bluuebunny/crossref_metadata_2025 huggingface dataset:
Rap1a activation by CalDAG‐GEFI and p38 MAPK is involved in E‐selectin‐dependent slow leukocyte rolling
Authors: Stadtmann Anika , Brinkhaus Laura , Mueller Helena , Rossaint Jan , Bolomini‐Vittori Matteo , Bergmeier Wolfgang , Van Aken Hugo , Wagner Denisa D. , Laudanna Carlo , Ley Klaus , Zarbock Alexander
Published: April 2011

Rolling leukocytes are exposed to different adhesion molecules and chemokines. Neutrophils rolling on E‐selectin induce integrin αLβ2‐mediated slow rolling on ICAM‐1 by activating a phospholipase C (PLC)γ2‐dependent and a separate PI3Kγ‐dependent pathway. E‐selectin‐signaling cooperates with chemokine signaling to recruit neutrophils into inflamed tissues. However, the distal signaling pathway linking PLCγ2 (Plcg2) to αLβ2‐activation is unknown. To identify this pathway, we used different Tat‐fusion‐mutants and gene‐deficient mice in intravital microscopy, autoperfused flow chamber, peritonitis, and biochemical studies. We found that the small GTPase Rap1 is activated following E‐selectin engagement and that blocking Rap1a in Pik3cg−/− mice by a dominant‐negative Tat‐fusion mutant completely abolished E‐selectin‐mediated slow rolling. We identified CalDAG‐GEFI (Rasgrp2) and p38 MAPK as key signaling intermediates between PLCγ2 and Rap1a. Gαi‐independent leukocyte adhesion to and transmigration through endothelial cells in inflamed postcapillary venules of the cremaster muscle were completely abolished in Rasgrp2−/− mice. The physiological importance of CalDAG‐GEFI in E‐selectin‐dependent integrin activation is shown by complete inhibition of neutrophil recruitment into the inflamed peritoneal cavity of Rasgrp2−/− leukocytes treated with pertussis toxin to block Gαi‐signaling. Our data demonstrate that Rap1a activation by p38 MAPK and CalDAG‐GEFI is involved in E‐selectin‐dependent slow rolling and leukocyte recruitment.
High‐order compact scheme for Boussinesq equations: implementation and numerical boundary condition issue
Authors: Ghader S. , Ghasemi A. , Banazadeh M. R. , Mansoury D.
Published: April 2011

Application of the three‐point fourth‐order compact scheme to spatial differencing of the vorticity‐stream function‐density formulation of the two‐dimensional incompressible Boussinesq equations is presented. The details for the derivation of difference relations at boundaries to generate accurate and stable solutions are also given. To assess the numerical accuracy, two linear prototype test problems with known exact solution are used. The two‐dimensional planar and cylindrical lock‐exchange flow configurations are used to conduct the numerical experiments for the Boussinesq equations. Quantitative measures for the two linear prototype test problems and comparison of the results of this work with the published results for the planar lock‐exchange flow indicates the validity and accuracy of the three‐point fourth‐order compact scheme for numerical solution of two‐dimensional incompressible Boussinesq equations. In addition, the study of using different high‐order numerical boundary conditions for the implementation of the no‐penetration boundary condition for the density at no‐slip walls is considered. It is shown that the numerical solution is sensitive to the choice of difference relation for the density at boundaries and using an inappropriate difference relation leads to spurious numerical solution. Copyright © 2011 John Wiley & Sons, Ltd.
The management of heat flow in deep mines (part 2)
Authors: Wagner Horst
Published: April 2011

In Part 1 of “The Management of Heat Flow in Deep Mines” the sources of heat, mechanism of heat transfer and strategies of controlling heat transfer have been discussed. Part 2 deals with the effects of heat on the human body and mine cooling strategies for deep mines. In detail the effects of heat on a worker are examined, heat stress and heat tolerance discussed and methods of assessing heat stress in different mining situations presented. Experiences from deep South African gold mines highlight the adverse effects of heat stress environment on safety and labour productivity. The principal methods of cooling of deep and ultra deep mines are discussed. It is shown that auto‐compression of ventilation air is a deciding factor governing the choice of surface or underground cooling of ventilation air. In the case of deep and ultra deep mines, the use of chilled service water and ice slurry has shown to be the most cost effective means of mine cooling. In the case of ice slurry as cooling medium advantage is taken of the latent heat of ice which significantly reduces the amount of water required for mine cooling and hence the cost of pumping the water to surface. Cooling strategies for moderately deep, deep and ultra deep mines are discussed. Examples of cooling of deep long mine tunnels are given.
Kopswerk II headrace tunnel – geomechanical and construction design / Triebwasserstollen Kopswerk II – geomechanische und bautechnische Planung
Authors: Vigl Alois , Barwart C.
Published: April 2011

The Kopswerk II power plant of the Vorarlberger Illwerke AG with a capacity of 510 MW was constructed between 2004 and 2008 as a pumped storage scheme parallel to the existing Kopswerk I (247 MW) constructed in 1969. The design of the headrace was confronted with borderline conditions concerning both construction and operation. The construction concept had to take into consideration the external constraints and ensure continuous construction in winter in the high mountains. On account of the formation water situation, the intention was to relieve formation water pressure during the construction period.

In operation, the components of the headrace system including pressure tunnel are subject to enormous internal pressure fluctuations within a very short time on account of the pumped storage peak flow operation of Kopswerk II. In addition, the external formation water pressure can reach a head of 450 m, which could scarcely be resisted with an economic lining alone. This resulted in a basic design concept to integrate the surrounding rock mass into the structural system as far as possible, both with regard to rock pressure and formation water pressure. Such a concept has to include systematic and differentiated grouting of the rock mass, which is not always simple to achieve under high formation water pressure.

Das Kopswerk II der Vorarlberger Illwerke AG mit einer Leistung von 510 MW wurde in den Jahren 2004 bis 2008 parallel zum seit 1969 bestehenden Kopswerk I (247 MW) als Pumpspeicherwerk neu errichtet. Die Planung der Oberwasserführung war sowohl im Hinblick auf die Errichtung wie auch auf den Betrieb mit grenzwertigen Bedingungen konfrontiert. Das Baukonzept musste hinsichtlich der äußeren Bedingungen einen Durchlaufbetrieb im Winter und im Hochgebirge ermöglichen. Hinsichtlich der Bergwassersituation war eine Entlastung des Bergwasserdrucks während der Bauarbeiten anzustreben.

Im Betrieb unterliegen die Komponenten der Oberwasserführung einschließlich Druckstollen wegen des Pumpspeicher‐ Spitzenstrom‐Einsatzes des Kopswerks II enormen Innendruckschwankungen innerhalb kürzester Zeitspannen. Zudem steht von außen ein Bergwasser‐Druckpotenzial von bis zu 450 m Wassersäule an, das durch eine wirtschaftliche Auskleidung allein kaum zu beherrschen wäre. Somit musste ein planerisches Grundkonzept verfolgt werden, welches das umgebende Gebirge möglichst weitgehend in das Tragkonzept mit einbezieht und zwar sowohl hinsichtlich Gebirgslast wie auch hinsichtlich Bergwasserdruck. Ein solches Konzept schließt eine systematische und differenzierte Gebirgsbehandlung mittels Injektionen konsequent ein, was unter Bergwasserandrang nicht immer leicht umsetzbar ist.
Serum levels of polychlorinated biphenyls in Mexican women and breast cancer risk
Authors: Recio‐Vega Rogelio , Velazco‐Rodriguez Victor , Ocampo‐Gómez Guadalupe , Hernandez‐Gonzalez Sandra , Ruiz‐Flores Pablo , Lopez‐Marquez Francisco
Published: April 2011

The most prevalent female cancer across the world is breast cancer. Current established breast cancer risk factors explain only a fraction of the breast cancer cases diagnosed, and for this reason, other environmental factors have been studied. Exposure to organochlorine compounds has been linked to an increased incidence of breast cancer, although not all data have been consistent. This study was designed to evaluate the relation between polychlorinated biphenyls (PCB) exposure and breast cancer risk in Mexican women. We recruited 140 women from the General Hospital. The cases were 70 newly diagnosed women. We collected environmental and reproductive information by questionnaire. Blood samples were taken for measurement of serum levels of 20 PCB congeners. Risk of breast cancer was found to be positively associated with heavy congeners, age, postmenopausal status, family history of breast cancer and living close to an industrial facility. When PCB were grouped by structure–activity relationships, the risk of breast cancer was positively associated with groups 2b (odds ratio, OR = 1.90, 95% confidence interval, CI, 1.25–2.88), 3 (OR = 1.81, 95% CI 1.08–3.04) and group 4 (OR = 1.57, 95% CI 1.20–2.07). Among postmenopausal women, PCB levels from groups 1a, 2b, and 4 and total PCB were higher in cases, and an association between risk of breast cancer with groups 1a (OR = 7.59, 95% CI 1.1–51.4), 2b (OR = 3.7, 95% CI 1.2–11.2) and 4 (OR = 1.8, 95% CI 1.1–3.1) was found in this group of women. This study showed an association between heavy and potentially estrogenic PCB congeners and breast cancer risk. Copyright © 2011 John Wiley & Sons, Ltd.
Role of stereoelectronic features of imine and enamine in (S)‐proline catalyzed mannich reaction of acetaldehyde: An in silico study
Authors: Ajitha Manjaly J. , Suresh Cherumuttathu H.
Published: April 2011

A detailed mechanistic investigation of sixteen possible diastereomeric pathways for the C‐C bond formation step in (S)‐proline catalyzed Mannich reaction of acetaldehyde with N‐acetyl protected benzaldimine in acetonitrile solvent has been carried out to understand how stereoelectronic features invoke enantioselectivity of the final product. Both kinetic and thermodynamic factors of the reaction obtained using various density functional theory methods point out that si‐enantiofacial nucleophilic attack of anti‐enamine on the iminium carbon of the E, s‐cis N‐acetyl protected imine is the stereoselective pathway. Structural features of the transition states predicted that enamine in anti conformation attacks the imine through a Burgi‐Dunitz trajectory to yield the stereocenter. Computations at B3LYP‐PCM/6‐311++G(3df,2p)//B3LYP‐PCM/6‐31G(d,p) level showed a strong linear correlation between Burgi‐Dunitz angle and activation energy when anti‐enamine is used as nucleophile to react with all the configurations of the imine. Further, energy decomposition analysis has been carried out at B3LYP/TZ2P+ level for all the transition states, which revealed that the most dominant factor that control the enantioselectivity of the (S)‐proline catalyzed Mannich reaction is steric effect. Though the less favored transition states showed high amount of stabilizing orbital interaction, the destabilizing steric effects from both Pauli repulsion and preparation energy for the reactant molecules are very high and overshadowed the stabilizing effects. However, in the most favored transition state, a balanced outcome of electronic and steric effects was observed. Solvation effect was nearly same for all the transition states and electrostatic effects showed no correlation to the rank order of the energy of the transition states. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011.
Risk factor model to predict venous thromboembolism in hospitalized medical patients
Authors: Rothberg Michael B. , Lindenauer Peter K. , Lahti Maureen , Pekow Penelope S. , Selker Harry P.
Published: April 2011

BACKGROUND:

The Joint Commission requires that all medical inpatients be assessed for venous thromboembolism (VTE) risk, but available risk stratification tools have never been validated.

METHODS:

We conducted a retrospective cohort study of patients age ≥18 years, admitted to 374 US hospitals in 2004–2005, with a primary diagnosis of pneumonia, heart failure, chronic obstructive pulmonary disease (COPD), stroke, and urinary tract infection, and length of stay ≥3 days. Subjects were randomly assigned (80/20) to a derivation or validation set. We then assessed VTE (International Classification of Diseases, Ninth Revision [ICD‐9] code plus diagnostic test plus treatment), patient demographics, 21 potential risk factors, and other comorbidities. We created a VTE risk stratification tool using multivariable regression modeling and applied it to the validation sample.

RESULTS:

Of 242,738 patients, 612 (0.25%) patients fulfilled our criteria for VTE during hospitalization, and an additional 440 (0.18%) were readmitted for VTE within 30 days (overall incidence of 0.43%). In the multivariable model, age, sex, and 10 additional risk factors were associated with VTE. The strongest risk factors were inherited thrombophilia (OR 4.00), length of stay ≥6 days (OR 3.22), inflammatory bowel disease (OR 3.11), central venous catheter (OR 1.87), and cancer. In the validation set, the model had a c‐statistic of 0.75 (95% CI 0.71, 0.78). Deciles of predicted risk ranged from 0.11% to 1.46% with observed risk over the same deciles from 0.17% to 1.81%.

CONCLUSIONS:

The risk of symptomatic VTE in general medical patients is low. A risk factor model can identify those at sufficient risk to warrant pharmacologic prophylaxis. Journal of Hospital Medicine 2011. © 2011 Society of Hospital Medicine.
ENSO‐conditioned rainfall drought frequency analysis in northwest Baja California, Mexico
Authors: Hallack‐Alegria M. , Ramirez‐Hernandez J. , Watkins D. W.
Published: April 2011

Located in northwest Baja California, Mexico, the Guadalupe River Basin is situated in a semiarid region where periods of drought pose serious economic, social and environmental concerns. The study area has highly variable climate, with mean annual precipitation ranging from less than 12 mm to over 750 mm a year across the basin, and with most of the annual precipitation occurring during the autumn and winter seasons. To quantify the frequency and severity of meteorological droughts at the local (watershed) scale, this study investigates seasonal and annual precipitation data from 34 sites in northwest Baja California. Along with the analysis of precipitation climatology and interannual variability, El Niño/Southern Oscillation (ENSO) and related Pacific Ocean sea surface temperature (SST) patterns are shown to be potential predictors of seasonal precipitation. Analysis of precipitation variability at seasonal and annual time scales is performed using the standardized precipitation index (SPI) methodology, and annual, seasonal, and ENSO‐conditioned precipitation frequency analyses are executed using the regional L‐moment algorithm. The SPI and regional rainfall drought frequency estimates developed in this study may be useful for monitoring meteorological droughts and could serve as critical components of a comprehensive drought management plan. Furthermore, the methods applied in this study may be transferred to other semi‐arid locations to mitigate drought risk and, potentially, impacts of drier conditions in the 21st century. Copyright © 2011 Royal Meteorological Society
Immune response to cancer and its regulation in regional lymph nodes
Authors: Zheng Rongxiu , Shu Suyu
Published: April 2011

Regional draining lymph nodes (LNs) play a pivotal role in initiating immune responses. However, the presence of metastases may compromise their normal immunological function. Preclinical studies indicate that despite metastases, early tumor‐draining LNs are still a rich source of sensitized T cells. Recently, we found that dendritic (DC)‐tumor fusion hybrids were capable of stimulating therapeutic T‐cell generation in the LN. However, this response is regulated by a tumor‐specific suppression mechanism(s). Reversal of these dysfunctions would help the success of immunotherapy. J. Surg. Oncol. 2011;103:550–554. © 2011 Wiley‐Liss, Inc.
Thyroid cancer and lymph node metastases
Authors: Clark Orlo H.
Published: April 2011

There is considerable controversy about the prognostic implications of lymph node metastases in patients with papillary thyroid cancer and whether patients with papillary thyroid cancer should have a prophylactic or selective central (level VI) neck dissection. Some experts report that a prophylactic ipsilateral neck dissection results in fewer patients having elevated thyroglobulin levels but others do not agree. A comprehensive review of the literature suggests that the presence of macroscopic metastases of papillary thyroid cancer in cervical lymph nodes results in a higher recurrence rate and increased death rate, especially in patients 45 years of age or older, whereas microscopic nodal metastases do not appear to adversely influence survival. Until more information is available we recommend preoperative ultrasonography and a selective ipsilateral neck dissection for patients with papillary thyroid cancer. J. Surg. Oncol. 2011;103:615–618. © 2011 Wiley‐Liss, Inc.
The prognostic significance of the insulin‐like growth factor‐1 ligand and receptor expression in breast cancer tissue
Authors: Chong Kelvin Y.M. , Subramanian Ashok , Mokbel Kefah , Sharma Anup K.
Published: April 2011

Background and Objectives

Previous in vitro studies have suggested that IGF‐1 stimulation can lead a more aggressive breast cancers and subsequent poor prognosis in breast cancer patients. We aim to how IGF‐1 and IGF‐1R mRNA levels in breast cancer are associated with disease‐free survival (DFS) and other clinicopathological factors.

Methods

IGF‐1 and IGF‐1R mRNA levels were measured in breast cancer tissue from 132 patients using real‐time PCR. DFS and clinicopathological information were obtained from patient case notes.

Results

IGF‐1 and IGF‐1R mRNA levels did not correlate with any clinicopathological factors. Patients who relapsed had lower IGF‐1 mRNA levels in their tumour tissue compared to those who remained disease‐free during the 5‐year follow‐up period. Patients who had ER‐positive breast cancers with high IGF‐1 mRNA levels had longer DFS compared to those with low IGF‐1 mRNA levels. IGF‐1 mRNA levels was not associated with DFS in patients with ER‐negative cancers. IGF‐1R mRNA levels was not associated with DFS in any subgroup analysis. Multivariate analysis showed that IGF‐1 mRNA levels and histopathological grade were independent predictors of DFS.

Conclusions

Breast cancer tissue IGF‐1 expression is a favourable prognostic indicator and could be used in clinical setting in planning for adjuvant treatment. J. Surg. Oncol. 2011; 104:228–235. © 2011 Wiley‐Liss, Inc.
Ultraviolet radiation and 12‐O‐tetradecanoylphorbol‐13‐acetate‐induced interaction of mouse epidermal protein kinase Cε with Stat3 involve integration with ERK1/2
Authors: Sand Jordan Marshall , Hafeez Bilal Bin , Aziz Moammir Hasan , Siebers Emily Marie , Dreckschmidt Nancy Ellen , Verma Ajit Kumar
Published: April 2011

We have reported that protein kinase C epsilon (PKCε) expression level in epidermis dictates the susceptibility of mice to the development of squamous cell carcinomas (SCC) elicited either by repeated exposure to ultraviolet radiation (UVR) or by the DMBA‐TPA tumor promotion protocol. To find clues about the mechanism by which PKCε mediates susceptibility to UVR‐induced development of SCC, we found that PKCε‐over‐expressing transgenic mice, as compared to their wild‐type littermates, when exposed to UVR, elicit enhanced phosphorylation of Stat3 at Ser727 residues. Stat3 is constitutively activated in SCC and UVR fails to induce SCC in Stat3 mutant mice. Stat3Ser727 phosphorylation is essential for Stat3 transcriptional activity (Cancer Res. 67: 1385, 2007). We now present several novel findings including that PKCε integrates with its downstream partner ERK1/2 to phosphorylate Stat3Ser727. In these experiments, mice were either exposed to UVR (2 kJ/m2/dose) emitted by Kodacel‐filtered FS‐40 sun lamps or treated with TPA (5 nmol). Both UVR and TPA treatment stimulated PKCε–Stat3 interaction, Stat3Ser727 phosphorylation and Stat3‐regulated gene COX‐2 expression. PKCε–Stat3 interaction and Stat3Ser727 phosphorylation was also observed in SCC elicited by repeated UVR exposures of mice. PKCε–Stat3 interaction was PKCε specific. UVR or TPA‐stimulated Stat3Ser727 phosphorylation accompanied interaction of PKCε with ERK1/2 in intact mouse skin in vivo. Deletion of PKCε in wild‐type mice attenuated both TPA and UVR‐induced expression of phosphoforms of ERK1/2 and Stat3Ser727. These results indicate that PKCε integrates with ERK1/2 to mediate both TPA and UVR‐induced epidermal Stat3Ser727 phosphorylation. PKCε and Stat3 may be potential molecular targets for SCC prevention. © 2011 Wiley Periodicals, Inc.
Ion currents involved in oocyte maturation, fertilization and early developmental stages of the ascidian Ciona intestinalis
Authors: Tosti Elisabetta , Gallo Alessandra , Silvestre Francesco
Published: April 2011

Electrophysiological techniques were used to study the role of ion currents in the ascidian Ciona intestinalis oocyte plasma membrane during different stages of growth, meiosis, fertilization and early development. Three stages of immature oocytes were discriminated in the ovary, with the germinal vesicle showing specific different features of growth and maturation. Stage‐A (pre‐vitellogenic) oocytes exhibited the highest L‐type calcium current activity and were incompetent for meiosis resumption. Stage‐B (vitellogenic) oocytes showed a progressive disappearance of calcium currents and the first appearance of sodium currents that remained high during the maturation process, up to the post‐vitellogenic stage‐C oocytes. The latter had acquired meiotic competence, undergoing spontaneous in vitro maturation and interacting with the spermatozoon. However, fertilized oocytes did not produce normal larvae, suggesting that cytoplasmic maturation may affect embryo development. In mature oocytes at the metaphase I stage, sodium currents were present and remained high up to the zygote stage. Oocytes fertilized in the absence of sodium showed significant reduction of the fertilization current amplitude and high development of anomalous “rosette” embryos. Current amplitudes became negligible in embryos at the 2‐ and 4‐cell stage, whereas resumption of all the current activities occurred at the 8‐cell embryo. Taken together, these results suggest: (i) an involvement of L‐type calcium currents in initial oocyte meiotic progression and growth; (ii) a role of sodium currents at fertilization; (iii) a role of the fertilization current in ensuring normal embryo development. Mol. Reprod. Dev. 78:854–860, 2011. © 2011 Wiley Periodicals, Inc.
Variational principles in dissipative electro‐magneto‐mechanics: A framework for the macro‐modeling of functional materials
Authors: Miehe C. , Rosato D. , Kiefer B.
Published: April 2011

This paper presents a general framework for the macroscopic, continuum‐based formulation and numerical implementation of dissipative functional materials with electro‐magneto‐mechanical couplings based onincremental variational principles. We focus on quasi‐static problems, where mechanical inertia effects and time‐dependent electro‐magnetic couplings area priorineglected and a time‐dependence enters the formulation only through a possible rate‐dependent dissipative material response. The underlying variational structure of non‐reversible coupled processes is related to a canonical constitutive modeling approach, often addressed to so‐called standard dissipative materials. It is shown to have enormous consequences with respect to all aspects of the continuum‐based modeling in macroscopic electro‐magneto‐mechanics. At first, thelocal constitutive modelingof the coupled dissipative response, i.e. stress, electric and magnetic fields versus strain, electric displacement and magnetic induction, is shown to be variational based, governed by incremental minimization and saddle‐point principles. Next, the implications on the formulation ofboundary‐value problemsare addressed, which appear in energy‐based formulations as minimization principles and in enthalpy‐based formulations in the form of saddle‐point principles. Furthermore, thematerial stabilityof dissipative electro‐magneto‐mechanics on the macroscopic level is defined based on the convexity/concavity of incremental potentials. We provide a comprehensive outline of alternative variational structures and discuss details of their computational implementation, such as formulation of constitutive update algorithms and finite element solvers. From the viewpoint of constitutive modeling, including the understanding of the stability in coupled electro‐magneto‐mechanics, anenergy‐based formulationis shown to be the canonical setting. From the viewpoint of the computational convenience, anenthalpy‐based formulationis the most convenient setting. A numerical investigation of a multiferroic composite demonstrates perspectives of the proposed framework with regard to the future design of new functional materials. Copyright © 2011 John Wiley & Sons, Ltd.
Modelling dynamic crack propagation using the scaled boundary finite element method
Authors: Ooi E. T. , Yang Z. J.
Published: April 2011

This study presents a novel application of the scaled boundary finite element method (SBFEM) to model dynamic crack propagation problems. Accurate dynamic stress intensity factors are extracted directly from the semi‐analytical solutions of SBFEM. They are then used in the dynamic fracture criteria to determine the crack‐tip position, velocity and propagation direction. A simple, yet flexible remeshing algorithm is used to accommodate crack propagation. Three dynamic crack propagation problems that include mode‐I and mix‐mode fracture are modelled. The results show good agreement with experimental and numerical results available in the literature. It is found that the developed method offers some advantages over conventional FEM in terms of accuracy, efficiency and ease of implementation. Copyright © 2011 John Wiley & Sons, Ltd.
Hydrogen‐bonded supramolecular polymers from derivatives of α‐amino‐ε‐caprolactam: A bio‐based material
Authors: Tarkin‐Tas Eylem , Lange Christopher A. , Mathias Lon J.
Published: April 2011

Hydrogen‐bonded supramolecular polymers were prepared from the derivatives of α‐amino‐ε‐caprolactam (ACL), obtained from a renewable resource. Several self‐complimentary bis‐ or tetra‐caprolactam monomers were synthesized by varying the number of carbons of the spacer between the hydrogen‐bonding end groups. Physical properties of these hydrogen‐bonded polymers were clearly demonstrated by differential scanning colorimetry, solid‐state NMR, and X‐ray powder diffraction analyses. The supramolecular behavior was also supported by fiber formation from the melt for several of these compounds, and stable glassy materials were prepared from the physical mixtures of two different biscaprolactams. The self‐association ability of ACL was also used by incorporating ACL at the chain ends of low‐molecular weight Jeffamine (Mn = 900 g/mol) using urea and amide linkages. The transformation of this liquid oligomer at room temperature into a self‐standing, transparent film clearly showed the improvement in mechanical properties obtained by the introduction of terminal hydrogen‐bonding groups. Finally, the use of monomers with a functionality of four gave rise to network formation either alone or combination with bifunctional monomers. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011
Association of psychosocial risk screening in pediatric cancer with psychosocial services provided
Authors: Kazak Anne E. , Barakat Lamia P. , Hwang Wei‐Ting , Ditaranto Susan , Biros Daniel , Beele David , Kersun Leslie , Hocking Matthew C. , Reilly Anne
Published: April 2011

Objective: How screening for psychosocial risk in pediatric oncology may relate to the number and type of psychosocial services provided is a critical step in linking screening with treatment. We predicted that screening at diagnosis would be associated with the delivery of more psychosocial services over 8 weeks and that these services would be consistent with Universal, Targeted, or Clinical psychosocial risk level based on the Pediatric Psychosocial Preventative Health Model (PPPHM).

Methods: Parents of children newly diagnosed with cancer received either the Psychosocial Assessment Tool (PAT; n = 49) or psychosocial care as usual (PAU; n = 47), based on their date of diagnosis and an alternating monthly schedule. Medical record review and surveys completed by social workers and child life specialists were used to determine psychosocial services provided to patients and their families over the first eight weeks of treatment.

Results: As predicted, families in the PAT condition received more services than those in PAU based on social worker and child life specialist report and medical record review. Within the PAT group, families at the Targeted and Clinical levels of risk received more intensive services than those at the Universal level.

Conclusions: This initial report shows how psychosocial risk screening may impact psychosocial care in pediatric cancer, supporting the importance of screening as well as matching services to risk level. Copyright © 2011 John Wiley & Sons, Ltd.
Combined treatment targeting HIF‐1α and Stat3 is a potent strategy for prostate cancer therapy
Authors: Reddy Kavitha Ramasamy , Guan Yongli , Qin Guoting , Zhou Zhou , Jing Naijie
Published: April 2011

BACKGROUND

The Stat3 pathway and the hypoxia‐sensing pathway are both up‐regulated in prostate cancer. Stat3 is a specific regulator of pro‐carcinogenic inflammation and represents a promising therapeutic target. Hypoxia‐inducible factor‐1 (HIF‐1)α, which mediates the cellular response to hypoxia, has been demonstrated to be over‐expressed in many human cancers and is associated with poor prognosis and treatment failure in clinic. To develop a potent strategy to increase therapeutic efficacy and reduce drug resistance in prostate cancer therapy, we combined two anti‐cancer agents: T40214 (a p‐Stat3 inhibitor) and JG244 (a HIF‐1α inhibitor) together to treat nude mice bearing human prostate tumor (DU145) and immunocompetent mice (C57BL/6) bearing murine prostate tumor (TRAMP‐C2).

METHODS

We employed in vitro and in vivo assays, including Western blots, cell cycle analysis, immunohistochemistry, TUNEL and xenograft models to determine the drug efficacy and mechanism of combination treatment of T40214 and JG244.

RESULTS

We found that compared to treatment by T40214 or JG244 alone, the combination treatment using T40214 and JG244 together significantly suppressed growth of human or murine prostate tumors. Also, compared with apoptotic cells induced by T40214 or JG244 alone, the combined treatment greatly increased apoptosis in DU145 (P < 0.006) and TRAMP‐C2 tumors (P < 0.008).

CONCLUSIONS

Our results suggested that combination treatment including a HIF‐1α/2α inhibitor not only has therapeutic efficacy in targeting HIF‐1α/2α, but also could reduce the hypoxia‐induced drug resistance to other therapies (e.g., T40214) and enhance drug efficacy. This approach could make prostate cancer treatments more effective. Prostate 71:1796–1809, 2011. © 2011 Wiley Periodicals, Inc.
A security enhanced authentication and key distribution protocol for wireless networks
Authors: Lv Chao , Ma Maode , Li Hui , Ma Jianfeng , Niu Ben
Published: April 2011

Authentication and key distribution (AKD) protocols become more and more important in the design of wireless networks. Especially, the communication efficiency and security are the critical factors. In this paper, we first analyse the vulnerabilities of an AKD protocol for wireless networks under three types of attacks. Then, we propose an enhanced AKD protocol to overcome those vulnerabilities with the security functionality to prevent those malicious attacks. Security analysis and formal verification mainly using Automated Validation of Internet Security Protocols and Applications toolkit show that the proposed protocol is secure against those attacks. Copyright © 2011 John Wiley & Sons, Ltd.
Performance analysis of Alamouti scheme with transmit antenna selection in non‐identical Nakagami‐m fading channels
Authors: Coşkun Ahmet F. , Kucur Oğuz , Altunbaş İbrahim
Published: April 2011

In this paper, error performances of multiple‐input multiple‐output systems that employ Alamouti‐coded transmission with transmit antenna selection are examined for binary phase‐shift keying, binary frequency‐shift keying, M‐ary phase‐shift keying, and M‐ary quadrature amplitude‐modulation signals in independent but non‐identically distributed flat Nakagami‐m fading channels. Exact symbol error rate expressions are derived by using the moment‐generating function‐based analysis method. Upper bound expressions have been obtained in order to examine the asymptotic diversity order of transmit antenna selection/Alamouti scheme. Also, outage probability analysis of investigated systems has been given in order to examine the system capacity. Monte Carlo simulations have validated the analytical symbol error rate performance results. Copyright © 2011 John Wiley & Sons, Ltd.
Preoperative Positron Emission Tomography/Computed Tomography Predicts Advanced Lymph Node Metastasis in Esophageal Squamous Cell Carcinoma Patients
Authors: Hsu Po‐Kuei , Lin Ko‐Han , Wang Shyh‐Jen , Huang Chien‐Sheng , Wu Yu‐Chung , Hsu Wen‐Hu
Published: April 2011

Background

We aimed to study whether positron emission tomography/computed tomography (PET/CT) findings are associated with lymph node staging, as outlined by the 7th edition American Joint Committee on Cancer (AJCC) TNM staging system in patients with esophageal squamous cell carcinoma (ESCC).

Methods

A series of 76 ESCC patients undergoing esophagectomy were included in this study. The relation between PET/CT findings [maximum standardized uptake value (SUVmax)] and pathologic lymph node status (N stage) was studied.

Results

The SUVmax of extra‐tumor uptake, but not that of the main tumor, was significantly associated with the N classification. N2/N3 disease was observed in 61.1% of patients with an SUVmax for extra‐tumor uptake of >4.9, whereas only 17.2% of patients with an SUVmax of extra‐tumor uptake of <4.9 were classified as N2/N3 The number of PET abnormalities (NPAs) was also significantly associated with the N classification. Patients with three or more NPAs had a 65% chance of being classified as N2/N3, whereas patients with one or two NPAs had less than a 20% chance of being classified as N2/N3.

Conclusions

The SUVmax of extra‐tumor uptake and the NPAs were significantly associated with the N classification outlined by the 7th edition of the AJCC TNM staging system. PET/CT does help identify patients with advanced lymph node metastasis (N2/N3 stage) instead of simply indicating nodal involvement.
Optimal Period for the Prophylactic Administration of Neutrophil Elastase Inhibitor for Patients with Esophageal Cancer Undergoing Esophagectomy
Authors: Iwahashi Makoto , Nakamori Mikihito , Nakamura Masaki , Ojima Toshiyasu , Naka Teiji , Yamaue Hiroki
Published: April 2011

Background

The present study was designed to determine the optimal period for the prophylactic administration of the neutrophil elastase inhibitor, Sivelestat, in patients undergoing transthoracic esophagectomy. Sivelestat is reported to be effective in patients who undergo esophagectomy by providing an increased oxygenation ability and suppressing the serum inflammatory cytokines in the postoperative period. However, the optimal period for the prophylactic administration of Sivelestat remains to be elucidated.

Methods

The 30 patients who underwent esophagectomy for thoracic esophageal cancer were enrolled in one of two groups. The initial 15 patients were assigned to group A and received intravenous infusion of Sivelestat sodium hydrate until postoperative day (POD) 2, and the subsequent 15 patients were assigned to group B and received Sivelestat until POD 5. Historical controls without Sivelestat administration were used. The postoperative courses and serum inflammatory cytokines were evaluated.

Results

Sivelestat improved oxygenation in the postoperative period; however, there were no differences between the two groups in terms of duration of mechanical ventilation, intensive care unit stay, systemic inflammatory response syndrome, and postoperative change of oxygenation. In addition, there were no differences in the postoperative changes in the serum interleukin (IL)‐6 and high mobility group box chromosomal protein 1. Although the serum IL‐8 on POD 3 was lower in group B than in group A, the neutrophil elastase showed no difference between these groups. None of the patients in either group suffered respiratory complications.

Conclusions

The two‐day administration of Sivelestat initiated immediately after intrathoracic manipulation was found to be sufficient for prophylactic use to prevent pulmonary complications by suppressing hypercytokinemia after esophagectomy.
Tetradecylthioacetic Acid Increases Hepatic Mitochondrial β‐Oxidation and Alters Fatty Acid Composition in a Mouse Model of Chronic Inflammation
Authors: Burri Lena , Bjørndal Bodil , Wergedahl Hege , Berge Kjetil , Bohov Pavol , Svardal Asbjørn , Berge Rolf K.
Published: April 2011

The administration of tetradecylthioacetic acid (TTA), a hypolipidemic and anti‐inflammatory modified bioactive fatty acid, has in several experiments based on high fat diets been shown to improve lipid transport and utilization. It was suggested that increased mitochondrial and peroxisomal fatty acid oxidation in the liver of Wistar rats results in reduced plasma triacylglycerol (TAG) levels. Here we assessed the potential of TTA to prevent tumor necrosis factor (TNF) α‐induced lipid modifications in human TNFα (hTNFα) transgenic mice. These mice are characterized by reduced β‐oxidation and changed fatty acid composition in the liver. The effect of dietary treatment with TTA on persistent, low‐grade hTNFα overexpression in mice showed a beneficial effect through decreasing TAG plasma concentrations and positively affecting saturated and monounsaturated fatty acid proportions in the liver, leading to an increased anti‐inflammatory fatty acid index in this group. We also observed an increase of mitochondrial β‐oxidation in the livers of TTA treated mice. Concomitantly, there were enhanced plasma levels of carnitine, acetyl carnitine, propionyl carnitine, and octanoyl carnitine, no changed levels in trimethyllysine and palmitoyl carnitine, and a decreased level of the precursor for carnitine, called γ‐butyrobetaine. Nevertheless, TTA administration led to increased hepatic TAG levels that warrant further investigations to ascertain that TTA may be a promising candidate for use in the amelioration of inflammatory disorders characterized by changed lipid metabolism due to raised TNFα levels.
Aerobic Exercise Improves Reverse Cholesterol Transport in Cholesteryl Ester Transfer Protein Transgenic Mice
Authors: Rocco D. D. F. M. , Okuda L. S. , Pinto R. S. , Ferreira F. D. , Kubo S. K. , Nakandakare E. R. , Quintão E. C. R. , Catanozi S. , Passarelli M.
Published: April 2011

We analyzed the effect of a 6‐week aerobic exercise training program on the in vivo macrophage reverse cholesterol transport (RCT) in human cholesteryl ester transfer protein (CETP) transgenic (CETP‐tg) mice. Male CETP‐tg mice were randomly assigned to a sedentary group or a carefully supervised exercise training group (treadmill 15 m/min, 30 min sessions, five sessions per week). The levels of plasma lipids were determined by enzymatic methods, and the lipoprotein profile was determined by fast protein liquid chromatography (FPLC). CETP activity was determined by measuring the transfer rate of 14C‐cholesterol from HDL to apo‐B containing lipoproteins, using plasma from CETP‐tg mice as a source of CETP. The reverse cholesterol transport was determined in vivo by measuring the [3H]‐cholesterol recovery in plasma and feces (24 and 48 h) and in the liver (48 h) following a peritoneal injection of [3H]‐cholesterol labeled J774‐macrophages into both sedentary and exercise trained mice. The protein levels of liver receptors were determined by immunoblot, and the mRNA levels for liver enzymes were measured using RT‐PCR. Exercise training did not significantly affect the levels of plasma lipids or CETP activity. The HDL fraction assessed by FPLC was higher in exercise‐trained compared to sedentary mice. In comparison to the sedentary group, a greater recovery of [3H]‐cholesterol from the injected macrophages was found in the plasma, liver and feces of exercise‐trained animals. The latter occurred even with a reduction in the liver CYP7A1 mRNA level in exercised trained animals. Exercise training increased the liver LDL receptor and ABCA‐1 protein levels, although the SR‐BI protein content was unchanged. The RCT benefit in CETP‐tg mice elicited by exercise training helps to elucidate the role of exercise in the prevention of atherosclerosis in humans.
Treatment of poor-risk myelodysplastic syndromes and acute myeloid leukemia with a combination of 5-azacytidine and valproic acid
Authors: Kuendgen Andrea , Bug Gesine , Ottmann Oliver G. , Haase Detlef , Schanz Julie , Hildebrandt Barbara , Nachtkamp Kathrin , Neukirchen Judith , Dienst Ariane , Haas Rainer , Germing Ulrich , Gattermann Norbert
Published: April 2011

5-azacytidine (AZA) has become standard treatment for patients with higher-risk myelodysplastic syndrome (MDS). Response rate is about 50% and response duration is limited. Histone deactylase (HDAC) inhibitors are attractive partners for epigenetic combination therapy. We treated 24 patients with AZA (100 mg/m2, 5 days) plus valproate (VPA; continuous dosing, trough serum level 80–110 μg/ml). According to WHO classification, 5 patients had MDS, 2 had MDS/MPD, and 17 had acute myeloid leukemia (AML). Seven patients (29%) had previously received intensive chemotherapy, and five had previous HDAC inhibitor treatment. The overall response rate was 37% in the entire cohort but significantly higher (57%) in previously untreated patients, especially those with MDS (64%). Seven (29%) patients achieved CR (29%) and two PR (8%), respectively. Hematological CR was accompanied by complete cytogenetic remission according to conventional cytogenetics in all evaluable cases. Some patients also showed complete remission according to FISH on bone marrow mononuclear cells and CD34+ peripheral blood cells, as well as by follow-up of somatic mitochondrial DNA mutations. Four additional patients achieved at least marrow remissions. Factors influencing response were AML (vs. MDS), marrow blast count, pretreatment, transfusion dependency, concomitant medication with hydroxyurea, and valproic acid (VPA) serum level. This trial is the first to assess the combination of AZA plus VPA without additional ATRA. A comparatively good CR rate, relatively short time to response, and the influence of VPA serum levels on response suggest that VPA provided substantial additional benefit. However, the importance of HDAC inhibitors in epigenetic combination therapy can only be proven by randomized trials.
Chronic dietary supplementation with turmeric protects against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-mediated neurotoxicity in vivo: implications for Parkinson's disease
Authors: Mythri Rajeswara Babu , Veena Jayagopalan , Harish G. , Shankaranarayana Rao B. S. , Srinivas Bharath M. M.
Published: April 2011

Multiple pathways including oxidative stress and mitochondrial damage are implicated in neurodegeneration during Parkinson's disease (PD). The current PD drugs provide only symptomatic relief and have limitations in terms of adverse effects and inability to prevent neurodegeneration. Therefore, there is a demand for novel compound(s)/products that could target multiple pathways and protect the dying midbrain dopaminergic neurons, with potential utility as adjunctive therapy along with conventional drugs. Turmeric is a spice used in traditional Indian cuisine and medicine with antioxidant, anti-inflammatory and potential neuroprotective properties. To explore the neuroprotective property of turmeric in PD, mice were subjected to dietary supplementation with aqueous suspensions of turmeric for 3 months, mimicking its chronic consumption and challenged in vivo with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Brain samples from untreated and treated groups were characterised based on mitochondrial complex I (CI) activity, protein nitration and tyrosine hydroxylase immunoreactivity. Chronic turmeric supplementation induced the enzyme activity of γ-glutamyl cysteine ligase, which in turn increased glutathione levels and protected against peroxynitrite-mediated inhibition of brain CI. These mice were also protected against MPTP-mediated protein nitration, CI inhibition and degeneration of substantia nigra neurons in the brain. We conclude that chronic dietary consumption of turmeric protects the brain against neurotoxic insults, with potential application in neurodegeneration. Further characterisation of the active constituents of turmeric that potentially promote neuroprotection could improve the utility of dietary turmeric in brain function and disease.
Bounds for the multiplicities of the roots of a complex polynomial
Authors: Bonciocat A. I. , Bonciocat N. C. , Zaharescu A.
Published: April 2011

We refine a result of Dubickas on the maximal multiplicity of the roots of a complex polynomial, and obtain several separability criteria for complex polynomials with large leading coefficient. We also give p-adic analogous results for polynomials with integer coefficients.
The Other Side of Omnipotence: Anselm on the Dialectics of Divine Power
Authors: Whitman Jon
Published: April 2011

One of the features distinguishing the work of Anselm of Canterbury is the systematic attempt to coordinate linguistic nuances with logical distinctions. At times this effort promotes subtle but provocative shifts in perspective that pass far beyond the frameworks of language and logic in their own right. Such a shift in perspective, I believe, marks Anselm's approach to a long-standing problem in Christian theology regarding the power of God. In seeking to clarify the ambiguous terminology of divine omnipotence, Anselm develops an intriguing sense of the “other side” of divine power—the susceptibilities and capacities of this world—that anticipates some of the most important philosophic tendencies of the twelfth century. It seems to me that Anselm's position in this respect has not been adequately recognized, and in this essay I would like briefly to try to situate him in that historic turn.
Becoming Heretical: Affection and Ideology in Recruitment to Early Christianities
Authors: Eshleman Kendra
Published: April 2011

A growing consensus recognizes that the differences among Christians in the late second and early third centuries were neither as obvious nor as great as representatives of later orthodoxy would have us believe, and that what divided Christians in this period were not so much different beliefs and ideas as different hermeneutical and ritual practices. This article approaches the same conclusion from a different angle: from the perspective of potential recruits to Christianity, drawing on social-scientific models of conversion. For them, the peculiarities of doctrine and even of practice that obsess ancient polemicists and modern scholars were often largely invisible. While those features could take center stage for mature converts—and hence in retrospective accounts of conversion—they seem to have played little role in bringing people to specific versions of the faith in the first place. Rather, for many Christian recruits, the road to “orthodoxy” or “heresy” began not in ideological attraction, but in attachments to family, friends, and patrons already inside the group.