bluuebunny/crossref_metadata_2025 huggingface dataset:
Tailings fans and valley‐spur cutoffs created by hydraulic mining
Authors: James L. Allan
Published: July 2004

Sand and gravel tailings from nineteenth century open‐pit hydraulic gold mines formed large alluvial fans at tributary conﬂuences in the northwestern Sierra Nevada, California. In the Bear River watershed, several of these fans were so large that they blocked main channels for decades. Some channels not only aggraded deeply, but also moved laterally and cut across the inner bends of valley spurs. Now locked in bedrock channels, these valley‐spur cutoffs impose local controls on geomorphic, hydraulic, and sedimentary processes. One cutoff has incised 25 m into bedrock over the past century (25 cm a−1) with rapid initial incision rates of up to 50 cm a−1 (1884–1890). Recognition of spur cutoffs in the geological record may help to identify large landslides and provide an analogue for a type of natural earthﬁll dam spillway not prone to catastrophic failures. Tailing fans, valley‐spur cutoffs, and the sediment they trap are described from contemporary accounts and recent ﬁeld conditions in the Bear River watershed. These anthropogenic changes represent a major shift in the watershed from supply‐limited to transport‐limited sediment budgets and a change in geomorphic processes away from long‐term drainage evolution dominated by ingrown meanders. The large volumes of mining sediment stored in these landforms will be slowly released over the next millennium and could be signiﬁcant to contemporary ecological and public health issues due to recent ﬁndings of high mercury loadings associated with hydraulic mines. Copyright © 2004 John Wiley & Sons, Ltd.
Analysis of crack movements observed in an alpine bedrock cliff
Authors: Ishikawa Mamoru , Kurashige Yoshimasa , Hirakawa Kazuomi
Published: July 2004

Crack widths and rock temperatures were monitored on an andestic bedrock cliff in the summit area of the Daisetsu Mountains, Hokkaido, northern Japan. Sequential data recorded the gradual widening of a crack to the point of critical crack extension, which resulted in catastrophic rock breakage. The data indicate that a combination of liquid water inﬁltration into crack tip and subsequent freezing is the most signiﬁcant factor contributing to critical crack extension. The recorded sub‐critical crack movements involved a number of minor crack extensions and contractions, the timing of which correlates well with the magnitude of the reconstructed thermal stresses at the crack tip derived from thermal deformation of the plate‐shaped rock fragment. Larger crack extensions occurred when stress at the crack tip exceeded a threshold value, possibly reﬂecting the control of rock fracture mechanics by which cracks are thought to propagate when the stress intensity factor at the crack tip exceeds the threshold values for stress corrosion cracking and the fracture toughness of the material. Copyright © 2004 John Wiley & Sons, Ltd.
Application of lidar digital terrain modelling to predict intertidal habitat development at a managed retreat site: Abbotts Hall, Essex, UK
Authors: Blott Simon J. , Pye Kenneth
Published: July 2004

A key question in designing any managed retreat site concerns the nature of the habitats which will be created, and their likely long‐term sustainability and development. Studies of historical sea wall failures in Essex have shown that former reclaimed areas may respond to renewed tidal ﬂooding in different ways depending on a number of factors, most importantly the elevation of the land at the time of breach, which governs the frequency and duration of tidal ﬂooding. This paper demonstrates how digital terrain modelling using airborne lidar data can be used to calculate the elevation of the land behind a breach and to predict the likely habitats which will be created. When combined with data from sites of historical sea wall failure, predictions can also be made about the likely geomorphological and biological evolution of the created habitats in the longer term. At Abbotts Hall on the northern side of Salcott Creek, Essex, where a managed retreat scheme was activated in October 2002, the highest areas above 2·35 m OD were predicted to develop stable saltmarsh, intermediate areas between 2·1 and 2·34 m OD to develop potentially unstable saltmarsh which is likely undergo internal dissection, and the lowest areas below 2·1 m OD to remain as mudﬂat or lagoon. Approximately 38 per cent of the site was predicted to develop stable saltmarsh, and nearly 50 per cent to remain as lagoon or mudﬂat. Monitoring is now being undertaken but it will be several years before the accuracy of the predictions can be assessed. Copyright © 2004 John Wiley & Sons, Ltd.
Hypsometry of glaciated landscapes
Authors: Brocklehurst Simon H. , Whipple Kelin X.
Published: July 2004

Hypsometry (frequency distribution of elevations) is often used to characterize landscape morphology, traditionally in the context of the degree of ﬂuvial dissection. Recently, the hypsometry of glaciated regions has been used to infer how rates of glacial erosion compare with tectonic uplift rates. However, many factors other than tectonics can also exert a major inﬂuence on the hypsometry of a glaciated landscape, resulting in a wide variety of hypsometries. Using examples from the eastern Sierra Nevada, California, the western Sangre de Cristo Range, Colorado, and the Ben Ohau Range, New Zealand, we demonstrate that, all else being equal, the hypsometries of neighbouring basins can indicate the relative degree of glacial modiﬁcation in each. A selection of drainage basins from the Rocky Mountains shows that the position of the equilibrium line altitude (ELA) within the drainage basin relief is a dominant variable in determining the hypsometry of a glaciated basin. This is a non‐linear effect: once the ELA falls to some critical level, the glaciers scour deeply below the ELA, causing a noticeably different hypsometry. The hypsometry of an arbitrary region encompassing many drainage basins can disguise the variation present in the hypsometries, and thus landforms, of the individual basins. Unique local circumstances, such as the presence of a mountain iceﬁeld (Waiho Basin, Southern Alps), substantial hanging valleys (Avalanche Creek, Glacier National Park), a narrow outlet canyon (Sawmill Creek, Sierra Nevada), and isolated geologic structures (Baker Creek, Sierra Nevada), can have a major impact on the hypsometry of an individual basin. Copyright © 2004 John Wiley & Sons, Ltd.
Pollution prevention success stories at the Oklahoma City Air Logistics Center
Authors: Hall Freddie E.
Published: July 2004

The goal of the Oklahoma City Air Logistics Center's (OC‐ALC) Pollution Prevention Program is simple, direct, and fundamental: reduce the purchase and use of targeted toxic chemicals. The OC‐ALC has become the Air Force leader in introducing new prototype technologies into all maintenance processes and quantifying their environmental benefits. The innovative technologies are reducing the handling of hazardous materials and eliminating hazardous waste. The success of the program lies in coordinating efforts, promoting awareness, transferring technology, obtaining funds, and executing projects. The OC‐ALC Pollution Prevention Program involves efforts to reduce the use of toxic chemicals through a hierarchy of actions: source reduction, chemical substitution, recycle and reuse, treatment, and disposal. Pollution prevention first seeks to change processes to eliminate the purchase and generation of undesirable targeted materials (source reduction). Where source reduction is not feasible, environmentally compliant materials may be substituted for the noncompliant products. The next P2 action is to recycle and reuse the hazardous materials. The following P2 actions include the treatment and disposal of wastes and emissions control (abatement) to reduce environmental impacts prior to disposal and only when source reduction and chemical substitution actions are not feasible (cost‐prohibitive, immature technology, etc.). At the root of the program is a compliance site assessment that identified four major processes in aircraft depot maintenance activities (painting, depainting, cleaning, and electroplating) that generate the majority of the installation's hazardous waste. Purchase and use of hazardous chemicals are tracked to verify the validity of implemented technologies and monitor trends. The objective of this article is to highlight technologies that have reduced targeted hazardous chemical purchases by 1.5 million pounds, reduced the generation of hazardous industrial waste by 8 million pounds, and reduced the use of ozone‐depleting substances (ODSs) by 330,000 pounds, annually. This article will highlight the following technologies: abrasive carbon dioxide blasting, environmentally acceptable chemical depainting agents, radome chemical depainting, medium‐pressure water jet knife, high‐pressure aircraft component subsystem, advanced vapor degreaser, National Emissions Standards for Hazardous Air Pollutants (NESHAP)‐compliant wipe solvents, powder coatings, and alternative electroplating technologies (i.e., ion vapor deposition, high‐velocity oxygen fuel, electromagnetic particle deposition, etc.). © 2004 Wiley Periodicals, Inc.
Toxic mold assessment, mitigation, and prevention at DOD facilities
Authors: Taylor Kim , Clifford Regina , Kollmeyer Ben , Pielak Janine
Published: July 2004

The objective of this article is to discuss emerging toxic mold issues facing Department of Defense (DOD) facilities. Mold exposure has been blamed as the cause of serious human health problems, and several mold species commonly found indoors have recently been identified as potential human health hazards. This article discusses common types and causes of indoor mold; exposure routes for mold; potential health impacts attributed to mold; disclosure obligations during property transactions; recent mold litigation; emerging regulations; and the application of a mold assessment, mitigation, and prevention program (AMPP) to DOD facilities undergoing closure under the Base Realignment and Closure (BRAC) Act, to active DOD facilities, and to new DOD construction projects. © 2004 Wiley Periodicals, Inc.
Planning for the Future Force: The sustainable Fort Bragg story
Authors: Davis Addison D. , Hull Christine G.
Published: July 2004

“We need to consider managing [the environment] to operational requirements, not just regulatory requirements.” This observation from Air Force Deputy Assistant Secretary Maureen Koetz in the autumn 2003 issue of FFEJ highlights the fundamental challenge facing military environmental programs as they attempt to support transforming missions. It has been said that “change is the Army's steady state; the Army is always in transition.” To ensure that U.S. military forces can continue to perform their current and future missions without being constrained by environmental issues, the current “stovepiped” installation planning processes for infrastructure, budget, military training and deployment, and environment must become interdependent and integrated. Integrated planning is inherently tied to the concept of living within the limits of available resources, both natural and manmade. This article highlights a developing approach to resource and planning processes at Army installations. The Army Installation Sustainability Program focuses long‐term resource planning and execution on an installation's ability to support the Future Force and coexist with the communities that grow on its borders. The authors discuss the overall process and specific accomplishments of Fort Bragg's sustainability program and demonstrate how this paradigm shift toward a sustainability management system is successfully helping the installation staff prepare for the future. © 2004 Wiley Periodicals, Inc.
Integrating NEPA, environmental permitting, and contracting actions into a DOD hazardous waste treatment facility construction project to successfully meet budget and schedule
Authors: Pringle William J. B.
Published: July 2004

Environmental managers responsible for high‐profile Department of Defense (DOD) construction projects entailing National Environmental Policy Act (NEPA) and environmental permitting requirements must constantly monitor cost and schedule. For numerous interrelated reasons, NEPA and environmental permitting are the initial critical path activities and are constantly scrutinized by higher management levels, as they have the potential to significantly affect life‐cycle budgets and schedule if mismanaged. Maintaining effective management vigilance is therefore required to ensure environmental actions remain on schedule and support projected contract award dates and submitted budgets. This article provides some insights into how to integrate NEPA, permitting, contracting, and budgeting to achieve and maintain success from project inception to conclusion. © 2004 Wiley Periodicals, Inc.
Different roles of the frontal and parietal regions in memory‐guided saccade: A PCA approach on time course of BOLD signal changes
Authors: Sugiura Motoaki , Watanabe Jobu , Maeda Yasuhiro , Matsue Yoshihiko , Fukuda Hiroshi , Kawashima Ryuta
Published: July 2004

Although involvement of the frontoparietal regions in visually guided saccade and visuospatial attention has been established, functional difference of the frontal and parietal regions suggested in neuropsychological observations and lesion studies in animals has not been explicitly supported by functional imaging studies. Considering a possible disadvantage of cognitive subtraction in an interregional comparison, we directly compared the time course of BOLD signal changes across regions. Normal subjects performed a modified version of a memory‐guided saccade task in which saccade was performed both during encoding and execution phases. In addition, the delay period was fixed and the peripheral target was presented also during the execution phase together with distracters. Therefore, visuospatial representation was likely maintained in the sensory domain during the delay phase. A principal component analysis on the time‐course data separated the 20 activated areas into three groups, which largely coincided with the cerebral lobes. The frontal group included the putative human FEF and SEF, and the parietal group PEF. The frontal and occipital groups exhibited the time course of activation with two peaks corresponding to neural responses during the encoding and execution phases, and the parietal group exhibited a single‐humped activation pattern corresponding to neural activity during the delay phase. The results suggest that the frontal regions are more associated with the execution of saccade, and the parietal regions with visuospatial representation, presumably in the sensory domain. Hum Brain Mapp 23:129–139, 2004. © 2004 Wiley‐Liss, Inc.
Variability of fMRI activation during a phonological and semantic language task in healthy subjects
Authors: Seghier Mohamed L. , Lazeyras François , Pegna Alan J. , Annoni Jean‐Marie , Zimine Ivan , Mayer Eugène , Michel Christoph M. , Khateb Asaid
Published: July 2004

Assessing inter‐individual variability of functional activations is of practical importance in the use of functional magnetic resonance imaging (fMRI) in a clinical context. In this fMRI study we addressed this issue in 30 right‐handed, healthy subjects using rhyme detection (phonologic) and semantic categorization tasks. Significant activations, found mainly in the left hemisphere, concerned the inferior frontal gyrus, the superior/middle temporal gyri, the prefrontal cortex, the inferior parietal lobe, the superior parietal lobule/superior occipital gyrus, the pre‐central gyrus, and the supplementary motor area. Intensity/spatial analysis comparing activations in both tasks revealed an increased involvement of frontal regions in the semantic task and of temporo‐parietal regions in the phonologic task. The frequency of activation analyzed in nine regional subdivisions revealed a high inter‐subject variability but showed that the most frequently activated regions were the inferior frontal gyrus and the prefrontal cortex. Laterality indices, strongly lateralizing in both tasks, were slightly higher in the semantic (0.76 ± 0.19) than the phonologic task (0.66 ± 0.27). Frontal dominance indices (a measure of frontal vs. posterior left hemisphere dominance) indicated more robust frontal activations in the semantic than the phonologic task. Our study allowed the characterization of the most frequently involved foci in two language tasks and showed that the combination of these tasks constitutes a suitable tool for determining language lateralization and for mapping major language areas. Hum. Brain Mapping 23:140–155, 2004. © 2004 Wiley‐Liss, Inc.
Seasonal inundation patterns in two large savanna floodplains of South America: the Llanos de Moxos (Bolivia) and the Llanos del Orinoco (Venezuela and Colombia)
Authors: Hamilton Stephen K. , Sippel Suzanne J. , Melack John M.
Published: July 2004

Inundation patterns in two of the largest savanna floodplains of South America were studied by analysis of the 37‐GHz polarization difference observed by the Scanning Multichannel Microwave Radiometer (Nimbus‐7 satellite). Flooded area was estimated at monthly intervals for January 1979 through to August 1987 using mixing models that account for the major landscape units with distinctive microwave emission characteristics. Results are presented separately for five subregions in each of the two floodplain regions to show the spatial as well as temporal variability in inundation patterns. The total area inundated during the 9 years varied between 2069 and 78 460 km2 in the Llanos de Moxos (also spelled as Mojos; median area, 23 383 km2) and 1278 and 105 454 km2 in the Llanos del Orinoco (median, 25 374 km2), not including the open‐water area of permanent lakes and river channels. The correlation between flooded area and river stage was used to extend the inundation records over a 30‐year period in the Moxos (1967–97) and a 58‐year period (1927–85) in the Orinoco. Interannual variability in inundation is greater in the Moxos than the Orinoco. Comparison of these data, however, with a previously published analysis of the Pantanal wetland shows that inundation patterns in these two floodplain regions are not as variable across years as they are in the Pantanal. Copyright © 2004 John Wiley & Sons, Ltd.
Vascular density in colorectal liver metastases increases after removal of the primary tumor in human cancer patients
Authors: Peeters Charlotte F.J.M. , Westphal Johan R. , de Waal Robert M.W. , Ruiter Dirk J. , Wobbes Theo , Ruers Theo J.M.
Published: July 2004

In animal models, explosive growth of metastases after removal of the primary tumor has been attributed to abolishment of angiogenesis inhibition. We investigated the influence of (removal of) the primary tumor on vascularization of liver metastases in human colorectal cancer patients. We analyzed vascular density in synchronous liver metastases from patients with the primary tumor in situ, in synchronous metastases from patients with the primary tumor resected and in metachronous metastases. In a limited number of cases, biopsies from metastases from the same patient before and within 3 months after resection were analyzed. In addition, vascular density in metastases was compared to the vascular density in the corresponding primary tumor. Peritumoral and intratumoral vascular density were determined by staining for endothelial antigens CD31 and CD34, respectively. Both peritumoral and intratumoral vascular density were elevated in synchronous metastases from patients with the primary tumor removed compared to synchronous metastases from patients with the primary tumor in situ. Comparable results were observed in patients with metachronous metastases. An increase in vascular density after resection of the colorectal malignancy was also observed in biopsies taken from the same patient before and after tumor resection. Remarkably, vascular density in the liver metastases was always lower than that in the corresponding primary tumor. Our data show for the first time in humans that the presence of a primary tumor is correlated with decreased vascularization of its distant metastases. Resection of the primary tumor results in an increased vascularization of metastatic lesions. © 2004 Wiley‐Liss, Inc.
Coamplification and coexpression of GRB7 and ERBB2 is found in high grade intraepithelial neoplasia and in invasive Barrett's carcinoma
Authors: Walch Axel , Specht Katja , Braselmann Herbert , Stein Hubert , Siewert Jörg Rüdiger , Hopt Ulrich , Höfler Heinz , Werner Martin
Published: July 2004

The human growth factor receptor‐bound protein 7 gene (GRB7), the founding member of a family of adaptor molecules has been shown to regulate cell migration and has been implicated in tumor progression. GRB7 is localized in close proximity to the ERBB2 gene within an amplicon previously identified in Barrett's adenocarcinoma (BCA). We evaluated gene amplification and mRNA expression of GRB7 and ERBB2 in Barrett's carcinoma and its associated precursor lesions to assess their possible role in Barrett's malignant transformation. Copy number and expression levels were analyzed by Q‐PCR (GRB7, ERBB2) and QRT‐PCR (GRB7, ERBB2) using TaqMan technology and fluorescence in situ hybridization (ERBB2) in a series of 24 laser‐microdissected samples of Barrett's carcinomas and 32 samples of associated premalignant lesions. Parallel analysis of gene copy number changes and expression levels demonstrated that GRB7 and ERBB2 displayed concomitant elevated expression levels and increased copy numbers in 32% of Barrett's carcinomas. There was a correlation between GRB7 and ERBB2 in BCA at the DNA level (rs = 0.76, p < 0.001) and the mRNA level (rs = 0.89, p < 0.001). Moreover, coamplification (rs = 0.97, p < 0.001) and coexpression (rs = 0.81, p < 0.001) of GRB7 and ERBB2 are shown to be already present in a subset of BCA associated high‐grade intraepithelial neoplasia (HGIN), possibly reflecting a role of a concerted expression of GRB7 and ERBB2. No alterations, neither gene amplification nor overexpression were detected in Barrett's carcinoma associated low grade intraepithelial neoplasia (LGIN), intestinal metaplasia (IM) and squamous epithelium, indicating that alterations of GRB7 and ERBB2 are late events in the carcinogenesis of Barrett's esophagus. These findings may be of particular interest because the transition from high grade intraepithelial neoplasia to invasive carcinoma is a crucial step in malignant transformation in Barrett's carcinogenesis and might underline the putative role of GRB7 and ERBB2 in cell migration and tumor invasion. © 2004 Wiley‐Liss, Inc.
Epigenetic inactivation of RUNX3 in microsatellite unstable sporadic colon cancers
Authors: Goel Ajay , Arnold Christian N. , Tassone Pierfrancesco , Chang Dong K. , Niedzwiecki Donna , Dowell Jeannette M. , Wasserman Linda , Compton Carolyn , Mayer Robert J. , Bertagnolli Monica M. , Boland C. Richard
Published: July 2004

Runt domain transcription factors are important targets of TGF‐β superfamily proteins and play a crucial role in mammalian development. Three mammalian runt‐related genes, RUNX1, RUNX2 and RUNX3, have been described. RUNX3 has been shown to be a putative tumor suppressor gene localized to chromosome 1p36, a region showing frequent loss of heterozygosity events in colon, gastric, breast and ovarian cancers. Because of the important role of TGF‐β signaling in the human colon, we hypothesized that RUNX3 may serve as a key tumor suppressor in human colon cancers and colon cancer‐derived cell lines. We examined RUNX3 expression and the frequency of RUNX3 promoter hypermethylation in 17 colon cancer cell lines and 91 sporadic colorectal cancers. Semiquantitative analysis of RUNX3 transcripts was performed by RT‐PCR and de novo methylation of the RUNX3 promoter was studied by a methylation‐specific PCR (MSP) assay. Nineteen of 91 informative tumors (21%) and 11 of 17 (65%) colon cancer cell lines exhibited hypermethylation of the RUNX3 promoter. Interestingly, RUNX3 promoter hypermethylation was more common in tumors exhibiting high frequency of microsatellite instability (MSI‐H) (33% of MSI‐H vs. 12% of MSI‐L/MSS tumors; p = 0.012). Hypermethylation of the RUNX3 promoter correlated with loss of mRNA transcripts in all cell lines. RUNX3 promoter methylation was reversed and its expression restored in SW48 and HCT15 colon cancer cells after treatment with the demethylating agent 5‐aza‐2′‐deoxycytidine, indicating that loss of expression is caused by epigenetic inactivation in colon carcinogenesis. This is the first demonstration of frequent de novo hypermethylation of the RUNX3 promoter in sporadic colon cancers. The significant association of RUNX3 promoter hypermethylation with MSI‐H colon cancers suggests that RUNX3 is a novel target of methylation, along with the hMLH1 gene, in the evolution of MSI‐H colorectal cancers. © 2004 Wiley‐Liss, Inc.
In vitro and in vivo antitumor effect of 2‐methoxyestradiol on human melanoma
Authors: Dobos Judit , Tímár József , Bocsi József , Burián Zsuzsanna , Nagy Katalin , Barna Gábor , Peták István , Ladányi Andrea
Published: July 2004

2‐methoxyestradiol (2ME2) is an endogenous metabolite of estradiol with estrogen‐receptor‐independent antitumor and antiangiogenic activity. We examined the effects of 2ME2 on the cellular proliferation of 8 human melanoma cell lines. We show that 2ME2 inhibited cell proliferation by inducing apoptosis and an arrest in the G2/M phase, and the mechanism of action involved microtubules, mitochondrial damage and caspase activation. In male SCID mice, 2ME2 was effective in reducing primary tumor weight and the number of liver metastases after intrasplenic injection of human melanoma cells. In the metastases, we found a significantly higher rate of apoptotic cells after 2ME2 treatment. These findings on the antitumor effect of 2ME2 in cell culture as well as in an animal model may have implications for designing alternative treatment options for patients with advanced malignant melanoma. © 2004 Wiley‐Liss, Inc.
DNA repair gene XRCC2 and XRCC3 polymorphisms and susceptibility to cancers of the upper aerodigestive tract
Authors: Benhamou Simone , Tuimala Jarno , Bouchardy Christine , Dayer Pierre , Sarasin Alain , Hirvonen Ari
Published: July 2004

Cigarette smoke can generate reactive oxygen species, which are capable of inducing double‐strand breaks (DSBs) in DNA. Polymorphisms in XRCC2 and XRCC3 genes, involved in DSBs repair pathways, may alter an individual's susceptibility to smoking‐related cancers. We investigated the effect of XRCC2 Arg188His and XRCC3 Thr241Met polymorphisms in cancer proneness in 121 oral/pharynx cancer cases, 129 larynx cancer cases and 172 noncancer controls, all Caucasian smokers. The XRCC2 His‐allele was associated with a significantly increased risk of pharyngeal cancer (OR=2.9, 95% CI: 1.3–6.2). No significant associations were observed between the XRCC3 Thr241Met polymorphism and overall risk of developing UADT cancers. However, quite opposite to the expectations, a reduced risk of supraglottic cancer was found for carriers of the XRCC3 Met variant allele (OR=0.3, 95% CI: 0.2–0.7). These findings provide evidence for the view that polymorphisms in DNA repair genes may modify individual susceptibility to smoking‐related cancers. © 2004 Wiley‐Liss, Inc.
Follicle stimulating hormone‐induced growth promotion and gene expression profiles on ovarian surface epithelial cells
Authors: Ji Qing , Liu Paul I. , Chen Peter K. , Aoyama Chisa
Published: July 2004

Epidemiologic data have implicated reproductive follicle‐stimulating hormone (FSH) as a probable risk factor for ovarian cancer (OC) development. Although pituitary and sex hormones have been reported to regulate OC cell growth, no information is available on the influence of FSH on gene expression profiles during ovarian surface epithelial (OSE) cell proliferation. This study evaluated the effect of FSH treatment on cell proliferation of various OSE cell lines and gene expression profiles with FSH treatment. Follicle‐stimulating hormone receptor (FSHR) was found at higher expression at both transcriptional and protein levels in ovarian cancerous tissues compared to normal tissues, and FSH was shown to promote cell growth in 3 OSE cell lines. Furthermore, it was also found that overexpression of FSHR in Chinese hamster ovary (CHO) cells leads to cell proliferation. Using cDNA MicroArray analysis on MCV152 cells with FSH treatment, 91 genes were found upregulated and 68 genes downregulated for more than 2‐fold after FSH treatment. Most of the genes were related to metabolism, cell proliferation and oncogenes. Downregulated genes included tumor suppressor genes (RB1, BRCA1, BS69) and the genes related to cell proliferation control. Pathway analysis found that FSH activates certain important enzymes in sterol biosynthesis pathways. FSH‐induced gene expression profiles on MCV152 cells support the standing hypothesis that FSH is a probable risk factor for ovarian cancerous development. © 2004 Wiley‐Liss, Inc.
IL‐12 receptor‐mediated upregulation of FasL in human ovarian carcinoma cells
Authors: Gorelik Elieser , Edwards Robert P. , Feng Xin , Marrangoni Adele M. , Grandis Jennifer R. , Drenning Stephanie D. , Velikokhatnaya Lyudmila , Kwon Jeong‐Ah , Lokshin Anna E.
Published: July 2004

The expression and functions of IL‐12 receptor (IL‐12R) in human ovarian carcinoma cell lines have been investigated. Ovarian carcinoma cells express both the IL‐12Rβ1 and the IL‐12Rβ2 subunits. IL‐12R crosslinking resulted in phosphorylation of Tyk2, p44 (ERK1) and Akt kinases and activation of STATs 2, 3, 4 and 5. IL‐12 induced substantial upregulation of Fas ligand (FasL) surface expression in ovarian carcinoma cells paralleled by an increased ability to induce apoptosis in Jurkat cells and PHA‐activated lymphocytes. The induction of surface expression of FasL by IL‐12 was not due to upregulation of FasL gene expression, but resulted from downregulation of matrix metalloproteinases (MMPs)‐3 and ‐7 and consequently reduced cleavage of FasL from the cell surface. These findings bring new insights into the significance of IL‐12‐mediated effects in nonlymphoid cancer cells that might be of importance for improving the design of IL‐12‐based therapies for ovarian cancer. © 2004 Wiley‐Liss, Inc.
N‐glycosylation of CD97 within the EGF domains is crucial for epitope accessibility in normal and malignant cells as well as CD55 ligand binding
Authors: Wobus Manja , Vogel Björn , Schmücking Eike , Hamann Jörg , Aust Gabriela
Published: July 2004

CD97 is an EGF‐TM7 receptor found on various carcinomas where expression levels correlate with dedifferentiation and tumor stage, smooth muscle cells and leukocytes. CD97 acts as an adhesion molecule by binding to its cellular ligand, CD55. In this study, we demonstrate that 2 immunodominant CD97 epitopes are not equally present in the various cell types. Differences were apparent in gastrointestinal tumors and smooth muscle cells where monoclonal antibodies (mAbs) to the first epidermal growth factor (EGF) domain (CD97EGF) showed a more restricted staining pattern than mAbs to the stalk region (CD97stalk). This discrepancy was not detectable in cultured gastrointestinal tumor cell lines. In fact, the selection of the CD97 mAb influences the result of clinical studies. Thus, we clarified the reason(s) for these differences in CD97 mAb staining on various cell types. We provide evidence that epitope accessibility for CD97EGF mAbs depends on N‐glycosylation. Immunoprecipitation of CD97 from the Colo 205 tumor cell line revealed the established 78 and 83 kDa products, while a 52 and 57 kDa band were obtained from smooth muscle cells. N‐glycosidase F reduced the size of CD97 in Colo 205 cells to 52–57 kDa. Culturing these cells with tunicamycin resulted in the same decrease in size and impaired CD97EGF mAb binding. As shown by site‐directed mutagenesis, deletion of the N‐glycosylation sites located within the EGF domains efficiently disturbed CD97EGF mAb immunoreactivity and, importantly, binding of CD55. In conclusion, CD97EGF epitope accessibility for mAbs and ligand binding is influenced by cell type‐specific N‐glycosylation. © 2004 Wiley‐Liss, Inc.
Single nucleotide polymorphism in the 5′ tandem repeat sequences of thymidylate synthase gene predicts for response to fluorouracil‐based chemotherapy in advanced colorectal cancer patients
Authors: Marcuello Eugenio , Altés Albert , del Rio Elisabeth , César Angeles , Menoyo Anna , Baiget Montserrat
Published: July 2004

Thymidylate synthase (TS) is the primary target of 5‐fluorouracil (5‐FU). A VNTR polymorphism in the TS promoter region is associated with the efficacy of 5‐FU‐based chemotherapy in colorectal cancer. A common G>C SNP at the 12th nucleotide of the second repeat in the TS*3 alleles has been recently described. The combination of SNP and VNTR allows the definition of 3 TS alleles: *2, *3G and *3C. The aim of our study was to evaluate the predictive value of clinical response and survival of these new defined TS alleles. TS genotypes of 89 patients diagnosed with metastatic colorectal cancer and undergoing 5‐FU‐based chemotherapy were carried out. The clinical outcome was evaluated according to the genotype (high expression genotype: *2R/*3G; *3C/*3G; *3G/*3G; and low expression genotype: *2R/*2R; *2R/*3C; *3C/*3C. A higher overall response was observed in the group of patients with a low expression genotype (p = 0.035). The probability of achieving a clinical response of patients with a low expression‐related genotype was 2.9 higher than that of the other group (95% CI = 1.03–5.6, p = 0.04). The median time to progression was 12 months and 9 months in the low and high expression groups, respectively (p = 0.07, log rank test). Overall survival was significantly longer in the low expression group. In this group the median OS was not achieved at 50 months of follow‐up in contrast to the 20 months observed in the high expression group (p = 0.03). TS genotype was an independent predictor of progression‐free and overall survival in the Cox regression models after adjustment to the other clinical variables. The selection of patients who are likely to respond to 5‐FU therapy may be considerably improved if the TS genotype were to include both the VNTR and the SNP located within the promoter region of the gene. © 2004 Wiley‐Liss, Inc.
Hollow‐fiber dispersion‐free extraction and stripping of Pb(II) in the presence of Cd(II) using D2EHPA under recirculating operation mode
Authors: Escobar Armando , Schimmel Keith A , de Gyves Josefina , de San Miguel Eduardo Rodríguez
Published: July 2004

Lead(II) and cadmium(II) solvent extraction (SX) with D2EHPA dissolved in heptane and kerosene from aqueous chloride media was studied. Extraction reaction stoichiometries and extraction equilibrium constants were evaluated. Application of a dispersion‐free membrane‐based extraction and stripping technique with two hollow‐fiber contactors under recirculating operation mode allowed a quantitative (>97%) removal of lead from the aqueous solution in the extraction module with a separation factor of 19 and a 62% recovery in the back‐extraction module with a separation factor of 6.3 after 7 h under optimum conditions. Mass‐transfer coefficients for the system were evaluated. Optimal conditions for transport and separation are reported and compared using SX and the membrane‐based technique. Copyright © 2004 Society of Chemical Industry
The effect of operational parameters on the performance of a bipolar trickle tower reactor
Authors: Trinidad Pedro , Walsh Frank C , Sheppard Sally A , Gillard Stephen P , Campbell Sheelagh A
Published: July 2004

A bipolar trickle tower reactor (BTTR) (of 7.9 cm internal diameter and 75 cm length containing 57 layers, each layer having 30 carbon Raschig rings, each of 1.25 cm outside diameter) has been studied under a range of operational conditions. The batch recycle mode of operation has been used for the removal of Cu(II) ions (at an initial concentration of 50–200 ppm) from an acid sulfate solution (typically 3000 cm3) at 295 K. Non‐ideal flow and Peclet number values have been considered to establish the degree of deviation from ideal reactor flow models. Operational variables included the potential difference per layer (1.0–3.0 V), volumetric flow rate (8.3–50 cm3 s−1) and the effect of H2SO4 concentration (which increased conductivity and lowered pH) in the electrolyte. The reactor has been shown to be best suited to the treatment of a moderately high reactant concentration (eg 100–200 ppm) and low electrolyte conductivity. The final concentration can be as low as a few parts per million but the performance of the reactor (as judged by the current efficiency and the rate of concentration decay) markedly decreased as the dissolved metal ion concentration fell. Copyright © 2004 Society of Chemical Industry
The application of reticulated vitreous carbon rotating cylinder electrodes to the removal of cadmium and copper ions from solution
Authors: Reade Gavin W , Bond Peter , de Leon Carlos Ponce , Walsh Frank C
Published: July 2004

The removal of cadmium and cupric ions from 0.50 mol dm−3 Na2SO4 at pH 2 and 298 K was studied using a reticulated vitreous carbon (RVC) rotating cylinder electrode (RCE). The cathode was a 100 pores per linear inch porosity grade with a radius of 0.5 cm, a height of 1.2 cm and a volume of 0.94 cm3. The cathode was rotated a constant speed of 1500 rev min−1. A rate enhancement of approximately three times is reported for the removal of cupric ions from a chloride solution (0.05 mol dm−3 cupric ions in 0.1 mol dm−3 NaCl at pH 7) when compared with the analogous reaction in acid sulfate solutions (0.50 mol dm−3 Na2SO4 at pH 2). SEM images of the metal deposit morphology allow the morphology of the metal deposits to be characterised. The deposits showed incomplete coverage of the RVC surface and appreciable roughness developed with time due to dendritic growths. Copyright © 2004 Society of Chemical Industry
Synthesis and preliminary in vivo evaluation of 4‐[18F]fluoro‐N‐{2‐[4‐(6‐trifluoromethylpyridin‐2‐yl)piperazin‐1‐yl]ethyl}benzamide, a potential PET radioligand for the 5‐HT1A receptor
Authors: Vandecapelle M. , Dumont F. , De Vos F. , Strijckmans K. , Leysen D. , Audenaert K. , Dierckx R. A. , Slegers G.
Published: July 2004

4‐Fluoro‐N‐{2‐[4‐(6‐trifluoromethylpyridin‐2‐yl)piperazin‐1‐yl]ethyl}benzamide is a full 5‐HT1A agonist with high affinity (pKi=9.3), selectivity and a c log P of 3.045. The corresponding PET radioligand 4‐[18F]fluoro‐N‐{2‐[4‐(6‐trifluoromethylpyridin‐2‐yl)piperazin‐1‐yl]ethyl}benzamide was synthesized by nucleophilic aromatic substitution on the nitro precursor. The fluorinating agent K[18F]F/Kryptofix 2.2.2 was both dried (9 min, 700 W) and incorporated in the precursor (5 min, 700 W) using a commercially available microwave oven. In a total synthesis time of 60 min, an overall radiochemical yield of 18% (SD=5, n=7, EOS) was obtained. Radiochemical purity was always higher than 99% and specific activity always higher than 81.4 GBq/µmol (2.2 Ci/µmol). Initial brain uptake in mice was 2.19% ID (5.47% ID/g, 2 min) but decreased rapidly (0.17% ID, 0.45% ID/g (60 min)). During the first 20 min p.i., radioactivity concentration of the brain was significantly higher than that of blood demonstrating good brain entry of the tracer. Copyright © 2004 John Wiley & Sons, Ltd.
Synthesis and radioiodination of 7‐(3′‐ammoniopropyl)‐7,8‐dicarba‐nido‐undecaborate(‐1), (ANC)
Authors: Ghirmai Senait , Malmquist Jonas , Lundquist Hans , Tolmachev Vladimir , Sjöberg Stefan
Published: July 2004

Derivatives of nido‐carborate have potential use in tumour targeting as hydrophilic boron‐rich compounds for boron neutron capture therapy (BNCT) and as pendant groups for attachment of radiohalogens to tumour‐seeking molecules. For this purpose, functionalized derivatives of nido‐carborates that can be conjugated to biomolecules should be synthesized and evaluated. In this study, racemic 1, 7‐(3′‐ammoniopropyl)‐7,8‐dicarba‐nido‐undecaborate(‐1) (acronym ANC) was obtained by degradation of the corresponding aminopropyl‐o‐carborane, which was synthesized in three steps from 1‐tert‐butyldimethylsilyl‐2‐(3‐bromopropyl)‐o‐carborane, with sodium hydroxide in absolute ethanol. The racemate 1 was radioiodinated (125I) using the Chloramine‐T method. Radio‐TLC results showed that radiolabelling with 125I was achieved in a yield greater than 95%. Copyright © 2004 John Wiley & Sons, Ltd.
Synthesis of a carbon‐14 labeled 1‐(indole‐6‐carbonyl‐D‐phenylglycinyl)‐4‐(1‐methylpiperidin‐4‐YL)piperazine‐[carbonyl‐14C], LY517717‐[14C], a factor Xa inhibitor
Authors: Kuo Fengjiun , Clodfelter Dean K. , Priest Tamara R. , Kau Donald L. K.
Published: July 2004

Human Factor Xa is a trypsin‐like serine protease, which serves a critical role in blood coagulation events. LY517717 is currently under clinical investigation as a Factor Xa inhibitor. To support the ADME studies, LY517717 was synthesized usingD‐phenylglycine with a carbon‐14 labeled carboxyl moiety. This key component,D‐phenylglycine‐[carboxyl‐14C], was synthesized by a Strecker synthesis on benzaldehyde with potassium [14C]cyanide, followed by a resolution ofDL‐phenyl‐glycine methyl ester‐[carbonyl‐14C] with (+)‐tartaric acid in the presence of benzaldehyde. Copyright © 2004 John Wiley & Sons, Ltd.
Differentiation of metastases from high‐grade gliomas using short echo time 1H spectroscopy
Authors: Opstad Kirstie S. , Murphy Mary M. , Wilkins Peter R. , Bell B. Anthony , Griffiths John R. , Howe Franklyn A.
Published: July 2004

Purpose

To determine if short echo time (TE) 1H magnetic resonance spectroscopy (MRS) can distinguish between intracranial metastases and glioblastomas.

Materials and Methods

TE 30‐msec spectra were acquired (1.5 T) from voxels entirely within tumors from 23 glioblastoma patients and 24 metastases patients (3 breast carcinomas, 1 bladder carcinoma, 8 lung carcinomas, 3 probable lung carcinomas, 6 melanomas, 1 stomach carcinoma, and 2 undetermined). Spectra were analyzed quantitatively (LCModel) to determine metabolite, lipid, and macromolecule concentrations. All tumors were previously untreated and classified histopathologically.

Results

The lipid peak area (LPA) ratio (total peak area at ca. δ1.3 to that at ca. δ0.9) was 2.6 ± 0.6 (N = 25) for glioblastomas and 3.8 ± 1.4 (N = 34) for metastases (P < 0.0001). There were no significant differences in metabolite or lipid concentrations between the tumor groups. The LPA ratio provided 80% sensitivity and 80% specificity for discriminating metastases from glioblastomas.

Conclusion

Lipid and macromolecule (LM) signals can dominate 1H spectra of high‐grade tumors and have characteristics that allow significant discrimination of metastases from glioblastomas. Work is now needed to determine the source and biophysical characteristics of these LM signals to further improve differentiation by optimizing the data acquisition and analysis protocol. J. Magn. Reson. Imaging 2004;20:187–192. © 2004 Wiley‐Liss, Inc.
Myocardial delayed enhancement imaging using inversion recovery single‐shot steady‐state free precession: Initial experience
Authors: Li Wei , Li Belinda S.Y. , Polzin Jason A. , Mai Vu M. , Prasad Pottumarthi V. , Edelman Robert R.
Published: July 2004

Purpose

To evaluate the feasibility of using an inversion recovery single‐shot steady‐state free precession (SS_SSFP) sequence for myocardial delayed enhancement (MDE) imaging, and to compare SS_SSFP with the conventional inversion recovery segmented fast gradient echo (IR_FGRE) technique.

Materials and Methods

Ten subjects (four volunteers and six patients with suspected or known coronary disease) were included in this study. All subjects were scanned with both IR_FGRE and SS_SSFP sequences 15–25 minutes after gadopentetate dimeglumine injection. Overall image quality, signal‐to‐noise ratios (SNRs), and contrast‐to‐noise ratios (CNRs) between the two techniques were compared.

Results

Compared to IR_FGRE, SS_SSFP exhibited adequate image quality (average scores = 3.8 for IR_FGRE and 3.9 for SS_SSFP) with much shorter acquisition time (14.4 seconds for IR_FGRE and 1.3 seconds for SS_SSFP). SS_SSFP images showed higher SNRs (P < 0.05) and less motion artifact from breathing. Enhanced myocardium was detected by both techniques in three patients, but the image sharpness is compromised in SS_SSFP images.

Conclusion

SS_SSFP provides adequate image quality compared to IR_FGRE, while requiring a much shorter acquisition time. It is feasible to use SS_SSFP as an alternative method for MDE imaging, especially in patients who have difficulty with holding their breath. J. Magn. Reson. Imaging 2004;20:327–330. © 2004 Wiley‐Liss, Inc.
Early heterogeneous enhancement of the liver: Magnetic resonance imaging findings and clinical significance
Authors: Kanematsu Masayuki , Danet Maria I. , Leonardou Polytimi , Mastropasqua Maria , Mosetti Maria A. , Braga Larissa , Woosley John T. , Semelka Richard C.
Published: July 2004

Purpose

To investigate and assess the radiologic, serological, and histopathologic findings in patients who presented with early heterogeneous enhancement (EHE) on gadolinium‐enhanced early‐phase magnetic resonance imaging (MRI) of the liver.

Materials and Methods

We searched our radiologic records of MRI of the liver from July 1999 to April 2002 to identify patients with EHE. Three investigators retrospectively evaluated in consensus the MR images in each patient for intensity and characteristic of EHE blinded to clinical information. Serological laboratory values and clinical information were obtained in all patients, and histologic findings were available in 19.

Results

We identified 67 patients with EHE. Of them, 62 patients (93%) had underlying chronic liver disease. Twenty‐seven patients had viral hepatitis, 13 had alcohol abuse, 6 had primary sclerosing cholangitis, and the others had miscellaneous etiologies. The five patients without chronic liver disease had the following clinical histories: concurrent chemotherapy for extrahepatic malignancy (two patients), concurrent intraabdominal infection (one), and no known associated disease (two). Intensity of EHE was intense in 6 (9%), moderate in 22 (33%), and mild in 39 (58%). Pattern of EHE was geographic in 15 patients (22%), patchy in 37 (55%), and miliary in 15 (22%). All EHE showed rapid fading on postcontrast late‐phase images. EHE showed mild to moderate hyperintensity on T2‐weighted images in 30 patients (45%). In the 19 patients with histological correlation, 19 (100%) had hepatocellular necrosis, 19 (100%) had fibrosis, 18 (95%) had inflammatory cell infiltration, 17 (89%) had capillary‐size vessels within fibrous septa, and 16 (84%) had ductal proliferation. No statistical correlation was found between the intensity or pattern of EHE on MR images and the extent of elevation of serological laboratory values or severity of histologic findings.

Conclusion

Several different types of underlying chronic liver disease were observed in most of the patients with EHE. Hepatocyte necrosis, fibrosis, or inflammatory processes were found in all patients with EHE who had histopathological correlation. J. Magn. Reson. Imaging 2004;20:242–249. © 2004 Wiley‐Liss, Inc.