms increase or decrease in respiratory sinus arrhythmia resulted in a parallel ∼1-mmHg change in diastolic pressure fluctuations. Thus, in young healthy individuals during supine rest, respiratory fluctuations in R-R interval do not buffer against diastolic pressure fluctuations but actually cause diastolic pressure fluctuations. Therefore, our data provide little evidence for a predominant role of a baroreflex feedback mechanism underlying respiratory sinus arrhythmia during supine rest.
Toll-like receptor 2 mediates mesenchymal stem cell-associated myocardial recovery and VEGF production following acute ischemia-reperfusion injury
Authors: Abarbanell Aaron M. , Wang Yue , Herrmann Jeremy L. , Weil Brent R. , Poynter Jeffrey A. , Manukyan Mariuxi C. , Meldrum Daniel R.
Published: February 2010

Toll-like receptor 2 (TLR2), a key component of the innate immune system, is linked to inflammation and myocardial dysfunction after ischemia-reperfusion injury (I/R). Treatment of the heart with mesenchymal stem cells (MSCs) is known to improve myocardial recovery after I/R in part by paracrine factors such as VEGF. However, it is unknown whether TLR2 activation on the MSCs affects MSC-mediated myocardial recovery and VEGF production. We hypothesized that the knockout of TLR2 on the MSCs (TLR2KO MSCs) would 1) improve MSC-mediated myocardial recovery and 2) increase myocardial and MSC VEGF release. With the isolated heart perfusion system, Sprague-Dawley rat hearts were subjected to I/R and received one of three intracoronary treatments: vehicle, male wild-type MSCs (MWT MSCs), or TL2KO MSCs. All treatments were performed immediately before ischemia, and heart function was measured continuously. Postreperfusion, heart homogenates were analyzed for myocardial VEGF production. Contrary to our hypothesis, only MWT MSC treatment significantly improved the recovery of left ventricular developed pressure and the maximal positive and negative values of the first derivative of pressure. In addition, VEGF production was greatest in hearts treated with MWT MSCs. To investigate MSC production of VEGF, MSCs were activated with TNF in vitro and the supernatants collected for ELISA. In vitro basal levels of MSC VEGF production were similar. However, with TNF activation, MWT MSCs produced significantly more VEGF, whereas activated TLR2KO MSC production of VEGF was unchanged. Finally, we observed that MWT MSCs proliferated more rapidly than TLR2KO MSCs. These data indicate that TLR2 may be essential to MSC-mediated myocardial recovery and VEGF production.
A role for caveolin-1 in mechanotransduction of fetal type II epithelial cells
Authors: Wang Yulian , Maciejewski Benjamin S. , Drouillard Diana , Santos Melissa , Hokenson Michael A. , Hawwa Renda L. , Huang Zheping , Sanchez-Esteban Juan
Published: February 2010

Mechanical forces are critical for fetal lung development. Using surfactant protein C (SP-C) as a marker, we previously showed that stretch-induced fetal type II cell differentiation is mediated via the ERK pathway. Caveolin-1, a major component of the plasma membrane microdomains, is important as a signaling protein in blood vessels exposed to shear stress. Its potential role in mechanotransduction during fetal lung development is unknown. Caveolin-1 is a marker of type I epithelial cell phenotype. In this study, using immunocytochemistry, Western blotting, and immunogold electron microscopy, we first demonstrated the presence of caveolin-1 in embryonic day 19 (E19) rat fetal type II epithelial cells. By detergent-free purification of lipid raft-rich membrane fractions and fluorescence immunocytochemistry, we found that mechanical stretch translocates caveolin-1 from the plasma membrane to the cytoplasm. Disruption of the lipid rafts with cholesterol-chelating agents further increased stretch-induced ERK activation and SP-C gene expression compared with stretch samples without disruptors. Similar results were obtained when caveolin-1 gene was knocked down by small interference RNA. In contrast, adenovirus overexpression of the wild-type caveolin-1 or delivery of caveolin-1 scaffolding domain peptide inside the cells decreased stretch-induced ERK phosphorylation and SP-C mRNA expression. In conclusion, our data suggest that caveolin-1 is present in E19 fetal type II epithelial cells. Caveolin-1 is translocated from the plasma membrane to the cytoplasm by mechanical stretch and functions as an inhibitory protein in stretch-induced type II cell differentiation via the ERK pathway.
Aminoterminal Pro B-Type Natriuretic Peptide (NT-proBNP) Levels for Monitoring Interventions in Paediatric Cardiac Patients with Stenotic Lesions
Authors: Welisch Eva , Kleesiek Knut , Haas Nikolaus , Norozi Kambiz , Rauch Ralf , Filler Guido
Published: February 2010

Background.Serum concentration of NT-proBNP correlates well with the severity of cardiac disease in adults. Few studies have been performed on the applicability of NT-proBNP for monitoring children with congenital heart disease.Objective.To assess the potential of NT-proBNP for monitoring the success of interventions in children with stenotic cardiac lesions.Methods.NT-proBNP was measured in 42 children aged 1 day to 17 years (y) before and 6 to 12 weeks after surgical or interventional correction of obstructive lesions of the heart. Comparison is made with the clinical status and echocardiographic data of the child.Results.NT-proBNP levels (median 280, range 10–263,000 pg/mL) were above the reference value in all but 6 patients (pts) prior to the intervention. Higher levels were found in more compromised patients. The 35 children with clinical improvement after the procedure showed a decline of their NT-proBNP level in all but 4 patients, whose levels remained unchanged. Five patients with unchanged gradients despite a therapeutic intervention also demonstrated unchanged NT-proBNP levels after the intervention. Thus, the success rate of the procedure correlated well to clinical and echocardiographic findings.Conclusion.NT-proBNP can be used to assess the efficiency of an intervention.
IL-1β Suppresses the Formation of Osteoclasts by Increasing OPG Production via an Autocrine Mechanism Involving Celecoxib-Related Prostaglandins in Chondrocytes
Authors: Watanabe Yusuke , Namba Aki , Aida Yukiko , Honda Kazuhiro , Tanaka Hideki , Suzuki Naoto , Matsumura Hideo , Maeno Masao
Published: February 2010

Elevated interleukin (IL)-1 concentrations in synovial fluid have been implicated in joint bone and cartilage destruction. Previously, we showed that IL-1βstimulated the expression of prostaglandin (PG) receptor EP4 via increasedPGE2production. However, the effect of IL-1βon osteoclast formation via chondrocytes is unclear. Therefore, we examined the effect of IL-1βand/or celecoxib on the expression of macrophage colony-stimulating factor (M-CSF), receptor activator of NF-κB ligand (RANKL), and osteoprotegerin (OPG) in human chondrocytes, and the indirect effect of IL-1βon osteoclast-like cell formation using RAW264.7 cells. OPG and RANKL expression increased with IL-1β; whereas M-CSF expression decreased. Celecoxib blocked the stimulatory effect of IL-1β. Conditioned medium from IL-1β-treated chondrocytes decreased TRAP staining in RAW264.7 cells. These results suggest that IL-1βsuppresses the formation of osteoclast-like cells via increased OPG production and decreased M-CSF production in chondrocytes, and OPG production may increase through an autocrine mechanism involving celecoxib-related PGs.
The Effects of Extended Release Niacin in Combination with Omega 3 Fatty Acid Supplements in the Treatment of Elevated Lipoprotein (a)
Authors: Helmbold Alan F. , Slim Jennifer N. , Morgan Jennifer , Castillo-Rojas Laudino M. , Shry Eric A. , Slim Ahmad M.
Published: February 2010

Objective. To assess the effectiveness of niacin/fish oil combination therapy in reducing Lipoprotein (a) [Lp(a)] levels after twelve weeks of therapy.
Background. Lipoprotein (a) accumulates in atherosclerotic lesions and promotes smooth muscle cell growth and is both atherogenic and thrombogenic. A clinical trials of combination therapy for the reduction of Lp(a) has not been previously reported.
Methods. The study was an observational study following subjects with an elevated Lp(a) (70 nmol/L) to assess impact of 12 weeks of combination Omega 3FA, niacin, and the Mediterranean diet on Lp(a).
Results. Twenty three patients were enrolled with 7 patients lost to follow up and 2 patients stopped due to adverse events. The average Lp(a) reduction in the remaining 14 subjects after 12 weeks of combination therapy was 17% with a significant association of the reduction of Lp(a) with increasing baseline levels of Lp(a) [, ].
Conclusions. There was a significant reduction in Lp(a) levels with combination therapy. A more pronounced effect was noted in patients with higher baseline levels of Lp(a).
Reconstruction-Dependent Recovery from Anorexia and Time-Related Recovery of Regulatory Ghrelin System in Gastrectomized Rats
Authors: Koizumi Masaru , Dezaki Katsuya , Hosoda Hiroshi , Damdindorj Boldbaatar , Sone Hideyuki , Ming Lu , Hosoya Yoshinori , Sata Naohiro , Kobayashi Eiji , Kangawa Kenji , Nagai Hideo , Yasuda Yoshikazu , Yada Toshihiko
Published: February 2010

Gastrectomy reduces food intake and body weight (BW) hampering recovery of physical conditions. It also reduces plasma levels of stomach-derived orexigenic ghrelin. This study explored changes in orexigenic ghrelin system in rats receiving total gastrectomy with Billroth II (B-II) or Roux-en-Y (R-Y) method. Feeding and BW were reduced by gastrectomy and subsequently recovered to a greater extent with R-Y than B-II while plasma ghrelin decreased similarly. At postoperative 12th week, ghrelin contents increased in the duodenum and pancreas, plasma ghrelin levels increased upon fasting, and ghrelin injection promoted feeding but not in earlier periods. In summary, gastrectomized rats partially recover feeding and BW, in a reconstruction-dependent manner. At 12th week, ghrelin is upregulated in extra-stomach tissues, plasma ghrelin levels are physiologically regulated, and orexigenic effect of exogenous ghrelin is restored. This time-related recovery of ghrelin system may provide a strategy for promoting feeding, BW, and thereby physical conditions in gastrectomized patients.
Immunobiology of African Trypanosomes: Need of Alternative Interventions
Authors: Baral Toya Nath
Published: February 2010

Trypanosomiasis is one of the major parasitic diseases for which control is still far from reality. The vaccination approaches by using dominant surface proteins have not been successful, mainly due to antigenic variation of the parasite surface coat. On the other hand, the chemotherapeutic drugs in current use for the treatment of this disease are toxic and problems of resistance are increasing (see Kennedy (2004) and Legros et al. (2002)). Therefore, alternative approaches in both treatment and vaccination against trypanosomiasis are needed at this time. To be able to design and develop such alternatives, the biology of this parasite and the host response against the pathogen need to be studied. These two aspects of this disease with few examples of alternative approaches are discussed here.
Suppression of Cyclin D1 by Hypoxia-Inducible Factor-1 via Direct Mechanism Inhibits the Proliferation and 5-Fluorouracil–Induced Apoptosis of A549 Cells
Authors: Wen Wen , Ding Jin , Sun Wen , Wu Kun , Ning Beifang , Gong Wenfeng , He Guoping , Huang Shanna , Ding Xinyu , Yin Peipei , Chen Lei , Liu Qiong , Xie Weifen , Wang Hongyang
Published: February 2010

Hypoxia-inducible factor (HIF) and cyclin D1 are both key mediators of cell growth and proliferation in normal and cancer cells. However, the interrelation between HIF and cyclin D1 remains unclear. In the present study, we observed the inverse correlation between cyclin D1 and HIF-1 in hypoxia condition. Overexpression of the dominant negative mutant of HIF-1α (DN-HIF) significantly enhanced cyclin D1 expression upon hypoxia or arsenite exposure, suggesting the negative regulation of cyclin D1 by HIF-1. Furthermore, we found that the impairment of HIF-1 increased cyclin D1 expression in A549 pulmonary cancer cells, which in turn promoted G1-S cell cycle transition and cell proliferation. Cyclin D1 expression was increased in s.c. xenograft of DN-HIF stably transfected A549 cells in nude mice compared with that of control cells. Chromatin immunoprecipitation assay revealed that HIF-1 was able to directly bind to the promoter region of cyclin D1, which indicates that the negative regulation of cyclin D1 by HIF-1 is through a direct mechanism. Inhibition of histone deacetylase (HDAC) by pretreatment of cells with trichostatin A or specific knockdown of HDAC7 by its shRNA antagonized the suppression of cyclin D1 by HIF-1, suggesting that HDAC7 is required for HIF-1–mediated cyclin D1 downregulation. Moreover, we found that 5-fluorouracil–triggered apoptosis of DN-HIF–transfected A549 cells was reduced by sicyclin D1 (cyclin D1–specific interference RNA) introduction, suggesting that clinical observation of HIF-1 overexpression–associated chemoresistance might be, at least partially, due to the negative regulation of cyclin D1. Cancer Res; 70(5); 2010–9
Modulating Tumor Vasculature through Signaling Inhibition to Improve Cytotoxic Therapy
Authors: Maity Amit , Bernhard Eric J.
Published: February 2010

The tumor microenvironment is a key factor in cancer treatment response. Recent work has shown that changes in the tumor vasculature can be achieved by inhibiting tumor cell signaling, resulting in enhanced tumor oxygenation. These changes could promote responses to both chemo- and radiation therapy. Cancer Res; 70(6); 2141–5
Vascular Endothelial Growth Factor-C Induces Lymphangitic Carcinomatosis, an Extremely Aggressive Form of Lung Metastases
Authors: Das Suvendu , Ladell Daniel S. , Podgrabinska Simona , Ponomarev Vladimir , Nagi Chandandeep , Fallon John T. , Skobe Mihaela
Published: February 2010

The lymphatic system is an important pathway for tumor dissemination to the lymph nodes, but to which extent it contributes to the formation of distant metastases remains unknown. We report that induction of lymphangiogenesis by vascular endothelial growth factor-C (VEGF-C) at the secondary site, in the lung, facilitates expansion of already disseminated cancer cells throughout the lung tissue. By using orthotopic spontaneous metastasis models in nude mice, we show that VEGF-C expression by tumor cells altered the pattern of pulmonary metastases from nodular to diffuse and facilitated disease progression. Metastases expressing VEGF-C were tightly associated with the airways, in contrast to the control cells that were scattered in the lung parenchyma, throughout the alveolar region. VEGF-C induced lung lymphangiogenesis and promoted intralymphatic spread of metastases in the lung and formation of tumor emboli in the pulmonary arteries. This pattern of metastasis corresponds to lymphangitic carcinomatosis metastatic phenotype in human cancer patients, an extremely aggressive pattern of pulmonary metastases. In accordance, pulmonary breast cancer metastases from patients which were classified as lymphangitic carcinomatosis showed high levels of VEGF-C expression in cancer cells. These data show that VEGF-C promotes late steps of the metastatic process and identify the VEGF-C/VEGF receptor-3 pathway as the target not only for prevention of metastases, but also for treatment of established metastatic disease. Cancer Res; 70(5); 1814–24
Protection from Rapamycin-Induced Apoptosis by Insulin-Like Growth Factor-I Is Partially Dependent on Protein Kinase C Signaling
Authors: Thimmaiah Kuntebommanahalli N. , Easton John B. , Houghton Peter J.
Published: February 2010

Rapamycin-induced apoptosis in sarcoma cells is inhibited by insulin-like growth factor-I (IGF-I) through a signaling pathway independent of Ras-extracellular signal-regulated kinase 1/2 and Akt. IGF-I induces Bad phosphorylation (Ser112, Ser136, and Ser155) in a pathway involving phosphoinositide 3′ kinase (PI3K) and protein kinase C (PKC; μ, ϵ, or θ) resulting in sequestering Bad from mitochondria and subsequently interacting with 14-3-3γ in the cytosol. Gene knockdown of Bad, Bid, Akt1, Akt2, PKC-μ, PKC-ϵ, or PKC-θ was achieved by transient transfection using small interfering RNAs. Results indicate that IGF-I signaling to Bad requires activation of PI3K and PKC (μ, θ, ϵ) but not mTOR, Ras-extracellular signal-regulated kinase 1/2, protein kinase A, or p90RSK. Wortmannin blocked the phosphorylation of PKC-μ (Ser744/Ser748), suggesting that PI3K is required for the activation of PKCs. PKCs phosphorylate Bad under in vitro conditions, and the association of phosphorylated Bad with PKC-μ or PKC-ϵ, as shown by immunoprecipitation, indicated direct involvement of PKCs in Bad phosphorylation. To confirm these results, cells overexpressing pEGFP-N1, wt-Bad, or Bad with a single site mutated (Ser112Ala; Ser136Ala; Ser155Ala), two sites mutated (Ser112/136Ala; Ser112/155Ala; Ser136/155Ala), or the triple mutant were tested. IGF-I protected completely against rapamycin-induced apoptosis in cells overexpressing wt-Bad and mutants having either one or two sites of phosphorylation mutated. Knockdown of Bid using small interfering RNA showed that Bid is not required for rapamycin-induced cell death. Collectively, these data suggest that IGF-I–induced phosphorylation of Bad at multiple sites via a pathway involving PI3K and PKCs is important for protecting sarcoma cells from rapamycin-induced apoptosis. Cancer Res; 70(5); 2000–9
Maternally Expressed Gene 3, an Imprinted Noncoding RNA Gene, Is Associated with Meningioma Pathogenesis and Progression
Authors: Zhang Xun , Gejman Roger , Mahta Ali , Zhong Ying , Rice Kimberley A. , Zhou Yunli , Cheunsuchon Pornsuk , Louis David N. , Klibanski Anne
Published: February 2010

Meningiomas are common tumors, representing 15% to 25% of all central nervous system tumors. NF2 gene inactivation on chromosome 22 has been shown as an early event in tumorigenesis; however, few factors underlying tumor growth and progression have been identified. The chromosomal abnormalities of 14q32 are often associated with meningioma pathogenesis and progression; therefore, it has been proposed that an as yet unidentified tumor suppressor is present at this locus. Maternally expressed gene 3 (MEG3) is an imprinted gene located at 14q32 which encodes a noncoding RNA with an antiproliferative function. We found that MEG3 mRNA is highly expressed in normal arachnoidal cells. However, MEG3 is not expressed in the majority of human meningiomas or the human meningioma cell lines IOMM-Lee and CH157-MN. There is a strong association between loss of MEG3 expression and tumor grade. Allelic loss at the MEG3 locus is also observed in meningiomas, with increasing prevalence in higher grade tumors. In addition, there is an increase in CpG methylation within the promoter and the imprinting control region of MEG3 gene in meningiomas. Functionally, MEG3 suppresses DNA synthesis in both IOMM-Lee and CH157-MN cells by ∼60% in bromodeoxyuridine incorporation assays. Colony-forming efficiency assays show that MEG3 inhibits colony formation in CH157-MN cells by ∼80%. Furthermore, MEG3 stimulates p53-mediated transactivation in these cell lines. Therefore, these data are consistent with the hypothesis that MEG3, which encodes a noncoding RNA, may be a tumor suppressor gene at chromosome 14q32 involved in meningioma progression via a novel mechanism. Cancer Res; 70(6); 2350–8
Estrogen Receptor-α Phosphorylation at Serine 305, Nuclear p21-Activated Kinase 1 Expression, and Response to Tamoxifen in Postmenopausal Breast Cancer
Authors: Bostner Josefine , Skoog Lambert , Fornander Tommy , Nordenskjöld Bo , Stål Olle
Published: February 2010

Purpose: In vitro, p21-activated kinase 1 (Pak1) phosphorylates the serine 305 residue of the estrogen receptor α (ERα) and influences the response of breast cancer cells to tamoxifen. We investigated the influence of Pak1 and pERαser305 on breast cancer prognosis and results of tamoxifen therapy.

Experimental Design: We examined Pak1 and pERαser305 protein by immunohistochemistry in a series of 912 tumors from node-negative breast cancer patients randomized to tamoxifen or no adjuvant endocrine treatment.

Results: Cytoplasmic Pak1 correlated to large tumors and ER negativity, whereas nuclear Pak1 and pERαser305 correlated to small tumors and ER positivity. Nuclear expression of Pak1 and pERαser305 predicted reduced response to tamoxifen in patients with ERα-positive tumors (tamoxifen versus no tamoxifen: hazard ratio (HR), 1.33; 95% confidence interval (95% CI), 0.42-4.2; P = 0.63), whereas patients lacking this combination benefitted significantly from tamoxifen (HR, 0.43; 95% CI, 0.30-0.62; P < 0.0001). Similar nonsignificant trends were detected in analyses of the proteins separately. Pak1 in the cytoplasm was an independent prognostic marker, indicating increased recurrence rate (HR, 1.79; 95% CI, 1.17-2.74; P = 0.0068) and breast cancer mortality (HR, 1.98; 95% CI, 1.14-3.46; P = 0.016) for patients randomized to no adjuvant treatment.

Conclusion: Our results suggest that patients with tumors expressing Pak1 and pERαser305 in combination are a group in which tamoxifen treatment is insufficient. In addition, the pathway may be of interest as a drug target in breast cancer. Furthermore, the findings support previous studies showing that Pak1 has differential roles in the cytoplasm and the nucleus. Clin Cancer Res; 16(5); 1624–33
The Prolyl Isomerase Pin1 Enhances HER-2 Expression and Cellular Transformation via Its Interaction with Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase Kinase 1
Authors: Khanal Prem , Namgoong Gwang Mo , Kang Bong Seok , Woo Eun-Rhan , Choi Hong Seok
Published: February 2010

The HER-2 oncogene, a member of the erythroblastosis oncogene B (ERBB)-like oncogene family, has been shown to be amplified in many types of cancer, including breast cancer. However, the molecular mechanism of HER-2 overexpression is not completely understood. The phosphorylation of proteins on the serine or threonine residues that immediately precede proline (pSer/Thr-Pro) is specifically catalyzed by the prolyl isomerase Pin1 and is a key signaling mechanism in cell proliferation and transformation. Here, we found that Pin1 interacts with mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK) protein kinase 1, resulting in the induction of HER-2 expression. Pin1−/− mouse embryonic fibroblasts exhibited a decrease in epidermal growth factor (EGF)–induced MEK1/2 phosphorylation compared with Pin1+/+ mouse embryonic fibroblast. In addition, a knockdown of Pin1 resulted in the inhibition of MEK1/2 phosphorylation induced by EGF in MCF-7 cells. Furthermore, PD98059, a specific inhibitor of MEK1/2, and Juglone, a potent Pin1 inhibitor, markedly suppressed the expression of activator protein-2α and the HER-2 promoter activity induced by EGF or 12-O-tetradecanoylphorbol-13-acetate in MCF-7 cells. Importantly, these inhibitors inhibited the neoplastic cell transformation induced by EGF in Pin1-overexpressing JB6 Cl41 cells, which showed enhanced cellular formation compared with the control cells. Therefore, Juglone and PD98059 inhibited the colony formation of MCF-7 breast cancer cells in soft agar. These results indicate that Pin1 amplifies EGF signaling in breast cancer cells through its interaction with MEK1 and then enhances HER-2 expression, suggesting that Pin1 plays an important role in the overexpression of HER-2 through Pin1-MEK1-activator protein-2α signaling in breast cancer. Mol Cancer Ther; 9(3); 606–16
Identification of Expression Signatures Predictive of Sensitivity to the Bcl-2 Family Member Inhibitor ABT-263 in Small Cell Lung Carcinoma and Leukemia/Lymphoma Cell Lines
Authors: Tahir Stephen K. , Wass John , Joseph Mary K. , Devanarayan Viswanath , Hessler Paul , Zhang Haichao , Elmore Steve W. , Kroeger Paul E. , Tse Christin , Rosenberg Saul H. , Anderson Mark G.
Published: February 2010

ABT-263 inhibits the antiapoptotic proteins Bcl-2, Bcl-xL, and Bcl-w and has single-agent efficacy in numerous small cell lung carcinoma (SCLC) and leukemia/lymphoma cell lines in vitro and in vivo. It is currently in clinical trials for treating patients with SCLC and various leukemia/lymphomas. Identification of predictive markers for response will benefit the clinical development of ABT-263. We identified the expression of Bcl-2 family genes that correlated best with sensitivity to ABT-263 in a panel of 36 SCLC and 31 leukemia/lymphoma cell lines. In cells sensitive to ABT-263, expression of Bcl-2 and Noxa is elevated, whereas expression of Mcl-1 is higher in resistant cells. We also examined global expression differences to identify gene signature sets that correlated with sensitivity to ABT-263 to generate optimal signature sets predictive of sensitivity to ABT-263. Independent cell lines were used to verify the predictive power of the gene sets and to refine the optimal gene signatures. When comparing normal lung tissue and SCLC primary tumors, the expression pattern of these genes in the tumor tissue is most similar to sensitive SCLC lines, whereas normal tissue is most similar to resistant SCLC lines. Most of the genes identified using global expression patterns are related to the apoptotic pathway; however, all but Bcl-rambo are distinct from the Bcl-2 family. This study leverages global expression data to identify key gene expression patterns for sensitivity to ABT-263 in SCLC and leukemia/lymphoma and may provide guidance in the selection of patients in future clinical trials. Mol Cancer Ther; 9(3); 545–57
The Impact of Fish Oil on the Chemopreventive Efficacy of Tamoxifen against Development ofN-Methyl-N-Nitrosourea–Induced Rat Mammary Carcinogenesis
Authors: Manni Andrea , Xu Haifang , Washington Sharlene , Aliaga Cesar , Cooper Timothy , Richie John P. , Bruggeman Richard , Prokopczyk Bogdan , Calcagnotto Ana , Trushin Neil , Mauger David , Verderame Michael F. , El-Bayoumy Karam
Published: February 2010

The antiestrogen tamoxifen reduces breast cancer incidence in high-risk women but is unable to inhibit the development of hormone-independent tumors. Omega-3 polyunsaturated fatty acids (n-3 PUFA), known ligands of the peroxisome proliferator activated receptor-γ (PPARγ), generally exert tumor-suppressive effects. Based on the known crosstalk between the estrogen and the PPARγ receptors, we tested the hypothesis that the combination of tamoxifen with n-3 PUFA results in a superior antitumor action over the individual interventions. In this study, we report for the first time that the combination of a fish oil diet rich in n-3 PUFA and tamoxifen seemed to inhibit N-methyl-N-nitrosourea–induced mammary carcinogenesis, tumor multiplicity, and volume to a greater extent than the individual interventions. The potential superiority of the combination was particularly evident at a suboptimal dose of tamoxifen, which, by itself, was unable to significantly decrease tumor development. Because activation of PPARγ is known to inhibit oxidative stress, we examined the effects of our interventions on circulating and tumor levels of glutathione, a major intracellular antioxidant. Our results indicate that reduction in the level of oxidative stress may be a potential mechanism by which the n-3 PUFA–rich diet potentiated the tumor-suppressive effect of tamoxifen. Our interventions were well tolerated without evidence of toxicity. Combined administration of tamoxifen and n-3 PUFA is a promising new approach to breast cancer prevention. Because of its safety, this combination can quickly be translated to the clinic if its superiority can be supported by future studies. Cancer Prev Res; 3(3); 322–30
On Tracking the Course of Cerebral Oxygen Saturation and Pilot Performance During Gravity-Induced Loss of Consciousness
Authors: Tripp Lloyd D. , Warm Joel S. , Matthews Gerald , Chiu Peter Y. , Bracken R. Bruce
Published: February 2010

Objective: The aim of this study was to track the course of cerebral tissue oxygen saturation (rSO2) and pilot performance during an episode of gravity-induced loss of consciousness (GLOC). Background: GLOC, a major problem facing pilots of high-performance aircraft, is brought about by a sudden reduction in rSO2 as a result of increased +Gz force. It consists of 24 s of complete functional impairment followed by a prolonged period of performance recovery. This study tested the hypothesis that delayed recovery in GLOC is caused by a slow return of rSO2 following removal of the g-force that induced the episode. Method: GLOC was induced in U.S. Air Force personnel via a centrifuge with math and tracking tasks emulating flight performance. A near-infrared spectroscopy unit provided the rSO2 measure. Results: Declines in rSO2 from baseline pinpointed when pilots would cease active flight control and when GLOC would set in. Counter to expectation, rSO2 returned to baseline levels shortly after the centrifuge came to a complete stop following GLOC onset. Nevertheless, performance deficits continued for 49.45 s thereafter. Conclusion: The prolonged performance recovery time in GLOC cannot be attributed to delays in the return of rSO 2. This finding explains why previous ergonomic efforts to shorten the duration of GLOC episodes by increasing the rate of return of rSO 2 have not been fruitful. Evidently, another approach is needed. Application: Such an approach might use the close linkage between loss of rSO2, performance deterioration, and GLOC onset to develop a warning system that would permit pilots to take effective action to avoid GLOC incapacitation.
Competing Roles of TGFβ and Nma/BAMBI in Odontoblasts
Authors: Gonzales C.B. , Simmons D. , MacDougall M.
Published: February 2010

Nma/BAMBI is a novel pseudoreceptor with homology to a TGFβ type I receptor that lacks a serine/threonine kinase domain. Nma/BAMBI functions as a dominant-negative protein that regulates reciprocal epithelial-mesenchymal interactions during organogenesis. Therefore, we hypothesized that Nma/BAMBI regulates TGFβ signaling and downstream gene expression during dentinogenesis. To test this hypothesis, we examined the downstream gene expression profiles of major dentin extracellular matrix proteins in response to Nma/BAMBI, and we examined the roles of Nma/BAMBI and TGFβ-1 during dentinogenesis. Overexpression of Nma/BAMBI in the mouse odontoblast-like cell line MD10-A2 down-regulated expression of DSPP by 66% and up-regulated expression of DMP1 four-fold. TGFβ treatment reversed Nma/BAMBI’s negative effect on DSPP expression. Furthermore, we demonstrated that TGFβ negatively regulates Nma/BAMBI’s expression levels in MD10-A2 odontoblast-like cells. Analysis of these data, together, indicates that TGFβ and Nma/BAMBI are inversely regulated and that the sequence of expression determines the net effect on downstream gene expression.
Rehabilitation Counselor Work Environment: Examining Congruence With Prototypic Work Personality
Authors: Zanskas Stephen , Strohmer Douglas C.
Published: February 2010

The profession of rehabilitation counseling has undergone extensive empirical study. Absent from this research has been a theoretical basis for describing and understanding the profession and its associated work environment. The focus of this study was to further our understanding of the nature of the rehabilitation counselor’s work environment and the person— environment congruence through the framework of Holland’s career theory and the Position Classification Inventory (PCI). Data concerning the work environment of 366 rehabilitation counselors were collected using a Web adaptation of the PCI to empirically establish the Holland code for the prototypical rehabilitation counselor work environment and examine its congruence with the prototypical Strong Interest Inventory interest patterns.
Lisdexamfetamine Dimesylate: Linear Dose‐Proportionality, Low Intersubject and Intrasubject Variability, and Safety in an Open‐Label Single‐Dose Pharmacokinetic Study in Healthy Adult Volunteers
Authors: Ermer James , Homolka Robert , Martin Patrick , Buckwalter Mary , Purkayastha Jaideep , Roesch Benno
Published: February 2010

The pharmacokinetics of lisdexamfetamine dimesylate, a long‐acting prodrug stimulant, and its active moiety, d‐amphetamine, including dose‐proportionality and variability, were assessed in 20 healthy adults. Subjects received a single dose, sequentially, of 50, 100, 150, 200, and 250 mg of lisdexamfetamine dimesylate. Plasma lisdexamfetamine dimesylate and d‐amphetamine were measured before dosing and 0.25 to 96 hours postdose. Dose‐proportionality and intersubject and intrasubject variability of pharmacokinetic parameters were examined. Safety assessments included adverse events. All 20 subjects received 50 and 100 mg while 18, 12, and 9 subjects received 150, 200, and 250 mg of lisdexamfetamine dimesylate, respectively. Ten subjects were discontinued during the study for prespecified stopping rules (2 consecutive hourly readings of blood pressure: systolic >160 mm Hg or diastolic >100 mm Hg). Mean maximum observed plasma concentration (Cmax) and area under the concentration—time curve from time 0 to infinity (AUC0‐∞) increased linearly and dose‐dependently for d‐amphetamine. Median time to Cmax ranged from 4 to 6 hours for d‐amphetamine and 1.0 to 1.5 hours for lisdexamfetamine dimesylate. Intersubject and intrasubject variability over doses from 50 to 150 mg was low (<20%) for both Cmax and AUC0‐∞. Adverse events included nausea, dizziness, headache, psychomotor hyperactivity, and dysuria. These findings indicate that the pharmacokinetic parameters of d‐amphetamine were dose‐proportional and predictable over a wide range of lisdexamfetamine dimesylate doses.
Dose Proportionality of Once‐Daily Trazodone Extended‐Release Caplets Under Fasting Conditions
Authors: Karhu David , Groenewoud Gerhard , Potgieter Maria A. , Mould Diane R.
Published: February 2010

An extended‐release trazodone HCl formulation, Trazodone Contramid OAD (TzCOAD), was developed as scored 150‐mg and 300‐mg caplets for once‐daily administration. Dose proportionality of intact and bisected caplets (dose range, 75–375 mg) was evaluated in a single‐dose, randomized, 5‐way crossover study. Plasma trazodone and m‐chlorophenylpiperazine (mCPP) levels were determined using a validated liquid chromatography‐tandem mass spectroscopy method. Dose proportionality was assessed based on confidence intervals for logarithmically transformed, dose‐normalized maximum plasma concentration (Cmax), area under the plasma concentration versus time data pairs (AUC0‐t), and area under the curve from time 0 to infinity (AUC0‐∞) in relation to the acceptance range of 80% to 125% (bioequivalence approach). The power method, combined with confidence interval criteria, was also used to assess proportionality. The conclusion of dose proportionality was generally supported using the bioequivalence approach. Based on the power model, values of the slope and corresponding 90% confidence interval for trazodone Cmax, AUC0‐t, and AUC0‐∞ were 0.948 (0.899‐0.997), 0.920 (0.875‐0.964), and 0.913 (0.867‐0.958), respectively. All were within the acceptance interval (0.861‐1.139). Results for mCPP also fell within the acceptance interval. TzCOAD exhibits linear pharmacokinetics over doses ranging from 75 to 375 mg and maintains its controlled‐release properties when the caplets are bisected along the score line.
Stage-driven information seeking process: Value and uncertainty of work tasks from initiation to resolution
Authors: Kallehauge Jesper
Published: February 2010

The stage-driven information seeking process to reduce uncertainty and increase value is systematically validated with real users (n=60) with real work tasks from social sciences and applied sciences domains in a UK and Danish university. A broad set of information sources are applied and core relevance criteria are measured. The research seeks to test the hypothesis that the information seeking process is seen as a dynamic and iterative development to reduce uncertainty through four stages until the problem is solved: (1) problem recognition: kind of problem, (2) problem definition: nature of the problem, (3) problem resolution: finding an answer to the problem, (4) solution statement: answer to the problem or how to deal with it. The hypothesis can be rejected in this case since there is no significant decrease in uncertainty level from stage 1 to 4.
The new role of the perfusionist in adult extracorporeal life support
Authors: McCoach Robert M. , Baer Larry D. , Wise Robert K. , Woitas Karl R. , Palanzo David A. , Pae Walter E. , El Banayosy Aly
Published: February 2010

Adult and pediatric extracorporeal life support (ECLS) has been transformed by the European1 and Australian 2 experiences with a reduction of the circuit to its most basic form (Figure 1). Many factors have converged at this point in time to allow us to offer this support. The availability in the U.S.A. of an advanced oxygenator (QuadroxD) (Maquet Inc., Bridgewater, NJ), long-term centrifugal pumps and circuit coatings offers us the means to provide ECLS. The other equally important factor is the intensivist trained in extracorporeal therapies. Once the intensive care unit registered nurse (ICU RN) is trained to safely and effectively manage both the patient and ECLS circuit, this support may be offered. The perfusionist is in an unique position to educate and mentor the ICU RN in ECLS. There is, perhaps, no one in a better position to explain this equipment and its uses in an interdisciplinary-oriented pediatric and adult ECLS program than a perfusionist.
Developing Pedagogical Competence: Issues and Implications for Marketing Education
Authors: Madhavaram Sreedhar , Laverie Debra A.
Published: February 2010

Competence in pedagogy and research is the sine qua non of marketing educators’ careers. However, there is evidence in the literature that marketing academics focus more on and are more competent in research than teaching. This imbalance, in a majority of instances, can be traced back to doctoral education. Doctoral programs in marketing are designed to prepare students for becoming successful marketing professors. An important component of becoming a successful professor is learning how to teach effectively. Yet doctoral programs fall short of providing adequate pedagogical training. Consequently, marketing educators, from their doctoral days through their professorial careers, have a responsibility to continuously work on their competence in teaching. However, how can marketing educators in general and marketing doctoral students in particular develop pedagogical competence (PC)? In this article, the authors deconstruct PC into five components: content knowledge (or knowledge of subject matter), knowledge of pedagogical approaches, course management capability, classroom management capability, and student management capability. Next, they discuss how individuals can develop PC and the implications of PC for marketing education. Specifically, the authors discuss issues and implications for doctoral students, doctoral programs, marketing departments, and marketing faculty. Finally, the authors conclude with a discussion of the contributions of the article to marketing academe.
Teaching Information Privacy in Marketing Courses: Key Educational Issues for Principles of Marketing and Elective Marketing Courses
Authors: Peltier James W. , Milne George R. , Phelps Joseph E. , Barrett Jennifer T.
Published: February 2010

An “information privacy gap” exists in marketing education, with little research addressing the state of information privacy and how appropriate privacy strategies and tactics should be communicated to students. The primary purpose of this article is to provide educators an understanding of information privacy and how they can incorporate this evolving and important topic into the marketing curriculum. To accomplish this goal, a comprehensive information privacy framework is presented, and specific recommendations are provided to assist marketing educators in their efforts to expand consumer information privacy issues in their courses.