bluuebunny/crossref_metadata_2025 huggingface dataset:
Crystallographic controls on the frictional behavior of dry and water‐saturated sheet structure minerals
Authors: Moore Diane E. , Lockner David A.
Published: March 2004

We compare the frictional strengths of 17 sheet structure mineral powders, measured under dry and water‐saturated conditions, to identify the factors that cause many of them to be relatively weak. The dry coefficient of friction μ ranges upward from 0.2 for graphite, leveling off at 0.8 for margarite, clintonite, gibbsite, kaolinite, and lizardite. The values of μ (dry) correlate directly with calculated (001) interlayer bond strengths of the minerals. This correlation occurs because shear becomes localized along boundary and Riedel shears and the platy minerals in them rotate into alignment with the shear planes. For those gouges with μ (dry) < 0.8, shear occurs by breaking the interlayer bonds to form new cleavage surfaces. Where μ (dry) = 0.8, consistent with Byerlee's law, the interlayer bonds are sufficiently strong that other frictional processes dominate. The transition in dry friction mechanisms corresponds to calculated surface energies of 2–3 J/m2. Adding water causes μ to decrease for every mineral tested except graphite. If the minerals are separated into groups with similar crystal structures, μ (wet) increases with increasing interlayer bond strength within each group. This relationship also holds for the swelling clay montmorillonite, whose water‐saturated strength is consistent with the strengths of nonswelling clays of similar crystal structure. Water in the saturated gouges forms thin, structured films between the plate surfaces. The polar water molecules are bonded to the plate surfaces in proportion to the mineral's surface energy, and μ (wet) reflects the stresses required to shear through the water films.
Observations of PKiKP/PcP amplitude ratios and implications for Earth structure at the boundaries of the liquid core
Authors: Koper Keith D. , Pyle Moira L.
Published: March 2004

Mining of the database produced by seismic array stations of the International Monitoring System has resulted in hundreds of new observations of precritical reflections from Earth's inner core. Here we present short‐period amplitude ratios between these PKiKP phases and corresponding reflections (PcP) from the core‐mantle boundary (CMB). PKiKP/PcP amplitude ratios are one of the few seismic observations that directly constrain the change in S velocity and density across the inner core‐outer core boundary. We measure the amplitude ratios from optimally tuned array beams and use a bootstrap technique to estimate observational uncertainties. We also use a model resampling technique to estimate uncertainties associated with the background reference model. The optimal models have S velocities at the top of the inner core less than about 2.5 km/s and density jumps across the inner core‐outer core boundary of less than about 0.45 g/cm3. These values can be reconciled with the higher estimates from normal mode constraints if strong radial gradients are present in the top of the inner core or if the outermost inner core has material properties distinct from the bulk of the inner core. We also find evidence for an ultralow‐velocity zone in the lowermost mantle beneath the eastern coast of Australia. A unique, best fitting model cannot be determined, but an example that is consistent with the data has a reduction in P velocity of 10%, a reduction in S velocity of 35%, and an increase in density of 20%. This type of structure could be explained by the presence of partial melt and increased iron content just above the CMB.
Numerical modeling of the global semidiurnal tide in the present day and in the last glacial maximum
Authors: Egbert Gary D. , Ray Richard D. , Bills Bruce G.
Published: March 2004

A hydrodynamic model incorporating a self‐consistent treatment of ocean self‐attraction and loading (SAL), and a physically based parameterization of internal tide (IT) drag, is used to assess how accurately barotropic tides can be modeled without benefit of data, and to explore tidal energetics in the last glacial maximum (LGM). M2 solutions computed at high resolution with present day bathymetry agree with estimates of elevations from satellite altimetry within 5 cm RMS in the open ocean. This accuracy, and agreement with atlimetric estimates of energy dissipation, are achieved only when SAL and IT drag are included in the model. Solutions are sensitive to perturbations to bathymetry, and inaccuracies in available global databases probably account for much of the remaining error in modeled elevations. The ≈100 m drop in sea level during the LGM results in significant changes in modeled M2 tides, with some amplitudes in the North Atlantic increasing by factors of 2 or more. Dissipation is also significantly changed by the drop in sea level. If IT drag estimated for the modern ocean is assumed, dissipation increases by about 50% globally, and almost triples in the deep ocean. However, IT drag depends on ocean stratification, which is poorly known for the LGM. Tests with modified IT drag suggest that the tendency to a global increase in dissipation is a robust result, but details are sensitive to stratification. Significant uncertainties about paleotides thus remain even in this comparatively simple case where bathymetry is well constrained.
On the remote sensing of oceanic and atmospheric convection in the Greenland Sea by synthetic aperture radar
Authors: Romeiser Roland , Ufermann Susanne , Androssov Alexei , Wehde Henning , Mitnik Leonid , Kern Stefan , Rubino Angelo
Published: March 2004

In this paper we discuss characteristic properties of radar signatures of oceanic and atmospheric convection features in the Greenland Sea. If the water surface is clean (no surface films or ice coverage), oceanic and atmospheric features can become visible in radar images via a modulation of the surface roughness, and their radar signatures can be very similar. For an unambiguous interpretation and for the retrieval of quantitative information on current and wind variations from radar imagery with such signatures, theoretical models of current and wind phenomena and their radar imaging mechanisms must be utilized. We demonstrate this approach with the analysis of some synthetic aperture radar (SAR) images acquired by the satellites ERS‐2 and RADARSAT‐1. In one case, an ERS‐2 SAR image and a RADARSAT‐1 ScanSAR image exhibit pronounced cell‐like signatures with length scales on the order of 10–20 km and modulation depths of about 5–6 dB and 9–10 dB, respectively. Simulations with a numerical SAR imaging model and various input current and wind fields reveal that the signatures in both images can be explained consistently by wind variations on the order of ±2.5 m/s, but not by surface current variations on realistic orders of magnitude. Accordingly, the observed features must be atmospheric convection cells. This is confirmed by visible typical cloud patterns in a NOAA AVHRR image of the test scenario. In another case, the presence of an oceanic convective chimney is obvious from in situ data, but no signatures of it are visible in an ERS‐2 SAR image. We show by numerical simulations with an oceanic convection model and our SAR imaging model that this is consistent with theoretical predictions, since the current gradients associated with the observed chimney are not sufficiently strong to give rise to significant signatures in an ERS‐2 SAR image under the given conditions. Further model results indicate that it should be generally difficult to observe oceanic convection features in the Greenland Sea with ERS‐2 or RADARSAT‐1 SAR, since their signatures resulting from pure wave‐current interaction will be too weak to become visible in the noisy SAR images in most cases. This situation will improve with the availability of future high‐resolution SARs such as RADARSAT‐2 SAR in fine resolution mode (2004) and TerraSAR‐X (2005), which will offer significantly reduced speckle noise fluctuations at comparable spatial resolutions and thus a much better visibility of small image intensity variations on spatial scales on the order of a few hundred meters.
Negligible long‐term temperature trend in the upper atmosphere at 23°S
Authors: Clemesha Barclay , Simonich Dale , Batista Paulo , Vondrak Tomas , Plane John M. C.
Published: March 2004

Measurements of the vertical distribution of atmospheric sodium, made at São José dos Campos (23°S, 46°W) from 1972 to 2001 show a negligible net long‐term trend in the layer over this time period. In view of the fact that cooling of the upper atmosphere, as indicated by some experimental studies and predicted by models, would be expected to influence the vertical distribution of sodium, this result can be used to estimate the limits of such cooling. In order to investigate the sensitivity of the sodium layer to changes in the atmospheric temperature profile, and thus estimate an upper limit to the changes it should be possible to detect, we have used a comprehensive model for the mesosphere and lower thermosphere (65–110 km) that includes all species and reactions thought to be relevant to the sodium chemistry. On the basis of this study we find that the sodium layer observations are consistent with model calculations for the global effects of increased CO2 but are not consistent with many of the experimental studies, which show cooling trends much larger than expected from theoretical studies.
Interdecadal changes in seasonal freeze and thaw depths in Russia
Authors: Frauenfeld Oliver W. , Zhang Tingjun , Barry Roger G. , Gilichinsky David
Published: March 2004

Seasonal freezing and thawing processes in cold regions play a major role in ecosystem diversity, productivity, and the Arctic hydrological system. Long‐term changes in seasonal freeze and thaw depths are also important indicators of climate change. Only sparse historical measurements of seasonal freeze and thaw depths are available for permafrost and seasonally frozen ground regions. Using mean monthly soil temperature data for 1930–1990 for 242 stations located throughout Russia, we employed a linear interpolation method to determine the depth of the 0°C isotherm based on soil temperature data measured between 0.2 m and 3.2 m depth. The relationship between available observed annual maximum freeze and thaw depths and our interpolated values indicates a perfect correlation. A comprehensive evaluation of long‐term trends in these new interpolated data for Russia indicates that in permafrost regions, active layer depths have been steadily increasing. In the period 1956–1990 the active layer exhibited a statistically significant deepening by approximately 20 cm. The changes in the seasonally frozen ground areas are even greater: The depth of the freezing layer decreased 34 cm between 1956 and 1990. Potential forcings of the observed changes include air temperature, freezing and thawing index, and snow depth. Correlation and multiple regression reveal that active layer depth is most strongly related to snow depth. Air temperature, both mean annual and thawing index, is also significantly related to changes in the active layer. Freeze depth is influenced most strongly by the freezing index and mean annual air temperature, although snow depth is also a significant contributor. Air temperature and snow depth have been changing less in the seasonally frozen ground regions of Russia compared to permafrost regions, although observed changes in freeze depth are greater than changes in active layer depth for 1930–1990. This indicates that the seasonally frozen ground regions of the Russian high latitudes are more susceptible to climate change than the Russian permafrost. However, as temperatures have been rising, especially in the high‐latitude continental regions, both permafrost and seasonally frozen ground regions are being greatly impacted. These changes can potentially result in increased river runoff and changes in discharge throughout the Russian Arctic drainage basin, as well as changes in high‐latitude ecosystems.
Planar inverted‐F antennas loaded with very high permittivity ceramics
Authors: Hwang Y. , Zhang Y. P. , Lo T. K.
Published: March 2004

With reference to a conventional air planar inverted‐F antenna this paper describes the miniaturization of the planar inverted‐F antenna by dielectric loading of barium tetratitanate ceramics of very high permittivity (εr = 38, 80) at 1.8 GHz. It is found that a simple loading method can reduce the antenna size but at the cost of the antenna performance. For instance, the antenna gain becomes lower. Then a sophisticated loading approach based on a novel substrate‐superstrate structure is developed to improve the antenna gain. The whole process of the gain enhancement is analyzed by using the finite difference time domain method. The simulations are excellently correlated with the experiments. They both show that the sophisticated loading technique can reduce the antenna size by four times and still maintains the comparable performance.
A model of rapid preferential hillslope runoff contributions to peak flow generation in a temperate rain forest watershed
Authors: Beckers Jos , Alila Younes
Published: March 2004

A model for the 10 km2 Carnation Creek watershed on Vancouver Island, British Columbia, is used to assess preferential hillslope runoff contributions to peak flow generation. The model combines the matrix flow algorithm of the distributed hydrology soil vegetation model with a Green‐Ampt formulation for calculating matrix and by‐pass infiltration, preferential hillslope runoff initiation controlled by rainfall depth, and downslope subsurface flow rates prescribed based on at‐site tracer tests. Model evaluation using 1972–1990 hydrometeorological data reveals that this formulation is successful in simulating subannual and larger peak flows. Model results suggest that preferential flow contributions to streamflow generation become greater than matrix flow contributions for unit area discharge values in excess of 2.8 mm/hr, corresponding to a peak flow return period of 2–3 months. This transition from matrix flow dominated runoff to preferential flow dominated runoff is consistent with an observed upper limit of groundwater response to precipitation for return periods in excess of 2 months. A break in slope in peak flow frequency curves at a return period of about 20 months appears to correspond to a change in storm characteristics. Thus at least three physically distinct populations of peak flows may exist at Carnation Creek. The ability of the model to simulate peak flows and groundwater responses for small and large storms suggests that it may be useful for addressing runoff process considerations in the debate whether forest management effects for annual and larger peak flows are similar to those inferred from analyses dominated by subannual peak flows.
A note on well boundary condition for flow through heterogeneous formations
Authors: Indelman Peter , Dagan Gedeon
Published: March 2004

In modeling flow toward wells it is mathematically convenient to replace the well by a singularity line along its axis. In the case of homogeneous aquifers, confined flow, and fully penetrating wells the strength of the sources is constant, and the common condition of constant head on the well is satisfied exactly. It also leads to constant flux on the well envelope. In the case of aquifers of spatially variable conductivity the constant head boundary condition can be satisfied accurately, if the well radius is much smaller than the log conductivity horizontal integral scale, by selecting a variable source strength that is proportional to the local conductivity along the well [Indelman et al., 1996; Fiori et al., 1998; Indelman, 2003a, 2003b]. In this case the equivalent conductivity tends to the arithmetic mean near the well. It changes with distance, approaching from above the effective conductivity in uniform horizontal mean flow far from the well. Selecting inadvertently a constant source strength violates the condition of constant well head. The equivalent conductivity tends to the harmonic mean near the well and approaches from below the effective one in uniform mean flow. The equivalent conductivity is derived for both types of sources for stratified formations as well as for aquifers of a three‐dimensional heterogeneous structure. The implications on interpretation of head measurements by the two models is illustrated by a few examples.
Psychology's Status as a Scientific Discipline: Its Empirical Placement within an Implicit Hierarchy of the Sciences
Authors: Simonton Dean Keith
Published: March 2004

Psychology's standing within a hypothesized hierarchy of the sciences was assessed in a 2-part analysis. First, an internally consistent composite measure was constructed from 7 primary indicators of scientific status (theories-to-laws ratio, consultation rate, obsolescence rate, graph prominence, early impact rate, peer evaluation consensus, and citation concentration). Second, this composite measure was validated through 5 secondary indicators (lecture disfluency, citation immediacy, anticipation frequency, age at receipt of Nobel Prize, and rated disciplinary hardness). Analyses showed that the measures reflected a single dimension on which 5 disciplines could be reliably ranked in the following order: physics, chemistry, biology, psychology, and sociology. Significantly, psychology placed much closer to biology than to sociology, forming a pair of life sciences clearly separated from the other sciences.
The evolution and population genetics of theALDH2locus: random genetic drift, selection, and low levels of recombination
Authors: Oota Hiroki , Pakstis Andrew J. , Bonne‐Tamir Batsheva , Goldman David , Grigorenko Elena , Kajuna Sylvester L. B. , Karoma Nganyirwa J. , Kungulilo Selemani , Lu Ru‐Band , Odunsi Kunle , Okonofua Friday , Zhukova Olga V. , Kidd Judith R. , Kidd Kenneth K.
Published: March 2004

The catalytic deficiency of human aldehyde dehydrogenase 2 (ALDH2) is caused by a nucleotide substitution (G1510A; Glu487Lys) in exon 12 of theALDH2locus. This SNP, and four non‐coding SNPs, including one in the promoter, span 40 kb ofALDH2; these and one downstream STRP have been tested in 37 worldwide populations. Only four major SNP‐defined haplotypes account for almost all chromosomes in all populations. A fifth haplotype harbours the functional variant and is only found in East Asians. Though the SNPs showed virtually no historic recombination, LD values are quite variable because of varying haplotype frequencies, demonstrating that LD is a statistical abstraction and not a fundamental aspect of the genome, and is not a function solely of recombination. Among populations, different sets of tagging SNPs, sometimes not overlapping, can be required to identify the common haplotypes. Thus, solely because haplotype frequencies vary, there is no common minimum set of tagging SNPs globally applicable. TheFstvalues of the promoter region SNP and the functional SNP were about two S.D. above the mean for a reference distribution of 117 autosomal biallelic markers. These highFstvalues may indicate selection has operated at these or very tightly linked sites.
DNM1DN: a new class of paralogous genomic segments (duplicons) with highly conserved copies on chromosomes Y and 15
Authors: Makrinou E. , Fox M. , Wolfe J. , Cameron J. , Taylor K. , Edwards Y. H.
Published: March 2004

Screening a testis cDNA selection library for Y‐linked genes yielded 79 cDNAs. Of these, 9 matched the 3′ region of the dynamin 1 gene (DNM1) on chromosome 9q34 with >90% identity. Fluoresence in situ hybridisation and PCR amplification were used to localise a large number of DNM1‐like sequences to human chromosomes 15 and Y. PCR amplification of overlapping Y‐linked YACs allowed a more accurate mapping of the Y‐linked DNM1‐like cDNAs to a euchromatic locus in close proximity to heterochromatin at Yq11.23. A search of the genome database identified 64 highly homologous copies of the DNM1 fragment. Most of these copies were localised to chromosomes 15 and Y, but others mapped to chromosomes 5, 8, 10, 12, 19 and 22. These sequences exhibit all the major features of a duplicon and have been designated DNM1DN (DNM1 duplicon). Evolutionary studies using fluorescence in situ hybridisation indicate that transposition of the DNM1DN sequence to chromosome 15 took place earlier in primate evolution than the transposition to the Y chromosome. The translocation to the Y took place at a time following the divergence of a common ancestor from gorilla, approximately 4‐7 million years ago.
Population differences in DNA sequence variation and linkage disequilibrium at the PON1 gene
Authors: Koda Y. , Tachida H. , Soejima M. , Takenaka O. , Kimura H.
Published: March 2004

Polymorphisms of the promoter region (−108C/T) and the coding region (192Q/R) of the paraoxonase 1 gene (PON1) showed differences in association with cardiovascular disease risk in various populations. To characterize the genetic variation underlying these important polymorphisms, we examined DNA sequence variation both in a 1.3‐kb promoter region 16.5 kb from codon 192, and in a 1.7‐kb region centered on the 192Q/R polymorphic site of the coding region of PON1, in 30 Africans, 30 Europeans and 64 Japanese. We found 10 polymorphic sites and 11 haplotypes in the 1.3‐kb promoter region and 10 biallelic polymorphic sites and 10 haplotypes in the 1.7‐kb region. From the PON1 sequences of chimpanzees and an orangutan, the ancestral type of codon 192 was found to be R. The number of pairs of polymorphic sites between the promoter and 1.7‐kb regions that were in significant linkage disequilibrium was much higher in a Japanese population than in African and European populations. In addition, the pairs of polymorphic sites in linkage disequilibrium differed among the three populations. These results suggest that some of the population differences in association with risk for coronary heart disease can be explained by population differences in haplotype frequency of PON1 haplotypes.
Complex segregation analyses of bone mineral density in Chinese
Authors: Liu P. Y. , Qin Y. J. , Zhou Q. , Recker R. R. , Deng H. W.
Published: March 2004

China has the largest population in the world; approximately 7% of the total population suffers from primary osteoporosis. Osteoporosis is mainly characterized by low bone mineral density (BMD). In the present study, familial correlation and segregation analyses for spine and hip BMDs have been undertaken for the first time in a Chinese sample composed of 401 nuclear families with a total of 1,260 individuals. The results indicate a major gene of additive inheritance for hip BMD, whereas there is no evidence of a major gene influencing spine BMD. Significant familial residual effects are found for both traits, and heritability estimates (±SE) for spine and hip BMDs are 0.807(0.099) and 0.897(0.101), respectively. Sex and age differences in genotype‐specific average BMD are also observed. This study provides the first evidence quantifying the high degree of genetic determination of BMD variation in the Chinese.
Genetic structure and affinities among tribal populations of southern India: a study of 24 autosomal DNA markers
Authors: Vishwanathan H. , Deepa E. , Cordaux R. , Stoneking M. , Usha Rani M. V. , Majumder P. P.
Published: March 2004

We describe the genetic structure and affinities of five Dravidian‐speaking tribal populations inhabiting the Nilgiri hills of Tamil Nadu, in south India, using 24 autosomal DNA markers. Our goals were: (i) to examine what evolutionary forces have most significantly impacted south Indian tribal genetic variation, and (ii) to test whether the phenotypic similarities of some south Indian tribal groups to Africans represent a signature of close relationship to Africans or are due to convergence. All loci were polymorphic and average heterozygosities were substantial (range: 0.347–0.423). Genetic differentiation was high (Gst= 6.7%) and genetic distances were not significantly correlated with geographic distances. Genetic drift therefore probably played a significant role in shaping the patterns of genetic variation observed in southern Indian tribal populations. Otherwise, analyses of population relationships showed that Indian populations are closely related to one another, regardless of phenotypic characteristics, and do not show particular affinities to Africans. We conclude that the phenotypic similarities of some Indian groups to Africans do not reflect a close relationship between these groups, but are better explained by convergence.
A new algorithm for haplotype‐based association analysis: the Stochastic‐EM algorithm
Authors: Tregouet D. A. , Escolano S. , Tiret L. , Mallet A. , Golmard J. L.
Published: March 2004

It is now widely accepted that haplotypic information can be of great interest for investigating the role of a candidate gene in the etiology of complex diseases. In the absence of family data, haplotypes cannot be deduced from genotypes, except for individuals who are homozygous at all loci or heterozygous at only one site. Statistical methodologies are therefore required for inferring haplotypes from genotypic data and testing their association with a phenotype of interest. Two maximum likelihood algorithms are often used in the context of haplotype‐based association studies, the Newton‐Raphson (NR) and the Expectation‐Maximisation (EM) algorithms. In order to circumvent the limitations of both algorithms, including convergence to local minima and saddle points, we here described how a stochastic version of the EM algorithm, referred to as SEM, could be used for testing haplotype‐phenotype association. Statistical properties of the SEM algorithm were investigated through a simulation study for a large range of practical situations, including small/large samples and rare/frequent haplotypes, and results were compared to those obtained by use of the standard NR algorithm. Our simulation study indicated that the SEM algorithm provides results similar to those of the NR algorithm, making the SEM algorithm of great interest for haplotype‐based association analysis, especially when the number of polymorphisms is quite large.
Septin collar formation in budding yeast requires GTP binding and direct phosphorylation by the PAK, Cla4
Authors: Versele Matthias , Thorner Jeremy
Published: March 2004

Assembly at the mother–bud neck of a filamentous collar containing five septins (Cdc3, Cdc10, Cdc11, Cdc12, and Shs1) is necessary for proper morphogenesis and cytokinesis. We show that Cdc10 and Cdc12 possess GTPase activity and appropriate mutations in conserved nucleotide-binding residues abrogate GTP binding and/or hydrolysis in vitro. In vivo, mutants unable to bind GTP prevent septin collar formation, whereas mutants that block GTP hydrolysis do not. GTP binding-defective Cdc10 and Cdc12 form soluble heteromeric complexes with other septins both in yeast and in bacteria; yet, unlike wild-type, mutant complexes do not bind GTP and do not assemble into filaments in vitro. Absence of a p21-activated protein kinase (Cla4) perturbs septin collar formation. This defect is greatly exacerbated when combined with GTP binding-defective septins; conversely, the septin collar assembly defect of such mutants is suppressed efficiently by CLA4 overexpression. Cla4 interacts directly with and phosphorylates certain septins in vitro and in vivo. Thus, septin collar formation may correspond to septin filament assembly, and requires both GTP binding and Cla4-mediated phosphorylation of septins.
MHC Class II Expression Restricted to CD8α+ and CD11b+ Dendritic Cells Is Sufficient for Control of Leishmania major
Authors: Lemos Maria P. , Esquivel Fatima , Scott Phillip , Laufer Terri M.
Published: March 2004

Control of the intracellular protozoan, Leishmania major, requires major histocompatibility complex class II (MHC II)–dependent antigen presentation and CD4+ T cell T helper cell 1 (Th1) differentiation. MHC II–positive macrophages are a primary target of infection and a crucial effector cell controlling parasite growth, yet their function as antigen-presenting cells remains controversial. Similarly, infected Langerhans cells (LCs) can prime interferon (IFN)γ–producing Th1 CD4+ T cells, but whether they are required for Th1 responses is unknown. We explored the antigen-presenting cell requirement during primary L. major infection using a mouse model in which MHC II, I-Aβb, expression is restricted to CD11b+ and CD8α+ dendritic cells (DCs). Importantly, B cells, macrophages, and LCs are all MHC II–negative in these mice. We demonstrate that antigen presentation by these DC subsets is sufficient to control a subcutaneous L. major infection. CD4+ T cells undergo complete Th1 differentiation with parasite-specific secretion of IFNγ. Macrophages produce inducible nitric oxide synthase, accumulate at infected sites, and control parasite numbers in the absence of MHC II expression. Therefore, CD11b+ and CD8α+ DCs are not only key initiators of the primary response but also provide all the necessary cognate interactions for CD4+ T cell Th1 effectors to control this protozoan infection.
Designer Glycopeptides for Cytotoxic T Cell–based Elimination of Carcinomas
Authors: Xu Yanfei , Gendler Sandra J. , Franco Alessandra
Published: March 2004

Tumors express embryonic carbohydrate antigens called tumor-associated carbohydrate antigens (TACA). TACA-containing glycopeptides are appealing cytotoxic T cell (CTL)-based vaccines to prevent or treat cancer because the same sugar moieties are expressed in a variety of tumors, rendering a vaccination strategy applicable in a large population. Here we demonstrate that by using glycopeptides with high affinity for the major histocompatibility complex and glycosylated in a position corresponding to a critical T cell receptor (TcR) contact, it is possible to induce anti-TACA CTL in vivo. In the current study we show that designer glycopeptides containing the Thomsen-Freidenreich (TF) antigen (β-Gal-[1→3]-α-GalNAc-O-serine) are immunogenic in vivo and generate TF-specific CTL capable of recognizing a variety of tumor cells in vitro including a MUC1-expressing tumor. The fine specificity of the TF-specific CTL repertoire indicates that the TcR recognize the glycosylated amino acid residue together with TF in a conventional major histocompatibility complex class I–restricted fashion. These results have high potential for immunotherapy against a broad range of tumors.
Mapping of a Functional Recombination Motif that Defines Isotype Specificity for μ→γ3 Switch Recombination Implicates NF-κB p50 as the Isotype-specific Switching Factor
Authors: Kenter Amy L. , Wuerffel Robert , Dominguez Carmen , Shanmugam Ananth , Zhang Hongmei
Published: March 2004

Ig class switch recombination (CSR) requires expression of activation-induced deaminase (AID) and production of germline transcripts to target S regions for recombination. However, the mechanism of CSR remains unclear. Here we show that an extrachromosomal S plasmid assay is AID dependent and that a single consensus repeat is both necessary and sufficient for isotype-specific CSR. Transfected switch substrates specific for μ→γ3 and μ→γ1 are stimulated to switch with lipopolysaccharide (LPS) alone or LPS and interleukin-4, respectively. An Sγ3/Sγ1 substrate containing only three Sγ3-associated nucleotides reconstituted LPS responsiveness and permitted mapping of a functional recombination motif specific for μ→γ3 CSR. This functional recombination motif colocalized with a binding site for NF-κB p50, and p50 binding to this site was previously established. We show a p50 requirement for plasmid-based μ→γ3 CSR using p50-deficient B cells. Switch junctions from p50-deficient B cells showed decreased lengths of microhomology between Sμ and Sγ3 relative to wild-type cells, indicating a function for p50 in the mechanics of CSR. We note a striking parallel between the affects of p50 and Msh2 deficiency on Sμ/Sγ3 junctions. The data suggest that p50 may be the isotype-specific factor in μ→γ3 CSR and epistatic with Msh2.
Synthesizing Activities and Interactions in the Concept of a Mechanism
Authors: Tabery James G.
Published: March 2004

Stuart Glennan, and the team of Peter Machamer, Lindley Darden, and Carl Craver have recently provided two accounts of the concept of a mechanism. The main difference between these two versions rests on how the behavior of the parts of the mechanism is conceptualized. Glennan considers mechanisms to be an interaction of parts, where the interaction between parts can be characterized by direct, invariant, change-relating generalizations. Machamer, Darden, and Craver criticize traditional conceptualizations of mechanisms which are based solely on parts interacting and introduce a new concept—activity. This essay is an attempt at carving out a relationship between these two philosophical interpretations of a mechanism. I will claim that, rather than being in conflict, Glennan's concept of interaction and Machamer, Darden, and Craver's notion of activity actually complement one another, each emphasizing a missing element of the other.
Can a Constructive Empiricist Adopt the Concept of Observability?
Authors: Muller F. A.
Published: March 2004

Alan Musgrave, Michael Friedman, Jeffrey Foss, and Richard Creath raised different objections against theDistinctionbetween observables and unobservables when drawn within the confines of Bas C. van Fraassen's Constructive Empiricism (CE), to the effect that the Distinction cannot be drawn there coherently. Van Fraassen has only responded to Musgrave but Musgrave claimed not to understand van Fraassen's succinct response. I argue that van Fraassen's response is not enough. What remains in the end is an unsolved problem which CE cannot afford to leave unsolved, or so I argue; I then strengthen Musgrave's criticism and indicate that an extension of the epistemic policy of CE is mandatory to solve the problem. I also argue that Friedman's and Foss' objection against the Distinction in CE misses the mark on closer inspection. An objection due to Creath does hit the mark but can be taken care of without too much ado. All these objections seem alive and kicking until the present day; I try (and hope) to put them all to rest.
Discussion Note: Positive Relevance Defended
Authors: Roush† Sherrilyn
Published: March 2004

This paper addresses two examples due to Peter Achinstein purporting to show that the positive relevance view of evidence is too strong, that is, that evidence need not raise the probability of what it is evidence for. The first example can work only if it makes a false assumption. The second example fails because what Achinstein claims is evidence is redundant with information we already have. Without these examples Achinstein is left without motivation for his account of evidence, which uses the concept of explanation in addition to that of probability.
Has the Philosophy of Technology Arrived? A State-of-the-Art Review
Authors: Ihde Don
Published: March 2004

Using the occasion of the publication of a Blackwell anthology in the philosophy of technology,Philosophy of Technology: The Technological Condition(2003), as a key to the contemporary role of this subdiscipline, this article reviews the current state-of-this-art. Both philosophy of science and philosophy of technology are twentieth century inventions, but each has followed a somewhat different set of philosophical traditions and pursued sometimes divergent questions. Here the primary developments of recent philosophy of technology are examined with emphasis upon issues which might also be of greater interest to philosophers of science. These include epistemological, but also environmental and cultural issues. The bibliographical spread includes references to some fifty recent books in the field.
A systematic method to identify genomic islands and its applications in analyzing the genomes of Corynebacterium glutamicum and Vibrio vulnificus CMCP6 chromosome I
Authors: Zhang Ren , Zhang Chun-Ting
Published: March 2004

Motivation: Some genomic islands contain horizontally transferred genes, which play critical roles in altering the genotypes and phenotypes of organisms, and horizontal gene transfer has been recognized as a universal event throughout bacterial evolution. A windowless method to display the distribution of genomic GC content, the cumulative GC profile, is proposed to identify genomic islands in genomes whose complete genome sequences are available. Two new indices are proposed to assess the codon usage bias and amino acid usage bias in genomic islands.

Results: A 211 kb genomic island (CGGI-1) has been identified in the genome of Corynebacterium glutamicum, and three genomic islands VVGI-1, VVGI-2 and VVGI-3, with lengths 167, 40 and 33 kb, respectively, have been identified in the genome of Vibrio vulnificus CMCP6 chromosome I. The CGGI-1 is flanked by two ∼500 bp direct repeats, and utilizes a Val-tRNA as the integration site. For the VVGI-1 and VVGI-2, each has an integrase gene at 5′ junction. All the identified genomic islands show unusual GC content, codon usage and amino acid usage, compared with the rest of the genomes. In addition, it is found that genomic islands are fairly homogenous in terms of GC content variation. An index, h, to quantify the homogeneity of GC content for genomic islands is proposed, and it is shown that h is less than 0.1 for all the genomic islands analyzed. The cumulative GC profile, as well as various indices to assess the codon usage bias, amino acid usage bias and homogeneity of the genomic islands, will be useful in the analysis of other genomes.

Availability: Programs used in this work and numerical results are available upon request.
Enhancing scatterplots with smoothed densities
Authors: Eilers Paul H. C. , Goeman Jelle J.
Published: March 2004

Motivation: Scatterplots of microarray data generally contain a very large number of dots, making it difficult to get a good impression of their distribution in dense areas.

Results: We present a fast and simple algorithm for two-dimensional histogram smoothing, to visually enhance scatterplots.

Availability: Functions for Matlab and R are available from the corresponding author.
Phylo-VISTA: interactive visualization of multiple DNA sequence alignments
Authors: Shah Nameeta , Couronne Olivier , Pennacchio Len A. , Brudno Michael , Batzoglou Serafim , Bethel E. Wes , Rubin Edward M. , Hamann Bernd , Dubchak Inna
Published: March 2004

Motivation: The power of multi-sequence comparison for biological discovery is well established. The need for new capabilities to visualize and compare cross-species alignment data is intensified by the growing number of genomic sequence datasets being generated for an ever-increasing number of organisms. To be efficient these visualization algorithms must support the ability to accommodate consistently a wide range of evolutionary distances in a comparison framework based upon phylogenetic relationships.

Results: We have developed Phylo-VISTA, an interactive tool for analyzing multiple alignments by visualizing a similarity measure for multiple DNA sequences. The complexity of visual presentation is effectively organized using a framework based upon interspecies phylogenetic relationships. The phylogenetic organization supports rapid, user-guided interspecies comparison. To aid in navigation through large sequence datasets, Phylo-VISTA leverages concepts from VISTA that provide a user with the ability to select and view data at varying resolutions. The combination of multiresolution data visualization and analysis, combined with the phylogenetic framework for interspecies comparison, produces a highly flexible and powerful tool for visual data analysis of multiple sequence alignments.

Availability: Phylo-VISTA is available at http://www-gsd.lbl.gov/phylovista. It requires an Internet browser with Java Plug-in 1.4.2 and it is integrated into the global alignment program LAGAN at http://lagan.stanford.edu
Optimization models for cancer classification: extracting gene interaction information from microarray expression data
Authors: Antonov Alexey V. , Tetko Igor V. , Mader Michael T. , Budczies Jan , Mewes Hans W.
Published: March 2004

Motivation: Microarray data appear particularly useful to investigate mechanisms in cancer biology and represent one of the most powerful tools to uncover the genetic mechanisms causing loss of cell cycle control. Recently, several different methods to employ microarray data as a diagnostic tool in cancer classification have been proposed. These procedures take changes in the expression of particular genes into account but do not consider disruptions in certain gene interactions caused by the tumor. It is probable that some genes participating in tumor development do not change their expression level dramatically. Thus, they cannot be detected by simple classification approaches used previously. For these reasons, a classification procedure exploiting information related to changes in gene interactions is needed.

Results: We propose a MAximal MArgin Linear Programming (MAMA) method for the classification of tumor samples based on microarray data. This procedure detects groups of genes and constructs models (features) that strongly correlate with particular tumor types. The detected features include genes whose functional relations are changed for particular cancer types. The proposed method was tested on two publicly available datasets and demonstrated a prediction ability superior to previously employed classification schemes.

Availability: The MAMA system was developed using the linear programming system LINDO http://www.lindo.com. A Perl script that specifies the optimization problem for this software is available upon request from the authors.
Adplot: detection and visualization of repetitive patterns in complete genomes
Authors: Taneda Akito
Published: March 2004

Motivation: Repetitive DNA sequences are abundant in genomes and efficient mining of significant repeats is important as the first step of repetitive sequence research. Although many computational tools for the purpose, either automatic or visualization ones, have been developed, detection and analysis of approximate repeats are still non-trivial task.

Results: Auto Dot PLOT (Adplot), a dotplot-like repetitive pattern visualization program with a window filtering based on iid Bernoulli trials, is developed and applied to yeast chromosomes and human T cell receptor locus sequence. Typical examples found in yeast chromosomes 1 and 10 and a tandem repeat of periods longer than 10 000 bp in human T cell receptor locus are presented. A complex structure composed of both direct and palindromic repeats found in yeast chromosome 10 is also visualized as specific dot pattern. Computational time measured by a Pentium 3 PC for each yeast auto chromosome with a standard parameter setting is linearly scaled and below 10 s per one chromosome, indicating efficiency of the program. From the examples, it is shown that Adplot can visualize approximate local repeat structures and give us a diagnosis power for inferring a duplicational history of repeats.

Availability: Adplot can be obtained by an e-mail request.
Using functional and organizational information to improve genome-wide computational prediction of transcription units on pathway-genome databases
Authors: Romero P. R. , Karp P. D.
Published: March 2004

Motivation: The prediction of transcription units (TUs, which are similar to operons) is an important problem that has been tackled using many different approaches. The availability of complete microbial genomes has made genome-wide TU predictions possible. Pathway-genome databases (PGDBs) add metabolic and other organizational (i.e. protein complexes) information to the annotated genome, and are able to capture TU organization information. These characteristics of PGDBs make them a suitable framework for the development and implementation of TU predictors.

Results: We implemented a TU predictor that uses only intergenic distance and functional classification of genes to predict TU boundaries, and applied it to EcoCyc, our PGDB of Escherichia coli. To this original predictor, we added information on metabolic pathways, protein complexes and transporters, all readily available in EcoCyc, in order to generate an enhanced predictor. The enhanced predictor correctly predicted 80% of the known E.coli TUs (69% of the known operons), a moderate improvement over the original predictor's performance (75% of TUs and 65% of operons correctly predicted), demonstrating that the extra information available in the PGDB does indeed improve prediction performance. Performance of this E.coli-based predictor on a genome other than that of E.coli was tested on BsubCyc, our computationally generated PGDB for Bacillus subtilis, for which a set of 100 known operons is available. Prediction accuracy decreased substantially (46% of the known operons correctly predicted). This was due in part to missing information in BsubCyc, which prevented full use of the predictor's features. The augmented predictor has been implemented as part of our Pathway Tools software suite, and can be used to populate a PGDB with predicted TUs.

Availability: The TU predictor is included in version 7.0 of the Pathway Tools software suite. Pathway Tools 7.0 is available free of charge to academic institutions and for a fee to commercial enterprises. It runs on Sun Solaris 8, Linux and Windows. TUs predicted on the Caulobacter crescentus and Mycobacterium tuberculosis (H37Rv) genomes are available in our CauloCyc and MtbrvCyc databases, available at the BioCyc web site (http://biocyc.org). To obtain version 7.0 of Pathway Tools, follow the directions in our web site, http://biocyc.org/download.shtml.
Genotyping of single nucleotide polymorphism using model-based clustering
Authors: Fujisawa H. , Eguchi S. , Ushijima M. , Miyata S. , Miki Y. , Muto T. , Matsuura M.
Published: March 2004

Motivation: Single nucleotide polymorphisms have been investigated as biological markers and the representative high-throughput genotyping method is a combination of the Invader assay and a statistical clustering method. A typical statistical clustering method is the k-means method, but it often fails because of the lack of flexibility. An alternative fast and reliable method is therefore desirable.

Results: This paper proposes a model-based clustering method using a normal mixture model and a well-conceived penalized likelihood. The proposed method can judge unclear genotypings to be re-examined and also work well even when the number of clusters is unknown. Some results are illustrated and then satisfactory genotypings are shown. Even when the conventional maximum likelihood method and the typical k-means clustering method failed, the proposed method succeeded.
Bio-support vector machines for computational proteomics
Authors: Yang Zheng Rong , Chou Kuo-Chen
Published: March 2004

Motivation: One of the most important issues in computational proteomics is to produce a prediction model for the classification or annotation of biological function of novel protein sequences. In order to improve the prediction accuracy, much attention has been paid to the improvement of the performance of the algorithms used, few is for solving the fundamental issue, namely, amino acid encoding as most existing pattern recognition algorithms are unable to recognize amino acids in protein sequences. Importantly, the most commonly used amino acid encoding method has the flaw that leads to large computational cost and recognition bias.

Results: By replacing kernel functions of support vector machines (SVMs) with amino acid similarity measurement matrices, we have modified SVMs, a new type of pattern recognition algorithm for analysing protein sequences, particularly for proteolytic cleavage site prediction. We refer to the modified SVMs as bio-support vector machine. When applied to the prediction of HIV protease cleavage sites, the new method has shown a remarkable advantage in reducing the model complexity and enhancing the model robustness.