bluuebunny/crossref_metadata_2025 huggingface dataset:
Evidence for Activation of Toll-Like Receptor and Receptor for Advanced Glycation End Products in Preterm Birth
Authors: Noguchi Taketoshi , Sado Toshiyuki , Naruse Katsuhiko , Shigetomi Hiroshi , Onogi Akira , Haruta Shoji , Kawaguchi Ryuji , Nagai Akira , Tanase Yasuhito , Yoshida Shozo , Kitanaka Takashi , Oi Hidekazu , Kobayashi Hiroshi
Published: November 2010

Objective. Individuals with inflammation have a myriad of pregnancy aberrations including increasing their preterm birth risk. Toll-like receptors (TLRs) and receptor for advanced glycation end products (RAGE) and their ligands were all found to play a key role in inflammation. In the present study, we reviewed TLR and RAGE expression, their ligands, and signaling in preterm birth.Research Design and Methods. A systematic search was performed in the electronic databases PubMed and ScienceDirect up to July 2010, combining the keywords “preterm birth,” “TLR”, “RAGE”, “danger signal”, “alarmin”, “genomewide,” “microarray,” and “proteomics” with specific expression profiles of genes and proteins.Results. This paper provides data on TLR and RAGE levels and critical downstream signaling events including NF-kappaB-dependent proinflammatory cytokine expression in preterm birth. About half of the genes and proteins specifically present in preterm birth have the properties of endogenous ligands “alarmin” for receptor activation. The interactions between the TLR-mediated acute inflammation and RAGE-mediated chronic inflammation have clear implications for preterm birth via the TLR and RAGE system, which may be acting collectively.Conclusions. TLR and RAGE expression and their ligands, signaling, and functional activation are increased in preterm birth and may contribute to the proinflammatory state.
Spatial Diversity Scheme to Efficiently Cancel ISI and ICI in OFDM-OQAM Systems
Authors: Zorba Nizar , Bader Faouzi
Published: November 2010

This paper is based on an Offset Quadrature Amplitude Modulation (OQAM) Orthogonal Frequency Division Multiplexing (OFDM) transmission scheme that is operated without a Cyclic Prefix (CP), where the multiple transmitting antennas are employed to substantially reduce the inherent intersymbol and intercarrier interference. The proposed scheme avoids the use of the CDMA technology to get rid of the interference. The nonemployment of the CP increases the spectral efficiency in comparison with classical CP-OFDM systems, as it does not employ the CP for its correct performance. On the other hand, the non-employment of the CP comes at cost of Intersymbol Interference (ISI). This paper presents a method which cancels the interference terms by employing a multiantenna precoding strategy based on spatial diversity OQAM-OFDM scheme, so that the overall system can get the advantage of the CP removal while no ISI is generated. Moreover, the proposed system benefits from the multiuser gain through an opportunistic scheduler at the transmitter side to select the user with the best channel characteristics at each instant. The resultant scheme OQAM-OFDM-MIMO data rate is obtained in a closed form expression and proved to be higher than the classical CP-OFDM systems.
Koenigs-Knorr Glycosylation with Neuraminic Acid Derivatives
Authors: Pazynina Galina , Nasonov Vitaly , Belyanchikov Ivan , Brossmer Reinchard , Maisel Maxim , Tuzikov Alexander , Bovin Nicolai
Published: December 2010

Earlier we reported a convenient and efficient method of preparing α2-6 sialooligosaccharides in conditions of
Koenigs-Knorr reaction. The use of Ag2CO3 allowed carrying out α2-6 sialylation of galacto-4,6-diol of mono- and disaccharides with chloride of acetylated N-acetylneuraminic acid methyl ester as glycosyl donor. In this study we applied this approach to other derivatives of neuraminic acid, namely, Neu5Gc, 9-deoxy-9-NAc-Neu5Ac, Neu5Acα2-8Neu5Ac, and Neu5Acα2-8Neu5Acα2-8Neu5Ac as glycosyl donors; eight compounds were synthesized: Neu5Gcα-O(CH2)3NH2 (8), Neu5Gcα2-6Galβ1-4GlcNAcβ-O(CH2)3NH2 (10), 9-deoxy-9-NAc-Neu5Ac-O(CH2)3NH2 (15), 9-deoxy-9-NAc-Neu5Acα2-6Galβ1-4GlcNAcβ-O(CH2)3NH2 (17), Neu5Acα2-8Neu5Acα-O(CH2)3NH2(23) Neu5Acα2-8Neu5Acα-OCH3 (24), Neu5Acα2-8Neu5Acα-OCH2(p-C6H4)NHCOCH2NH2 (25), and Neu5Acα2-8Neu5Acα2-8Neu5Acα-O(CH2)3NH2 (32). These sialosides were used for characterization of siglecs and other carbohydrate-binding proteins.
Zinc Selenide-Based Schottky Barrier Detectors for Ultraviolet-A and Ultraviolet-B Detection
Authors: Naval V. , Smith C. , Ryzhikov V. , Naydenov S. , Alves F. , Karunasiri G.
Published: December 2010

Wide-bandgap semiconductors such as zinc selenide (ZnSe) have become popular for ultraviolet (UV) photodetectors due to their broad UV spectral response. Schottky barrier detectors made of ZnSe in particular have been shown to have both low dark current and high responsivity. This paper presents the results of electrical and optical characterization of UV sensors based on ZnSe/Ni Schottky diodes fabricated using single-crystal ZnSe substrate with integrated UV-A (320–400 nm) and UV-B (280–320 nm) filters. For comparison, characteristics characterization of an unfiltered detector is also included. The measured photoresponse showed good discrimination between the two spectral bands. The measured responsivities of the UV-A and UV-B detectors were 50 mA/W and 10 mA/W, respectively. A detector without a UV filter showed a maximum responsivity of about 110 mA/W at 375 nm wavelength. The speed of the unfiltered detector was found to be about 300 kHz primarily limited by the RC time constant determined largely by the detector area.
Reversal Rate of Clustering of Cardiovascular Disease Risk Factors of Metabolic Syndrome in the General Population: The Niigata Preventive Medicine Study
Authors: Okada Shinsuke , Suzuki Akiko , Watanabe Hiroshi , Watanabe Toru , Aizawa Yoshifusa
Published: November 2010

The reversal rate from clustering of cardiovascular disease (CVD) risk factors—components of the metabolic syndrome (MetS) is not known.Methods and Results. Among 35,534 subjects who received the annual health examinations at the NiigataHealth Foundation (Niigata, Japan), 4,911 subjects had clustering of 3 or more of the following CVD risk factors: (1) body mass index (BMI) ≥25 Kg/m2, (2) blood pressure ≥130 mm Hg in systolic and/or ≥85 mm Hg in diastolic, (3) triglycerides ≥150 mg/dL, (4) high-density lipoprotein cholesterol ≤40 mg/dL in men, ≤50 mg/dL in women, and (5) fasting blood glucose ≥100 mg/dL. After 5 years 1,929 subjects had a reversal of clustering (39.4%). A reversal occurred more often in males. The subjects with a reversal of clustering had milder level of each risk factor and a smaller number of risk factors, while BMI was associated with the least chance of a reversal.Conclusion. We concluded that a reversal of clustering CVD risk factors is possible in 4/10 subjects over a 5-year period by habitual or medical interventions. Gender and each CVD risk factor affected the reversal rate adversely, and BMI was associated with the least chance of a reversal.
The Comparative Study of Vibration Control of Flexible Structure Using Smart Materials
Authors: Fei Juntao , Fang Yunmei , Yan Chunyan
Published: December 2010

Considerable attention has been devoted to active vibration control using intelligent materials as PZT actuators. This paper presents results on active control schemes for vibration suppression of flexible steel cantilever beam with bonded piezoelectric actuators. The PZT patches are surface bonded near the fixed end of flexible steel cantilever beam. The dynamic model of the flexible steel cantilever beam is derived. Active vibration control methods: optimal PID control, strain rate feedback control (SRF), and positive position feedback control (PPF) are investigated and implemented using xPC Target real‐time system. Experimental results demonstrate that the SRF and PPF controls have better performance in suppressing the vibration of cantilever steel beam than the optimal PID control.
Unsupervised Topographic Learning for Spatiotemporal Data Mining
Authors: Cabanes Guénaël , Bennani Younès
Published: November 2010

In recent years, the size and complexity of datasets have shown an exponential growth. In many application areas, huge amounts of data are generated, explicitly or implicitly containing spatial or spatiotemporal information. However, the ability to analyze these data remains inadequate, and the need for adapted data mining tools becomes a major challenge. In this paper, we propose a new unsupervised algorithm, suitable for the analysis of noisy spatiotemporal Radio Frequency IDentification (RFID) data. Two real applications show that this algorithm is an efficient data-mining tool for behavioral studies based on RFID technology. It allows discovering and comparing stable patterns in an RFID signal and is suitable for continuous learning.
Chaotic Attractor Generation via a Simple Linear Time‐Varying System
Authors: Ou Baiyu , Liu Desheng
Published: December 2010

A novel generation method of chaotic attractor is introduced in this paper. The underlying mechanism involves a simple three‐dimensional time‐varying system with simple time functions as control inputs. Moreover, it is demonstrated by simulation that various attractor patterns are generated conveniently by adjusting suitable system parameters. The largest Lyapunov exponent of the system has been obtained.
Lentiviral-Mediated RNA Interference against TGF-Beta Receptor Type II in Renal Epithelial and Fibroblast Cell Populations In Vitro Demonstrates Regulated Renal Fibrogenesis That Is More Efficient than a Nonlentiviral Vector
Authors: Yang Tao , Zhang Bing , Pat Betty K. , Wei Ming Q. , Gobe Glenda C.
Published: November 2010

Background. Lentiviral constructs reportedly can integrate into the genome of non-dividing, terminally differentiated cells and dividing cells, for long-term gene expression. This investigation tested whether a third generation lentiviral-mediated small interfering RNA (siRNA) delivered into renal epithelial and fibroblast cells against type II transforming growth factor-beta receptor (siRNA-TBRII) could better attenuate renal fibrogenesis in comparison with a non-lentiviral construct.Methods. HIV-derived lentiviral and non-lentiviral constructs were used to transfect cells with siRNA-TBRII or siRNA-EGFP control. Human embryonic kidney (HEK-293T), renal epithelial cells (NRK-52E) and renal fibroblasts (NRK-49F) were transfected and gene silencing quantified (fluorescence microscopy, Western blotting, fluorescence-activated cell sorting). Renal fibrogenesis was assessed using extracellular matrix protein synthesis (fibronectin and collagen-III; Western immunoblot), and α-smooth muscle actin (α-SMA) was analysed as a marker of fibroblast activation and epithelial-to-mesenchymal transdifferentiation (EMT).Results. Lentiviral-mediated siRNA-TBRII significantly suppressed TBRII expression in all cell lines, and also significantly suppressed renal fibrogenesis. In comparison with the non-lentiviral construct, lentiviral-mediated siRNA-TBRII produced stronger and more persistent inhibition of collagen-III in NRK-49F cells, fibronectin in all renal cell lines, and α-SMA in renal epithelial cells.Conclusions. Lentiviral vector systems against TBRII can be delivered into renal cells to efficiently limit renal fibrogenesis by sequence-specific gene silencing.
Fibromatous Uterus in a 16-Year-Old Girl: A Case Report
Authors: Tsili Athina C. , Lentoudi Ekaterini D. , Argyropoulou Maria I. , Dalkalitsis Nikolaos , Batistatou Anna , Paraskevaidis Evangelos , Tsampoulas Konstantine
Published: November 2010

Although uterine leiomyomas are the most common neoplasms of the female genital tract, this is not the case when referring to women under the age of 20. Only a few cases of uterus leiomyomas have been reported in this age. Preoperative imaging evaluation is mandatory in adolescent women for the accurate detection, localization, and characterization of uterus leiomyomas. We report a case of a 16-year-old girl admitted to our hospital for pain and abdominal distention. The patient underwent multidetector CT examination of the abdomen and MR examination of the pelvis. Both imaging modalities revealed uterine enlargement and the presence of innumerable variably sized leiomyomas. Histopathologic examination following exploratory laparotomy confirmed the presence of uterus leiomyomas. The patient underwent laparoscopic myomectomy two years after the first operation, following MR examination of the pelvis.
A Multiobjective Optimization Approach to Solve a Parallel Machines Scheduling Problem
Authors: Li Xiaohui , Amodeo Lionel , Yalaoui Farouk , Chehade Hicham
Published: December 2010

A multiobjective optimization problem which focuses on parallel machines scheduling is considered. This problem consists of scheduling independent jobs on identical parallel machines with release dates,
due dates, and sequence-dependent setup times. The preemption of jobs is forbidden. The aim is to minimize
two different objectives: makespan and total tardiness. The contribution of this paper is to propose first a new mathematical
model for this specific problem. Then, since this problem is NP hard in the strong sense, two well-known approximated methods,
NSGA-II and SPEA-II, are adopted to solve it. Experimental results show the advantages of NSGA-II for the
studied problem. An exact method is then applied to be compared with NSGA-II algorithm in order to prove the efficiency of
the former. Experimental results show the advantages of NSGA-II for the studied problem. Computational experiments show that on
all the tested instances, our NSGA-II algorithm was able to get the optimal solutions.
Pop-Cola Acids and Tooth Erosion: AnIn Vitro,In Vivo, Electron-Microscopic, and Clinical Report
Authors: Borjian Amirfirooz , Ferrari Claudia C. F. , Anouf Antoni , Touyz Louis Z. G.
Published: December 2010

Introduction. Manufactured Colas are consumed universally as soft drinks. Evidence about the acid contents of Cola-beverages and its effects on teeth is rare.Aim. To assess (i) cola acidity and buffering capacityin vitro, (ii) tooth erosion after swishing with colasin vivo(iii) scanning electronmicroscopic effectson teeth of colas, and tooth-brush abrasion, and (iv) report aclinical caseof erosion from cola consumption.Materials and Methods. (i) We measured six commercially available pop “Cola beverages”, pH, and buffering capacities using a pH-Mettler Automatic Titrator, with weak solution of Sodium Hydroxide (ii) two cohorts, onewith teeth, the secondwithout teethrinsed with aliquots of Cola for 60 seconds. Swished cola samples tested for calcium and phosphorus contents using standardized chemical analytical methods (iii) enamel, dentine, and the enamel-cemental junction from unerupted extracted wisdom teeth were examined with a scanning electron microscope after exposure to colas, and tested for tooth-brush abrasion; (iv) a clinical case of pop cola erosion presentation, are all described.Results. Comparisons among pop colas testedin vitroreveal high acidity with very low pH. Buffering capacities in millilitres of 0.5 M NaOH needed to increase one pH unit, to pH 5.5 and pH 7 are reported. Rinsingin vivowith pop cola causes leeching of calcium from teeth; SEM shows dental erosion, and pop-cola consumption induces advanced dental erosion and facilitates abrasion.Conclusions. (i) Pop-Cola acid activity is below the critical pH 5.5 for tooth dissolution, with high buffering capacities countering neutralization effects of saliva; (ii) calcium is leeched out of teeth after rinsing with pop colas; (iii) SEM evidence explains why chronic exposure to acid pop colas causes dental frangibles; (iv) aclinical caseof pop-cola erosion confirms this.
A Perturbative Method for Calculating the Impedance of Coils on Laminated Ferromagnetic Cores
Authors: Maximov Serguei , Castillo Allen A. , Venegas Vicente , Guardado José L. , Melgoza Enrique
Published: December 2010

A new set of formulas for calculating the self and mutual impedances of coils on straight and closed laminated ferromagnetic cores of circular cross‐section has been derived. The obtained formulas generalize the well‐known formulas for impedances of coils on homogeneous ferromagnetic cores, for the case of laminated cores, and improve the previously known formulas for laminated cores. The obtained formulas are fully consistent with Maxwell′s equations and, therefore, offer an excellent accuracy. The perturbation theory and the average field technique are used to solve Maxwell′s equations inside and outside the core. The solution inside the core can also be used in the analysis of thermal effects occurring inside the laminated core.
Propagation of Blood Function Errors to the Estimates of Kinetic Parameters with Dynamic PET
Authors: Cheng Yafang , Yetik İmam Şamil
Published: November 2010

Dynamic PET, in contrast to static PET, can identify temporal variations in the radiotracer concentration. Mathematical modeling of the tissue of interest in dynamic PET can be simplified using compartment models as a linear system where the time activity curve of a specific tissue is the convolution of the tracer concentration in the plasma and the impulse response of the tissue containing kinetic parameters. Since the arterial sampling of blood to acquire the value of tracer concentration is invasive, blind methods to estimate both blood input function and kinetic parameters have recently drawn attention. Several methods have been developed, but the effect of accuracy of the estimated blood function on the estimation of the kinetic parameters is not studied. In this paper, we present a method to compute the error in the kinetic parameter estimates caused by the error in the blood input function. Computer simulations show that analytical expressions we derive are sufficiently close to results obtained from numerical methods. Our findings are important to observe the effect of the blood function on kinetic parameter estimation, but also useful to evaluate various blind methods and observe the dependence of kinetic parameter estimates to certain parts of the blood function.
Monitoring Antiretroviral Therapy in HIV-Infected Children in Resource-Limited Countries: A Tale of Two Epidemics
Authors: Paintsil Elijah
Published: December 2010

Twenty-nine years into the HIV epidemic, several advances have been made; however, there remain several challenges particularly with pediatric HIV in resource-limited countries. The obstacles facing pediatric antiretroviral therapy (ART) delivery in resource-limited countries are multifaceted: lack of health care infrastructure, limited availability of pediatric drug formulations, lack of early HIV diagnostic and monitoring techniques, limited manpower with expertise in pediatric HIV care, limited donor funding, and competing public health priorities with limited health care budget. In this paper, the challenges with various ART monitoring tools in resource-limited countries are discussed. Noninvasive (e.g., patient, clinical events outcome, and adherence) and invasive (e.g., immunologic and virologic) monitoring tools are discussed. Several cheap and technically less complex laboratory tests for monitoring are becoming available. Funding agencies and country programs should invest in validating the use of current technologies to optimize pediatric HIV care in resource-limited countries.
Aqueous and EthanolicValeriana officinalisExtracts Change the Binding of Ligands to Glutamate Receptors
Authors: Del Valle-Mojica Lisa M. , Cordero-Hernández José M. , González-Medina Giselle , Ramos-Vélez Igmeris , Berríos-Cartagena Nairimer , Torres-Hernández Bianca A. , Ortíz José G.
Published: December 2010

The effects of two valerian extracts (aqueous and hydroalcoholic) were investigated through [3H]Glutamate ([3H]Glu) and [3H]Fluorowillardine ([3H]FW) receptor binding assays using rat synaptic membranes in presence of different receptor ligands. In addition, the extract stability was monitored spectrophotometrically. Both extracts demonstrated interaction with ionotropic glutamate receptors (iGluRs). However, the extracts displayed considerable differences in receptor selectivity. The hydroalcoholic extract selectively interacted with quisqualic acid (QA), group I metabotropic glutamate receptor (mGluR) ligand, while the aqueous extract did not alter the binding of QA. The stability of the extracts was examined during several weeks. Freshly prepared extract inhibited 38–60% of [3H]FW binding (AMPA). After 10 days, the aqueous extract inhibited 85% of [3H]FW binding while the hydroalcoholic extract markedly potentiated (200%) [3H]FW binding to AMPA receptors. Thus, our results showed that factors such as extraction solvent and extract stability determine the selectivity for glutamate receptor (GluR) interactions.
Comparison of Myocardial Remodeling between Cryoinfarction and Reperfused Infarction in Mice
Authors: Duerr Georg D. , Elhafi Naziha , Bostani Toktam , Ellinger Joerg , Swieny Louay , Kolobara Elvis , Welz Armin , Dewald Oliver
Published: November 2010

Myocardial infarction is associated with inflammatory reaction leading to tissue remodeling. We compared tissue remodeling between cryoinfarction (cMI) and reperfused myocardial infarction (MI) in order to better understand the local environment where we apply cell therapies. Models of closed‐chest one‐hour ischemia/reperfusion MI and cMI were used in C57/Bl6‐mice. The reperfused MI showed rapid development of granulation tissue and compacted scar formation after 7 days. In contrast, cMI hearts showed persistent cardiomyocyte debris and cellular infiltration after 7 days and partially compacted scar formation accompanied by persistent macrophages and myofibroblasts after 14 days. The mRNA of proinflammatory mediators was transiently induced in MI and persistently upregulated in cMI. Tenascin C and osteopontin‐1 showed delayed induction in cMI. In conclusion, the cryoinfarction was associated with prolonged inflammation and active myocardial remodeling when compared to the reperfused MI. These substantial differences in remodeling may influence cellular engraftment and should be considered in cell therapy studies.
IL-6 Trans-Signaling in Formation and Progression of Malignant Ascites in Ovarian Cancer
Authors: Lo Chi-Wen , Chen Min-Wei , Hsiao Michael , Wang Shiuan , Chen Chi-An , Hsiao Sheng-Mou , Chang Jeng-Shou , Lai Tsung-Ching , Rose-John Stefan , Kuo Min-Liang , Wei Lin-Hung
Published: December 2010

Classic signaling by the proinflammatory cytokine interleukin 6 (IL-6) involves its binding to target cells that express the membrane-bound IL-6 receptor α. However, an alternate signaling pathway exists in which soluble IL-6 receptor (sIL-6Rα) can bind IL-6 and activate target cells that lack mIL-6Rα, such as endothelial cells. This alternate pathway, also termed trans-signaling, serves as the major IL-6 signaling pathway in various pathologic proinflammatory conditions including cancer. Here we report that sIL-6Rα is elevated in malignant ascites from ovarian cancer patients, where it is associated with poor prognosis. IL-6 trans-signaling on endothelial cells prevented chemotherapy-induced apoptosis, induced endothelial hyperpermeability, and increased transendothelial migration of ovarian cancer cells. Selective blockade of the MAPK pathway with ERK inhibitor PD98059 reduced IL-6/sIL-6Rα–mediated endothelial hyperpermeability. ERK activation by the IL-6/sIL-6Rα complex increased endothelial integrity via Src kinase activation and Y685 phosphorylation of VE-cadherin. Selective targeting of IL-6 trans-signaling in vivo reduced ascites formation and enhanced the taxane sensitivity of intraperitoneal human ovarian tumor xenografts in mice. Collectively, our results show that increased levels of sIL-6Rα found in ovarian cancer ascites drive IL-6 trans-signaling on endothelial cells, thereby contributing to cancer progression. Selective blockade of IL-6 trans-signaling may offer a promising therapeutic strategy to improve the management of patients with advanced ovarian cancer. Cancer Res; 71(2); 424–34. ©2010 AACR.
Pharmacokinetic Modeling of Tumor Bioluminescence Implicates Efflux, and Not Influx, as the Bigger Hurdle in Cancer Drug Therapy
Authors: Sim Hoon , Bibee Kristin , Wickline Samuel , Sept David
Published: December 2010

In vivo bioluminescence imaging is a powerful tool for assessing tumor burden and quantifying therapeutic response in xenograft models. However, this technique exhibits significant variability as a consequence of differences in substrate administration, as well as the tumor size, type, and location. Here, we present a novel pharmacokinetic (PK) approach that utilizes bioluminescence image data. The sample data are taken from mice implanted with a melanoma tumor cell line that was transfected to express the firefly (Photinus pyralis) luciferase gene. At 5, 7, and 10 days postimplant, intraperitoneal injections of D-luciferin were given to monitor the uptake into the tumor, and the tumor volume was measured using ultrasound. A multicompartment PK model was used to simultaneously fit all experiments for each mouse. We observed that the rates of luciferin transport in and out of the tumor exhibited a clear dependence on the tumor volume. Also, the rate of tumor influx increased faster than did the efflux, resulting in a shortening of the time to peak-luciferin concentration as the tumor grows. The time of the peak concentration correlated poorly with the tumor volume, but the peak bioluminescence signal and the area under the curve both exhibited a dependence on the tumor surface area. These results agree with Starling's hypothesis relating the higher interstitial fluid pressure in the tumor with flux across the boundary, and suggest that drug transport may depend more strongly on the surface area of the tumor than its volume. These observations provide a quantitative physical rationale for molecular targeting of therapeutics that enhance trapping and overcome the accelerated efflux kinetics. Cancer Res; 71(3); 686–92. ©2010 AACR.
Small Molecule Inhibition of GDC-0449 Refractory Smoothened Mutants and Downstream Mechanisms of Drug Resistance
Authors: Dijkgraaf Gerrit J. P. , Alicke Bruno , Weinmann Lasse , Januario Thomas , West Kristina , Modrusan Zora , Burdick Dan , Goldsmith Richard , Robarge Kirk , Sutherlin Dan , Scales Suzie J. , Gould Stephen E. , Yauch Robert L. , de Sauvage Frederic J.
Published: December 2010

Inappropriate Hedgehog (Hh) signaling has been directly linked to medulloblastoma (MB), a common malignant brain tumor in children. GDC-0449 is an Hh pathway inhibitor (HPI) currently under clinical investigation as an anticancer agent. Treatment of a MB patient with GDC-0449 initially regressed tumors, but this individual ultimately relapsed with a D473H resistance mutation in Smoothened (SMO), the molecular target of GDC-0449. To explore the role of the mutated aspartic acid residue in SMO function, we substituted D473 with every amino acid and found that all functional mutants were resistant to GDC-0449, with positively charged residues conferring potential oncogenic properties. Alanine scan mutagenesis of SMO further identified E518 as a novel prospective mutation site for GDC-0449 resistance. To overcome this form of acquired resistance, we screened a panel of chemically diverse HPIs and identified several antagonists with potent in vitro activity against these GDC-0449–resistant SMO mutants. The bis-amide compound 5 was of particular interest, as it was able to inhibit tumor growth mediated by drug resistant SMO in a murine allograft model of MB. However, focal amplifications of the Hh pathway transcription factor Gli2 and the Hh target gene cyclin D1 (Ccnd1) were observed in two additional resistant models, indicating that resistance may also occur downstream of SMO. Importantly, these HPI resistant MB allografts retained their sensitivity to PI3K inhibition, presenting additional opportunities for the treatment of such tumors. Cancer Res; 71(2); 435–44. ©2010 AACR.
L1-Mediated Colon Cancer Cell Metastasis Does Not Require Changes in EMT and Cancer Stem Cell Markers
Authors: Gavert Nancy , Vivanti Alessia , Hazin John , Brabletz Thomas , Ben-Ze'ev Avri
Published: December 2010

Aberrant activation of Wnt/β-catenin signaling is common in most sporadic and inherited colorectal cancer (CRC) cells leading to elevated β-catenin/TCF transactivation. We previously identified the neural cell adhesion molecule L1 as a target gene of β-catenin/TCF in CRC cells. Forced expression of L1 confers increased cell motility, invasion, and tumorigenesis, and the induction of human CRC cell metastasis to the liver. In human CRC tissue, L1 is exclusively localized at the invasive front of such tumors in a subpopulation of cells displaying nuclear β-catenin. We determined whether L1 expression confers metastatic capacities by inducing an epithelial to mesenchymal transition (EMT) and whether L1 cosegregates with cancer stem cell (CSC) markers. We found that changes in L1 levels do not affect the organization or expression of E-cadherin in cell lines, or in invading CRC tissue cells, and no changes in other epithelial or mesenchymal markers were detected after L1 transfection. The introduction of major EMT regulators (Slug and Twist) into CRC cell lines reduced the levels of E-cadherin and induced fibronectin and vimentin, but unlike L1, Slug and Twist expression was insufficient for conferring metastasis. In CRC cells L1 did not specifically cosegregate with CSC markers including CD133, CD44, and EpCAM. L1-mediated metastasis required NF-κB signaling in cells harboring either high or low levels of endogenous E-cadherin. The results suggest that L1-mediated metastasis of CRC cells does not require changes in EMT and CSC markers and operates by activating NF-κβ signaling. Mol Cancer Res; 9(1); 14–24 ©2010 AACR.
α-Synuclein Levels Are Elevated in Cerebrospinal Fluid following Traumatic Brain Injury in Infants and Children: The Effect of Therapeutic Hypothermia
Authors: Su Erik , Bell Michael J. , Wisniewski Stephen R. , Adelson P. David , Janesko-Feldman Keri L. , Salonia Rosanne , Clark Robert S.B. , Kochanek Patrick M. , Kagan Valerian E. , Bayır Hülya
Published: December 2010

α-Synuclein is one of the most abundant proteins in presynaptic terminals. Normal expression of α-synuclein is essential for neuronal survival and it prevents the initiation of apoptosis in neurons through covalent cross-linking of cytochrome c released from mitochondria. Exocytosis of α-synuclein occurs with neuronal mitochondrial dysfunction, making its detection in cerebrospinal fluid (CSF) of children after severe traumatic brain injury (TBI) a potentially important marker of injury. Experimental therapeutic hypothermia (TH) improves mitochondrial function and attenuates cell death, and therefore may also affect CSF α-synuclein concentrations. We assessed α-synuclein levels in CSF of 47 infants and children with severe TBI using a commercial ELISA for detection of monomeric protein. 23 patients were randomized to TH based on published protocols where cooling (32–33°C) was initiated within 6–24 h, maintained for 48 h, and then followed by slow rewarming. CSF samples were obtained continuously via an intraventricular catheter for 6 days after TBI. Control CSF (n = 9) was sampled from children receiving lumbar puncture for CSF analysis of infection that was proven negative. Associations of initial Glasgow Coma Scale (GCS) score, age, gender, treatment, mechanism of injury and Glasgow Outcome Scale (GOS) score with CSF α-synuclein were compared by multivariate regression analysis. CSF α-synuclein levels were elevated in TBI patients compared to controls (p = 0.0093), with a temporal profile showing an early, approximately 5-fold increase on days 1–3 followed by a delayed, >10-fold increase on days 4–6 versus control. α-Synuclein levels were higher in patients treated with normothermia versus hypothermia (p = 0.0033), in patients aged <4 years versus ≧4 years (p < 0.0001), in females versus males (p = 0.0007), in nonaccidental TBI versus accidental TBI victims (p = 0.0003), and in patients with global versus focal injury on computed tomography of the brain (p = 0.046). Comparisons of CSF α-synuclein levels with initial GCS and GOS scores were not statistically significant. Further studies are needed to evaluate the conformational status of α-synuclein in CSF, and whether TH affects α-synuclein aggregation.
Expression Pattern of Enkephalinergic Neurons in the Developing Spinal Cord Revealed by Preproenkephalin-Green Fluorescent Protein Transgenic Mouse and Its Colocalization with GABA Immunoreactivity
Authors: Huang Jing , Chen Jing , Wang Wen , Wang Ya Yun , Wang Wei , Wei Yan Yan , Shi Ri Yi , Kaneko Takeshi , Li Yun Qing , Wu Sheng Xi
Published: December 2010

To gain better insight into the ontogenic function of enkephalin (ENK) in the spinal cord, it is necessary to have a clear picture of the developing pattern of the ENKergic neurons. To address this question, we used transgenic mice which reveal ENKergic neurons easily by expressing enhanced green fluorescent protein (GFP) under the specific transcriptional control of the preproenkephalin (PPE) gene. GFP-positive neurons first appeared at embryonic day (E) 11.5 in the ventromedial part of the cervical ventral gray matter. At E13, they were mainly present in the intermediate zone. Thereafter, GFP-positive neurons increased progressively in number and extended from ventral to dorsal regions. Quantitative analysis showed that GFP-positive neurons peaked in number at postnatal day (P) 7 at the cervical level. The number of GFP-positive neurons reached a peak at P3 at the lumbar level. At P21, the distribution pattern of GFP immunoreactivity was similar to that in the adult spinal cord. Double-labeling results showed that about one-third of the total γ-aminobutyric acid cell population colocalized with GFP: 34.9 ± 3.5% at E16 and 32.4 ± 3.7% at P3. Double-labeled neurons accounted for nearly half of the GFP-positive neurons: 42.4 ± 2.4% at E16 and 44.1 ± 2.9% at P3. Taken together, the present results suggest that ENKergic neurons develop according to a rostrocaudal and ventrodorsal gradient. These results have broad implications for understanding the functional roles of ENKergic neurotransmission in the developing spinal cord.
The Diagnostic Yield and Safety of Ultrasound-Assisted Transthoracic Biopsy of Mediastinal Masses
Authors: Koegelenberg Coenraad F.N. , Diacon Andreas H. , Irusen Elvis M. , von Groote-Bidlingmaier Florian , Mowlana Abdurasiet , Wright Colleen A. , Louw Mercia , Schubert Pawel T. , Bolliger Chris T.
Published: December 2010

Background: Ultrasound (US)-assisted transthoracic biopsy offers a less invasive alternative to surgical biopsy in the setting of mediastinal masses. Objectives: The aim of this 1-year prospective study was to assess the diagnostic yield and safety of a novel single-session sequential approach of US-assisted transthoracic fine-needle aspirations (TTFNA) with rapid on-site evaluation (ROSE) followed by cutting needle biopsies (CNB) performed by physicians on patients with anterosuperior mediastinal masses. Methods: US-assisted TTFNA with ROSE was performed on 45 consecutive patients (49.5 ± 27.7 years, 24 males), immediately followed by CNB where a provisional diagnosis of epithelial carcinoma or tuberculosis could not be established, provided a safety range could be assured. Results: TTFNA alone was deemed adequate by means of ROSE in 27 (60%) patients. CNB could be performed in 17 of the remaining 18. The on-site diagnosis corresponded to the final diagnosis in 26/45 (57.8%). An accurate cytological diagnosis was made in 33 (73.3%), and was more likely to be diagnostic in epithelial carcinoma and tuberculosis (28/30) than all other pathologies (5/15, p < 0.001). CNB yielded a diagnosis in 15/17 (88.2%). Overall, 42/45 patients were diagnosed by the single-session approach (93.3%). The final diagnoses included 41 neoplasms, with small cell lung cancer (n = 13) the commonest diagnosis. We observed no pneumothorax or major haemorrhage. Conclusions: A single-session sequential approach of US-assisted TTFNA with ROSE followed by CNB, where indicated, has a high diagnostic yield for anterosuperior mediastinal masses, is safe and offers an alternative to surgical biopsy.
Prepregnancy Body Mass Index and Resting Metabolic Rate during Pregnancy
Authors: Melzer Katarina , Schutz Yves , Soehnchen Nina , Othenin Girard Veronique , Martinez de Tejada Begona , Pichard Claude , Irion Olivier , Boulvain Michel , Kayser Bengt
Published: December 2010

Aim: The resting metabolic rate (RMR) varies among pregnant women. The factors responsible for this variability are unknown. This study aimed to assess the influence of the prepregnancy body mass index (BMI) on the RMR during late pregnancy. Methods: RMR, height, weight, and total (TEE) and activity (AEE) energy expenditures were measured in 46 healthy women aged 31 ± 5 years (mean ± SD) with low (<19.8), normal (19.8–26.0), and high (>26.0) prepregnancy BMI at 38.2 ± 1.5 weeks of gestation (tgest) and 40 ± 7 weeks postpartum (tpost) (n = 27). Results: The mean tgest RMR for the low-, normal-, and high-BMI groups was 1,373, 1,807, and 2,191 kcal/day, respectively (p = 0.001). The overall mean tgest RMR was 316 ± 183 kcal/day (21%), higher than the overall mean tpost value and this difference was correlated with gestational weight gain (r = 0.78, p < 0.001). The scaled metabolic rate by allometry (RMR/kilograms0.73) was similar in the low-, normal-, and high-BMI groups, respectively (p = 0.45). Changes in tgest TEE closely paralleled changes in tgest RMR (r = 0.84, p < 0.001). AEE was similar among the BMI groups. Conclusion: The RMR is significantly increased in the third trimester of pregnancy. The absolute gestational RMR is higher in women with high prepregnancy BMI due to increased body weight. The scaled metabolic rate (RMR/kilograms0.73) is similar among the BMI groups of pregnant women.
Predictors of School Victimization: Individual, Familial, and School Factors
Authors: Wynne Susan L. , Joo Hee-Jong
Published: December 2010

Recent deadly school crime incidents have caused great concern regarding school safety. From criminal acts to bullying and verbal abuse, school disorder compromises student safety and the learning environment. Using a series of logistic regression analyses and data from the National Crime Victimization Survey’s School Crime Supplement of 2003, this research seeks to identify a combination of individual, family, and school characteristics that can be used to predict student victimization at school. Results indicate that school victimization can be predicted from knowledge of student academic performance, prior victimization experiences, family characteristics, presence of gangs and drugs in the school, and certainty of punishment for school rule breaking. Findings support the need to adopt a multifaceted approach to provide a safer school environment, reduce juvenile offending, and facilitate learning.
Does Prison-Based Adult Basic Education Improve Postrelease Outcomes for Male Prisoners in Florida?
Authors: Cho Rosa Minhyo , Tyler John H.
Published: December 2010

The authors use administrative data from Florida to determine the extent to which prison-based adult basic education (ABE) improves inmate’s postrelease labor market outcomes, such as earnings and employment. Using two nonexperimental comparison groups, the authors find evidence that ABE participation is associated with higher postrelease earnings and employment rates, especially for minorities. The authors find that the relationship is the largest for ABE participants who had uninterrupted ABE instruction and for those who received other education services. However, the results do not find any positive effects of ABE participation on reducing recidivism.
Peer Crowds in Singapore
Authors: Sim Tick Ngee , Yeo Geck Hong
Published: December 2010

This study examined peer crowds in the Singapore context. A total of 598 Secondary 1 and 2 adolescents were asked to identify the crowds they perceived to exist in their schools and to describe these crowds’ characteristics. The adolescents had no difficulty identifying crowds, generating a total of 1,534 crowds. Among the crowds identified, seven major crowds (nerd, gangster, athlete, joker, computer geek, ordinary, loner) emerged, some perceived as more similar to each other and others as almost direct opposites of one another. These crowds showed both similarities with and differences from typical American crowds. Results also suggest that crowds in the Singapore context reflect more of adolescents’ increased cognitive abilities than challenges arising from negotiating a larger peer world.
Online Pauses and Silence: Chronemic Expectancy Violations in Written Computer-Mediated Communication
Authors: Kalman Yoram M. , Rafaeli Sheizaf
Published: December 2010

This study examines e-mail response latency as an expectancy violation and explores its impact. Managers evaluate job candidates who varied in their response latency to an e-mail (1 day, 2 weeks, and silence for more than a month) and in their reward valence. As predicted by expectancy violations theory, candidate reward valence moderates the effect of response latency on variables such as applicant evaluation, credibility, and attractiveness. A norms-based definition of online silence is presented, and the influential and complex role of response latency and of online silence as nonverbal chronemic cues in written CMC is elaborated.
Continuing an Alternative View of Public Administration
Authors: McGuire John Thomas
Published: December 2010

This article argues that from 1918 through 1927 prominent social scientist and reformer Mary van Kleeck (1883-1972) pursued an alternative theory of public administration enunciated by women reformers in the early 1900s. van Kleeck continued to support the theory through her idea of industrial citizenship, through which labor and capital would work as equals. Two new forums for her idea—the International Taylor Society and Herbert Hoover’s Special Committee on Business Cycles—did not prove satisfactory, so van Kleeck helped promote the successful passage of a 48-hr bill for working women in New York by 1927 through social justice feminism.
Pathology of GM2 Gangliosidosis in Jacob Sheep
Authors: Porter B. F. , Lewis B. C. , Edwards J. F. , Alroy J. , Zeng B. J. , Torres P. A. , Bretzlaff K. N. , Kolodny E. H.
Published: December 2010

The GM2 gangliosidoses are a group of lysosomal storage diseases caused by defects in the genes coding for the enzyme hexosaminidase or the GM2 activator protein. Four Jacob sheep from the same farm were examined over a 3-year period for a progressive neurologic disease. Two lambs were 6-month-old intact males and 2 were 8-month-old females. Clinical findings included ataxia in all 4 limbs, proprioceptive deficits, and cortical blindness. At necropsy, the nervous system appeared grossly normal. Histologically, most neurons within the brain, spinal cord, and peripheral ganglia were enlarged, and the cytoplasm was distended by foamy to granular material that stained positively with Luxol fast blue and Sudan black B stains. Other neuropathologic findings included widespread astrocytosis, microgliosis, and scattered spheroids. Electron microscopy revealed membranous cytoplasmic bodies within the cytoplasm of neurons. Biochemical and molecular genetic studies confirmed the diagnosis of GM2 gangliosidosis. This form of GM2 gangliosidosis in Jacob sheep is very similar to human Tay-Sachs disease and is potentially a useful animal model.
Prognostic Evaluation of Ki67 Threshold Value in Canine Oral Melanoma
Authors: Bergin I. L. , Smedley R. C. , Esplin D. G. , Spangler W. L. , Kiupel M.
Published: December 2010

Oral melanoma is a common canine cancer with a historically poor prognosis. Recent evidence suggests that a subset of cases may have a more favorable outcome, defined as long-term survival in the absence of intervention other than initial surgery. Traditional histological parameters have had prognostic significance in some studies but not in others, potentially due to interobserver variation. We evaluated the prognostic utility of Ki67 immunohistochemistry in a group of 79 canine oral melanomas using a technique easily applied in a veterinary diagnostic laboratory. A threshold Ki67 value of >19.5 had a sensitivity and specificity of 87.1% and 85.4%, respectively, at predicting death or euthanasia due to melanoma by 1 year postdiagnosis. Threshold values for classical histological parameters were also identified for most cases and were >4 (>30%; sensitivity = 83.9%, specificity = 86.0%) for the nuclear atypia score and >4/10 hpfs (sensitivity = 90.3%, specificity = 84.4%) for the mitotic index. In this study, the percentages correctly classified with respect to death by 1 year postdiagnosis were comparable for Ki67 (86.1%, 68/79), the nuclear atypia score (86.3%, 63/73), and the mitotic index (86.8%, 66/76). High pigmentation (>50%) had a high negative predictive value of 90.9% (18/20), but overall, only 61.0% (47/77) of cases could be correctly classified by this parameter. Based on these results, we recommend a panel of prognostic parameters, including the nuclear atypia score, the mitotic index, Ki67, and pigmentation quantification to more accurately predict the likely outcome of canine oral melanomas.
Poetic Justice in Obadiah
Authors: Anderson Bradford A.
Published: December 2010

The book of Obadiah has long been recognized for its message of lex talionis. This is not, however, simply a theme of this short book. Rather, the present article argues that the idea that Edom’s deeds will return upon its head is embedded in the language of the book itself. This ‘poetic justice’ occurs in a series of word plays and allusions that can be traced throughout Obadiah. The word plays juxtapose the identities and futures of Edom and Judah, and allude in various ways to Edom’s coming reckoning. A recognition of these dimensions of the Hebrew text may help the reader more fully appreciate the rhetorical force and literary artistry of this shortest of prophetic books.
Housing Patterns of Homeless People: The Ecology of the Street in the Era of Urban Renewal
Authors: Wasserman Jason Adam , Clair Jeffrey Michael
Published: December 2010

In this article, the authors examine the political and economic community dynamics of the street homeless as well as other groups involved in conflicts regarding the process of urban renewal. Since postwar suburban flight, homeless people have lived largely in the shadows of vacated city centers. But “not-in-my-backyard” (NIMBY) battles over the homeless have become increasingly common, especially as the influx of comfortably housed residents bring suburban expectations to urban centers, generating conflicts that affect homeless urban camp communities. Drawing on four years of ethnographic data, the authors describe social conflicts revolving around homelessness and urban renewal. Moreover, through examining the patterns of economy and polity among sectors with different economic positions in the city, the authors illustrate how “problematic” groups of people, such as the homeless, are not antithetical to community. Instead, they are key stakeholders in urban communities with goals, concerns, and desired boundaries similar to those who “legitimately” live downtown.