bluuebunny/crossref_metadata_2025 huggingface dataset:
Processes, spatio‐temporal factors and measurements of current erosion in the French Southern Alps: a review
Authors: Descroix Luc , Mathys Nicolle
Published: August 2003

Present erosion in mountainous areas of Western Europe causes land management problems, particularly for areas located downstream of erosion zones. Except for transalpine roads and ski resorts, economic activities no longer require as much space as they did in the past. Therefore, natural reforestation has provided signiﬁcant protection for alpine hillslopes during the 20th century. However, extreme ﬂoods continue to cause severe damage in intra‐alpine valleys, as well as in piedmont and surrounding plains, making the study of present water erosion phenomena very important.

Many studies have investigated the processes and factors of water erosion on slopes at both the catchment and plot scales. They have focused on rock fragmentation and transportation in different ﬁelds, the spatial and temporal explanatory variables, the consequences downstream (ﬂooding, sedimentation, river bed evolution) and the impact of ﬂoods.

In the French Alps, present erosion has been studied in a variety of outcrops, with several recent studies conducted in ﬁelds such as marls, clayey deposits, molasses and moraines. These kinds of outcrops are found throughout the alpine massif, including an area of special interest on the great Jurassic black marl outcrop where badlands are frequently observable. Geomorphologists and hydrologists have been particularly interested in the strong erosion processes in marls, seeking to determine the main patterns and the impact of spatial and temporal factors on soil loss quantities.

The main climatic factors of rock disaggregation were found to be the freeze–thaw and wet–dry cycles, which destroy rock cohesion, and the splash effect of rain. The principal site variables are vegetation cover, exposure and dip–slope angle. Erosion rates are two or three orders of magnitude higher on bare soils than on pastures; northern aspect slopes suffer two to four times as much soil loss as southern aspect slopes. Finally, the angle formed by the slope and the dip also determines different behaviours: erosion rates are higher when slope and dip are perpendicular than when they are parallel. The transportation agents are mostly debris ﬂows and runoff caused by intense precipitation. Annual erosion depth in the marls is generally assumed to be substantial, up to 10 mm. The high value can be explained by the severity of the climatic conditions and the brittleness of the lithology, which results in numerous fractures. Copyright © 2003 John Wiley & Sons, Ltd.
Mid‐Holocene sub‐blanket‐peat alluvia and sediment sources in the upper Liffey valley, Co. Wicklow, Ireland
Authors: Thorp Martin , Glanville Peter
Published: August 2003

A recently exposed section across a ﬁrst‐order valley buried beneath the regional blanket peat on hillside slopes in the upper Liffey valley, Co. Wicklow, is described. The section shows two alluvia within a shallow valley form underlain by an extensive boulder and stone line over regional till and weathered granite. 14C dates from wood in the alluvia indicate the older alluvium to have formed between 4324 ± 53 BP and 4126 ± 45 BP and the younger between 3217 ± 53 BP and 2975 ± 53 BP. The basal layer of the overlying peat yielded a date of 2208 ± 61 BP. The younger alluvium shows the effects of soil paludiﬁcation prior to the peat expansion. Dated pollen analyses elsewhere in the upper catchment conﬁrm the spread of blanket peat over most areas above 350 m after 4000–3600 BP. The buried valley was contributing sediments to the mid‐Holocene ﬂoodplains in the upper Liffey valley prior to the extension of blanket peat over the catchment after which sediment yields from it and the other catchment slopes declined. Copyright © 2003 John Wiley & Sons, Ltd.
A vertically moving grid finite‐element modelling of tidal flow in the Changjiang Estuary, China
Authors: Shi Z. , Li S. S. , Petersen O. S.
Published: August 2003

An estuarine two‐dimensional vertical finite‐element model of tidal flow has been established by laterally integrating Navier–Stokes equation. To this end, a moving grid finite‐element method has been used. An arbitrarily shaped quadrilateral element has been selected. This model has been validated by using field data from two monitoring stations at the North Passage of the Changjiang Estuary. Using this numerical model, two types of modelled results were obtained: (1) vertical distributions of tidal current velocities at the North Passage of the Changjiang Estuary; (2) longitudinal distributions of tidal current velocities at maximum flood tide, at high slack water, at maximum ebb tide and at low slack water tide at the North Passage of the Changjiang Estuary. The conclusion is that the model provides a reasonable agreement with observed data. Copyright © 2003 John Wiley & Sons, Ltd.
Coupled lubrication and Stokes flow finite elements
Authors: Stay Matthew S. , Barocas Victor. H.
Published: August 2003

A method is developed for performing a local reduction of the governing physics for fluid problems with domains that contain a combination of narrow and non‐narrow regions, and the computational accuracy and performance of the method are measured. In the narrow regions of the domain, where the fluid is assumed to have no inertia and the domain height and curvature are assumed small, lubrication, or Reynolds, theory is used locally to reduce the two‐dimensional Navier–Stokes equations to the one‐dimensional Reynolds equation while retaining a high degree of accuracy in the overall solution. The Reynolds equation is coupled to the governing momentum and mass equations of the non‐narrow region with boundary conditions on the mass and momentum flux. The localized reduction technique, termed ‘stitching,’ is demonstrated on Stokes flow for various geometries of the hydrodynamic journal bearing—a non‐trivial test problem for which a known analytical solution is available. The computational advantage of the coupled Stokes–Reynolds method is illustrated on an industrially applicable fully‐flooded deformable‐roll coating example. The examples in this paper are limited to two‐dimensional Stokes flow, but extension to three‐dimensional and Navier–Stokes flow is possible. Copyright © 2003 John Wiley & Sons, Ltd.
A fully implicit method for steady and unsteady viscous flow simulations
Authors: Li Jie , Li Fengwei , E Qin
Published: August 2003

In this paper a time‐accurate, fully implicit method has been applied to solve a variety of steady and unsteady viscous flow problems. It uses a finite volume cell‐centred formulation on structured grids and employs central space discretization with artificial dissipation for the residual computation. In order to obtain a second‐order time‐accurate implicit scheme, a Newton‐like subiteration is performed in the original LU‐SGS method to converge the calculations at each physical time step by means of a dual‐time approach proposed by Jameson. The numerical experiments show that the present method is very efficient, reliable, and robust for steady and unsteady viscous flow simulations, especially for some low speed flow problems. Copyright © 2003 John Wiley & Sons, Ltd.
Numerical analysis of supersonic combustion ramjet with upstream fuel injection
Authors: Savino Raffaele , Pezzella Giuseppe
Published: August 2003

This paper describes possible fuel injection scheme for airbreathing engines that use hydrocarbon fuels. The basic idea is to inject fuel at the spike tip of the supersonic inlet to achieve mixing and combustion efficiency with a limited length combustion chamber. A numerical code, able to solve the full Navier–Stokes equations in turbulent and reacting flows, is employed to obtain numerical simulations of the thermo‐fluidynamic fields at different scramjet flight conditions, at Mach numbers of M=6.5 and 8. The feasibility of the idea of the upstream injection is checked for a simple axisymmetric configuration and relatively small size. The results are discussed in connection with the potential benefits deriving from the use of new ultra high temperature ceramics (UHTC). Copyright © 2003 John Wiley & Sons, Ltd.
Lattice Boltzmann simulations for flow and heat/mass transfer problems in a three‐dimensional porous structure
Authors: Yoshino M. , Inamuro T.
Published: August 2003

The lattice Boltzmann method (LBM) for a binary miscible fluid mixture is applied to problems of transport phenomena in a three‐dimensional porous structure. Boundary conditions for the particle distribution function of a diffusing component are described in detail. Flow characteristics and concentration profiles of diffusing species at a pore scale in the structure are obtained at various Reynolds numbers. At high Reynolds numbers, the concentration profiles are highly affected by the flow convection and become completely different from those at low Reynolds numbers. The Sherwood numbers are calculated and compared in good agreement with available experimental data. The results indicate that the present method is useful for the investigation of transport phenomena in porous structures. Copyright © 2003 John Wiley & Sons, Ltd.
The partition‐of‐unity method for linear diffusion and convection problems: accuracy, stabilization and multiscale interpretation
Authors: Munts E. A. , Hulshoff S. J. , des Borst R.
Published: August 2003

We investigate the effectiveness of the partition‐of‐unity method (PUM) for convection–diffusion problems. We show that for the linear diffusion equation, an exponential enrichment function based on an approximation of the analytic solution leads to improved accuracy compared to the standard finite‐element method. It is illustrated that this approach can be more efficient than using polynomial enrichment to increase the order of the scheme. We argue that the PUM enrichment, can be interpreted as a subgrid‐scale model in a multiscale framework, and that the choice of enrichment function has consequences for the stabilization properties of the method. The exponential enrichment is shown to function as a near optimal subgrid‐scale model for linear convection. Copyright © 2003 John Wiley & Sons, Ltd.
A substructure‐based iterative inner solver coupled with Uzawa's algorithm for the Stokes problem
Authors: Zsaki Attila , Rixen Daniel , Paraschivoiu Marius
Published: August 2003

A domain decomposition method with Lagrange multipliers for the Stokes problem is developed and analysed. A common approach to solve the Stokes problem, termed the Uzawa algorithm, is to decouple the velocity and the pressure. This approach yields the Schur complement system for the pressure Lagrange multiplier which is solved with an iterative solver. Each outer iteration of the Uzawa procedure involves the inversion of a Laplacian in each spatial direction. The objective of this paper is to effectively solve this inner system (the vector Laplacian system) by applying the finite‐element tearing and interconnecting (FETI) method. Previously calculated search directions for the FETI solver are reused in subsequent outer Uzawa iterations. The advantage of the approach proposed in this paper is that pressure is continuous across the entire computational domain. Numerical tests are performed by solving the driven cavity problem. An analysis of the number of outer Uzawa iterations and inner FETI iterations is reported. Results show that the total number of inner iterations is almost numerically scalable since it grows asymptotically with the mesh size and the number of subdomains. Copyright © 2003 John Wiley & Sons, Ltd.
Preparation of Gas Diffusion Electrodes with Silver Catalysts for Alkaline Fuel Cells
Authors: Gülzow E. , Wagner N. , Schulze M.
Published: August 2003

In alkaline fuel cells (AFC) silver can be used as the cathode catalyst in gas diffusion electrodes. To prepare the gas diffusion electrodes, the metal catalyst was mixed with polytetraflourethylene (PTFE), as the organic binder, in a knife mill and rolled onto a metal web in a calender. The electrodes are manufactured as an endless tape with a thickness of approx. 0.4 mm and widths of up to 20 cm. Raney‐silver, carbon supported silver, or silver deposited as a closed film on PTFE are used as the catalyst. In the gas diffusion electrode preparation process the silver catalyst can be used in this oxidized form. Before using the gas diffusion silver cathodes in the alkaline fuel cell the catalyst will be reduced to the metallic form.
Optical Measurements of Platinum Based Electrocatalysts for the Electrooxidation of Methanol
Authors: Gruber K. , Kronberger H. , Fafilek G. , Nauer G. , Besenhard J.‐O.
Published: August 2003

In a combinatorial electrochemistry experiment quinine was used as a pH sensitive fluorescing indicator to detect the catalytic activity of methanol oxidation catalysts. During electrochemical experiments the surface of the electrode array was monitored with a CCD camera. The dependence of the intensity of the fluorescence on the applied potential was used as an analytical tool; to investigate the electrochemical performance of Pt based electrocatalysts, for the electrooxidation of methanol, in both short and long term tests.
Progress in DMFC Development Using the Dry Spraying Preparation Technique
Authors: Gülzow E. , Reissner R. , Weisshaar S. , Kaz T.
Published: August 2003

A dry MEA (membrane electrode assembly) preparation technique developed at DLR was applied to DMFC (direct methanol fuel cell) MEAs using different preparation parameters. It turned out that for cathode and anode backings with high hydrophobicity the high current density performance of the MEA at low cathode airflow and thus low stoichiometry is better than for backings with low hydrophobicity. The anode reaction layer does not need to contain Nafion™. It has been demonstrated that at catalyst loadings similar to or lower than generally reported, power densities of technical interest are within reach.
Membrane Durability in a PEM Fuel Cell Studied Using PVDF Based Radiation Grafted Membranes
Authors: Gode P. , Ihonen J. , Strandroth A. , Ericson H. , Lindbergh G. , Paronen M. , Sundholm F. , Sundholm G. , Walsby N.
Published: August 2003

The durability testing of membranes for use in a polymer electrolyte fuel cell (PEFC) has been studied in situ by a combination of galvanostatic steady‐state and impedance measurements. The PEFC measurements, which are time consuming, have been compared to fast ex situ testing in 3% H2O2 solution. For the direct assessment of membrane degradation micro‐Raman spectroscopy and determination of ion exchange capacity (IEC) have been used. PVDF based membranes, radiation grafted with styrene and sulfonated, were used as model membranes. By using low degrees of grafting, below about 35%, the durability of this type of membrane can be increased. Degradation in the fuel cell was found to be highly localised. It was found that in situ measurements in the PEFC alone are not sufficient. Measurement of the cell resistance via impedance is not always a reliable indicator of changes in membrane resistance because other resistance changes in the cell can easily interfere and cannot be separated from those caused by the membrane. Micro‐Raman is an ideal complementary method to in situ testing, but it is time consuming. For fast pre‐screening of membrane durability mass loss measurements during exposure to 3% H2O2 solution combined with the determination of changes in the IEC can be performed.
Hydrogen Evolution on Zeolite Supported Platinum Clusters
Authors: Mentus S. , Mojovic Z. , Cvjeticanin N. , Tesic Z.
Published: August 2003

NaX type zeolite was loaded with platinum, by the thermal decomposition of Pt(II) acetylacetonate, up to the Pt/NaX mass ratio of 0.174. The sample, dispersed on a glassy carbon rotating disc, was used in slightly acidic solution to observe the kinetics of the hydrogen evolution reaction. A comparison was made with the rate of hydrogen evolution on smooth polycrystalline platinum, and both slower and faster evolution rates were observed, depending on the percentage of carbon black added to the zeolite sample.
Electro‐Oxidation of Methanol and Ethanol on Poly(3,4‐Ethylenedioxythiophene) with Dispersed Pt, Pt + Sn, and Pt + Pb Particles
Authors: Biallozor S. , Kupniewska A. , Jasulaitene V.
Published: August 2003

The influence of tin and lead additives on the catalytic activity of platinum particles dispersed on a poly(3,4‐dioxyethylenethiophene) (PEDT) layer deposited on gold or steel towards anodic oxidation of methanol and ethanol was studied. It was found that these additives increase the rate of anodic oxidation of both alcohols. It was also found that the electro‐catalytic properties of PEDT depend on the kind of support used for its deposition.

The authors have shown that these additives (Pb and Sn) increase the rate of anodic oxidation of both alcohols on platinum deposited on PEDT, but tin was evidently more effective than lead. In the presence of Sn, the steady‐state current density of methanol oxidation increases about 100 times, while Pb only promotes the platinum catalyst activity by about 2 times. In the authors opinion the most probable mechanism for the tin promotion effect seems to be a homogenous catalytic reaction with the participation of the Sn (IV) and Sn (II) ions as mediators.
A Method for Characterizing CO Transients in a PEMFC
Authors: Lee W.‐k. , Van Zee J.W. , Murthy M.
Published: August 2003

A method for characterizing the response of a PEMFC to transients in the CO concentration in the fuel is presented. The method uses the well‐known First Order Plus Dead Time (FOPDT) model to separate the system effects from the poisoning characteristics of CO as a function of concentration and dosage. The method is more representative of the data and should be used as an alternative to a simple slope measurement for reporting the experimental data of the poisoning and recovery processes. The results characterize a specific MEA by showing that the time constant for the poisoning process is extended from 4 – 48 s when 15% air was injected with an anode stream of 3,000 ppm CO/H2. For the recovery process, a 15% air‐bleed reduces the dead time from 122 – 36 s and the time constant from 89 – 18 s. In addition, the gain is shown to be relatively independent of the high CO concentrations but it is affected by air bleeding. The gain changes from –0.10 to –0.08 mV/ppm CO for a poisoning process and from 0.09 – 0.08 mV/ppm CO for a recovery process with 15% air bleeding in the 3,000 ppm CO/H2. In general, the dead times and time constants for the poisoning process decreased as the CO concentrations increased at equal CO dosage. On the other hand, these parameters (dead time and time constant) for the recovery process increased as the CO concentration increased at equal CO dosage. The method is critical for comparison of the dynamic response of MEAs between laboratories and for the design of reformate fuel‐processing systems.
Operation of Direct Methanol Fuel Cell in a Centrifugal Field
Authors: Cheng H. , Scott K. , Ramshaw C.
Published: August 2003

Direct methanol fuel cells were operated and evaluated in a centrifugal field. It was observed that the methanol oxidation was significantly intensified in a centrifugal field. The application of centrifugal fields greatly enhanced mass transfer and accelerated gas bubble disengagement from the electrode surfaces, the electrolytes and the membrane during the methanol oxidation. The high acceleration field caused a significant reduction in the anode potential up to 500 mV at 300 mA cm–2 at a relative acceleration rate of 190 g and 80 °C. Increases in methanol concentration and operating temperature contributed to increase the methanol oxidation rate. These beneficial effects were improved further in a centrifugal field, compared to the gravitational field. A beneficial effect of the centrifugal field on the direct methanol fuel cell performance was observed. More effort is required to guarantee efficient oxygen supply to the cathode under the centrifugal acceleration conditions and thus to increase power output by this particular approach.
Looking for contagion in currency futures markets
Authors: Tai Chu‐Sheng
Published: August 2003

This article tests whether there are pure contagion effects in both conditional means and volatilities among
British pound, Canadian dollar, Deutsche mark, and Swiss franc futures markets during the 1992 ERM crisis. A
conditional version of international capital asset pricing model (ICAPM) in the absence of purchasing
power parity (PPP) is used to control for economic fundamentals. The empirical results indicate that
overall there are no mean spillovers among those futures markets, but they are detected during the crisis
period. That is, past return shocks originating in any one of the four markets have no impact on the other three
markets during the entire sample period, suggesting that these markets are weak‐form efficient. However,
this weak‐form market efficiency fails to hold during the market turmoil, especially for British pound
and Swiss franc, and the sources of contagion‐in‐mean effects are mainly due to the return shocks
originating in three European currency futures markets. As for the contagion‐in‐volatility, it is
detected for British pound only because its conditional volatility is influenced by the negative volatility
shocks from Canadian dollar, Deutsche mark, and Swiss franc, with Deutsche mark playing the dominant role in
generating these shocks. JEL Classifications: C32; F31; G12. © 2003 Wiley Periodicals, Inc. Jrl Fut Mark
23:957–988, 2003
A first look at the empirical relation between spot and futures electricity prices in the United States
Authors: Shawky Hany A. , Marathe Achla , Barrett Christopher L.
Published: August 2003

In this article we investigate the statistical properties of wholesale electricity spot and futures prices
traded on the New York Mercantile Exchange for delivery at the California–Oregon Border. Using daily data
for the years 1998 and 1999, we find that many of the characteristics of the electricity market can be viewed to
be broadly consistent with efficient markets. The futures risk premium for 6‐month futures contracts is
estimated to be 0.1328% per day or about 4% per month. Using a GARCH specification, we estimate
minimum variance hedge ratios for electricity futures. Finally, we study the dynamic relation between spot and
futures prices using an Exponential GARCH model and between the spot and futures returns series using a vector
autoregression. © 2003 Wiley Periodicals, Inc. Jrl Fut Mark 23:931–955, 2003
On the adequacy of single‐stock futures margining requirements
Authors: Dutt Hans R. , Wein Ira L.
Published: August 2003

Unlike the traditional futures contract risk‐based approach to margining, new security futures
contracts
are margined under a strategy‐based margining system similar to that which applies in the equity options
markets. As a result, these new margin requirements are potentially much less sensitive to changes in market
conditions. This article performs a simulation to evaluate whether these alternative margining methodologies can
be
expected to produce comparable outcomes. The analysis suggests that a 1‐day settlement period will likely
lead to collection of customer margins that are virtually always greater than that which its traditional
risk‐based counterpart would require. A 4‐day settlement period would lead to margin requirements
that both significantly under‐ and overmargin relative to a comparable risk‐based system. This
study
argues that exchanges may approach the preferred probability of customer exhaustion by managing margin
settlement
intervals. Thus, the new strategy‐based rules, in and of themselves, will not necessarily inhibit new
security futures trading activity. © 2003 Wiley Periodicals, Inc. Jrl Fut Mark 23:989–1002, 2003
Commodity trading advisors' leverage and reported margin‐to‐equity ratios
Authors: Diz Fernando
Published: August 2003

We investigate the effect of leverage on Commodity Trading Advisors' (CTAs) performance
measurement. We find that leverage has important effects on the cross section of CTA returns, volatility, and
survival experience. On average, a 100‐basis points increase in leverage is associated with a
27‐basis points increase in returns. After performance is adjusted for leverage, volatility, and survival
experience, CTAs' style variables have no significant effect on performance. The amount of leverage used by a
CTA is found to reduce the likelihood of survival. However, the total effect of leverage on survival is much
smaller than its partial effect. Contrary to common beliefs, we find that CTA diversification leads to higher
levels of leverage and volatility. This apparent contradiction is related to how the diversification process
affects the use of leverage. The findings in this study have implications for measuring and comparing
managers' performance track records. © 2003 Wiley Periodicals, Inc. Jrl Fut Mark 23:1003–1017,
2003
Approximating American option prices in the GARCH framework
Authors: Duan Jin‐Chuan , Gauthier Geneviève , Sasseville Caroline , Simonato Jean‐Guy
Published: August 2003

This article proposes an efficient approach for computing the prices of American style options in the GARCH
framework. Rubinstein's (1998) Edgeworth tree idea is combined with the analytical formulas for
moments of the cumulative return under GARCH developed in Duan et al. (1999, 2002) to yield a simple
recombining binomial tree for option valuation in the GARCH context. Because the resulting tree is univariate, the
proposed approach represents a convenient approximation of the bivariate GARCH system. Numerical analysis is used
to demonstrate the speed and accuracy of the proposed approximation. © 2003 Wiley Periodicals, Inc. Jrl Fut
Mark 23:915–929, 2003
Disruption of a novel gene, DIRC3, and expression of DIRC3‐HSPBAP1 fusion transcripts in a case of familial renal cell cancer and t(2;3)(q35;q21)
Authors: Bodmer Daniëlle , Schepens Marga , Eleveld Marc J. , Schoenmakers Eric F.P.M. , Geurts van Kessel Ad
Published: August 2003

Previously, we identified a family with renal cell cancer and a t(2;3)(q35;q21). Positional cloning of the chromosome 3 breakpoint led to the identification of a novel gene, DIRC2, that spans this breakpoint. Here we have characterized the chromosome 2 breakpoint in detail and found that another novel gene, designated DIRC3, spans this breakpoint. In addition, we found that the first two exons of DIRC3 can splice to the second exon of HSPBAP1, a JmjC‐Hsp27 domain gene that maps proximal to the breakpoint on chromosome 3. This splice results in the formation of DIRC3‐HSPBAP1 fusion transcripts. We propose that these fusion transcripts may affect normal HSPBAP1 function and concomitant chromatin remodeling and/or stress response signals within t(2;3)(q35;q21)‐positive kidney cells. As a consequence, familial renal cell cancer may develop. © 2003 Wiley‐Liss, Inc.
High‐resolution comparative genomic hybridization detects extra chromosome arm 12p material in most cases of carcinoma in situ adjacent to overt germ cell tumors, but not before the invasive tumor development
Authors: Ottesen Anne Marie , Skakkebæk Niels E. , Lundsteen Claes , Leffers Henrik , Larsen Jacob , Rajpert‐De Meyts Ewa
Published: August 2003

High‐resolution comparative genomic hybridization (HR‐CGH) analysis was performed on DNA purified from laser‐capture microdissected carcinoma in situ (CIS) cells from nine cases of CIS, either from tissue without any invasive tumor or from testicular parenchyma adjacent to seminoma, nonseminoma, or a combined germ cell tumor. Before CGH analysis, DNA was amplified by degenerate oligonucleotide primed PCR (DOP‐PCR) and directly labeled with a mixture of FITC‐dUTP and FITC‐dCTP. CGH analysis revealed extra chromosome arm 12p material in six out of seven cases with CIS adjacent to overt tumors, but only a diminutive gain of 12q was noted in one of the two cases of CIS without invasive elements. In addition, gains of parts of chromosome 8 (3/7) and losses of chromosome 5 (2/7) were demonstrated in CIS adjacent to invasive tumors. Gains of parts of chromosome 7 were found in CIS adjacent to seminoma (4/4), whereas relative gains of chromosome 15 were identified in some cases of CIS adjacent to seminoma and in isolated CIS in comparison to CIS adjacent to nonseminoma. Our data seem to indicate that extra 12p material is not present in the “dormant” CIS cell before development of an invasive tumor. The gain of extra chromosome 12 material may not be an early event in the neoplastic transformation, but is most likely associated with a more malignant progression of the CIS cell. © 2003 Wiley‐Liss, Inc.
Heterogeneity of the 7q36 breakpoints in the t(7;12) involving ETV6 in infant leukemia
Authors: Tosi Sabrina , Hughes Jim , Scherer Stephen W. , Nakabayashi Kazuhiko , Harbott Jochen , Haas Oskar A. , Cazzaniga Giovanni , Biondi Andrea , Kempski Helena , Kearney Lyndal
Published: August 2003

The t(7;12)(q36;p13) is a recurrent chromosome abnormality in infant leukemia. In these cases, the involvement of ETV6, with disruption of the gene consistently at its 5′ end, has been reported by several groups. A fusion transcript between ETV6 and HLXB9 has been detected in some, but not all, reported cases of t(7;12). We report here a study based on fluorescence in situ hybridization (FISH) mapping of the translocation breakpoints in seven patients and detailed molecular studies using Southern blotting on two of these patients. The FISH studies have shown a cluster of breakpoints within a cosmid contig proximal to the HLXB9 gene. Southern blotting analysis enabled us to define two distinct breakpoints within the area covered by the cosmid contig in two patients. The analysis of an unusual case of t(7;12)(q22;p13) [full karyotype: 46,XX,der(7)t(7;12)(q22;p13)del(7)(q22q36)] also revealed a break in 7q36, although in a region proximal to the overlapping cosmids. 5′ RACE PCR in one patient has shown a rearrangement involving the ETV6 allele not involved in the t(7;12), suggesting that no functional ETV6 allele might be present in this case. These data show some heterogeneity in the distribution of breakpoints in 7q36, indicating that the generation of a fusion gene might not be the mechanism responsible for leukemogenesis in the t(7;12), at least in some cases. © 2003 Wiley‐Liss, Inc.
Site‐directed mutagenesis of the ATM promoter: Consequences for response to proliferation and ionizing radiation
Authors: Gueven Nuri , Keating Karen , Fukao Toshiyuki , Loeffler Heidi , Kondo Naomi , Rodemann H. Peter , Lavin Martin F.
Published: August 2003

Although ATM, the protein defective in ataxia‐telangiectasia (A‐T), is activated primarily by radiation, there is also evidence that expression of the protein can be regulated by both radiation and growth factors. Computer analysis of the ATM promoter proximal 700‐bp sequence reveals a number of potentially important cis‐regulatory sequences. Using nucleotide substitutions to delete putative functional elements in the promoter of ATM, we examined the importance of some of these sites for both the basal and the radiation‐induced activity of the promoter. In lymphoblastoid cells, most of the mutations in transcription factor consensus sequences [Sp1(1), Sp1(2), Cre, Ets, Xre, γIre(2), a modified AP1 site (Fse), and GCF] reduced basal activity to various extents, whereas others [γIre(1), NF1, Myb] left basal activity unaffected. In human skin fibroblasts, results were generally the same, but the basal activity varied up to 8‐fold in these and other cell lines. Radiation activated the promoter approximately 2.5‐fold in serum‐starved lymphoblastoid cells, reaching a maximum by 3 hr, and all mutated elements equally blocked this activation. Reduction in Sp1 and AP1 DNA binding activity by serum starvation was rapidly reversed by exposure of cells to radiation. This reduction was not evident in A‐T cells, and the response to radiation was less marked. Data provided for interaction between ATM and Sp1 by protein binding and co‐immunoprecipitation could explain the altered regulation of Sp1 in A‐T cells. The data described here provide additional evidence that basal and radiation‐induced regulation of the ATM promoter is under multifactorial control. © 2003 Wiley‐Liss, Inc.
There is no increase in frequency of somatic mutations in metastases compared with primary colorectal carcinomas with microsatellite instability
Authors: Barnetson Rebecca , Eckstein Robert , Robinson Bruce , Schnitzler Margaret
Published: August 2003

This study investigates the molecular features of metastasis in sporadic colon carcinomas with high‐level microsatellite instability (MSI‐H). DNA from 51 regions from 10 MSI‐H metastatic carcinomas and 26 corresponding metastases was analyzed for mutations in TGFBRII, IGFIIR, BAX, MSH3, MSH6, and TCF4, which are associated with MSI‐H carcinomas. In addition, 10 metastatic and 10 non‐metastatic MSI‐H carcinomas and 10 metastatic microsatellite‐stable (MSS) carcinomas were examined for expression of vascular endothelial growth factor (VEGF) and mutant TP53. The frequency of microsatellite instability and somatic mutations was not significantly increased in the metastases compared with the that of primary carcinomas. Although significantly fewer MSI‐H carcinomas expressed VEGF (P < 0.01) and mutant TP53 (P < 0.005) than MSS carcinomas, there was no difference in VEGF and mutant TP53 expression in metastatic and non‐metastatic MSI‐H carcinomas. In conclusion, metastasis does not appear to be associated with an increase in somatic mutation rate in any of the genes examined in MSI‐H colon carcinomas. Furthermore, VEGF and TP53 expression did not appear to be involved in metastasis in MSI‐H colon carcinomas. © 2003 Wiley‐Liss, Inc.
Cytogenetic characterization of tumors of the vulva and vagina
Authors: Micci Francesca , Teixeira Manuel R. , Scheistrøen Marit , Abeler Vera M. , Heim Sverre
Published: August 2003

Neoplasms of the vulva and vagina account for less than 5% of all female genital tract cancers. Squamous cell carcinoma (SCC) represents more than 70% of the cases in both locales, followed by melanoma, basal cell carcinoma, Paget's disease, and other carcinoma subtypes. Until recently, only few cases had been analyzed by chromosome banding techniques and karyotyped, and also the number subjected to molecular cytogenetic analysis remains low. To understand better the genetic changes harbored by the neoplastic cells in cancer of the vulva and vagina, we analyzed cytogenetically 51 such tumors, finding karyotypic abnormalities in 37. All tumors were analyzed by G‐banding, sometimes supplemented by multicolor fluorescence in situ hybridization, and a subset of tumors was also analyzed by comparative genomic hybridization. The two cytogenetically abnormal cases of Paget's disease both had two clones, one with gain of chromosome 7 as the sole change, the other with loss of the X chromosome among, in one case, other aberrations. The four cytogenetically abnormal malignant melanomas (three of the vulva, one of the vagina) presented complex karyotypes with aberrations involving different chromosomes but most often chromosome 1, specifically 1p12–q41. In the 31 cytogenetically abnormal SCCs, different clonal karyotypic abnormalities were seen. Intratumor heterogeneity with multiple clones was observed in 11 cases. The clones were cytogenetically unrelated in eight tumors but related in three, indicating that in the latter clonal evolution had taken place from a single malignantly transformed cell. The main chromosomal imbalances were gains of, or from, chromosome arms 3q, 5p, 8q, 9q, and 19q, and loss from 11q. Breakpoint clusters were seen in 11q13–23, 2q22–35, and 19q13, as well as in the centromeres and pericentromeric bands of chromosomes 3, 8, 9, 13, 14, and 22. © 2003 Wiley‐Liss, Inc.
Classical Hodgkin lymphoma is associated with frequent gains of 17q
Authors: Chui Daniel T.Y. , Hammond David , Baird Margaret , Shield Lesley , Jackson Robert , Jarrett Ruth F.
Published: August 2003

The etiology of Hodgkin lymphoma (HL) is poorly understood, and studies of the genetics of this disease have been hampered by the scarcity of the Hodgkin and Reed–Sternberg (HRS) cells within tumors. To determine whether recurrent genomic imbalances are a feature of HL, CD30‐positive HRS cells were laser‐microdissected from 20 classical Hodgkin lymphomas (cHLs) and four HL‐derived cells lines and subjected to analyses by comparative genomic hybridization. In primary tumors, the most frequently involved chromosomal gains were 17q (70%), 2p (40%), 12q (40%), 17p (40%), 22q (35%), 9p (30%), 14q (30%), and 16p (30%), with minimal overlapping regions at 17q21, 2p23–13, 12q24, 17p13, 22q13, 9p24–23, 14q32, 16p13.3, and 16p11.2. The most frequent losses involved 13q (35%), 6q (30%), 11q (25%), and 4q (25%), with corresponding minimal overlapping regions at 13q21, 6q22, 11q22, and 4q32. Statistical analysis revealed significantly more gains of 2p and 14q in the older adult cases; loss of 13q was associated with a poor outcome. The results suggest that there is a set of recurrent chromosomal abnormalities associated with cHL and provide further evidence that cHL is genetically distinct from nodular lymphocyte predominance Hodgkin lymphoma (NLPHL). Abnormalities of 17q are infrequent in other lymphomas or NLPHL; this finding, coupled with current knowledge of gene expression in cHL, suggests that genes present on 17q may play an important role in the pathogenesis of cHL. © 2003 Wiley‐Liss, Inc.
ALK‐ATIC fusion in urinary bladder inflammatory myofibroblastic tumor
Authors: Debiec‐Rychter Maria , Marynen Peter , Hagemeijer Anne , Pauwels Patrick
Published: August 2003

In this report, we describe an inflammatory myofibroblastic tumor (IMT) of the urinary bladder in a 46‐year‐old man. Tumor cells presented striking cytoplasmatic ALK immunopositivity. Cytogenetic and FISH analysis, by use of a multicolor chromosome 2 banding probe, revealed a 46,XY,der(2)(2pter→2p23:2q35→2q37:2p11→2q35:2p23→2p11:2q37→2qter) karyotype. Subsequent FISH and RT‐PCR analysis confirmed the ALK‐ATIC chimeric fusion in tumor cells. This is the first evidence of a variant rearrangement involving the ATIC gene in IMT and the first cytogenetic description of an IMT originating from the urinary bladder. © 2003 Wiley‐Liss, Inc.
Premature chromosome condensation revisited: A novel chemical approach permits efficient cytogenetic analysis of cancers
Authors: Bezrookove Vladimir , Smits Ron , Moeslein Gabriela , Fodde Riccardo , Tanke Hans Johannes , Raap Anton Klaas , Darroudi Firouz
Published: August 2003

Chemical induction of premature chromosome condensation (PCC) was investigated and optimized to be able to analyze the chromosomal constitution of cancer cells independent of mitosis and with minimal culture artifacts. A potent protein phosphatase inhibitor, calyculin A, was used to induce PCC in normal diploid cells, in several established human tumor cell lines, and in cells isolated from freshly dissected adenomatous polyps of a patient with hereditary colorectal cancer. In parallel, mitotic arrest was pursued by use of Colcemid. In cell lines, a difference of up to 10‐fold was found between frequency of cells with PCC induced by calyculin A (PCC index) and the mitotic index after treatment with Colcemid. In the fresh tumor specimens, Colcemid failed to result in metaphase formation, whereas a regimen of 80 nM calyculin A for 75 min, after only 2 days of culturing, resulted in a PCC index of 2–5%. pq‐COBRA‐FISH (COmbined Binary RAtio labeling–fluorescence in situ hybridization) was used for a detailed analysis of four cell lines treated with calyculin A, which proved that PCC spreads are amenable to molecular karyotyping, and a comparison between PCC spreads and metaphases from mitotic arrest revealed no discrepancies in karyotypes. pq‐COBRA‐FISH on PCC spreads from fresh colon tumor samples revealed only numerical and no structural abnormalities. Calyculin A–induced PCC combined with multicolor FISH gives a new opportunity for analysis of the chromosomal constitution of G1 and G2 cancer cells and may find application in the study of the role of chromosome instability in cancer development. © 2003 Wiley‐Liss, Inc.
Evaluation of a whole‐genome amplification method based on adaptor‐ligation PCR of randomly sheared genomic DNA
Authors: Tanabe Chikako , Aoyagi Kazuhiko , Sakiyama Tokuki , Kohno Takashi , Yanagitani Noriko , Akimoto Shingo , Sakamoto Michiie , Sakamoto Hiromi , Yokota Jun , Ohki Misao , Terada Masaaki , Yoshida Teruhiko , Sasaki Hiroki
Published: August 2003

High‐throughput genetic studies often require large quantities of DNA for a variety of analyses. Developing and assessing a whole‐genome amplification method is thus important, especially with the current desire for large‐scale genotyping in previously collected samples for which limited DNA is available. The method we have developed, called PRSG, is based on an adaptor‐ligation–mediated PCR of randomly sheared genomic DNA. An unbiased representation was evaluated by performing PCR on 2,607 exons of 367 genes, which are randomly distributed throughout the genome, on PRSG products of hundreds of individuals. An infrequent loss (<1%) of the exon sequence on the PRSG products was found. Out of 307 microsatellites on various chromosomes, 258 (84%) were amplified in both the PRSG product and an original DNA, whereas 49 (16%) microsatellites were lost only in the PRSG product. Array CGH analysis of 287 loci for measuring the relative gene copy number demonstrated that a low bias was detected. Moreover, this method was validated on 100–1,000 laser‐captured cells from paraffin‐embedded tissues. These data show that PRSG can provide a sufficient amount of genomic sequence for a variety of genetic analyses as well as for long‐term storage for future work. © 2003 Wiley‐Liss, Inc.
Transient RNA interference in hematopoietic progenitors with functional consequences
Authors: Oliveira Daniela M. , Goodell Margaret A.
Published: August 2003

Summary: Short interfering (si) RNAs have now been shown to inhibit gene expression in several species, including mammals (Elbashir et al.: Nature 411:494–498, 2001; Fire et al.: Nature 391:806–811, 1998). RNA inhibition in primary cells such as stem cells would facilitate rapid gene discovery in a postgenome era. While retroviruses can deliver siRNA expression cassettes for stable expression (Barton and Medzhitov: Proc Natl Acad Sci USA 99:14943–14945, 2002; Paddison et al.: Proc Natl Acad Sci USA 99:1443–1448, 2002; Rubinson et al.: Nat Genet 33:401–406, 2003), an efficient method for direct transfer of siRNA to stem cells is still lacking. Here, we established electroporation to deliver siRNA to hematopoietic progenitors. On average, at least 80% of cells take up the RNA, and these display nearly 100% knockout of marker gene expression at both the RNA and protein level. Moreover, knockdown of the hematopoietic regulator, CD45, results in 3‐fold more hematopoietic colonies in a progenitor assay. These results demonstrate that transient transfection of siRNA to primary cells can have substantial functional consequences. This technology may be applicable to a variety of primary cell types. genesis 36:203–208, 2003. © 2003 Wiley‐Liss, Inc.
Peduncle of Hydra and the heart of higher organisms share a common ancestral origin
Authors: Shimizu Hiroshi , Fujisawa Toshitaka
Published: August 2003

Summary: The heart is assumed to have evolved as the organ for pumping blood. Here we report a pumping phenomenon in Hydra, a member of the phylum Cnidaria. We find that the peduncle, lower quarter of the body column, stores most of the gastrovascular fluid when the animal is an elongate form. Upon contraction of the polyp, the peduncle contracts and transfers the fluid into the rest of the cavity. We also find that Hydra RFamide III, a homolog of cardioexcitatory RFamide neuropeptides in higher organisms, elevates this transfer activity. Further, CnNk‐2, a homolog of a cardiomuscular tissue marker Nkx‐2.5, is expressed in the endodermal tissue of the peduncle. These observations indicate that the transfer of fluid by the peduncle has a similar neurological and genetic basis to the pumping of blood by the heart, suggesting that the Hydra peduncle and the heart of higher organisms share a common ancestral origin. genesis 36:182–186, 2003. © 2003 Wiley‐Liss, Inc.
Conditional knockout of the mouse NADPH‐cytochrome p450 reductase gene
Authors: Wu Lin , Gu Jun , Weng Yan , Kluetzman Kerri , Swiatek Pam , Behr Melissa , Zhang Qing‐Yu , Zhuo Xiaoliang , Xie Qiang , Ding Xinxin
Published: August 2003

Summary: NADPH‐cytochrome P450 reductase (CPR or POR) is the obligatory electron donor for all microsomal cytochrome P450 (CYP or P450)‐catalyzed monooxygenase reactions. Disruption of the mouse Cpr gene has been reported to cause prenatal developmental defects and embryonic lethality. In this study, we generated a mouse model with a floxed Cpr allele (termed Cprlox). Homozygous Cprlox mice are fertile and without any histological abnormality or any change in CPR expression. The floxed Cpr allele was subsequently deleted efficiently by crossing Cprlox mice with transgenic mice having liver‐specific Cre expression (Alb‐Cre); the result was a decrease in the level of CPR protein in liver microsomes. The Cprlox strain will be valuable for conditional Cpr gene deletion and subsequent determination of the impact of CPR loss on the metabolism of endogenous and xenobiotic compounds, as well as on postnatal development and other biological functions. genesis 36:177–181, 2003. © 2003 Wiley‐Liss, Inc.
Conservation of Dnmt1o cytosine methyltransferase in the marsupial Monodelphis domestica
Authors: Ding Feng , Patel Carol , Ratnam Sarayu , McCarrey John R. , Chaillet J. Richard
Published: August 2003

Summary: Imprinted genes have been identified in both eutherian mammals and in marsupials. In eutherian species, there is a conservation of the imprinting process, both in terms of the genes imprinted and the epigenetic inheritance mechanism. In the mouse, the inheritance of gametic methylation patterns depends on an oocyte‐derived isoform of the Dnmt1 (cytosine‐5)‐methyltransferase protein, Dnmt1o, which functions during preimplantation development to maintain methylation patterns on imprinted alleles. To determine if this component of genomic imprinting is also found in marsupials, Dnmt1 isoforms were examined in somatic cells and germ cells of the South American opossum Monodelphis domestica. There is a Dnmt1o protein in Monodelphis oocytes that is synthesized, as in the mouse, from a different transcript than the somatic Dnmt1 protein. Thus, an essential component of imprinting in eutherian mammals is found in a marsupial species, suggesting that marsupials and eutherian mammals imprint their genes with the same methylation‐dependent mechanism. genesis 36:209–213, 2003. © 2003 Wiley‐Liss, Inc.
Induction of string rescues the neuroblast proliferation defect in trol mutant animals
Authors: Park Youngji , Ng Cristina , Datta Sumana
Published: August 2003

Summary: In trol mutants, neuroblasts fail to exit G1 for S phase. Increasing string expression in trol mutants rescues the number of S phase neuroblasts without an increase in M phase neuroblasts. Decreasing string expression further decreased the number of S phase neuroblasts. Coexpression of cyclin E and string did not produce additional S phase cells. Unlike cyclin E, cdk2, and cdk2AF, elevated expression of neither cyclin A, cyclin D, nor cdk1AF was able to promote S phase progression in arrested neuroblasts, indicating that String‐induced activity of a Cyclin A or Cyclin D complex is unlikely to drive trol neuroblasts into S phase. Biochemical analyses revealed a rapid increase of Cyclin E‐Cdk2 kinase activity to wild‐type levels upon increased string expression. These results suggest that Drosophila Cdc25 may directly or indirectly increase the kinase activity of Cyclin E‐Cdk2 complexes in vivo, thus driving arrested neuroblasts into cell division. genesis 36:187–195, 2003. © 2003 Wiley‐Liss, Inc.