bluuebunny/crossref_metadata_2025 huggingface dataset:
Monitoring Ground‐Water Quality Near a Sanitary Landfill
Authors: Kunkle G. R. , Shade J. W.
Published: July 2006

At the Hagman Road Landfill refuse is buried in lacustrine and glacial till deposits consisting mainly of silty clays. These clays overlie a thick carbonate aquifer used locally for water supply. The dominant direction of ground‐water flow is vertically down. Time of groundwater travel from the refuse to the aquifer is estimated at 12 years, putting first arrivals in 1978. Water quality monitoring of bedrock waters shows decreases in total dissolved solids, sulfates, calcium, magnesium, chlorides, and total hardness with increases in alkalinity to exist locally beneath the landfill. The principal chemical reaction felt to explain some, but not all of the water quality changes is sulfate reduction. Theoretical geochemical modellings help to support this interpretation. The landfill is hypothesized to have either triggered or accelerated sulfate reduction by creating the reducing environment.
Design of Ground–Water Level Observation–Well Programs
Authors: Heath Ralph C.
Published: July 2006

Data obtained from observation–well programs are used to determine (1) the effect of withdrawals on recharge and natural discharge conditions, (2) the hydraulic characteristics of ground–water systems, and (3) the extent and degree of confinement of aquifers. Wells in these programs can usefully be divided into three networks: (1) a hydrologic network which includes wells needed to determine the extent of aquifers and changes in storage, (2) a water–management network which includes wells needed to determine the effect of withdrawals and hydraulic characteristics, and (3) a baseline network which includes wells needed to determine the response of ground–water systems to natural changes such as those related to climate.
Vyredox — In Situ Purification of Ground Water
Authors: Hallberg Rolf O , Martinell Rudolf
Published: July 2006

The abundance and relative purity of ground water guarantees its increase in usage. In some localities, the content of iron and manganese in ground water is so high that these metals must be removed before the water can be used for drinking or industrial purposes.

Iron occurs in two states of oxidation in nature–the divalent (ferrous) and trivalent (ferric) forms. The Vyredox method developed in Finland and used now also in Sweden and some other countries oxidizes the ferrous ion, which is soluble in water, to the ferric ion, which is insoluble, before the water enters the well.

The Vyredox method achieves a high degree of oxidation in the strata around the well. The method makes use of iron‐oxidizing bacteria and aeration wells. A number of aeration wells are placed in a ring around the supply well. Water is forced down the aeration wells but first it is degassed and then enriched with oxygen. The oxygen‐rich water provides a suitable habitat for the iron‐oxidizing bacteria which assist in the oxidation of ferrous iron. The process must be repeated at specific time intervals to avoid further increases of iron content.

The process of precipitating iron in the aquifer has only a slight effect on aquifer permeability. Cloggage of the aquifer surrounding the well should not occur for a period many times longer than the life span of a typical well.
A Seismic Ground – Water Survey in New Hampshire
Authors: Birch Francis S.
Published: July 2006

The drainage basin of Barbadoes Pond, Madbury and Dover, southeastern New Hampshire, was studied by seismic refraction and magnetic measurements as part of an interdisciplinary investigation. The purpose of the geophysical measurements was to provide boundary conditions (bedrock and water–table elevations) for a mathematical model of ground–water flow. The basin is intensively used for recreation, municipal water supply, and sand and gravel mining.

Barbadoes Pond is a kettle lake lying in the middle of a broad, flat–topped sand and gravel hill (a “kame plain”). The plain is surrounded by marine clay at a lower elevation.

A broad, deep, northwest–southwest trending trough underlies the plain according to seismic refraction measurements (45 lines) and water wells. The present form and location of the trough are attributed to glacial enlargement of a stream valley eroded along a bedrock shear zone. The bedrock topography and seismic velocity are directly related to erosion resistance of the vertically dipping metasedimentary bedrock. Magnetic anomalies are consistent with the seismic results.

Water–table elevation correlates with bedrock elevation, not surface elevation. This is a consequence of highly permeable sand and gravel, the principal surfical materials. Apparently the pond is not hydraulically independent of nearby wells and a large reservoir.

The results invite speculation that kame plains occur over bedrock troughs. Such a relationship, if generally true, would speed search for good well sites in this region of rapid population growth and industrial development.
An Integrated Approach to Delineating Contaminated Ground Water
Authors: Berk William J. , Yare Bruce S.
Published: July 2006

Disposal of industrial process water into an unlined lagoon in permeable Atlantic Coastal Plain sediments resulted in a ground‐water contamination problem caused by infiltration of the process water into a major unconfined aquifer which underlies the lagoon at shallow depth. Most of the area water‐supply wells terminate in this formation. Before this disposal method was discontinued, traces of the process water appeared in nearby wells.

Because of the relatively large area and depths involved, as indicated by preliminary data, delineation of the distribution of contaminant within the aquifer through a systematic well drilling program posed a significant economic problem. To keep costs within a reasonable range, a resistivity survey program was implemented to obtain information on the gross distribution of the contaminant and to provide data for the selective location of monitor wells. Eight wells were constructed to obtain samples of the ground water in order to measure contaminant concentrations and to verify the interpretations of areal contaminant distribution inferred from the resistivity data. The ground‐water sampling procedure developed during this investigation is described.

The combination of the resistivity survey with the ground‐water sampling procedure developed during this investigation proved a valuable and reliable technique for delineating in three dimensions a contaminant body within an aquifer in unconsolidated sediments. Utilization of the resistivity survey data to selectively locate the monitor wells and to define the lateral extent of the contamination increased the efficiency of the investigation and significantly reduced the cost of the program.
Flow to a Nonpenetrating Well in a Leaky Artesian Aquifer with Variable Dischargea
Authors: Jaiswal C. S. , Chauhan H. S.
Published: July 2006

A differential equation for axisymmetric radial transient flow to a nonpenetrating well in an infinite leaky aquifer in spherical coordinate system has been formulated. A general solution for nonsteady‐state flow was obtained for nonpenetrating wells in leaky artesian aquifers with a general time variable discharge function, as well as for the specific case of exponential decay discharge function. The solution is expressed in terms of standard mathematical functions.
A Procedure for Measuring Planar Cam Profiles and Their Follower Motions
Authors: Tsay Der-Min , Tseng Kuo-Shu , Chen Hsin-Pao
Published: July 2006

A procedure that can be used to inspect planar cam contours and to evaluate their follower displacement, velocity, and acceleration curves with a higher degree of accuracy, without the aid of approximating follower displacements in traditional methods, is constructed. Based on the geometric relationships at the contact point between a planar cam profile and its follower, analytical descriptions that can be utilized to determine the follower displacement curve and its derivatives are first identified. To verify the feasibility and accuracy of the proposed procedure, analytical results generated from a theoretical design are compared to those obtained by the application of the procedure. To demonstrate the effectiveness and usefulness of the developed procedure, a measuring test bed has been constructed for a practical application example. Furthermore, the results obtained by using the developed procedure with the built measuring test bed are also compared to those obtained by using a coordinate measuring machine with the proposed algorithms.
Influence of Machine Specific Instantaneous Current Wave Form on Resistance Spot Welding Process
Authors: De A. , Momeni K. , Thaddeus M. P. , Dorn L.
Published: July 2006

The influence of the machine specific instantaneous current wave forms on weld nugget dimensions and weld strength is investigated over six spot welding machines. It is observed that the nature of the real-time current wave forms corresponding to a common rms value can vary in different ac spot welding machines. The variations exist in the values of peak current and in the current-on and -off times in every ac cycle. It is observed that real-time current wave form involving higher peak current leads to slightly larger weld nugget diameter compared to wave form with smaller peak current even if the overall rms value remains similar. The real-time current wave form from a medium frequency dc confirms to a fast rise to the set weld current and remains steady for the complete weld time. A detailed experimental study has depicted that the real-time ac wave forms especially with high peak values and sharp rise characteristics offer a relatively smaller permissible range of weld currents compared to the wave forms with relatively flatter characteristics. The steady instantaneous current wave form confirming to the medium frequency dc machine has facilitated a larger permissible range of weld current. A numerical analysis of the spot welding process based on finite element process is carried out using both the instantaneous current wave forms and the corresponding rms values of weld current. The predicted weld dimensions using instantaneous current wave forms have showed slightly better agreement with the corresponding measured weld dimensions.
An Analysis of the Effect of Laser Beam Geometry on Laser Transformation Hardening
Authors: Safdar Shakeel , Li Lin , Sheikh M. A. , Liu Zhu
Published: July 2006

The effect of transformation hardening depends upon both heating and cooling rates. It is desirable to have a slow heating rate and a rapid cooling rate to achieve full transformation. To date laser transformation hardening has been carried out using circular or rectangular beams which result in rapid heating and cooling. Although the use of different beam intensity distributions within the circular or rectangular laser beams has been studied to improve the process, no other beam geometries have been investigated so far for transformation hardening. This paper presents an investigation into the effects of different laser beam geometries in transformation hardening. Finite element modeling technique has been used to simulate the steady state and transient effects of moving beams in transformation hardening of EN 43A steel. The results are compared with experimental data. The work shows that neither of the two commonly used beams, circular and rectangular, are optimum beam shapes for transformation hardening. The homogenization temperature exceeds the melting point for these beam shapes for the usual laser scanning speeds and power density. Triangular beam geometry has been shown to produce the best thermal history to achieve better transformation and highest hardness due to slower heating without sacrificing the processing rate and hardening depths.
Experimental and Numerical Analysis of the Friction Drilling Process
Authors: Miller Scott F. , Li Rui , Wang Hsin , Shih Albert J.
Published: July 2006

Friction drilling is a nontraditional hole-making process. A rotating conical tool is applied to penetrate a hole and create a bushing in a single step without generating chips. Friction drilling relies on the heat generated from the frictional force between the tool and sheet metal workpiece to soften, penetrate, and deform the work-material into a bushing shape. The mechanical and thermal aspects of friction drilling are studied in this research. Under the constant tool feed rate, the experimentally measured thrust force and torque were analyzed. An infrared camera is applied to measure the temperature of the tool and workpiece. Two models are developed for friction drilling. One is the thermal finite element model to predict the distance of tool travel before the workpiece reaches the 250°C threshold temperature that is detectable by an infrared camera. Another is a force model to predict the thrust force and torque in friction drilling based on the measured temperature, material properties, and estimated area of contact. The results of this study are used to identify research needs and build the foundation for future friction drilling process optimization.
Microstructure-Level Model for the Prediction of Tool Failure in WC-Co Cutting Tool Materials
Authors: Park Sunghyuk , Kapoor Shiv G. , DeVor Richard E.
Published: July 2006

A model to predict tool failure due to chipping in machining via the microstructure-level finite element cutting process simulation is presented and applied to a wide variety of WC-Co tool materials. The methodology includes the creation of arbitrary microstructures comprised of WC and Co phases to simulate various grades of WC-Co alloys. Equivalent stress, strain, and strain energy are then obtained via orthogonal microstructure-level finite element machining simulations. A model was developed to predict the occurrence of tool failure based on the mixed mode fracture criterion. Turning experiments were conducted to validate the model and the results showed that the model predictions agree well with the observations from the experiments. The model was then employed to study the effects of microstructural parameters and feedrate on chipping and failure.
Low meprin α expression differentiates primary ovarian mucinous carcinoma from gastrointestinal cancers that commonly metastasise to the ovaries
Authors: Heinzelmann-Schwarz Viola A , Scolyer Richard A , Scurry James P , Smith Alison N , Gardiner-Garden Margaret , Biankin Andrew V , Baron-Hay Sally , Scott Carolyn , Ward Robyn L , Fink Daniel , Hacker Neville F , Sutherland Robert L , O’Brien Philippa M
Published: July 2006

Background:Currently, no specific immunohistochemical markers are available to differentiate primary mucinous epithelial ovarian cancer (MOC) from adenocarcinomas originating at other sites that have metastasised to the ovary, which may have an impact on patient management and prognosis.

Aim:To investigate the expression of two intestinal markers, galectin 4 and meprin α, in mucinous carcinomas of the ovary and gastrointestinal tract.

Methods:Using immunohistochemical analysis, the expression of galectin 4 and meprin α was investigated in 10 MOCs and in 38 mucinous adenocarcinomas of colon, pancreas, stomach and appendix, the most common sites of origin of ovarian metastases.

Results:Total cytoplasmic galectin 4 expression was relatively consistent between the different carcinomas. Membranous meprin α expression was significantly lower in MOCs compared with gastrointestinal carcinomas. Moreover, meprin α expression showed greater discrimination between the ovarian and gastrointestinal carcinomas than the cytokeratins CK7 and CK20, the current standard immunohistochemical markers used to determine the tissue origin of mucinous carcinomas involving the ovaries.

Conclusions:Meprin α is a useful additional marker in differentiating primary from secondary mucinous adenocarcinomas of the ovary.
Running effective meetings: a primer for doctors
Authors: O'Dea N A , de Chazal P , Saltman D C , Kidd M R
Published: July 2006

This paper uses a series of exercises and practical examples to assist individuals and groups of doctors in training to gain skills in a critical area of management: conducting and participating in effective meetings. Through this paper, readers will be shown how to recognise and manage situations as they occur in meetings to work towards appropriate outcomes. By understanding the elements of conducting a meeting from preparation through to follow up, doctors will be able to conduct and participate more effectively in meetings that arise in their workplaces.
Management of acute ventilatory failure
Authors: Chakrabarti B , Calverley P M A
Published: July 2006

Acute ventilatory failure is a challenging yet increasingly common medical emergency reflecting the growing burden of respiratory disease. It is not a diagnosis in itself but the end result of a diversity of disease processes culminating in arterial hypoxaemia and hypercapnia. This review focuses on key management issues including giving appropriate oxygen therapy, treatment of the underlying aetiology as well as any precipitant factors and provision of assisted ventilation if required. Ventilatory assistance can be provided both invasively and non-invasively and the indications for either or both forms of assisted ventilation are discussed. Further emphasis is needed regarding advanced directives of care and clinicians should be aware of ethical issues regarding assisted ventilation.
Interleukin-8: novel roles in human airway smooth muscle cell contraction and migration
Authors: Govindaraju Vasanthi , Michoud Marie-Claire , Al-Chalabi Mustafa , Ferraro Pasquale , Powell William S. , Martin James G.
Published: July 2006

In patients with cystic fibrosis (CF) and asthma, elevated levels of interleukin-8 (IL-8) are found in the airways. IL-8 is a CXC chemokine that is a chemoattractant for neutrophils through CXCR1 and CXCR2 G protein-coupled receptors. We hypothesized that IL-8 acts directly on airway smooth muscle cells (ASMC) in a way that may contribute to the enhanced airway responsiveness and airway remodeling observed in CF and asthma. The aim of this study was to determine whether human ASMC (HASMC) express functional IL-8 receptors (CXCR1 and CXCR2) linked to cell contraction and migration. Experiments were conducted on cells harvested from human lung specimens. Real-time PCR and fluorescence-activated cell sorting analysis showed that HASMC expressed mRNA and protein for both CXCR1 and CXCR2. Intracellular Ca2+ concentration ([Ca2+]i) increased from 115 to 170 nM in response to IL-8 (100 nM) and decreased after inhibition of phospholipase C (PLC) with U-73122. On blocking the receptors with specific neutralizing antibodies, changes in [Ca2+]i were abrogated. IL-8 also contracted the HASMC, decreasing the length of cells by 15%, and induced a 2.5-fold increase in migration. These results indicate that HASMC constitutively express functional CXCR1 and CXCR2 that mediate IL-8-triggered Ca2+ release, contraction, and migration. These data suggest a potential role for IL-8 in causing abnormal airway structure and function in asthma and CF.
Cell biological aspects of the vasopressin type-2 receptor and aquaporin 2 water channel in nephrogenic diabetes insipidus
Authors: Robben Joris H. , Knoers Nine V. A. M. , Deen Peter M. T.
Published: July 2006

In the renal collecting duct, water reabsorption is regulated by the antidiuretic hormone vasopressin (AVP). Binding of this hormone to the vasopressin V2 receptor (V2R) leads to insertion of aquaporin-2 (AQP2) water channels in the apical membrane, thereby allowing water reabsorption from the pro-urine to the interstitium. The disorder nephrogenic diabetes insipidus (NDI) is characterized by the kidney's inability to concentrate pro-urine in response to AVP, which is mostly acquired due to electrolyte disturbances or lithium therapy. Alternatively, NDI is inherited in an X-linked or autosomal fashion due to mutations in the genes encoding V2R or AQP2, respectively. This review describes the current knowledge of the cell biological causes of NDI and how these defects may explain the patients' phenotypes. Also, the increased understanding of these cellular defects in NDI has opened exciting initiatives in the development of novel therapies for NDI, which are extensively discussed in this review.
Disruption of Autophagy at the Maturation Step by the Carcinogen Lindane Is Associated with the Sustained Mitogen-Activated Protein Kinase/Extracellular Signal–Regulated Kinase Activity
Authors: Corcelle Elisabeth , Nebout Marielle , Bekri Soumeya , Gauthier Nils , Hofman Paul , Poujeol Philippe , Fénichel Patrick , Mograbi Baharia
Published: July 2006

Macroautophagy (hereafter referred to as autophagy) has emerged as a key tumor suppressor pathway. During this process, the cytosolic constituents are sequestered into autophagosomes, which subsequently fuse with lysosomes to become autolysosomes where their contents are finally degraded. Although a reduced autophagy has been shown in human tumors or in response to oncogenes and carcinogens, the underlying mechanism(s) remain(s) unknown. Here, we show that widely used carcinogen Lindane promotes vacuolation of Sertoli cells. By electron and immunofluorescent microscopy analyses, we showed that these structures are acid autolysosomes, containing cellular debris, and labeled by LC3, Rab7, and LAMP1, markers of autophagosomes, late endosomes, and lysosomes, respectively. Such Lindane-induced vacuolation results from significant delay in autophagy degradation, in relation with a decline of the lysosomal activity of aryl sulfatase A. At molecular level, we show that this defect in autolysosomal maturation is independent of mammalian target of rapamycin and p38 inhibitions. Rather, the activation of the mitogen-activated protein kinase (MAPK)/extracellular signal–regulated kinase (ERK) pathway is required for Lindane to disrupt the autophagic pathway. Most importantly, we provide the first evidence that sustained activation of ERK pathway is sufficient to commit cell to autophagic vacuolation. Taken together, these findings strongly support that the aberrant sustained activation of ERK by the carcinogen Lindane disrupts the maturation of autophagosomes into functional autolysosomes. Our findings therefore suggest the possibility that high constitutive ERK activity found in all cancers may provide a malignant advantage by impeding the tumor suppressive function of autophagy. (Cancer Res 2006; 66(13): 6861-70)
Protein Kinase Casein Kinase 2 Mediates Inhibitor-κB Kinase and Aberrant Nuclear Factor-κB Activation by Serum Factor(s) in Head and Neck Squamous Carcinoma Cells
Authors: Yu Ming , Yeh Jason , Van Waes Carter
Published: July 2006

We showed previously that the signal transcription factor nuclear factor-κB (NF-κB) is aberrantly activated and that inhibition of NF-κB induces cell death and inhibits tumorigenesis in head and neck squamous cell carcinomas (HNSCC). Thus, identification of specific kinases underlying the activation of NF-κB could provide targets for selective therapy. Inhibitor-κB (IκB) kinase (IKK) is known to activate NF-κB by inducing NH2-terminal phosphorylation and degradation of its endogenous inhibitor, IκB. Casein kinase 2 (CK2) was previously reported to be overexpressed in HNSCC cells and to be a COOH-terminal IKK, but its relationship to NF-κB activation in HNSCC cells is unknown. In this study, we examined the contribution of IKK and CK2 in the regulation of NF-κB in HNSCC in vitro. NF-κB activation was specifically inhibited by kinase-dead mutants of the IKK1 and IKK2 subunits or small interfering RNA targeting the β subunit of CK2. CK2 and IKK kinase activity, as well as NF-κB transcriptional activity, was shown to be serum responsive, indicating that these kinases mediate aberrant activation of NF-κB in response to serum factor(s) in vitro. Recombinant CK2α was shown to phosphorylate recombinant IKK2 as well as to promote immunoprecipitated IKK complex from HNSCC to phosphorylate the NH2-terminal S32/S36 of IκBα. We conclude that the aberrant NF-κB activity in HNSCC cells in response to serum is partially through a novel mechanism involving CK2-mediated activation of IKK2, making these kinases candidates for selective therapy to target the NF-κB pathway in HNSCC. (Cancer Res 2006; 66(13): 6722-31)
A Role for Focal Adhesion Kinase Signaling in Tumor Necrosis Factor-α–Dependent Matrix Metalloproteinase-9 Production in a Cholangiocarcinoma Cell Line, CCKS1
Authors: Mon Naing Naing , Hasegawa Hitoki , Thant Aye Aye , Huang Pengyu , Tanimura Yoko , Senga Takeshi , Hamaguchi Michinari
Published: July 2006

We have previously reported that tumor necrosis factor-α (TNF-α) stimulation of CCKS1, a cell line established from cholangiocarcinoma with i.p. dissemination, dramatically increased matrix metalloproteinase-9 (MMP-9) production and tumor invasion. We investigated the role of focal adhesion kinase (FAK) in TNF-α–dependent production of MMP-9 in CCKS1 and FAK-null mouse fibroblast cells. TNF-α stimulation of CCKS1 or wild-type fibroblasts substantially activated FAK phosphorylation and increased MMP-9 production. In contrast, FAK-null fibroblasts could not respond well to TNF-α stimulation. Conditional expression of wild-type FAK in FAK-null cells restored the TNF-α–dependent production of MMP-9. TNF-α treatment activated the kinase activity of FAK and its phosphorylation especially at Y397 and Y925. Phosphorylated FAK accumulated at focal adhesions and formed a complex with growth factor receptor binding protein 2 and SOS. In contrast, Y397F FAK and Y925F FAK, whose Y397 and Y925 were replaced with phenylalanine, respectively, as well as KD FAK, whose kinase was inactivated, could not restore the MMP-9 production. In addition, small interfering RNA against FAK drastically suppressed the TNF-α–dependent production of MMP-9 and inhibited the TNF-α–dependent invasion of CCKS1. Taken together, our results suggest the pivotal role of FAK in TNF-α–dependent production of MMP-9 and subsequent activation of tumor invasion. (Cancer Res 2006; 66(13): 6778-84)
Antibody Targeting of Long-Circulating Lipidic Nanoparticles Does Not Increase Tumor Localization but Does Increase Internalization in Animal Models
Authors: Kirpotin Dmitri B. , Drummond Daryl C. , Shao Yi , Shalaby M. Refaat , Hong Keelung , Nielsen Ulrik B. , Marks James D. , Benz Christopher C. , Park John W.
Published: July 2006

We describe evidence for a novel mechanism of monoclonal antibody (MAb)–directed nanoparticle (immunoliposome) targeting to solid tumors in vivo. Long-circulating immunoliposomes targeted to HER2 (ErbB2, Neu) were prepared by the conjugation of anti-HER2 MAb fragments (Fab′ or single chain Fv) to liposome-grafted polyethylene glycol chains. MAb fragment conjugation did not affect the biodistribution or long-circulating properties of i.v.-administered liposomes. However, antibody-directed targeting also did not increase the tumor localization of immunoliposomes, as both targeted and nontargeted liposomes achieved similarly high levels (7-8% injected dose/g tumor tissue) of tumor tissue accumulation in HER2-overexpressing breast cancer xenografts (BT-474). Studies using colloidal gold-labeled liposomes showed the accumulation of anti-HER2 immunoliposomes within cancer cells, whereas matched nontargeted liposomes were located predominantly in extracellular stroma or within macrophages. A similar pattern of stromal accumulation without cancer cell internalization was observed for anti-HER2 immunoliposomes in non–HER2-overexpressing breast cancer xenografts (MCF-7). Flow cytometry of disaggregated tumors posttreatment with either liposomes or immunoliposomes showed up to 6-fold greater intracellular uptake in cancer cells due to targeting. Thus, in contrast to nontargeted liposomes, anti-HER2 immunoliposomes achieved intracellular drug delivery via MAb-mediated endocytosis, and this, rather than increased uptake in tumor tissue, was correlated with superior antitumor activity. Immunoliposomes capable of selective internalization in cancer cells in vivo may provide new opportunities for drug delivery. (Cancer Res 2006; 66(13): 6732-40)
HDJ-2 as a Target for Radiosensitization of Glioblastoma Multiforme Cells by the Farnesyltransferase Inhibitor R115777 and the Role of the p53/p21 Pathway
Authors: Wang Chun-Chieh , Liao Yu-Pei , Mischel Paul S. , Iwamoto Keisuke S. , Cacalano Nicholas A. , McBride William H.
Published: July 2006

Resistance of glioblastoma multiforme to radiotherapy poses a major clinical challenge. Farnesyltransferase inhibitors (FTI), such as R115777, have potential to increase radiotherapeutic benefit in this disease, although their mechanism of action is unclear. In our study with eight glioblastoma multiforme cell lines, the most sensitive ones underwent cell cycle arrest in response to FTI treatment. Radiosensitization by FTIs, however, seemed to involve other pathways. If R115777 treatment was initiated <6 hours before irradiation, all eight glioblastoma multiforme lines were radiosensitized. However, if the time between drug and radiation was extended to 24 hours, cells harboring wild type but not mutated p53 were able to counteract drug-induced radiosensitization. The involvement of the p53/p21 pathway in the development of resistance was confirmed by showing that U87 cells transfected with human papillomavirus E6 to block p53 or interfering RNA to inhibit p21 stayed radiosensitive for 24 hours after drug treatment. The time dependency of R115777-induced radiosensitization suggested that the initial FTI target for early radiosensitization was short-lived, and that a p21-directed pathway restored resistance. Consideration of prenylated molecules that could potentially be involved led us to consider HDJ-2, a co-chaperone of heat shock protein 70. This hypothesis was strengthened by finding that cellular radiosensitivity was increased by genetic inhibition of HDJ-2, whereas overexpression conferred radioresistance. Importantly, irradiation of cells caused HDJ-2 to migrate from the cytoplasm to the nucleus, and this migration was inhibited by prior FTI treatment. These results have clinical relevance in that they help explain the variability in responses to FTIs that occurs following radiotherapy and elucidate some of the reasons for the complexity underlying FTI-induced radiosensitization. (Cancer Res 2006; 66(13): 6756-62)
Conditional Activation of RET/PTC3 and BRAFV600E in Thyroid Cells Is Associated with Gene Expression Profiles that Predict a Preferential Role of BRAF in Extracellular Matrix Remodeling
Authors: Mesa Cleo , Mirza Mana , Mitsutake Norisato , Sartor Maureen , Medvedovic Mario , Tomlinson Craig , Knauf Jeffrey A , Weber Georg F. , Fagin James A.
Published: July 2006

Papillary thyroid cancers (PTC) are associated with nonoverlapping mutations of genes coding for mitogen-activated protein kinase signaling effectors (i.e., the TK receptors RET or NTRK and the signaling proteins RAS and BRAF). We examined the pattern of gene expression after activation of these oncoproteins in thyroid PCCL3 cells, with the goal of identifying pathways or gene subsets that may account for the phenotypic differences observed in human cancers. We hybridized cDNA from cells treated with or without doxycycline to induce expression of BRAFV600E, RET/PTC3, or RET/PTC3 with small interfering RNA–mediated knockdown of BRAF, respectively, to slides arrayed with a rat 70-mer oligonucleotide library consisting of 27,342 oligos. Among the RET/PTC3-induced genes, 2,552 did not require BRAF as they were similarly regulated by RET/PTC3 with or without BRAF knockdown and not by expression of BRAFV600E. Immune response and IFN-related genes were highly represented in this group. About 24% of RET/PTC3-regulated genes were BRAF dependent, as they were similarly modified by RET/PTC3 and BRAFV600E but not in cells expressing RET/PTC3 with knockdown of BRAF. A gene cluster coding for components of the mitochondrial electron transport chain pathway was down-regulated in this group, potentially altering regulation of cell viability. Metalloproteinases were also preferentially induced by BRAF, particularly matrix metalloproteinase 3 (MMP3), MMP9, and MMP13. Accordingly, conditional expression of BRAF was associated with markedly increased invasion into Matrigel compared with cells expressing RET/PTC3. The preferential induction of MMPs by BRAF could explain in part the more invasive behavior of thyroid cancers with BRAF mutations. (Cancer Res 2006; 66(13): 6521-9)
A Role for the WWOX Gene in Prostate Cancer
Authors: Qin Haiyan R. , Iliopoulos Dimitrios , Semba Shuho , Fabbri Muller , Druck Teresa , Volinia Stefano , Croce Carlo M. , Morrison Carl D. , Klein Russell D. , Huebner Kay
Published: July 2006

Expression of the WWOX gene, encompassing the common chromosome fragile site FRA16D, is altered in a large fraction of cancers of various types, including prostate cancer. We have examined expression and biological functions of WWOX in prostate cancer. WWOX mRNA and protein expression were significantly reduced in prostate cancer-derived cells (LNCaP, DU145, and PC-3) compared with noncancer prostate cells (PWR-1E), and WWOX expression was reduced in 84% of prostate cancers, as assessed by immunohistochemical staining. Down-modulation of WWOX expression in the prostate cancer-derived cells is due to DNA hypermethylation in the WWOX regulatory region. Treatment with 5-aza-2′-deoxycytidine (AZA), a DNA methyltransferase inhibitor, and trichostatin A, a histone deacetylase inhibitor, led to increased WWOX mRNA and protein expression in prostate cancer-derived cells, most strikingly in DU145 cells. Transfection-mediated WWOX overexpression in DU145 cells suppressed colony growth (P = 0.0012), and WWOX overexpression by infection with Ad-WWOX virus induced apoptosis through a caspase-dependent mechanism and suppressed cell growth. Lastly, ectopic expression of WWOX by Ad-WWOX infection suppressed tumorigenicity of xenografts in nude mice, and intratumoral AZA treatment halted tumor growth. The data are consistent with a role for WWOX as a prostate cancer tumor suppressor and suggest that WWOX signal pathways should be further investigated in normal and cancerous prostate cells and tissues. (Cancer Res 2006; 66(13): 6477-81)
First Three Years of the Microwave Radiometer aboard Envisat: In-Flight Calibration, Processing, and Validation of the Geophysical Products
Authors: Obligis E. , Eymard L. , Tran N. , Labroue S. , Femenias P.
Published: July 2006

The Envisat microwave radiometer is designed to correct the satellite altimeter data for the excess path delay resulting from tropospheric humidity. Neural networks have been used to formulate the inversion algorithm to retrieve this quantity from the measured brightness temperatures. The learning database has been built with European Centre for Medium-Range Weather Forecasts (ECMWF) analyses and simulated brightness temperatures by a radiative transfer model. The in-flight calibration has been performed in a consistent way by adjusting measurements on simulated brightness temperatures. Finally, coincident radiosonde measurements are used to validate the Envisat wet-tropospheric correction, and this comparison shows the good performances of the method.
Comparison of Reynolds Stress Estimates Derived from Standard and Fast-Ping ADCPs
Authors: Nidzieko Nicholas J. , Fong Derek A. , Hench James L.
Published: July 2006

A field experiment was conducted to directly compare the effects of different sampling modes on Reynolds stress estimates calculated from acoustic Doppler current profilers (ADCPs). Two 1.2-MHz ADCPs were deployed concurrently over a fortnightly cycle: one collected single-ping measurements using mode 1 and a second ADCP employed the fast-ping rate mode 12 with subping-averaged data recorded at the same sample rate as the first ADCP. While mode 12 clearly has a lower noise floor for the estimate of mean velocities, it has been an open question whether the averaging of subpings leads to a biased estimate of turbulence quantities, due to the temporal averaging inherent in this approach. Using the variance method, Reynolds stresses were estimated from the two ADCP datasets and compared with stresses computed directly from the velocity records obtained with a pair of fast sampling acoustic Doppler velocimeters (ADVs) collocated with the ADCPs. Mode-12 stresses were more accurate than mode 1 in comparison to ADV-derived stresses, and mode 12 exhibited much lower measurement uncertainty than mode 1. Mode 1 appears to overestimate stresses by 20% in this study. The lower noise floor associated with mode 12 suggests that the variance method may be used with mode 12 to resolve smaller stresses than would be possible with mode 1.
Exclusion for Democracy
Authors: Tebble Adam James
Published: July 2006

Recent consideration of the politics of culture and identity has failed to capture an emergent trend in political practice that raises important philosophical questions for normative political theory. To rectify this, identity politics is examined in terms of two distinctions. Examining that politics in terms of the distinction between left and right, as well in terms of the distinction between normative discourse and the policies that discourse justifies, enables us to do more than account for three standard accounts of the politics of cultural turn: multiculturalism, conservative nationalism, and liberal nationalism. It also captures the newly emergent position of identity liberalism. This is a perspective that employs a progressive identity-based normative discourse typically considered to be the preserve of the multicultural left to defend a right-wing politics of assimilation.
Postmodern Gargoyles, Simulated Power Aesthetics
Authors: Kien Grant
Published: July 2006

This work incorporates a camera as participant in the showing of experiences of surveillance, exploring some effects of defining power as the circulation of signifiers. This techno-ethnographic piece moves through numerous spaces, documenting how myth and aesthetics are experienced and play in everyday life, inducing performances that ultimately appear to stabilize and further legitimate a globally reaching network of surveillance.
Seeking Father
Authors: Adams Tony E.
Published: July 2006

Tension plagues the relationship between the author and his father when it comes to golf- and gay-related issues. The author is also stuck between two canonical stories, one that says he must work things out to fulfill his responsibilities as a son and another that tells him to let go, to realize that he “can’t choose his relatives,” and to view the relationship as a waste of time. In this project, the author uses a relational paradigm to reframe the father-son relationship in which he finds himself immersed. He’s a victim, so is his father. He’s an oppressor, so is his father. They victimize and oppress together, simultaneously hurting and being hurt while never deciding to quit. The story is about the troubled relationship that separates them. It’s a story of sexuality and sport, of gayness and hegemonic masculinity, of a fag and his golf clubs. It’s a story of love and hate.
A Buddhist View of Adult Learning in the Workplace
Authors: Johansen Barry-Craig P. , Gopalakrishna D.
Published: July 2006

The problem and the solution. Buddhism is a way of life practiced by more than 500 million people. The continued globalization of work and the expanding economic power and influence of Asian nations ensures that the beliefs, goals, practices, and traditions of Buddhism will take on increasing importance to business, education, and human resource development (HRD) professionals in every part of the world. Buddhism, like most worldviews, is not homogeneous and has many variations. Indeed, this adaptability is one of the hallmarks of Buddhism and is a major contributing factor to its spread and applicability around the world. The differences in these approaches are not as relevant to this article as are their commonalities in foundational beliefs, goals, and methods. Thus, this article presents a Buddhist view of learning, not the Buddhist view.
Jewish Adult Learning and the Workplace
Authors: Beck Jules K.
Published: July 2006

The problem and the solution. Employers can find in Judaism a tradition, philosophy, and methods of learning that can lead to invaluable contributions in the workplace, whether it is in the corporate, government, nongovernmental organization (NGO), or nonprofit sectors. An understanding of the evolution of Jewish learning thought and its relation to the contemporary workplace can offer additional strategies for human resource development practitioners to employ in organization settings.
Russian Orthodoxy Worldview and Adult Learning in the Workplace
Authors: Ardichvili Alexandre
Published: July 2006

The problem and the solution. A Western scholar and observer of Orthodox Christianity, Daniel Clendenin, wrote in 2003, “For Russians in particular...Orthodoxy is much more than simply a church; it is an entire way of life and culture.... Imagine living in Italy without understanding Catholicism, traveling to Kuwait and ignoring Islam, or trying to understand the people of Utah without ever studying the history of Mormonism. That will give an idea of catastrophic results of attempting to engage Eastern Europe and the former Soviet Union while neglecting the role of Orthodox Christianity” (p. 21). This article starts with a brief overview of history, doctrines, and practices of Russian Orthodoxy. Next, the chapter discusses the Orthodox view of work, vocation, and learning, and draws implications for work-based human resource development practice and research.
Analyzing Interviewer/Respondent Interactions while Using a Mobile Computer-Assisted Personal Interview Device
Authors: Childs Jennifer Hunter , Landreth Ashley
Published: July 2006

This article explores interviewer/respondent interactions using a handheld computer (HHC) and identifies issues arising from using a self-administered paper form to create a mobile computer-assisted personal interview (CAPI) instrument. To evaluate the success of this instrument, the authors used the behavior-coding method to evaluate a sample of about 220 audiotaped interviews to identify survey questions that cause problems at the administration and/or response stage. This article explores problems with the interview, as it was conductedon an HHC, both at a question level and overall. The objective of this study was to investigate whether the automation of this survey instrument encouraged standardized interviewing procedures by examining how interviewers read the questions and how respondents answer them. The authors discuss mode-specific problems that arose in the interview and proposesuggestionsfor futuresurveys thatuse a similar methodof datacollection.
Image Future
Authors: Manovich Lev
Published: July 2006

Today the techniques of traditional animation, cinematography, and computer graphics are often used in combination to create new hybrid moving image forms. This article discusses this process using the example of a particularly intricate hybrid – the Universal Capture method used in the second and third films of The Matrixtrilogy. Rather than expecting that any of the present ‘pure’ forms will dominate the future of visual and moving image cultures, it is suggested that the future belongs to such hybrids.
Routes to improving the reliability of low level DNA analysis using real-time PCR
Authors: Ellison Stephen LR , English Claire A , Burns Malcolm J , Keer Jacquie T
Published: July 2006

Background

Accurate quantification of DNA using quantitative real-time PCR at low levels is increasingly important for clinical, environmental and forensic applications. At low concentration levels (here referring to under 100 target copies) DNA quantification is sensitive to losses during preparation, and suffers from appreciable valid non-detection rates for sampling reasons. This paper reports studies on a real-time quantitative PCR assay targeting a region of the human SRY gene over a concentration range of 0.5 to 1000 target copies. The effects of different sample preparation and calibration methods on quantitative accuracy were investigated.

Results

At very low target concentrations of 0.5–10 genome equivalents (g.e.) eliminating any replicates within each DNA standard concentration with no measurable signal (non-detects) compromised calibration. Improved calibration could be achieved by eliminating all calibration replicates for any calibration standard concentration with non-detects ('elimination by sample'). Test samples also showed positive bias if non-detects were removed prior to averaging; less biased results were obtained by converting to concentration, including non-detects as zero concentration, and averaging all values.

Tube plastic proved to have a strongly significant effect on DNA quantitation at low levels (p = 1.8 × 10-4). At low concentrations (under 10 g.e.), results for assays prepared in standard plastic were reduced by about 50% compared to the low-retention plastic. Preparation solution (carrier DNA or stabiliser) was not found to have a significant effect in this study.

Detection probabilities were calculated using logistic regression. Logistic regression over large concentration ranges proved sensitive to non-detected replicate reactions due to amplification failure at high concentrations; the effect could be reduced by regression against log (concentration) or, better, by eliminating invalid responses.

Conclusion

Use of low-retention plastic tubes is advised for quantification of DNA solutions at levels below 100 g.e. For low-level calibration using linear least squares, it is better to eliminate the entire replicate group for any standard that shows non-detects reasonably attributable to sampling effects than to either eliminate non-detects or to assign arbitrary high Ct values. In calculating concentrations for low-level test samples with non-detects, concentrations should be calculated for each replicate, zero concentration assigned to non-detects, and all resulting concentration values averaged. Logistic regression is a useful method of estimating detection probability at low DNA concentrations.
Food neophobia and mealtime food consumption in 4–5 year old children
Authors: Cooke Lucy , Carnell Susan , Wardle Jane
Published: July 2006

Background

Previous research has documented a negative association between maternal report of child food neophobia and reported frequency of consumption of fruit, vegetables, and meat. This study aimed to establish whether neophobia is associated with lower intake of these food types in naturalistic mealtime situations.

Methods

One hundred and nine parents of 4–5 year olds completed questionnaires which included a six-item version of the Child Food Neophobia Scale (CFNS). The children took part in a series of 3 test lunch meals at weekly intervals at school at which they were presented with: chicken, cheese, bread, cheese crackers, chocolate biscuits, grapes and tomatoes or carrot sticks. Food items served to each child were weighed before and after the meal to assess total intake of items in four categories: Fruit and vegetables, Protein foods, Starchy foods and Snack foods. Pearson Product Moment Correlations and independent t tests were performed to examine associations between scores on the CFNS and consumption during lunches.

Results

Neophobia was associated with lower consumption of fruit and vegetables, protein foods and total calories, but there was no association with intake of starch or snack foods.

Conclusion

These results support previous research that has suggested that neophobia impacts differentially on consumption of different food types. Specifically it appears that children who score highly on the CFNS eat less fruit, vegetables and protein foods than their less neophobic peers. Attempts to increase intake of fruit, vegetables and protein might usefully incorporate strategies known to reduce the neophobic response.