bluuebunny/crossref_metadata_2025 huggingface dataset:
Glioblastoma targeting via integrins is concentration dependent
Authors: Rosca Elena V. , Gillies Robert J. , Caplan Michael R.
Published: June 2009

A novel approach to treat cancer more selectively is achieved by targeting drugs to cells via conjugating the drug or imaging agent to an antibody or ligand for a cell surface receptor that is over‐expressed by the target cell population. Previous work by us has suggested that enhanced specificity can be obtained by multivalency of binding moieties. In this study we investigated the binding specificity of a multivalent construct including three peptides segments (TWYKIAFQRNRK), which bind the α6β1‐integrin, linked by poly(ethylene glycol) spacers. The binding specificity of the constructs was calculated by quantifying their binding to target cells (glioma cells, SF 767) relative to non‐targeted cells (normal human astrocytes, NHA). Dodecapeptide constructs (monovalent) exhibit specificity equal to the ratio of receptor expression at all concentrations. However, trivalent constructs demonstrated a sharp increase in specificity at concentrations less than the affinity of the receptor–ligand bond (4.28 µM). These experiments (conducted at 4°C) were consistent with the theoretical prediction and indicate that the biophysical model captures the basic trend of the data in the absence of receptor internalization, although the concentration at which increased specificity is observed is greater than predicted. The biophysical model does not predict the results of 37°C experiments, and this is shown to be due to internalization which occurs at 37°C but not at 4°C. Biotechnol. Bioeng. 2009; 104: 408–417 © 2009 Wiley Periodicals, Inc.
A practical approach for exploration and modeling of the design space of a bacterial vaccine cultivation process
Authors: Streefland M. , Van Herpen P.F.G. , Van de Waterbeemd B. , Van der Pol L.A. , Beuvery E.C. , Tramper J. , Martens D.E. , Toft M.
Published: June 2009

A licensed pharmaceutical process is required to be executed within the validated ranges throughout the lifetime of product manufacturing. Changes to the process, especially for processes involving biological products, usually require the manufacturer to demonstrate that the safety and efficacy of the product remains unchanged by new or additional clinical testing. Recent changes in the regulations for pharmaceutical processing allow broader ranges of process settings to be submitted for regulatory approval, the so‐called process design space, which means that a manufacturer can optimize his process within the submitted ranges after the product has entered the market, which allows flexible processes. In this article, the applicability of this concept of the process design space is investigated for the cultivation process step for a vaccine against whooping cough disease. An experimental design (DoE) is applied to investigate the ranges of critical process parameters that still result in a product that meets specifications. The on‐line process data, including near infrared spectroscopy, are used to build a descriptive model of the processes used in the experimental design. Finally, the data of all processes are integrated in a multivariate batch monitoring model that represents the investigated process design space. This article demonstrates how the general principles of PAT and process design space can be applied for an undefined biological product such as a whole cell vaccine. The approach chosen for model development described here, allows on line monitoring and control of cultivation batches in order to assure in real time that a process is running within the process design space. Biotechnol. Bioeng. 2009; 104: 492–504 © 2009 Wiley Periodicals, Inc.
Evaluation of monoclonal antibody and phenolic extraction from transgenic Lemna for purification process development
Authors: Woodard Susan L. , Wilken Lisa R. , Barros Georgia O.F. , White Steven G. , Nikolov Zivko L.
Published: June 2009

Several pharmaceutical protein products made in transgenic plant hosts are advancing through clinical trials. Plant hosts present a different set of impurities from which the proteins must be purified compared to other expression hosts such as mammalian cells. In this work, phenolic compounds present in extracts of monoclonal antibody (mAb)‐expressing Lemna minor were examined. Two different extraction pHs were evaluated to assess the effect of extraction condition on the concentration of mAb and phenolics in the extracts. The extract prepared at pH 4.5 had an enriched level of mAb relative to native protein when compared to a pH 7.5 extract although similar overall mAb was extracted at either pH. Slightly more mAb was recovered from the pH 3 elution of the pH 4.5 extract run on a MabSelect column than was recovered from the pH 7.5 extract. Phenolic levels in extracts were assessed by spectrophotometry, Folin–Ciocalteu assay and by profiling on RP‐HPLC. The Folin–Ciocalteu assay results did not agree with those obtained by the other two methods. Therefore phenolic levels were quantified by RP‐HPLC comparing the total area of phenolic peaks to those of reference phenolic compounds. The pH 7.5 extract had 22% less phenolics than the pH 4.5 extract. Acidic precipitation of the pH 7.5 extract resulted in further reduction of phenolics originally present in the pH 7.5 extract. The total phenolics present in the extracts were effectively removed by incubation of extracts with a commercially available anion exchange resin, Amberlite IRA‐402. We anticipate that early removal of phenolic compounds will prolong the life of more expensive affinity columns used for the purification of potential pharmaceutical proteins and should therefore be considered in process development involving proteins extracted from transgenic plant hosts. Biotechnol. Bioeng. 2009; 104: 562–571 © 2009 Wiley Periodicals, Inc.
Children's nurses' experiences of child protection: what helps?
Authors: Rowse Vicki
Published: June 2009

This paper reports on one area of findings of a study undertaken in the spring of 2008 at a district general hospital in the south of England. Individual semi‐structured interviews using an interpretive phenomenological approach were undertaken with 15 nurses and midwives working in paediatrics who had been involved in child protection cases. The aim was to explore their views and feelings of the experience. Very little research was found to inform this subject and none specifically with nurses working with sick children. Interviews were taped, transcribed and analysed thematically. It was discovered that involvement in child protection has a lasting impact on individuals; nurses need procedural information from a knowledgeable supporter during a case; and they need support from the right person in the right place at the right time for them. The Named Nurse was identified as being crucial in giving effective support to individuals during child protection cases and trusted advice and support helps staff follow through on niggling concerns, potentially preventing abuse. Copyright © 2009 John Wiley & Sons, Ltd.
Fast EMG‐data driven skin deformation
Authors: Kasap Mustafa , Chaudhuri Parag , Magnenat‐Thalmann Nadia
Published: June 2009

Virtual characters are being modeled and animated with increasing accuracy and photorealism in current games and virtual reality simulations. However, the detailed modeling of dynamic skin deformations due to movement of the muscles during articulation is still prohibitively expensive for real‐time simulations. We present in this paper a fast approach for modeling such deformations driven by Electromyography (EMG) data. We demonstrate the method on the muscles of the upper leg during a gait cycle. A muscle map, created from a 3D muscle model, is applied as a deformation map to deform the skin surface as per the underlying muscle geometry. EMG signals recorded from a gait cycle are then used to dynamically vary the weights in the deformation map during animation thus producing the dynamic skin deformations. The whole operation is done on the GPU to make it very fast and suitable forreal‐time simulations. Copyright © 2009 John Wiley & Sons, Ltd.
A Highly Active Single‐Mutation Variant of P450BM3 (CYP102A1)
Authors: Whitehouse Christopher J. C. , Bell Stephen G. , Yang Wen , Yorke Jake A. , Blanford Christopher F. , Strong Anthony J. F. , Morse Edward J. , Bartlam Mark , Rao Zihe , Wong Luet‐Lok
Published: June 2009

The power of proline: Bold amino acid substitutions in sensitive protein regions are frequently unproductive, while more subtle mutations can be sufficient to bring about dramatic changes. But introducing proline at the residue next to the sulfur ligand in P450BM3 (CYP102A1) has the unexpected and desirable effect of enhancing the activity of this fatty acid hydroxylase with a broad range of non‐natural substrates, as illustrated by the figure.

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Photocatalytic Redox Reactions for In‐Source Peptide Fragmentation
Authors: Qiao Liang , Bi Hongyan , Busnel Jean‐Marc , Waser Jerome , Yang Pengyuan , Girault Hubert H. , Liu Baohong
Published: June 2009

In‐source oxidation: In‐source photocatalytic redox reactions for inducing peptide fragmentation are achieved on a TiO2‐derived target plate during laser desorption ionization mass spectrometry in the presence of samples and glucose acting as both an electron donor and a hole conductor (see scheme).

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In‐source photocatalytic redox reactions based on a photosensitive target plate have been developed to realize peptide fragmentation during laser desorption ionization. Sample peptides and glucose are simply deposited on a spot of sintered TiO2nanoparticles. With the irradiation of UV laser on TiO2, electrons are excited from the valence to the conduction band, leaving oxidative holes and reductive electrons to drive various in‐source redox reactions. Glucose, working here as a hole scavenger and conductor, can favor both on‐surface reduction and long distance in‐plume oxidation, therefore inducing peptide fragmentation. CαC backbone cleavage was observed to generatea,xfragment decay, while the NCαbond cleavage was also sometimes obtained to inducec,zfragmentation, but was rather weaker. The former dissociation is believed to originate from oxidative routes induced by the valence band holes, based on the oxidation of nitrogen atom at the peptide backbone, including hydrogen‐radical abstraction and electron transfer. In contrast, the latter dissociation is supposed to be the result of reductive processes by the conduction band electrons, which are then rather similar to electron capture dissociation in tandem mass spectrometry.
In vivo visualization of transplanted pancreatic islets by MRI: comparison between in vivo, histological and electron microscopy findings
Authors: Marzola Pasquina , Longoni Biancamaria , Szilagyi Erzsebet , Merigo Flavia , Nicolato Elena , Fiorini Silvia , Paoli Giacomo T. , Benati Donatella , Mosca Franco , Sbarbati Andrea
Published: June 2009

The aim of the work was to compare in vivo MRI visualization of pancreatic islets labeled with clinical‐grade superparamagnetic iron oxide (SPIOs) contrast agents with ex vivo examination of liver tissue in an experimental model of marginal mass transplantation in rats. Seven hundred IEq (Islet Equivalent) from Wistar rats, labeled by incubation with Endorem® or Resovist®, were transplanted into Sprague–Dawley rats through the portal vein. Liver MR images of recipient rats were acquired at different time points (3–42 days) after transplantation. Animals were sacrificed during this period and their livers were excised and prepared for histology and electron microscopy. Hypointense spots originating from iron particles were observed in MR images. The number of separate spots was counted. Three days after transplantation one spot for every three or four transplanted islets was observed. Seven days after transplantation, histological sections showed the presence of iron within pancreatic islets. The time course of MR images showed a decrease in the number of spots, at 42 days, amounting to 65 and 22% of the initial value, for Resovist® and Endorem® respectively, while no immunopositive endocrine cells were detected in histological slices. The present work shows that pancreatic islets can be labeled using clinically approved SPIO contrast agents and visualized using in vivo MRI with high sensitivity, consistently with findings in the literature. Differently from reports in the literature, our findings indicate that iron particles could last in the liver for long periods, independently of the presence of intact pancreatic islets. Copyright © 2009 John Wiley & Sons, Ltd.
Topography and Recognition Imaging of Protein‐Patterned Surfaces Generated by AFM Nanolithography
Authors: Zhu Rong , Ebner Andreas , Kastner Markus , Preiner Johannes , Howorka Stefan , Hinterdorfer Peter
Published: June 2009

Native‐protein nanolithography is combined with topography and recognition imaging to synergistically use AFM tips to write and image nanoscale protein patterns on a surface (see picture). The approach is validated with different feedback modes, using surface‐bound biotinylated bovine serum albumin (BSA) protein and AFM tips carrying streptavidin.

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A Substrate‐Independent Approach for the Surface Immobilization of Oligonucleotides using Aldehyde Functionalized Surfaces
Authors: McGettrick James D. , Schofield Wayne C. E. , Garrod Richard P. , Badyal Jas Pal S.
Published: June 2009

A highly efficient approach for the covalent immobilization of single‐strand DNA onto solid surfaces and their subsequent hybridization to complementary strands is described. This entails pulsed plasma deposition of poly(3‐vinylbenzaldehyde) followed by the Schiff‐base reaction. A range of substrates, including glass slides, silicon wafers, polystyrene microspheres, and single‐walled carbon nanotubes (SWNTs), are functionalized employing this methodology.
Growth of Polypyrrole‐like Films on Self‐Assembly Nanostructured Silicon Surfaces by PECVD
Authors: Yagüe Jose Luis , Agulló Núria , Borrós Salvador
Published: June 2009

The development of conducting polymers has become the aim of many research groups. This paper describes attempts to carry out a plasma polymerization of polypyrrole (PPy) on a nanostructured surface by attaching a 11‐(pyrrol‐1‐yl‐undecyl)dimethylchlorosilane molecule onto a silicon wafer surface in order to form a self‐assembled monolayer (SAM). The effect of the SAM in the polymerization process is also studied. Important differences in the polymer deposition are found whether or not the surface has been modified with a SAM. Atomic force microscopy (AFM) and time‐of‐flight secondary ion mass spectrometry (TOF‐SIMS) analyses are performed to study the morphology, deposition, and growth of polypyrrole.
Bridging Experiments and Simulations in Oblique Angle Polymerization
Authors: Cetinkaya Murat , Demirel Melik C.
Published: June 2009

In this paper, we report the growth of nanostructured poly(p‐xylylene) (PPX) films by oblique angle polymerization at various deposition angles. Additionally, a two‐dimensional computational (Monte Carlo) model is implemented to study the nanostructured growth process. The morphology of the nanostructured polymer films are characterized by atomic force microscopy and scanning electron microscopy. Based on the experimental results, a competitive growth model is proposed and quantified in terms of column geometry (i.e., diameter and height), column spacing (i.e., periodicity), and column packing (i.e., number of columns per unit area). We show that the nanostructured polymer growth obeys a universal power‐law scaling mechanism at various deposition angles. The computational model predicts similar nanostructured morphologies to the oblique angle polymerization obtained experimentally. Nanostructured polymer films may provide great advances in sensing and biomedical applications.
Partially Fluorinated Poly‐p‐xylylenes Synthesized by CVD Polymerization
Authors: Elkasabi Yaseen , Nandivada Himabindu , Chen Hsien‐Yeh , Bhaskar Srijanani , D'Arcy John , Bondarenko Lidija , Lahann Joerg
Published: June 2009

This paper describes partially fluorinated poly‐p‐xylylenes prepared by CVD polymerization. The synthesis, characterization, and surface modification of two partially fluorinated polymer coatings, namely poly(4,12‐dibromo‐1,1,9,9‐tetrafluoro‐p‐xylylene) (2) and poly(4‐heptadecafluorononanoyl‐p‐xylylene‐co‐p‐xylylene) (4), is described. Polymer 2 is synthesized from 4,12‐dibromo‐1,1,9,9‐tetrafluoro[2.2]paracyclophane (1), which is fluorinated at the aliphatic bridge, while 4‐heptadecafluorononanoyl[2.2]paracyclophane (3), which contains a perfluorinated keto group at the aromatic ring, is used to synthesize polymer 4. Furthermore, the keto‐functionalized polymer 4 introduces both extreme hydrophobicity and surface reactivity towards hydrazide‐containing ligands.
A review of family intervention guidelines for pediatric acquired brain injuries
Authors: Cole Wesley R. , Paulos Stephanie K. , Cole Carolyn A.S. , Tankard Carol
Published: June 2009

Pediatric acquired brain injury (BI) not only affects the child with the injury, but also greatly impacts their family. Studies suggest there are higher rates of caregiver and sibling psychological distress after a child in the family has sustained a BI. Also, family functioning after BI impacts the child's recovery. In reviewing the literature, we identified seven theoretical clinical guidelines for working with families of children and adolescents with BI. These clinical guidelines are as follows: (1) select developmentally appropriate interventions, (2) match the intervention to the family, (3) provide advocacy, (4) provide injury education, (5) focus on family realignment, (6) appropriately adjust the child's environment, and (7) provide skills training to the family and child. The existing research on family interventions for BI is reviewed within the context of these theoretical guidelines, and the empirical support for each guideline is subsequently evaluated using specific criteria for empirically supported treatments. Unfortunately, very few randomized controlled studies exist, and continued research is needed to classify all clinical guidelines as “efficacious.” In addition, continued research will aid in informing professionals of specific approaches to utilize when working with a family of a child with BI. Currently, clinicians and researchers can turn to the existing clinical guidelines to help address the numerous barriers posed by implementing and studying family interventions for pediatric BI. © 2009 Wiley‐Liss, Inc. Dev Disabil Res Rev 2009;15:159–166.
Behavior management for children and adolescents with acquired brain injury
Authors: Slifer Keith J. , Amari Adrianna
Published: June 2009

Behavioral problems such as disinhibition, irritability, restlessness, distractibility, and aggression are common after acquired brain injury (ABI). The persistence and severity of these problems impair the brain‐injured individual's reintegration into family, school, and community life. Since the early 1980s, behavior analysis and therapy have been used to address the behavioral sequelae of ABI. These interventions are based on principles of learning and behavior that have been robustly successful when applied across a broad range of other clinical populations. Most of the research on behavioral treatment after ABI has involved clinical case studies or studies employing single‐subject experimental designs across a series of cases. The literature supports the effectiveness of these interventions across ages, injury severities, and stages of recovery after ABI. Recommended guidelines for behavior management include: direct behavioral observations, systematic assessment of environmental and within‐patient variables associated with aberrant behavior, antecedent management to minimize the probability of aberrant behavior, provision of functionally equivalent alternative means of controlling the environment, and differential reinforcement to shape positive behavior and coping strategies while not inadvertently shaping emergent, disruptive sequelae. This package of interventions requires direction by a highly skilled behavioral psychologist or therapist who systematically monitors target behavior to evaluate progress and guide treatment decisions. A coordinated multisite effort is needed to design intervention protocols that can be studied prospectively in randomized controlled trials. However, there will continue to be an important role for single subject experimental design for studying the results of individualized interventions and obtaining pilot data to guide subsequent randomized controlled trails. © 2009 Wiley‐Liss, Inc. Dev Disabil Res Rev 2009;15:144–151.
How soil conservation affects the catchment sediment budget – a comprehensive study in the north Ethiopian highlands
Authors: Nyssen Jan , Clymans Wim , Poesen Jean , Vandecasteele Ine , De Baets Sarah , Haregeweyn Nigussie , Naudts Jozef , Hadera Amanuel , Moeyersons Jan , Haile Mitiku , Deckers Jozef
Published: June 2009

An overall approach to assess the effectiveness of soil conservation measures at catchment scale is the comparison of sediment budgets before and after implementation of a catchment management programme. In the May Zeg‐zeg catchment (187 ha) in Tigray, north Ethiopia, integrated catchment management has been implemented since 2004: stone bunds were built in the whole catchment, vegetation was allowed to re‐grow on steep slopes and other marginal land, stubble grazing abandoned, and check dams built in gullies. Land use and management were mapped and analysed for 2000 and 2006, whereby particular attention was given to the quantification of changes in soil loss due to the abandonment of stubble grazing. Sediment yield was also measured at the catchment's outlet. A combination of decreased soil loss (from 14·3 t ha–1 y–1 in 2000 to 9·0 t ha–1 y–1 in 2006) and increased sediment deposition (from 5·8 to 7·1 t ha–1 y–1) has led to strongly decreased sediment yield (from 8·5 to 1·9 t ha–1 y–1) and sediment delivery ratio (from 0·6 to 0·21). This diachronic comparison of sediment budgets revealed that integrated catchment management is most effective and efficient and is the advisable and desirable way to combat land degradation in Tigray and other tropical mountains. Copyright © 2009 John Wiley & Sons, Ltd.
Remote sensing of volumetric storage changes in lakes
Authors: Smith Laurence C. , Pavelsky Tamlin M.
Published: June 2009

Three‐dimensional remote sensing promises a giant leap forward for surface‐water hydrology in much the same way that radar altimetry transformed physical oceanography. However, the complex geometries of small terrestrial water bodies introduce difficulties, particularly with respect to trade‐offs between changing water depth and inundation area. We use in situ measurements of water‐surface stage (ΔH/dt) and remotely‐sensed area (A) to compute time varying storage changes (ΔS) in nine lakes of the Peace‐Athabasca Delta, Canada. Despite their identical geomorphic setting, regression slopes between ΔH and A vary significantly between lakes, primarily from a predictable ‘area‐effect’ but also small bathymetric variations between basins. On average, lateral contraction/expansion (versus stage adjustment) contributes as little as 7% (versus 93%) to as much as 76% (versus 24%) of overall storage change ΔS. We conclude that both surface‐area and ΔH/dt, rather than just either alone, must be measured to confidently estimate ΔS from space. Copyright © 2009 John Wiley & Sons, Ltd.
Pseudostress–velocity formulation for incompressible Navier–Stokes equations
Authors: Cai Zhiqiang , Wang Yanqiu
Published: June 2009

This paper presents a numerical algorithm using the pseudostress–velocity formulation to solve incompressible Newtonian flows. The pseudostress–velocity formulation is a variation of the stress–velocity formulation, which does not require symmetric tensor spaces in the finite element discretization. Hence its discretization is greatly simplified. The discrete system is further decoupled into an H(div) problem for the pseudostress and a post‐process resolving the velocity. This can be done conveniently by using the penalty method for steady‐state flows or by using the time discretization for nonsteady‐state flows. We apply this formulation to the 2D lid‐driven cavity problem and study its grid convergence rate. Also, computational results of the time‐dependent‐driven cavity problem and the flow past rectangular problem are reported. Copyright © 2009 John Wiley & Sons, Ltd.
A high‐fidelity low‐cost aerodynamic model using proper orthogonal decomposition
Authors: Mifsud M. J. , Shaw S. T. , MacManus D. G.
Published: June 2009

In this paper a high‐fidelity aerodynamic model is presented for use in parametric studies of weapon aerodynamics. The method employs a reduced‐order model obtained from the proper orthogonal decomposition (POD) of an ensemble of computational fluid dynamics (CFD) solutions with varying parameters. This decomposition produces an optimal linear set of orthogonal basis functions that best describe the ensemble of numerical solutions. These solutions are then projected onto this set of basis functions to provide a finite set of scalar coefficients that represent the solutions. A pseudo‐continuous representation of these projection coefficients is constructed, which allows predictions to be made of parameter combinations not in the original set of observations. The paper explores the performance of a few design‐of‐experiment approaches for the generation of the initial ensemble of computational experiments. Response surface construction methods based on parametric and non‐parametric models for the pseudo‐continuous representation of the projection coefficients are also evaluated. The model has been applied to two‐flow problems related to high‐speed weapon aerodynamics, inviscid flow around a flare‐stabilized hypersonic projectile and supersonic turbulent flow around a fin‐stabilized projectile with drooping nose control. Comparisons of model predictions with high‐fidelity CFD simulations suggest that the POD provides a reliable and robust approach to the construction of reduced‐order models. The practicality of the model is shown to be sensitive to the technique used to generate the ensemble of observations from which the model is constructed, while the accuracy of the approach depends on the pseudo‐continuous representation of the projection coefficients. Copyright © 2009 John Wiley & Sons, Ltd.
Big diameter tunnelling beneath low rock cover
Authors: Meyer Dieter , Brodbeck Frank , McKenzie Nick
Published: June 2009

The Clem Jones Tunnel (former North‐South Bypass Tunnel) is the first project to get underway as part of Brisbane's transport plan which aims to improve the urban road network. The total length to be excavated is 6.8 km which includes 4.8 km of driven tunnel and associated road connections. Construction commenced in August 2006 with project completion targeted well before the contractual completion date of October 2010. Due to the local geology, in particular the hard Brisbane tuff and Neranleigh‐Fernvale formation a combination of tunnel excavation methods are used. The majority of the tunnel is excavated by two tunnel boring machines in rock having a compressive strength of between 80 and 150 MPa. Ten roadheaders are excavating the remaining tunnels such as ramps, access tunnels, cross passages and merges.

A major challenge arose during the planning of the initial mainline excavation underneath the Royal National Association Showground in Bowen Hills. This section contains low rock cover and historical maps indicate that the Showground is located within a former topographic depression (alluvial valley) where a creek once flowed through. Due to traffic merge design requirements, both TBM and roadheader excavation methods were required to be used in this challenging geological profile. The answer was to stabilise the alluvium above both TBM section tunnels from the surface prior to excavation and to operate the TBM in single shield mode with immediate grouting of annular void from the tail shield. In addition, the roadheader section of tunnel required additional support by spiles and canopy tubes installed from the tunnel face.
The influence of grout and bentonite slurry on the process of TBM tunnelling
Authors: Bezuijen Adam
Published: June 2009

The bentonite and grout flow around a TBM is elaborated, as well as grout flow along the lining. The calculated grout flow along the lining is compared with the results of measurements. Measurement data for the flow around the TBM are not available. Both the bentonite and the grout are modelled as a Bingham liquid and it will be shown that, due to the relatively low flow velocities, the yield stress is the governing parameter. The results of the calculations show that both the flow around the TBM and the flow around the lining may significantly influence loading on the TBM, the soil, and the lining. The bentonite and grout flow around the TBM may result in a lower volume loss than calculated when assuming that the soil follows the tapered TBM. The grout flow and especially grout consolidation lead to lower pressures around the lining if the tunnel is constructed in sandy soil.
TRAIL receptor upregulation and the implication of KRAS/BRAF mutations in human colon cancer tumors
Authors: Oikonomou Eftychia , Kosmidou Vivian , Katseli Anastasia , Kothonidis Konstantinos , Mourtzoukou Despina , Kontogeorgos George , Andera Ladislav , Zografos Georgios , Pintzas Alexander
Published: June 2009

TRAIL raises hopes as a promising anti‐tumor agent due to its selectivity toward cancer cells. Higher expression of its pro‐death receptors TRAIL‐R1 (DR4) and TRAIL‐R2 (DR5) attenuates higher sensitivity to TRAIL‐induced apoptosis, and represents a marker for better cancer prognosis and treatment. Since receptor availability can be analogous to ligand efficacy, we performed RT‐PCR analysis of DR4 and DR5 in 51 colon cancer biopsy specimens and respective normal mucosa, while 11 of these tumors were determined immunohistochemically for protein expression. Transcriptional analysis showed that DR4 and DR5 were significantly upregulated in 37 and 47% of the tumor samples respectively, while both DR4 and DR5 were coinstantaneously upregulated in 31% of the samples analyzed. Positive transcriptional regulation of DRs was recorded as early as Dukes' A stage. Furthermore, protein expression analysis yielded results comparable to DR4 and DR5 increased mRNA levels. Possible contributing events to DR upregulation involve presence of frequent oncogenic mutations in the MAPK pathway, and was investigated by direct sequencing in all 51 tumors. Samples (6/8) hosting either a KRASG12Vor BRAFV600Emutation, significantly amplified the upregulated expression of DR4 and DR5, showing strong inter‐relation between overexpression and presence of oncogenic KRAS/ BRAF mutations. In the light of recent data concerning TRAIL receptor distribution, we contribute further by presenting DR5 as the most frequently upregulated DR in colon cancer. Furthermore, oncogenic mutations may directly or indirectly enhance DR expression, potentially sensitizing these tumors to TRAIL‐based therapies. © 2009 UICC
Carbonic anhydrase IX and human papillomavirus as diagnostic biomarkers of cervical dysplasia/neoplasia in women with a cytologic diagnosis of atypical glandular cells: A Gynecologic Oncology Group study in United States
Authors: Liao Shu‐Yuan , Rodgers William H. , Kauderer James , Bonfiglio Thomas A. , Walker Joan L. , Darcy Kathleen M. , Carter Randy , Hatae Masayuji , Levine Lyuba , Spirtos Nick M. , Stanbridge Eric J.
Published: June 2009

High‐risk human papillomavirus (H‐HPV) infection is strongly linked to cervical neoplasia, but its role in detecting glandular lesions (GLs) is unclear. In the cervix, carbonic anhydrase IX (CA‐IX) is expressed in cervical neoplasia, but rarely in the benign cervix. The diagnostic utility of these biomarkers was evaluated in women with a cytologic diagnosis of atypical glandular cells (AGC). H‐HPV was detected using hybrid capture 2 (HC2) in liquid‐based cytology, and CA‐IX immunoreactivity was studied on conventional Pap smears. Of 403 patients, 111 (28%) were positive for significant cervical lesions (SCLs) including CIN2, CIN3, adenocarcinoma in situ or invasive carcinoma. CA‐IX testing alone (n = 403) had a sensitivity of 75, 95 or 65% for SCLs, significant GLs or squamous lesions (SLs), respectively, with a specificity of 88% and a false negative rate (FNR defined as 1 minus negative predictive value) of 10%. Testing for H‐HPV (n = 122) had a sensitivity of 97, 100 or 96% for SCLs, GLs or SLs, respectively, with a specificity of 87% and a FNR of 1%. The combination of CA‐IX and H‐HPV testing (n = 122), collectively, had the same sensitivity, specificity and FNR for SCLs, GLs or SLs as H‐HPV testing alone. The conclusions of our study are that both H‐HPV and CA‐IX testing are useful diagnostic markers for GLs. However, H‐HPV testing is a better diagnostic marker for SLs. The combination of CA‐IX with H‐HPV testing does not improve the diagnostic accuracy for cervical neoplasia in women with AGC diagnosis over that of H‐HPV testing alone. © 2009 UICC
Breast cancer metastasis suppressor 1 coordinately regulates metastasis‐associated microRNA expression
Authors: Edmonds Mick D. , Hurst Douglas R. , Vaidya Kedar S. , Stafford Lewis J. , Chen Dongquan , Welch Danny R.
Published: June 2009

Breast cancer metastasis suppressor 1 (BRMS1) suppresses metastasis of multiple tumor types without blocking tumorigenesis. BRMS1 forms complexes with SIN3, histone deacetylases and selected transcription factors that modify metastasis‐associated gene expression (e.g., EGFR, OPN, PI4P5K1A, PLAU). microRNA (miRNA) are a recently discovered class of regulatory, noncoding RNA, some of which are involved in neoplastic progression. Based on these data, we hypothesized that BRMS1 may also exert some of its antimetastatic effects by regulating miRNA expression. MicroRNA arrays were done comparing small RNAs that were purified from metastatic MDA‐MB‐231 and MDA‐MB‐435 and their nonmetastatic BRMS1‐transfected counterparts. miRNA expression changed by BRMS1 were validated using SYBR Green RT‐PCR. BRMS1 decreased metastasis‐promoting (miR‐10b, ‐373 and ‐520c) miRNA, with corresponding reduction of their downstream targets (e.g., RhoC which is downstream of miR‐10b). Concurrently, BRMS1 increased expression of metastasis suppressing miRNA (miR‐146a, ‐146b and ‐335). Collectively, these data show that BRMS1 coordinately regulates expression of multiple metastasis‐associated miRNA and suggests that recruitment of BRMS1‐containing SIN3:HDAC complexes to, as yet undefined, miRNA promoters might be involved in the regulation of cancer metastasis. © 2009 UICC
RhoB induces apoptosis via direct interaction with TNFAIP1 in HeLa cells
Authors: Kim Dong‐Myung , Chung Kyung‐Sook , Choi Shin‐Jung , Jung Yu‐Jin , Park Song‐Kyu , Han Gyoon‐Hee , Ha Jae‐Seok , Song Kyung‐Bin , Choi Nam‐Song , Kim Hwan‐Mook , Won Misun , Seo Yeon‐Soo
Published: June 2009

RhoB, a tumor suppressor, has emerged as an interesting cancer target, and extensive studies aimed at understanding its role in apoptosis have been performed. In our study, we investigated the involvement of RhoB‐interacting molecules in apoptosis. To identify RhoB‐interacting proteins, we performed yeast‐two hybrid screening assays using RhoB as a bait and isolated TNFAIP1, a TNFα‐induced protein containing the BTB/POZ domain. The interaction between RhoB and TNFAIP1 was demonstrated in vivo through coimmunoprecipitation studies and in vitro binding assays. RFP‐TNFAIP1 was found to be partially colocalized with EGFP‐RhoB. The partial colocalization of RhoB and TNFAIP1 in endosomes suggests that RhoB‐TNFAIP1 interactions may have a functional role in apoptosis. TNFAIP1 elicited proapoptotic activity, while simultaneous expression of RhoB and TNFAIP1 resulted in a dramatic increase in apoptosis in HeLa cells. Furthermore, knockdown of RhoB using siRNA clearly rescued cells from apoptosis induced by TNFAIP1. This finding suggests that interactions between RhoB and TNFAIP1 are crucial for induction of apoptosis in HeLa cells. The observation of increased SAPK/JNK phosphorylation in apoptotic cells and the finding that a JNK inhibitor suppressed apoptosis indicates that SAPK/JNK signaling may be involved in apoptosis induced by RhoB‐TNFAIP1 interactions. In conclusion, we found that RhoB interacts with TNFAIP1 to regulate apoptosis via a SAPK/JNK‐mediated signal transduction mechanism. © 2009 UICC
Chromosomal abnormalities and novel disease‐related regions in progression from Barrett's esophagus to esophageal adenocarcinoma
Authors: Akagi Tadayuki , Ito Tetsuo , Kato Motohiro , Jin Zhe , Cheng Yulan , Kan Takatsugu , Yamamoto Go , Olaru Alexandru , Kawamata Norihiko , Boult Jessica , Soukiasian Harmik J. , Miller Carl W. , Ogawa Seishi , Meltzer Stephen J. , Koeffler H. Phillip
Published: June 2009

Barrett's esophagus (BE) is a metaplastic condition caused by chronic gastroesophageal reflux which represents an early step in the development of esophageal adenocarcinoma (EAC). Single‐nucleotide polymorphism microarray (SNP‐chip) analysis is a novel, precise, high‐throughput approach to examine genomic alterations in neoplasia. Using 250K SNP‐chips, we examined the neoplastic progression of BE to EAC, studying 11 matched sample sets: 6 sets of normal esophagus (NE), BE and EAC, 4 of NE and BE and 1 of NE and EAC. Six (60%) of 10 total BE samples and 4 (57%) of 7 total EAC samples exhibited 1 or more genomic abnormalities comprising deletions, duplications, amplifications and copy‐number‐neutral loss of heterozygosity (CNN‐LOH). Several shared abnormalities were identified, including chromosome 9p CNN‐LOH [2 BE samples (20%)], deletion of CDKN2A [4 BE samples (40%)] and amplification of 17q12‐21.2 involving the ERBB2, RARA and TOP2A genes [3.1 Mb, 2 EAC (29%)]. Interestingly, 1 BE sample contained a homozygous deletion spanning 9p22.3–p22.2 (1.2 Mb): this region harbors only 1 known gene, basonuclin 2 (BNC2). Real‐time PCR analysis confirmed the deletion of this gene and decreased the expression of BNC2 mRNA in the BE sample. Furthermore, transfection and stable expression of BNC2 caused growth arrest of OE33 EAC cells, suggesting that BNC2 functions as a tumor suppressor gene in the esophagus and that deletion of this gene occurs during the development of EAC. Thus, this SNP‐chip analysis has identified several early cytogenetic events and novel candidate cancer‐related genes that are potentially involved in the evolution of BE to EAC. © 2009 UICC
Administering and assessing culture‐specific interventions to address culture‐bound issues among Asian American college students
Authors: Kim Josephine M.
Published: June 2009

The administration and assessment of culturally sensitive interventions can help postsecondary educators address critical culture‐bound issues among minority groups.
Using culturally sensitive frameworks to study Asian American leaders in higher education
Authors: Neilson Patricia A. , Suyemoto Karen L.
Published: June 2009

Asian and Asian American cultural perspectives can add valuable insight to the process of designing and executing inquiries of the lived experiences.
A decision support tool for irrigation infrastructure investments
Authors: Khan Shahbaz , Mushtaq Shahbaz , Chen Charlie
Published: June 2009

Increasing water scarcity, climate change and pressure to provide water for environmental flows urge irrigators to be more efficient. In Australia, ongoing water reforms and most recently the National Water Security Plan offer incentives to irrigators to adjust their farming practices by adopting water‐saving irrigation infrastructures to match soil, crop and climatic conditions.

WaterWorks is a decision support tool to facilitate irrigators to make long‐ and short‐term irrigation infrastructure investment decisions at the farm level. It helps irrigators to improve the economic efficiency, water use efficiency and environmental performance of their farm businesses. WaterWorks has been tested, validated and accepted by the irrigation community and researchers in NSW, Australia. The interface of WaterWorks is user‐friendly and flexible. The simulation and optimisation module in WaterWorks provides an opportunity to evaluate infrastructure investment decisions to suit their seasonal or long‐term water availability. The sensitivity analysis allows substantiation of the impact of major variables. Net present value, internal rate of return, benefit–cost ratio and payback period are used to analyse the costs and benefits of modern irrigation technology.

Application of WaterWorks using a whole farm‐level case study indicates its effectiveness in making long‐ and short‐term investment decisions. WaterWorks can be easily integrated into commercial software such as spreadsheets, GIS, real‐time data acquisition and control systems to further enhance its usability. WaterWorks can also be used in regional development planning. Copyright © 2009 John Wiley & Sons, Ltd.
Drip irrigation lateral design procedure based on emission uniformity and field microtopography
Authors: Zhu D. L. , Wu P. T. , Merkley G. P. , Jin J.
Published: June 2009

Field microtopography, hydraulic variation of the emitter, and manufacturing variation of emitters were analyzed to study their influence on the uniformity of drip irrigation system water application. The manufacturing coefficient in the emitter flow equation is taken as a random variable that represents the emitter manufacturing variation. Uneven field microtopography resulting in emitter pressure and flow variations is also considered as a random variable. Microtopography and the manufacturing coefficient that are assumed to follow a normal distribution were generated with a computer code. The rate of emitter discharge variation, the coefficient of discharge variation, and Christiansen's coefficient of uniformity were calculated for drip irrigation systems. Finally, the emitter uniformity equation was determined through the statistical analysis of 100 data sets, and a new design method for drip irrigation laterals is proposed. The results indicate that neglecting the microtopography leads to inappropriate design of lateral pipe diameter and length, especially when emitter operating pressures are low. Copyright © 2009 John Wiley & Sons, Ltd.
On reproducible econometric research
Authors: Koenker Roger , Zeileis Achim
Published: June 2009

Recent software developments are reviewed from the vantage point of reproducible econometric research. We argue that the emergence of new tools, particularly in the open‐source community, have greatly eased the burden of documenting and archiving both empirical and simulation work in econometrics. Some of these tools are highlighted in the discussion of two small replication exercises. Copyright © 2009 John Wiley & Sons, Ltd.
The design and testing of a dual fiber textile matrix for accelerating surface hemostasis
Authors: Fischer Thomas H. , Vournakis John N. , Manning James E. , McCurdy Shane L. , Rich Preston B. , Nichols Timothy C. , Scull Christopher M. , McCord Marian G. , Decorta Joseph A. , Johnson Peter C. , Smith Carr J.
Published: June 2009

The standard treatment for severe traumatic injury is frequently compression and application of gauze dressing to the site of hemorrhage. However, while able to rapidly absorb pools of shed blood, gauze fails to provide strong surface (topical) hemostasis. The result can be excess hemorrhage‐related morbidity and mortality. We hypothesized that cost‐effective materials (based on widespread availability of bulk fibers for other commercial uses) could be designed based on fundamental hemostatic principles to partially emulate the wicking properties of gauze while concurrently stimulating superior hemostasis. A panel of readily available textile fibers was screened for the ability to activate platelets and the intrinsic coagulation cascade in vitro. Type E continuous filament glass and a specialty rayon fiber were identified from the material panel as accelerators of hemostatic reactions and were custom woven to produce a dual fiber textile bandage. The glass component strongly activated platelets while the specialty rayon agglutinated red blood cells. In comparison with gauze in vitro, the dual fiber textile significantly enhanced the rate of thrombin generation, clot generation as measured by thromboelastography, adhesive protein adsorption and cellular attachment and activation. These results indicate that hemostatic textiles can be designed that mimic gauze in form but surpass gauze in ability to accelerate hemostatic reactions. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2009
Spectroscopy techniques for analyzing the hydrolysis of PLGA and PLLA
Authors: Tan Hwee Yun , Widjaja Effendi , Boey Freddy , Loo Say Chye Joachim
Published: June 2009

The in vitro hydrolytic degradation of irradiated biodegradable polymers was studied. Poly(L‐lactide), poly(lactide‐co‐glycolic acid) (PLGA)(80:20), and PLGA(50:50) polymers were first electron beam irradiated at 5 Mrad before hydrolytic degradation. Hydrolysis of these films was characterized through their physical properties—mass loss, average molecular weight, and thermal properties. Changes to the chemical structures of these polyesters were also analyzed using Fourier‐transformed infrared (FTIR) and Raman spectroscopy, and the spectra results were correlated to their physical properties. The results showed that an increase in hydroxyl (OH) group, observed from the FTIR spectroscopy, indicates that the polymer is degrading through hydrolysis—first‐stage degradation. Subsequently, a decrease in CO group, observed from Raman spectroscopy, indicates that the polymer is experiencing mass loss—second‐stage degradation. Therefore, a good correlation exists in determining the extent of polymer degradation through the use of FTIR and Raman spectroscopy by observing changes to the OH and CO groups from the spectra of these nondestructive techniques. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2009
Evaluation of drug‐eluting stents' coating durability—Clinical and regulatory implications
Authors: Levy Yair , Mandler Daniel , Weinberger Judah , Domb Abraham J.
Published: June 2009

Drug‐eluting stents (DES) revolutionized cardiovascular treatment by virtually eliminating in‐stent restanosis. However, in the past 3 years the U.S. Food and Drug Administration and published studies have raised several safety issues regarding DES such as late state thrombosis and increased mortality. Recent publications have described DES coating delaminating, cracking, and peeling in commercially available stents. It has been suggested that these properties are responsible for the deleterious effects. The goal of this work is to describe a quantitative in vitro durability tests for DES, referred to as Quantified Defects (QD). The technique was implemented on various stent polymer‐coated models to determine its ability to differentiate between coating properties. Stents' coating defects were tested using light microscopy, scanning electron microscopy, and a micro‐balance. High‐performance liquid chromatography was used for measuring drug release. Stents were incubated at either 37 or 60°C and sampled at 0, 3, and 30 days. Stent coating durability was tested using stainless steel control stents versus stents having increased surface adhesion, both of which were then coated with conventional spray‐coating methods. Drug‐coated stents tested for defects demonstrated a deteriorating durability profile as reflected by QD indices. Different coating models showed unique QD indices that reflected their superior or inferior coating durability. These results indicated that the methodology was able to differentiate between different models. In conclusion, this simple low‐cost testing methodology can be easily used during DES development, with either durable or biodegradable polymers. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2009