bluuebunny/crossref_metadata_2025 huggingface dataset:
Poly[( N-Acylimino)ethylene] Derivatives for Advanced Materials
Authors: David Geta , Simionescu Bogdan C.
Published: September 2009

New segmented polyurethanes containing soft and hard segments of different polarity and hydrophilicity, based on 4,4′-methylenebis-(cyclohexyl isocyanate, 4,4′-methylenebis-(phenyl isocyanate) and poly(tetramethylene oxide) or poly(ethylene oxide) were prepared including poly[( N-acylimino) ethylene] sequences as a chain extender. They were comparatively characterized by spectral, thermal and mechanical techniques. Some preliminary investigations on their nanocomposites with montmorillonite as an inorganic component are presented.
High Temperature VARTM of Phenylethynyl Terminated Imides
Authors: Ghose Sayata , Watson Kent A. , Cano Roberto J. , Britton Sean M. , Jensen Brian J. , Connell John W. , Herring Helen M. , Lineberry Quentin J.
Published: September 2009

Depending on the part type and quantity, fabrication of composite structures using vacuum-assisted resin transfer molding (VARTM) can be more affordable than conventional autoclave techniques. Recent efforts have focused on adapting VARTM for the fabrication of high temperature composites. Due to their low melt viscosity and long melt stability, certain phenylethynyl terminated imides (PETI) can be processed into composites using high temperature VARTM (HT-VARTM). However, one of the disadvantages of the current HT-VARTM resin systems has been the high porosity of the resultant composites. For aerospace applications, the desired void fraction of less than 2% has not yet been achieved. In the current study, two PETI resins, LaRC PETI-330 and LaRC PETI-8 have been used to make test specimens using HT-VARTM. The resins were infused into ten layers of IM7-6K carbon fiber 5-harness satin fabric at 260 or 280 °C and cured at temperature up to 371 °C. Initial runs yielded composites with high void content, typically greater than 7% by weight. A thermogravimetric-mass spectroscopic study was conducted to determine the source of volatiles leading to high porosity. It was determined that under the thermal cycle used for laminate fabrication, the phenylethynyl endcap was undergoing degradation leading to volatile evolution. This finding was unexpected as high quality composite laminates have been fabricated under higher pressures using these resin systems. The amount of weight loss experienced during the thermal cycle was only about 1% by weight, but this led to a significant amount of volatiles in a closed system. By modifying the thermal cycle used in laminate fabrication, the void content was significantly reduced (typically ∼ 3% or less). The results of this work are presented herein.
Dynamic Mechanical Analysis of Polyurethane-Epoxy Interpenetrating Polymer Networks
Authors: Cristea Mariana , Ibanescu Sorin , Cascaval Constantin N. , Rosu Dan
Published: September 2009

A series of semi-interpenetrated polymer networks based on bisphenol A epoxy resin and polyurethane was synthesized by sequential procedure. The molecular dynamics of polyurethane incorporated in the resin network with increasing amounts of resin was followed by dynamic mechanical analysis. All phenomena that concur in the material are evaluated by cross-examination of the storage modulus ( E'), loss modulus ( E'') and loss factor (tan δ) variation with temperature. Complex aspects were elucidated in consecutive heating-cooling-heating cycles and by calculating the apparent activation energy of relaxations in multiplex experiments.
They’re stealing our lifeblood
Authors: Hinton Les
Published: September 2009

The first of two articles, from the perspectives of management and editorial, examining how newspapers must develop in order to survive
Holistic Personality Development through Education
Authors: Bhatta C. Panduranga
Published: September 2009

Ancient India recognized the supreme value of education in human life. The ancient thinkers felt that a healthy society was not possible without educated individuals. They framed an educational scheme carefully and wisely aiming at the harmonious development of the mind and body of students. What they framed was a very liberal, all-round education of a very high standard, calculated to prepare the students for a useful life in enjoying all aspects of life. This is essentially a universally applicable educational framework highlighting the purpose of human life and interconnectedness at all levels of existence as a basis of human values. Insights from ancient Indian educational system are of great help in facilitating the production of a creative, ethical and a learning mind, which will concern itself not only with greater ‘progress’, but primarily or more importantly with the inner transformation of the human consciousness.
Teacher-student negotiations and its relation to physical education students’ motivational processes: An approach based on self-determination theory
Authors: Dupont Jean-Philippe , Carlier Ghislain , Gérard Philippe , Delens Cécile
Published: September 2009

The aim of this study is to test a model of motivation based on self-determination theory (Deci and Ryan, 2002) and which explores the place of ‘teacher—student’ negotiation. Cross-sectional data were gathered from 549 secondary school students (317 male, 232 female) who answered a questionnaire which included measurements of perceived negotiation, of the satisfaction of needs, of motivation, of perceived enjoyment, of the perception of having learned, of the intention to practise a physical sporting activity outside school. Structural equation analysis has shown that the students who perceived integrative negotiation experienced higher levels of autonomy and relatedness. Autonomy and competence determined self-determined motivation, which in turn positively predicted consequences. The results support self-determination theory and support its application in the context of school physical education.
The role of transfer in games teaching: Implications for the development of the sports curriculum
Authors: García López Luis M. , Contreras Jordán Onofre R. , Penney Dawn , Chandler Tim
Published: September 2009

The purpose of this paper is to critically review and evaluate the significance for curriculum planning in PE of studies focused on transfer of tactical knowledge. The conceptual foundation and focus of research that has investigated transfer in learning across games and sports is explored. Selected studies are systematically analysed in relation to the particular dimension of transfer examined and evidence generated to support a case for curriculum planning to be grounded upon transfer. On the basis of findings to date, it is argued that curriculum planning in PE should foreground the principle of transfer. Recommendations are made in relation to further research in this field.
Sport or school? Dreams and dilemmas for talented young Danish football players
Authors: Christensen Mette Krogh , Sørensen Jan Kahr
Published: September 2009

Today’s young semi-professional football players are expected to continue their education while honing their talents as footballers. This means they must balance the contradictory demands that come from their education establishments and their football clubs. The present study explores how young Danish male football talents experience and describe these different forces in their life space (Lewin, 1951). Data for the study are gathered using a narrative and qualitative approach, including four focus group interviews with 25 footballers aged 15—19, followed by individual qualitative interviews with eight of the footballers. The elite football culture has an almost magnetic attraction for the young footballers in the study. Even if the espoused value (Schein, 1990) of a good set of academic qualifications does not entirely measure up to this, the insistence from the outside world on the importance of completing one’s education is manifest and associated with significant personal concerns, lower examinations results, stress, drop-out and mental breakdown.
Evaluating 1 Thessalonians: An Outline of Holistic Approaches to 1 Thessalonians in the Last 25 Years
Authors: Adams Sean A.
Published: September 2009

This article focuses on works that have been produced within the last 25 years which attempt to provide a holistic approach to the understanding and interpretation of 1 Thessalonians, such as: epistolary, rhetorical, theological, linguistic, and various combinations of the above. Proponents of each view and their perspectives will be outlined along with their structural division of the text. This article attempts to provide a general map of particular approaches to 1 Thessalonians, but also provides a brief outline of some of the critiques and weaknesses of the different methodologies. This article concludes with a brief statement regarding the trajectory of current studies.
Orality and the Gospels: A Survey of Recent Research
Authors: Iverson Kelly R.
Published: September 2009

In the last thirty years there have been significant developments in the application of orality studies to the Gospels. The objective of this article is to provide an overview of the field through a survey of its leading proponents, including Werner Kelber, Joanna Dewey, Paul Achtemeier, Peter Botha, Richard Horsley and Jonathan Draper, Kenneth Bailey, James Dunn, Richard Bauckham, David Rhoads and Whitney Shiner. The essay begins with a discussion of several foundational studies, before turning specifically to the reconception of orality and the implication of this research for the Gospels. The study concludes that, while an appreciation of orality has made inroads into certain segments of Gospels research, it remains a neglected and underexploited dimension of NT interpretation.
Greater Activation of Secondary Motor Areas Is Related to Less Arm Use After Stroke
Authors: Kokotilo Kristen J. , Eng Janice J. , McKeown Martin J. , Boyd Lara A.
Published: September 2009

Background. Past studies have identified reorganization of brain activity in relation to motor outcome through standardized laboratory measures, which are quantifiable surrogates for arm use in real life. In contrast, accelerometers can provide a real-life estimate of arm and hand usage. Methods. Ten persons with chronic, subcortical stroke and 10 healthy controls of similar age performed a squeeze motor task at 40% maximum voluntary contraction during functional magnetic resonance imaging (fMRI). Use of the upper extremity was quantified over 3 consecutive days using wrist accelerometers. Correlations were performed between arm use and peak percent signal change (PSC) during grasp force production in 6 regions of interest (ROIs): bilateral primary motor cortex (M1), supplementary motor area (SMA), and premotor cortex (PM). Results. Results demonstrate that in healthy controls, PSC across all ROIs did not show a relationship between arm use and brain activation during force production. In contrast, after stroke, contralesional PM and M1 showed a significant ( P ≤ .05) correlation between increasing activation and decreasing paretic arm use, whereas ipsilesional PM showed a significant correlation ( P ≤ .05) between increasing activation and decreasing nonparetic arm use. Conclusions. The results of this pilot study demonstrate a negative relationship between brain activation and actual arm use after stroke. Larger studies using accelerometers that can detect amount and types of movement may offer further insight into brain reorganization and rehabilitation interventions.
The automation of clinical trial serious adverse event reporting workflow
Authors: London Jack W , Smalley Karl J , Conner Kyle , Smith J Bruce
Published: September 2009

Background The reporting of serious adverse events is a requirement when conducting a clinical trial involving human subjects, necessary for the protection of the participants. The reporting process is a multi-step procedure, involving a number of individuals from initiation to final review, and must be completed in a timely fashion.

Purpose The purpose of this project was to automate the adverse event reporting process, replacing paper-based processes with computer-based processes, so that personnel effort and time required for serious adverse event reporting was reduced, and the monitoring of reporting performance and adverse event characteristics was facilitated.

Methods Use case analysis was employed to understand the reporting workflow and generate software requirements. The automation of the workflow was then implemented, employing computer databases, web-based forms, electronic signatures, and email communication.

Results In the initial year (2007) of full deployment, 588 SAE reports were processed by the automated system, eSAEyTM. The median time from initiation to Principal Investigator electronic signature was <2 days (mean 7 ± 0.7 days). This was a significant reduction from the prior paper-based system, which had a median time for signature of 24 days (mean of 45 ± 5.7 days). With eSAEyTM, reports on adverse event characteristics (type, grade, etc.) were easily obtained and had consistent values based on standard terminologies.

Limitation The automated system described was designed specifically for the workflow at Thomas Jefferson University. While the methodology for system design, and the system requirements derived from common clinical trials adverse reporting procedures are applicable in general, specific workflow details may not be relevant at other institutions.

Conclusion The system facilitated analysis of individual investigator reporting performance, as well as the aggregation and analysis of the nature of reported adverse events. Clinical Trials 2009; 6: 446—454. http://ctj.sagepub.com
Special Segment: Soft Tissue Matrices—One Form of Acellular Human Dermis for Use in Tendon and Ligament Repairs in the Foot and Ankle
Authors: Blum Barbara E. , Burgess Ann V.
Published: September 2009

Trauma to tendons and ligaments represents a significant part of orthopaedic and podiatric injuries. To improve the outcome of repair, complex or chronic injuries may require reinforcement of the primary repair with a graft. Biologic grafts currently available provide different handling, strength, and biological responses. One of the currently available grafts, an acellular human dermal membrane with specific properties, has been successfully used in the augmentation of tendon and ligament repairs for more than 6 years.
A protective role for early oral exposures in the etiology of young adult Hodgkin lymphoma
Authors: Cozen Wendy , Hamilton Ann S. , Zhao Peng , Salam Muhammad T. , Deapen Dennis M. , Nathwani Bharat N. , Weiss Lawrence M. , Mack Thomas M.
Published: September 2009

The pattern of adolescent/young adult Hodgkin lymphoma (YAHL) suggests causation by a relatively late infection with a common childhood virus, but no causal virus has been found. Susceptibility is heritable and linked to lower interleukin 12 (IL12) levels, which can also result from fewer fecal-oral microbial exposures early in life. We studied twin pairs discordant for YAHL to examine exposures capable of altering the IL12 response and T-helper type 1 (Th1)–Th2 balance. One hundred eighty-eight YAHL-discordant twin pairs from the International Twin Study returned questionnaires (70% response). Exposure history of YAHL case-twins was compared with that of their unaffected control-twins using conditional logistic regression for matched pairs to calculate odds ratios (ORs). Behaviors likely to produce oral exposure to microbes conveyed decreases in risk (univariable OR range = 0.2-0.5, P = .003-.11). Significant adjusted ORs were seen for appendectomy (OR = 4.3, P = .001), eczema (OR = 4.2, P = .025), smoking (OR = 2.2, P = .054), and relatively more frequent behaviors associated with oral exposures (OR = 0.1; P = .004). Kappa statistics for intrapair agreement were higher than 0.8 for each significant finding. Our observations support a protective role for increased early oral exposure to the microbiome, suggesting that factors associated with increased Th2 and decreased Th1 cytokines are etiologically relevant to YAHL.
A novel peptide (GX1) homing to gastric cancer vasculature inhibits angiogenesis and cooperates with TNF alpha in anti-tumor therapy
Authors: Chen Bei , Cao Shanshan , Zhang Yingqi , Wang Xin , Liu Jie , Hui Xiaoli , Wan Yi , Du Wenqi , Wang Li , Wu Kaichun , Fan Daiming
Published: September 2009

Background

The discovery of the importance of angiogenesis in tumor growth has emphasized the need to find specific vascular targets for tumor-targeted therapies. Previously, using phage display technology, we identified the peptide GX1 as having the ability to target the gastric cancer vasculature. The present study investigated the bioactivities of GX1, as well as its potential ability to cooperate with recombinant mutant human tumor necrosis factor alpha (rmhTNFα), in gastric cancer therapy.

Results

Tetrazolium salt (MTT) assay showed that GX1 could inhibit cell proliferation of both human umbilical vein endothelial cells (HUVEC) (44%) and HUVEC with tumor endothelium characteristics, generated by culturing in tumor-conditioned medium (co-HUVEC) (62%). Flow-cytometry (FCM) and western blot assays showed that GX1 increased the rate of apoptosis from 11% to 31% (p < 0.01) by up-regulating caspase 3 expression level. A chorioallantoic membrane assay indicated that GX1 could suppress neovascularization in vivo, with the microvessel count decreasing from 21 to 11 (p < 0.05). When GX1 was fused to rmhTNFα, GX1-rmhTNFα selectively concentrated in the gastric cancer vasculature, as shown by enzyme-linked immunosorbent assay, immunofluorescence and emission-computed tomography. In vitro MTT and FCM assays showed that, compared to rmhTNFα alone, GX1-rmhTNFα was more effective at suppressing co-HUVEC proliferation (45% vs. 61%, p < 0.05) and inducing apoptosis (11% vs. 23%, p < 0.05). In a tumor formation test, GX1-rmhTNFα more effectively inhibited tumor growth than rmhTNFα (tumor volume: 271 mm3 vs. 134 mm3, p < 0.05), with less systemic toxicity as measured by body weight (20.57 g vs. 19.30 g, p < 0.05). These therapeutic effects may be mediated by selectively enhanced tumor vascular permeability, as indicated by Evan's blue assay.

Conclusion

GX1 had both homing activity and the ability to inhibit vascular endothelial cell proliferation in vitro and neovascularization in vivo. Furthermore, when GX1 was conjugated to rmhTNFα, the fusion protein was selectively delivered to targeted tumor sites, significantly improving the anti-tumor activity of rmhTNFα and decreasing systemic toxicity. These results demonstrate the potential of GX1 as a homing peptide in vascular targeted therapy for gastric cancer.
Reciprocal regulation of microRNA and mRNA profiles in neuronal development and synapse formation
Authors: Manakov Sergei A , Grant Seth GN , Enright Anton J
Published: September 2009

Background

Synapse formation and the development of neural networks are known to be controlled by a coordinated program of mRNA synthesis. microRNAs are now recognized to be important regulators of mRNA translation and stability in a wide variety of organisms. While specific microRNAs are known to be involved in neural development, the extent to which global microRNA and mRNA profiles are coordinately regulated in neural development is unknown.

Results

We examined mouse primary neuronal cultures, analyzing microRNA and mRNA expression. Three main developmental patterns of microRNA expression were observed: steady-state levels, up-regulated and down-regulated. Co-expressed microRNAs were found to have related target recognition sites and to be encoded in distinct genomic locations. A number of 43 differentially expressed miRNAs were located in five genomic clusters. Their predicted mRNA targets show reciprocal levels of expression. We identified a set of reciprocally expressed microRNAs that target mRNAs encoding postsynaptic density proteins and high-level steady-state microRNAs that target non-neuronal low-level expressed mRNAs.

Conclusion

We characterized hundreds of miRNAs in neuronal culture development and identified three major modes of miRNA expression. We predict these miRNAs to regulate reciprocally expressed protein coding genes, including many genes involved in synaptogenesis. The identification of miRNAs that target mRNAs during synaptogenesis indicates a new level of regulation of the synapse.
ZifBASE: a database of zinc finger proteins and associated resources
Authors: Jayakanthan Mannu , Muthukumaran Jayaraman , Chandrasekar Sanniyasi , Chawla Konika , Punetha Ankita , Sundar Durai
Published: September 2009

Background

Information on the occurrence of zinc finger protein motifs in genomes is crucial to the developing field of molecular genome engineering. The knowledge of their target DNA-binding sequences is vital to develop chimeric proteins for targeted genome engineering and site-specific gene correction. There is a need to develop a computational resource of zinc finger proteins (ZFP) to identify the potential binding sites and its location, which reduce the time ofin vivotask, and overcome the difficulties in selecting the specific type of zinc finger protein and the target site in the DNA sequence.

Description

ZifBASE provides an extensive collection of various natural and engineered ZFP. It uses standard names and a genetic and structural classification scheme to present data retrieved from UniProtKB, GenBank, Protein Data Bank, ModBase, Protein Model Portal and the literature. It also incorporates specialized features of ZFP including finger sequences and positions, number of fingers, physiochemical properties, classes, framework, PubMed citations with links to experimental structures (PDB, if available) and modeled structures of natural zinc finger proteins. ZifBASE provides information on zinc finger proteins (both natural and engineered ones), the number of finger units in each of the zinc finger proteins (with multiple fingers), the synergy between the adjacent fingers and their positions. Additionally, it gives the individual finger sequence and their target DNA site to which it binds for better and clear understanding on the interactions of adjacent fingers. The current version of ZifBASE contains 139 entries of which 89 are engineered ZFPs, containing 3-7F totaling to 296 fingers. There are 50 natural zinc finger protein entries ranging from 2-13F, totaling to 307 fingers. It has sequences and structures from literature, Protein Data Bank, ModBase and Protein Model Portal. The interface is cross linked to other public databases like UniprotKB, PDB, ModBase and Protein Model Portal and PubMed for making it more informative.

Conclusion

A database is established to maintain the information of the sequence features, including the class, framework, number of fingers, residues, position, recognition site and physio-chemical properties (molecular weight, isoelectric point) of both natural and engineered zinc finger proteins and dissociation constant of few. ZifBASE can provide more effective and efficient way of accessing the zinc finger protein sequences and their target binding sites with the links to their three-dimensional structures. All the data and functions are available at the advanced web-based search interfacehttp://web.iitd.ac.in/~sundar/zifbase.
Hepatitis B virus: molecular genotypes and HBeAg serological status among HBV-infected patients in the southeast of Brazil
Authors: Tonetto Priscila A , Gonçales Neiva SL , Fais Viviane C , Vigani Aline G , Gonçales Eduardo SL , Feltrin Adriana , Gonçales Fernando L
Published: September 2009

Background

Knowledge of HBV genotype is very important for clinical treatment. Studies have suggested possible pathogenic and therapeutic differences among HBV genotypes. The aim of this study was to determine HBV subtypes and genotypes in HBV-infected patients in our region (southeast Brazil) and to correlate results with clinical and histopathological data.

Methods

One hundred and thirty-nine HBsAg-positive patients were included in the study. All patients were anti-HCV and anti-HIV negative (64% male; mean age 42 ± 14.5 years; range 7-80 years; 84% Caucasian) and were followed up at the University Hospital. A method for genotyping and subtyping HBV by partial HBsAg gene sequencing with primers common to all known genotypes was used. The viral load was measured by Amplicor Monitor assay (Roche).

Results

HBV genotype A was the most prevalent (55%), while genotypes C, D and F were found in 3%, 38% and 4% of HBV-infected patients, respectively. Among the patients infected by genotype A, 18.3% (14/76) were African descendents and, among the patients infected by genotype D, 11.3% (6/53) were also African descendents. In the four patients infected with genotype C, 2 were Asian descendents and 2 were Caucasians. All (7) genotype F infected patients were Caucasians. Seventy percent of our HBsAg-positive patients were HBeAg negative (62% genotypes A; 26.2% D; 7.1% C and 4.7%F). The viral load of HBV-DNA was about 5 times higher in HBeAg-positive than in HBeAg-negative patients. About 40% of these patients had alanine aminotransferase of up to 1.5 times the normal level. The mean stage of fibrosis in genotype A patients (2.8) was significantly higher than the mean stage of fibrosis in genotype D patients (2.0) (P = 0.0179).

Conclusion

The genotypes encountered in our HBV-infected patients were apparently a consequence of the types of immigration that occurred in our region, where European and African descendents predominate. The HBeAg-negative status predominated, possibly due to the length of time of infection. The viral load in HBeAg-positive patients was higher than in HBeAg-negative individuals. The fibrosis grade in genotype A-infected patients was more advanced than genotype D-infected patients.
Participation of ezrin in bacterial uptake by trophoblast giant cells
Authors: Watanabe Kenta , Tachibana Masato , Kim Suk , Watarai Masahisa
Published: September 2009

Background

Trophoblast giant (TG) cells are involved in systematic removal of bacterial pathogens from the maternal-fetal interface of the placenta. In particular, TG cells have the ability to take up extracellular antigens by active phagocytosis induced by interferon-gamma (IFN-gamma). We previously reported that heat shock cognate protein 70 (Hsc70) present on the surface of TG cells mediated the uptake of Brucella abortus. However, the mechanism of bacterial uptake by TG cells is not completely understood. Here we identified ezrin, a member of ezrin-radixin-moesin (ERM) protein family, as a molecule associated with Hsc70.

Methods

Mouse TG cells were employed in all experiments, and B. abortus was used as the bacterial antigen. Confirmation of the binding capacity of ERM protein was assessed by pull-down assay and ELISA using recombinant Hsc70 and ERM proteins. Ezrin was depleted using siRNA and the depletion examined by immunoblotting or immunofluorescence staining.

Results

The expression level of ezrin was higher in TG cells than in trophoblast stem (TS) cells, and ezrin knockdown TG cells showed a reduction in bacterial uptake ability. Although tyrosine phosphorylation of ezrin was not related to bacterial uptake activity, localization of Hsc70 on the membrane was affected by the depletion of ezrin in TG cells.

Conclusion

Ezrin associates with Hsc70 that locates on the membrane of TG cells and participates in the bacterial uptake by TG cells.
High throughput evaluation of gamma-H2AX
Authors: Avondoglio Dane , Scott Tamalee , Kil Whoon Jong , Sproull Mary , Tofilon Philip J , Camphausen Kevin
Published: September 2009

The DNA double-strand break (DSB) is the primary lethal lesion after therapeutic radiation. Thus, the development of assays to detect and to quantitate these lesions could have broad preclinical and clinical impact. Phosphorylation of histone H2AX to form γ-H2AX is a known marker for irradiation-induced DNA DSBs. However, the first generation assay involves the use of immunofluorescent staining of γ-H2AX foci. This assay is time consuming, operator dependent and is not scalable for high throughput assay development. Thus, we sought to develop a new assay using a high throughput electrochemiluminescent platform from Mesoscale Discovery Systems to quantify γ-H2AX levels. The results show that our assay utilizes significantly less time and labor, has greater intra-assay reproducibility and has a greater dynamic range of γ-H2AX versus irradiation dose.
Metabolism as means for hypoxia adaptation: metabolic profiling and flux balance analysis
Authors: Feala Jacob D , Coquin Laurence , Zhou Dan , Haddad Gabriel G , Paternostro Giovanni , McCulloch Andrew D
Published: September 2009

Background

Cellular hypoxia is a component of many diseases, but mechanisms of global hypoxic adaptation and resistance are not completely understood. Previously, a population ofDrosophilaflies was experimentally selected over several generations to survive a chronically hypoxic environment. NMR-based metabolomics, combined with flux-balance simulations of genome-scale metabolic networks, can generate specific hypotheses for global reaction fluxes within the cell. We applied these techniques to compare metabolic activity during acute hypoxia in muscle tissue of adapted versus "naïve" control flies.

Results

Metabolic profiles were gathered for adapted and control flies after exposure to acute hypoxia using1H NMR spectroscopy. Principal Component Analysis suggested that the adapted flies are tuned to survive a specific oxygen level. Adapted flies better tolerate acute hypoxic stress, and we explored the mechanisms of this tolerance using a flux-balance model of central metabolism. In the model, adapted flies produced more ATP per glucose and created fewer protons than control flies, had lower pyruvate carboxylase flux, and had greater usage of Complex I over Complex II.

Conclusion

We suggest a network-level hypothesis of metabolic regulation in hypoxia-adapted flies, in which lower baseline rates of biosynthesis in adapted flies draws less anaplerotic flux, resulting in lower rates of glycolysis, less acidosis, and more efficient use of substrate during acute hypoxic stress. In addition we suggest new specific hypothesis, which were found to be consistent with existing data.
Loss of imprinting of insulin-like growth factor 2 is associated with increased risk of lymph node metastasis and gastric corpus cancer
Authors: Lu Yang , Lu Ping , Zhu Zhi , Xu Huimian , Zhu Xike
Published: September 2009

Background

The aim of this study was to determine the clinicopathological features of gastric cancers with loss of imprinting (LOI) of LIT1. Insulin-like growth factor 2 (IGF2) and H19 in Chinese patients.

Methods

DNA and RNA from tumours were amplified and then digested with RsaI, ApaI and HinfI, and RsaI respectively to determine the LOI status. The demographic and clinicopathological characteristics in LOI positive and LOI negative patients were compared and tested with Statistical analysis.

Results

Of the 89 patients enrolled for analysis, 22, 40 and 35 were heterozygous and thus informative for LIT1, IGF2 and H19 LOI analyses respectively. The positive rate of LIT1, IGF2 and H19 LOI of gastric cancer tissues were 54.6% (12/22), 45% (18/40) and 8.6% (3/32) in Chinese patients. Gastric corpus cancer (8/10, 80%) were more likely to have LOI of IGF2 in tumours than antrum cancers (10/30, 33.3%){odds ratio (OR) = 8, 95% confidence intervals (CI) = 1.425-44.920, p = 0.018)}. LOI of IGF2 in tumours was also associated with the lymph node metastasis (LNM) (OR = 4.5, 95% CI = 1.084-18.689, p = 0.038).

Conclusion

IGF2 LOI is present in high frequency in Chinese gastric cancer patients, especially those with gastric corpus cancer.
Mining novel biomarkers for prognosis of gastric cancer with serum proteomics
Authors: Qiu Fu-Ming , Yu Jie-Kai , Chen Yi-Ding , Jin Qi-Feng , Sui Mei-Hua , Huang Jian
Published: September 2009

Background

Although gastric caner (GC) remains the second cause of cancer-related death, useful biomarkers for prognosis are still unavailable. We present here the attempt of mining novel biomarkers for GC prognosis by using serum proteomics.

Methods

Sera from 43 GC patients and 41 controls with gastritis as Group 1 and 11 GC patients as Group 2 was successively detected by Surface Enhanced Laser Desorption/ionization Time of Flight Mass Spectrometry (SELDI-TOF-MS) with Q10 chip. Peaks were acquired by Ciphergen ProteinChip Software 3.2.0 and analyzed by Zhejiang University-ProteinChip Data Analysis System (ZJU-PDAS). CEA level were evaluated by chemiluminescence immunoassay.

Results

After median follow-up periods of 33 months, Group 1 with 4 GC patients lost was divided into 20 good-prognosis GC patients (overall survival more than 24 months) and 19 poor-prognosis GC patients (no more than 24 months). The established prognosis pattern consisted of 5 novel prognosis biomarkers with 84.2% sensitivity and 85.0% specificity, which were significantly higher than those of carcinoembryonic antigen (CEA) and TNM stage. We also tested prognosis pattern blindly in Group 2 with 66.7% sensitivity and 80.0% specificity. Moreover, we found that 4474-Da peak elevated significantly in GC and was associated with advanced stage (III+IV) and short survival (p < 0.03).

Conclusion

We have identified a number of novel biomarkers for prognosis prediction of GC by using SELDI-TOF-MS combined with sophisticated bioinformatics. Particularly, elevated expression of 4474-Da peak showed very promising to be developed into a novel biomarker associated with biologically aggressive features of GC.
High Prevalence of Hepatitis B Virus Markers in Romanian Adolescents With Human Immunodeficiency Virus Infection
Authors: Ruta Simona Maria , Matusa Rodica Floarea , Sultana Camelia , Manolescu Loredana , Kozinetz Claudia A , Kline Mark W , Cernescu Costin
Published: September 2009

Background

We evaluated the frequency of hepatitis coinfection in Romanian adolescents who were diagnosed with human immunodeficiency virus (HIV) infection prior to 1995.

Methods

One hundred sixty‐one adolescents (13–18 years of age) with symptomatic HIV infection, but without signs of hepatic dysfunction, and 356 age‐matched, HIV‐uninfected controls underwent laboratory testing for markers of parenterally acquired hepatitis virus infection.

Results

Seventy‐eight percent of HIV‐infected adolescents had markers of past or present hepatitis B virus (HBV) infection, as compared with 32% of controls (P = .0001). The prevalence of HBV replicative markers was more than 5‐fold higher in HIV‐infected adolescents as compared with controls: 43.4% vs 7.9% (P = .0001), respectively, for hepatitis B surface antigen (HBsAg); and 11.2% vs 2.2% (P = .0001), respectively, for hepatitis B e antigen (HBeAg). The prevalence of HBsAg chronic carriers and the presence of HBV replicative markers was significantly higher in patients with immunologically defined AIDS (CD4+ cell counts < 200 cells/mcL): 59.6% vs 34.6% (P = .02) for HBsAg and 22.8% vs 5.7%, (P = .002) for HBV DNA. After 1 year of follow‐up, the proportion of those who cleared the HBeAg was considerably lower in severely immunosuppressed coinfected patients: 4.7% vs 37.1% (P = .003). Four additional HIV‐infected adolescents became HBsAg‐positive over the term of follow‐up (incidence rate, 24.9/1000 person‐years), despite a record of immunization against hepatitis B.

Conclusion

A substantial percentage of HIV‐infected and HIV‐uninfected Romanian adolescents have evidence of past or present HBV infection. In HIV‐infected adolescents, the degree of immunosuppression is correlated with persistence of HBV replicative markers, even in the absence of clinical or biochemical signs of liver disease.
Therapeutic targeting of the focal adhesion complex prevents oncogenic TGF-β signaling and metastasis
Authors: Wendt Michael K , Schiemann William P
Published: September 2009

Introduction

Mammary tumorigenesis is associated with the increased expression of several proteins in the focal adhesion complex, including focal adhesion kinase (FAK) and various integrins. Aberrant expression of these molecules occurs concomitant with the conversion of TGF-β function from a tumor suppressor to a tumor promoter. We previously showed that interaction between β3 integrin and TβR-II facilitates TGF-β-mediated oncogenic signaling, epithelial-mesenchymal transition (EMT), and metastasis. However, the molecular mechanisms by which the focal adhesion complex contributes to β3 integrin:TβR-II signaling and the oncogenic conversion of TGF-β remain poorly understood.

Methods

FAK expression and activity were inhibited in normal and malignant mammary epithelial cells (MECs) either genetically by using lentiviral-mediated delivery of shRNAs against FAK, or pharmacologically through in vitro and in vivo use of the FAK inhibitors, PF-562271 and PF-573228. Altered Smad2/3 and p38 MAPK activation, migration, EMT, and invasion in response to TGF-β1 were monitored in FAK-manipulated cells. TβR-II expression was increased in metastatic breast cancer cells by retroviral transduction, and the metastasis of FAK- and TβR-II-manipulated tumors was monitored by using bioluminescent imaging.

Results

TGF-β stimulation of MECs stabilized and activated FAK in a β3 integrin- and Src-dependent manner. Furthermore, by using the human MCF10A breast cancer progression model, we showed that increased FAK expression in metastatic breast cancer cells mirrored the acquisition of enhanced activation of p38 MAPK by TGF-β. Administering FAK inhibitors or rendering metastatic breast cancer cells FAK deficient abrogated the interaction between β3 integrin and TβR-II, thereby preventing TGF-β from (a) activating p38 MAPK; (b) stimulating MEC invasion, migration, and EMT; and (c) inducing early primary tumor dissemination to the lungs. Finally, in contrast to FAK depletion, adjuvant FAK chemotherapy of mammary tumors decreased their growth in part by diminished macrophage tumor infiltration.

Conclusions

Our studies identify an essential function for FAK in mediating the interaction between β3 integrin and TβR-II, and thus in facilitating the oncogenic conversion of TGF-β required for mammary tumor metastasis. Furthermore, this study establishes chemotherapeutic targeting of FAK as an effective, two-pronged approach in preventing tumor progression both by decreasing innate immune cell infiltration, and by inhibiting early TGF-β-dependent metastasis.
Phase II Trial of Combination Therapy With Bortezomib, Pegylated Liposomal Doxorubicin, and Dexamethasone in Patients With Newly Diagnosed Myeloma
Authors: Jakubowiak Andrzej J. , Kendall Tara , Al-Zoubi Ammar , Khaled Yasser , Mineishi Shin , Ahmed Asra , Campagnaro Erica , Brozo Christine , Braun Thomas , Talpaz Moshe , Kaminski Mark S.
Published: September 2009

Purpose

This single-center, open-label, phase II trial evaluated the bortezomib, pegylated liposomal doxorubicin (PLD), and dexamethasone combination regimen (VDD) as initial treatment for patients with newly diagnosed multiple myeloma (MM).

Patients and Methods

Enrolled patients (N = 40) received up to six 3-week cycles of treatment with bortezomib 1.3 mg/m2 intravenously (IV) on days 1, 4, 8, and 11; PLD 30 mg/m2 IV on day 4; and dexamethasone 20 to 40 mg daily as specified in the study design. The primary end point was the complete/near-complete response (CR/nCR) rate after six cycles. Secondary end points included overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). The impact of VDD on stem-cell mobilization and collection also was evaluated.

Results

After six cycles, the ORR was 85.0% (CR/nCR, 37.5%; very good partial response [VGPR] or better, 57.5%). Patients who underwent stem-cell transplantation (SCT) after VDD (n = 30) experienced increased rates of VGPR or better (53.3% to 76.6% after SCT). Overall, 1-year PFS and OS rates were 92.5% and 97.5%, respectively. Those who achieved VGPR or better after treatment with VDD showed a significantly greater 1-year PFS versus those who achieved less than VGPR (100% v 82%, respectively; P = .03). Similar results were observed in patients who underwent SCT. Grades 3 or 4 hematologic toxicities occurred in ≤ 10% of patients; grade 2 painful neuropathy occurred in 7.5%; and grade 3 palmar-plantar erythrodysesthesia occurred in 2.5%.

Conclusion

VDD is highly effective for initial treatment of MM followed by SCT in appropriate patients, and it has a reasonable safety profile. Achievement of VGPR or better with this initial therapy predicted longer PFS, regardless of the consolidation therapy given.
Serum Adiponectin As a Predictor of Childhood Non-Hodgkin's Lymphoma: A Nationwide Case-Control Study
Authors: Petridou Eleni Th. , Sergentanis Theodoros N. , Dessypris Nick , Vlachantoni Iris T. , Tseleni-Balafouta Sofia , Pourtsidis Apostolos , Moschovi Maria , Polychronopoulou Sofia , Athanasiadou-Piperopoulou Fani , Kalmanti Maria , Mantzoros Christos S.
Published: September 2009

Purpose

To our knowledge, this is the first study exploring the association of childhood non-Hodgkin's lymphoma (NHL) with serum adiponectin and leptin levels in a nationwide case-control series. In addition, expression of adiponectin receptors in NHL specimens was assessed, and the association between adipokines and childhood NHL survival and prognosis was examined.

Patients and Methods

We studied 121 incident childhood (0 to 14 years) NHL cases registered in the Nationwide Registry for Childhood Hematological Malignancies (1996 to 2006) and an equal number of matched controls, for whom sociodemographic, lifestyle, prenatal characteristics, and fasting blood serums were collected. Serum adiponectin and leptin levels were determined. Immunohistochemisty for adiponectin receptors expression was performed on commercially available adult NHL specimens (n = 30) and in a subset of childhood NHL cases (n = 6) that were available. Summary statistics, multiple conditional logistic regression analyses, and survival analysis were performed.

Results

Higher serum adiponectin, but not leptin, levels were independently associated with childhood NHL (odds ratio, 1.82; 95% CI, 1.30 to 2.56), after adjusting for obesity and established risk factors. Higher adiponectin levels at diagnosis were positively associated with relapse and poor survival, but hormone levels did not differ among NHL subtypes. Adiponectin receptors 1 and 2 were present in 90% and 57% of adult samples and in 83% and 100% of childhood NHL samples, respectively.

Conclusion

Elevated serum adiponectin, but not leptin, levels are independently associated with childhood NHL and poor prognosis. Adiponectin receptors are expressed in NHL, suggesting that adiponectin may represent not only a potential clinically significant diagnostic and prognostic marker but also a molecule that may be implicated in NHL pathogenesis.
Single-Drug Vinblastine As Salvage Treatment for Refractory or Relapsed Anaplastic Large-Cell Lymphoma: A Report From the French Society of Pediatric Oncology
Authors: Brugières Laurence , Pacquement Helene , Le Deley Marie-Cecile , Leverger Guy , Lutz Patrick , Paillard Catherine , Baruchel Andre , Frappaz Didier , Nelken Brigitte , Lamant Laurence , Patte Catherine
Published: September 2009

Purpose

To evaluate the efficacy of vinblastine for relapsed/refractory anaplastic large-cell lymphoma (ALCL).

Patients and Methods

Data were reviewed on all 36 patients included prospectively in the French database for pediatric ALCL who were treated with vinblastine (6 mg/m2/wk) for resistant primary disease (one), a first relapse (15), or subsequent relapses (20). Fifteen patients had undergone hematopoietic stem-cell transplantation (HSCT) for a previous relapse.

Results

Six patients were not evaluable for response, 25 (83%) of 30 evaluable patients achieved a complete remission (CR), and five experienced progressive disease. Among the 31 patients who achieved a CR with vinblastine or before its initiation, six patients were treated with HSCT and 25 with vinblastine alone (median duration, 14 months). Overall, nine of 25 patients treated with vinblastine alone have remained in CR (median, 7 years since the end of treatment), and 16 patients have relapsed. Vinblastine was still efficient for subsequent relapses. With a median follow-up of 9.2 years, 12 patients have died (four as a result of toxicity after HSCT and eight as a result of disease), and 24 patients are alive (15 following treatment with single-agent vinblastine for the last event). Five-year overall survival is 65% (95% CI, 48% to 79%), and 5-year event-free survival is 30% (95% CI, 17% to 47%).

Conclusion

Vinblastine is highly efficient in relapsed ALCL and may produce durable remissions. The optimal treatment duration still has to be assessed. These results should be borne in mind when designing future phase II studies with the targeted therapies directed against anaplastic lymphoma kinase.
Impact of Venous Thromboembolism and Anticoagulation on Cancer and Cancer Survival
Authors: Kuderer Nicole M. , Ortel Thomas L. , Francis Charles W.
Published: September 2009

Changes in the hemostatic system and chronic hemostatic activation are frequently observed in patients with cancer, even in the absence of venous thromboembolism (VTE). VTE is a leading cause of death among patients with cancer and contributes to long-term mortality in patients with early as well as advanced-stage cancer. Mounting evidence suggests that components of the clotting cascade and associated vascular factors play an integral part in tumor progression, invasion, angiogenesis, and metastasis formation. Furthermore, there are intriguing in vitro and animal findings that anticoagulants, in particular the low molecular weight heparins (LMWHs), exert an antineoplastic effect through multiple mechanisms, including interference with tumor cell adhesion, invasion, metastasis formation, angiogenesis, and the immune system. Several relatively small randomized controlled clinical trials of anticoagulation as cancer therapy in patients without a VTE diagnosis have been completed. These comprise studies with LMWH, unfractionated heparin, and vitamin K antagonists, with overall encouraging but nonconclusive results and some limitations. Meta-analyses performed for the American Society of Clinical Oncology VTE Guidelines Committee and the Cochrane Collaboration suggest overall favorable effects of anticoagulation on survival of patients with cancer, mainly with LMWH. However, definitive clinical trials have been elusive and questions remain regarding the importance of tumor type and stage on treatment efficacy, the impact of fatal thromboembolic events, optimal anticoagulation therapy, and safety with differing chemotherapy regimens. Although the LMWHs and related agents hold promise for improving outcomes in patients with cancer, additional studies of their efficacy and safety in this setting are needed.