bluuebunny/crossref_metadata_2025 huggingface dataset:
Introduction: A Special Issue on Nanoscale Characterization Using
Atom Probe Field Ion Microscopy
Authors: Larson D.J.
Published: July 2004

While searching the internet for “nanotechnology,” I was
not surprised to find many definitions. Two of these are as follows:
(1) nanotechnology is the development and use of devices that have a
size of only a few nanometers; and (2) nanotechnology can best be
considered as a “catch-all” description of activities at
the level of atoms and molecules that have applications in the real
world. While nanotechnology is usually focused on the building
of structures at the atomic scale, the characterization of
such structures should also be considered as nanotechnology. At the
Microscopy and Microanalysis 2002 Meeting in Quebec City, together with
Tom Kelly and Mike Thompson, I organized a symposium entitled
“Advances in Nanoscale Technology.” The response to this
symposium was impressive, with 32 contributed and 7 invited
presentations. Some of these presentations concentrated on atom probe
field ion microscopy and form the basis for the invited contributions
in this special issue of Microscopy and Microanalysis.
Seasonal variation of geostrophic velocity and heat flux at the entrance to the Gulf of California, Mexico
Authors: Mascarenhas A. S. , Castro Ruben , Collins Curtis A. , Durazo Reginaldo
Published: July 2004

The divergence of the surface heat flux in the Gulf of California is driven by the exchange of waters with the Pacific Ocean [Castro et al., 1994]. To estimate these exchanges, geostrophic velocities and heat fluxes were computed from nine sections of closely spaced conductivity‐temperature‐depth stations across the entrance to the Gulf of California between 1992 and 1999. The mean geostrophic velocity was composed of two alternating cores of inflow and outflow. The two cores that were adjacent to either coast were broader and contained the highest inflow (0.40 m/s) and outflow (−0.25 m/s) velocities, supporting the general idea of inflow along Sinaloa and outflow along Baja California (BC). During winter and spring the baroclinic outflow usually occurred near BC, and the baroclinic inflow occurred either through the center of the section and/or along the Sinaloa coast. Both inflow and outflow cores were ∼45 km wide and extended deeper than 700 dbar. Summer and fall showed a more complex pattern, with alternating cores of inflow and outflow but with inflow along Sinaloa on all cruises. During May the inflow was mainly in the center of the section, while outflow was concentrated along BC. The heat transport associated with the geostrophic flow was calculated and compared with estimates derived from surface heat budgets for the gulf [Castro et al., 1994]. Both the geostrophic flow and heat transport exhibited (for the first empirical orthagonal function mode) a strong seasonal signal with the maximum amplitude in May and the minimum amplitude in late October. A seasonal fit to the net heat transport had an amplitude of 50 × 1012 W and phase of 133 days, in good agreement with other authors, further validating the geostrophic velocity estimates. The heat added to (subtracted from) the Pacific Ocean accelerates (decelerates) alongshore currents and appears to propagate ∼10° westward as a Rossby wave.
Circulation in the South China Sea during summer 2000 as obtained from observations and a generalized topography‐following ocean model
Authors: Wang Huiqun , Yuan Yaochu , Guan Weibing , Lou Ruyun , Wang Kangshan
Published: July 2004

On the basis of the recently obtained hydrographic data in the South China Sea, the improved Princeton Ocean Model with a generalized topography‐following coordinate system is used to study the circulation in the region during summer 2000. Several sensitivity experiments are carried out to achieve reasonable model parameters for the South China Sea (SCS). It is shown from the resting stratification experiments that the generalized topography‐following coordinate scheme is better than the standard sigma grid scheme for reducing the pressure gradient errors. The combination of sea surface height anomaly derived from TOPEX/Poseidon and numerical results with both diagnostic and semidiagnostic simulations provides a consistent circulation pattern for the SCS in August, and the main circulation features can be summarized as follows: (1) There is a notable anticyclonic warm eddy southeast of Vietnam with a horizontal scale of ∼300 km, and there is a cyclonic cold eddy. The simultaneous existence of these cold and warm eddies is one of the important circulation characteristics in the SCS during summer 2000. (2) A secondary cold eddy is found east of Vietnam. (3) The northwestern part of the SCS is dominated by an anticyclonic circulation system. (4) There is also a secondary warm eddy southwest off the Luzon Island. (5) A cyclonic eddy is found west off the Borneo Island. (6) A western intensification phenomenon obviously occurs in the SCS. The dynamical mechanisms of the above‐mentioned circulation pattern in the SCS are the interaction between the wind stress and bottom topography and the joint effect of baroclinicity and relief.
Estimation of vertical stochastic scale parameters in the Earth's crystalline crust from seismic reflection data
Authors: Poppeliers C. , Levander A.
Published: July 2004

Its been shown that the statistical properties of a reflected seismic wavefield can be related to the statistical properties of the crust. In this paper, we report on a method to invert a reflected seismic wavefield for vertical stochastic parameters. The method is founded on a deconvolution, thresholding, and numerical integration procedure to estimate the Earth's bi‐modal velocity perturbation. We then fit a von Kármán autocorrelation function to the autocorrelation of the estimated velocity perturbation and record the von Kármán parameters which result in the minimum misfit. Tests show that our scheme is successful at recovering the vertical characteristic length in synthetic seismic reflection data.
Consistency of recent European summer precipitation trends and extremes with future regional climate projections
Authors: Pal Jeremy S. , Giorgi Filippo , Bi Xunqiang
Published: July 2004

Summer climate over Europe in recent decades has been characterized by a drying trend and by the occurrence of especially devastating drought and flood events, such as in the summers of 2002 and 2003. We compare these trends with results from regional climate model simulations of future climate over Europe under increased greenhouse gas concentrations (GHG). We find that the projected changes in mean summer precipitation and large‐scale circulations are remarkably consistent with the observed changes in recent decades. Although we cannot directly attribute the observed changes to an anthropogenic GHG forcing, this result suggests that the observed drying trend over most of Europe might continue in the future. Our experiments additionally indicate substantial changes in the intensity and persistence of summer drought and flood. We identify the Central Mediterranean and Central/Western Europe to be especially vulnerable to increases in both summer drought and flood.
Evidence of long‐term seasonal climate forcing in rhizolith isotopes during the last glaciation
Authors: Wang Hong , Ambrose Stanley H. , Fouke Bruce W.
Published: July 2004

High density carbonate rhizoliths were found from a loess‐paleosol succession from the late Wisconsin period (21–11 ka) in Illinois. Their morphology shows that they formed in a close contact with living and decomposing roots, suggesting a root/microbial respiration origin. Carbon (δ13C) and oxygen (δ18O) isotopic analyses were performed on 36 and 37 individual rhizoliths of two separate 10 cm intervals and 98 bulk rhizoliths of all 10 cm intervals. The results of the individual rhizolith δ13C and δ18O analyses suggest that the carbon source was largely derived from respiring C3, C4 and microbial biomass, and that meteoric water was controlled mainly by warm‐season precipitation. The results of bulk rhizolith δ13C and δ18O analyses show that warm‐season proxies varied in phase with glacial fluctuations at submillennial scales, suggesting long‐term seasonal forcing may have played an important role on climate change during the late Wisconsin glaciation in North America.
Detecting thermohaline circulation changes from ocean properties in a coupled model
Authors: Hu Aixue , Meehl Gerald A. , Han Weiqing
Published: July 2004

Significant changes of the thermohaline circulation (THC) are likely to cause abrupt climate change. Here we intend to find a simple measure to detect changes in THC through examining several factors proposed to control the THC variations using a coupled climate model. These factors are equatorial‐South Atlantic upper ocean temperature, Southern Ocean freshening, inter‐basin sea surface salinity contrast, and meridional steric height gradient. Three experiments are analyzed – a present‐day control run, a freshwater hosing run and a 1% CO2 run. Results show that if freshwater flux is the primary cause, all examined factors can predict the THC changes. If both thermal and haline forcings are involved, only the Atlantic meridional steric height gradient gives a consistent measure of the THC variations. A new result presented here is that the inter‐basin sea surface temperature contrast between North Atlantic and North Pacific is found to be an indicator of THC changes.
Alternating field demagnetization, single‐domain‐like memory, and the Lowrie‐Fuller test of multidomain magnetite grains (0.6–356 μm)
Authors: Dunlop David J. , Xu Song , Heider Franz
Published: July 2004

A fundamental question in paleomagnetism is how magnetite grains much larger than single‐domain size preserve stable remanence over millions of years. In an effort to answer this question we measured alternating field (AF) demagnetization of thermoremanent magnetization (TRM) and saturation isothermal remanent magnetization (SIRM) before and after low‐temperature demagnetization (LTD). LTD (zero‐field cycling through 120 K) unpins or nucleates domain walls, reducing the remanence of multidomain grains. We used two sets of sized crushed magnetites (0.6, 1, 3, 6, 9, 14, 20, 110, and 135 μm), one set unannealed and the other annealed, and a set of hydrothermally grown magnetites (0.8, 6.3, 25, 64, 94, and 356 μm). For all sizes, TRM and SIRM memories after LTD are much harder to AF demagnetize than the original remanences. AF demagnetization curves after LTD are flat for the first ∼10 mT. Such initial plateaus are one hallmark of single‐domain behavior. In high‐stress unannealed grains, after‐LTD response depends on grain size, larger grains demagnetizing more easily than smaller ones. In low‐stress annealed and hydrothermal magnetites, after‐LTD response is almost independent of grain size over nearly 3 decades in grain size. This size‐independent behavior could be due to grains in metastable single‐domain states in the smaller‐sized samples, but in >100 μm grains, there must be a source of single‐domain‐like AF behavior within the multidomain grains themselves. We propose an ad hoc model in which LTD triggers domain wall unpinning and nucleation events up to a coercivity threshold, producing the observed initial plateaus in AF demagnetization curves of TRM and SIRM memories. The size‐independent demagnetization behavior of memory in hydrothermal and annealed magnetites is ascribed to nucleation events above the threshold level, and the additional size‐dependent AF demagnetization of memory in high‐stress unannealed grains is explained by wall unpinning from strong stress centers. In both cases the AF properties merely mimic single‐domain behavior. Although LTD memory has single‐domain‐like AF curves and erased remanence has multidomain‐like curves in grains of all sizes, the Lowrie and Fuller [1971] test still works for the annealed samples. For memory, erased fraction and pre‐LTD remanence alike, TRM is more stable than SIRM in fine grains (1 μm), less stable in large grains (135 μm), and of comparable stability in medium‐size grains (9 and 20 μm).
Identification and Molecular Characterization of a de novo Supernumerary Ring Chromosome 18 in a Patient with Klippel‐Trenaunay Syndrome
Authors: Timur A. Anil , Sadgephour Azita , Graf Michael , Schwartz Stuart , Libby Eric D. , Driscoll David J. , Wang Qing
Published: July 2004

Klippel‐Trenaunay syndrome (KTS) is a congenital vascular disorder comprised of capillary, venous and lymphatic malformations associated with overgrowth of the affected tissues. In this study, we report the identification of a de novo supernumerary ring chromosome in a patient with mild mental retardation, long tapering fingers, elongated, thin feet and Klippel‐Trenaunay syndrome (KTS). The ring marker chromosome was found to be mosaic, present in 24% of cells, and was later shown to be derived from chromosome 18, r(18). Fluorescence in situ hybridization (FISH) was used to define the breakpoints involved in the formation of r(18). The chromosome 18p breakpoint was localized between the markers WI‐9619 and D18S1150, which is less than 10 cM to the centromere. The 18q breakpoint was localized between the centromere and BAC clone 666n19, which is a region of less than 40 kb. These data suggest that the r(18) mostly originated from 18p, with an estimated size of less than 10 cM. These studies identify and characterize a new marker chromosome 18, provide insights into the understanding of the relationships between the clinical phenotypes and marker chromosomes, and establish a framework for finding a potential vascular and/or overgrowth gene located on chromosome 18.
A Note on the Genome Scan Meta‐Analysis Statistic
Authors: Koziol J. A. , Feng A. C.
Published: July 2004

Wise and colleagues (Ann. Hum. Genet. (1999) 63: 263‐72) introduced a rank‐based statistical technique for meta‐analysis of genome scans, the Genome Scan Meta‐Analysis (GSMA) method. We provide an alternative derivation of the null distribution of the GSMA statistic, with extensions, and we suggest approximations to the distribution of the GSMA statistic that may be useful in applications.
Tracing the Origin of the Most Common Thiopurine Methyltransferase (TPMT) Variants: Preliminary Data from the Patterns of Haplotypic Association with Two CA Repeats
Authors: Alves S. , Rocha J. , Amorim A. , Prata M. J.
Published: July 2004

Thiopurine methyltransferase (TPMT) is an essential enzyme for normal metabolism of thiopurine drugs. In humans TPMT activity is largely dependent upon genetic variation at the TPMT locus, with TPMT*3A and TPMT*3C being the most frequent mutant alleles associated with reduced activity. TPMT*3C is a widespread allele reaching the highest frequencies in Africans, whereas TPMT*3A is virtually restricted to Caucasian descendent populations. To estimate the time of origin of these two alleles, we analyzed the levels of diversity at two CA repeats flanking the TPMT gene. In accordance to its pattern of geographical distribution, the study of the decay in linkage disequilibrium over time indicated that TPMT*3A was the younger allele. The estimated age was 5700 years, which coincides with the Neolithic, a period characterized by major population expansion that could have been responsible for the spread of TPMT*3A from its place of origin, maybe a western Eurasian population. TPMT*3C was found to have arisen earlier, roughly 14000 years ago, which could explain the worldwide dispersal of TPMT*3C.
Molecular Genetics of Late‐Onset Alzheimer's Disease
Authors: Kamboh M. Ilyas
Published: July 2004

Late‐onset Alzheimer's disease (AD) is a complex and multifactorial disease with the possible involvement of several genes. Apolipoprotein E (APOE), especially the APOE*4 allele, has been established as a strong susceptibility marker that accounts for nearly 30% of the risk in late‐onset AD. However, as the APOE*4 allele is neither necessary nor sufficient for the development of AD, it emphasizes the involvement of other genetic and/or environmental factors which, alone or in conjunction with APOE*4, can modify the risk of AD. Recently, genome‐wide linkage or linkage disequilibrium studies on late‐onset AD have provided informative data for the existence of multiple putative genes for AD on several chromosomes, with the strongest evidence on chromosomes 12, 10, 9 and 6. This paper attempts to review the current progress on the identification of additional genetic loci for late‐onset AD.
Parallel propagating electromagnetic modes with the generalized (r,q) distribution function
Authors: Qureshi M. N. S. , Shah H. A. , Murtaza G. , Schwartz S. J. , Mahmood F.
Published: July 2004

In the present paper, it is argued that non-Maxwellian distribution functions are better suited to model space plasmas. A new model distribution function called the generalized (r,q) distribution function which is the generalized form of the generalized Lorentzian (kappa) distribution function has been employed to carry out theoretical investigation for parallel propagating waves in general and for Alfvén waves in particular. New plasma dispersion functions have been derived and their properties investigated. The new linear dispersion relation for Alfvén waves is investigated in detail.
Relation between shear parameter and Reynolds number in statistically stationary turbulent shear flows
Authors: Schumacher Jörg
Published: July 2004

Studies of the relation between the shear parameter S* and the Reynolds number Re are presented for a nearly homogeneous and statistically stationary turbulent shear flow. The parametric investigations are in line with a generalized perspective on the return to local isotropy in shear flows that was outlined recently [J. Schumacher, K. R. Sreenivasan, and P. K. Yeung, Phys. Fluids 15, 84 (2003)]. Therefore, two parameters, the constant shear rate S and the level of initial turbulent fluctuations as prescribed by an energy injection rate εin, are varied systematically. The investigations suggest that the shear parameter levels off for larger Reynolds numbers which is supported by dimensional arguments. It is found that the skewness of the transverse derivative shows a different decay behavior with respect to Reynolds number when the sequence of simulation runs follows different pathways across the two-parameter plane. The study can shed new light on different interpretations of the decay of odd order moments in high-Reynolds number experiments.
On the restriction of quantum fields to a lightlike surface
Authors: Ullrich Peter
Published: July 2004

To treat the front-form Hamiltonian approach to quantum field theory, called light cone quantum field theory, in a mathematically rigorous way, the existence of a well-defined restriction of the corresponding free fields to the hypersurface {x0+x3=0} in Minkowski space is of an essential necessity. However, even in the situation of a real scalar free field such a restriction does canonically not exist; this is called the restriction problem. Furthermore, since the beginning of light cone quantum field theory there is the problem of nonexistence of a well-defined Fock space expansion of a free quantum field in terms of light cone momenta which is called the zero-mode problem. In this paper we present solutions to these long outstanding problems where the study of the zero-mode problem (of the corresponding classical field) will lead us to a solution of the restriction problem. We introduce a new function space of “squeezed” smooth functions which can canonically be embedded into the Schwartz space S(R3). The restriction of the free field to {x0+x3=0} is canonically definable on this function space and we show that the covariant field is uniquely determined by this “tame” restriction.
Langer–Cherry derivation of the multi-instanton expansion for the symmetric double well
Authors: Álvarez Gabriel
Published: July 2004

The multi-instanton expansion for the eigenvalues of the symmetric double well is derived using a Langer–Cherry uniform asymptotic expansion of the solution of the corresponding Schrödinger equation. The Langer–Cherry expansion is anchored to either one of the minima of the potential, and by construction has the correct asymptotic behavior at large distance, while the quantization condition amounts to imposing the even or odd parity of the wave function. This method leads to an efficient algorithm for the calculation to virtually any desired order of all the exponentially small series of the multi-instanton expansion, and with trivial modifications can also be used for nonsymmetric double wells.
Evolution of fluctuations in a suspension sedimenting in a container bounded by horizontal walls
Authors: Asmolov Evgeny S.
Published: July 2004

Evolution of linear large-scale disturbances in sedimenting suspension bounded by two horizontal walls is studied. Analytical solution is obtained for particle concentration and fluid velocity fields based on the continuum model of particle transport and linear-perturbation theory. The concentration inhomogeneities and velocity fluctuations are shown to decay with time. The decay is due to decrease of particles’ number because of their deposition on the bottom wall and the variation of sedimentation-front shape. Calculated velocity fluctuations and correlation functions agree qualitatively with experimental values. Fluctuations grow linearly with the height in a cubic container, but saturate or even decrease as the container width grows at fixed height. The mechanisms of inhomogeneity attenuation are discussed which are not described by linear theory but should be taken into account for large containers.
Thermocapillary convection due to a stationary bubble
Authors: Balasubramaniam R. , Subramanian R. Shankar
Published: July 2004

We analyze the velocity and temperature fields due to thermocapillary convection around a gas bubble that is stationary in a liquid. A linear temperature field is imposed in the undisturbed liquid. Our interest is in the effect of convective transport of momentum and energy on the velocity and temperature fields. We assume that buoyant convection is negligible. The relevant Reynolds and Marangoni numbers are assumed to be small compared with unity. When the Reynolds and Marangoni numbers are set equal to zero, the steady velocity field far from the bubble decays inversely with distance from it. We show that this behavior of the velocity field, coupled with the linear variation of the imposed temperature far away from the bubble, leads to an ill-posedness in the problem for the perturbation temperature field at steady state for small Marangoni numbers, when the Reynolds number is zero. We also consider the effect of convective transport of momentum for small Reynolds number, when the Marangoni number is zero. In this case, the velocity field far away from the bubble decays inversely as the distance from the bubble even in the presence of inertia. It follows that, for a fixed Prandtl number, when both the Marangoni and Reynolds number are nonzero, the behavior of the velocity field far from the bubble continues to yield an ill-posed problem for the steady perturbation temperature field. Therefore, inertia cannot relieve the ill-posedness of the perturbation problem for the steady temperature field. In order to understand the origin of this ill-posedness, we analyze a related problem involving the unsteady development of the temperature field in the liquid from the moment that a point force is applied to it, and held constant subsequently. We show that including the effect of convective transport of energy by a perturbation expansion leads to a temperature field in the liquid that is always time dependent. The temperature field never achieves a steady state.
The 70-kDa heat shock protein chaperone nucleotide-binding domain in solution unveiled as a molecular machine that can reorient its functional subdomains
Authors: Zhang Yongbo , Zuiderweg Erik R. P.
Published: July 2004

The 70-kDa heat shock cognate (Hsc70) chaperone plays a crucial role in protein (re-)folding and triage in the mammalian cytosol. Here we study, by NMR, the 44-kDa nucleotide-binding domain (NBD) of this molecule, which allosterically regulates, by binding either ADP or ATP in a cleft between the two main lobes, the chaperoning affinity of the attached substrate-binding domain. The NBD is also a center of interaction with cochaperones that couple into the allostery. By measuring residual dipolar couplings by NMR, we show that the orientation of two lobes of the Hsc70 NBD in solution deviates up to 10° from their positions in 14 superimposing x-ray structures. Additional orientational differences of subdomains within the lobes unveil the Hsc70 NBD in solution as a flexible molecular machine that can adjust the relative positions of all of its four subdomains. Because the residues interacting with the nucleotide emanate from all four subdomains, adjustments in subdomain orientation should affect the nucleotide chemistry and vice versa. Our data suggest a hypothesis that cochaperone or substrate domain binding perturbs the relative subdomain orientations, thereby functionally and allosterically coupling to the nucleotide state of the NBD.
Lamin B1 is required for mouse development and nuclear integrity
Authors: Vergnes Laurent , Péterfy Miklós , Bergo Martin O. , Young Stephen G. , Reue Karen
Published: July 2004

Lamins are key structural components of the nuclear lamina, an intermediate filament meshwork that lies beneath the inner nuclear membrane. Lamins play a role in nuclear architecture, DNA replication, and gene expression. Mutations affecting A-type lamins have been associated with a variety of human diseases, including muscular dystrophy, cardiomyopathy, lipodystrophy, and progeria, but mutations in B-type lamins have never been identified in humans or in experimental animals. To investigate the
in vivo
function of lamin B1, the major B-type lamin, we generated mice with an insertional mutation in
Lmnb1
. The mutation resulted in the synthesis of a mutant lamin B1 protein lacking several key functional domains, including a portion of the rod domain, the nuclear localization signal, and the
CAAX
motif (the carboxyl-terminal signal for farnesylation). Homozygous
Lmnb1
mutant mice survived embryonic development but died at birth with defects in lung and bone. Fibroblasts from mutant embryos grew under standard cell-culture conditions but displayed grossly misshapen nuclei, impaired differentiation, increased polyploidy, and premature senescence. Thus, the lamin B1 mutant mice provide evidence for a broad and nonredundant function of lamin B1 in mammalian development. These mutant mice and cell lines derived from them will be useful models for studying the role of the nuclear lamina in various cellular processes.
Learning modulates the ensemble representations for odors in primary olfactory networks
Authors: Daly Kevin C. , Christensen Thomas A. , Lei Hong , Smith Brian H. , Hildebrand John G.
Published: July 2004

Recent evidence suggests that odor-driven responses in the insect antennal lobe (AL) can be modified by associative and nonassociative processes, as has been shown in the vertebrate olfactory bulb. However, the specific network changes that occur in response to olfactory learning remain unknown. To characterize changes in AL network activity during learning, we developed an
in vivo
protocol in
Manduca sexta
that allows continuous monitoring of neural ensembles and feeding behavior over the course of olfactory conditioning. Here, we show that Pavlovian conditioning produced a net recruitment of responsive neural units across the AL that persisted after conditioning. Recruitment only occurred when odor reliably predicted food. Conversely, when odor did not predict food, a net loss of responsive units occurred. Simultaneous measures of feeding responses indicated that the treatment-specific patterns of neural recruitment were positively correlated with changes in the insect's behavioral response to odor. In addition to recruitment, conditioning also produced consistent and profound shifts in the temporal responses of 16% of recorded units. These results show that odor representations in the AL are dynamic and related to olfactory memory consolidation. We furthermore provide evidence that the basis of the learning-dependent changes in the AL is not simply an increase in activity in the neural network representing an odorant. Rather, learning produces a restructuring of spatial and temporal components of network responses to odor in the AL.
Ligation of CD8 leads to apoptosis of thymocytes that have not undergone positive selection
Authors: Grebe Kristie M. , Clarke Raedun L. , Potter Terry A.
Published: July 2004

Thymocytes that are not positively selected are said to undergo “death by neglect.” We have found that ligation of CD8, either by antibodies or MHC class I molecules, induces apoptosis of CD4+CD8+double-positive (DP) thymocytes. The susceptibility of thymocytes to CD8-mediated apoptosis is developmentally regulated and confined to a subpopulation of DP thymocytes. Stimulation through CD3 protects thymocytes from CD8-mediated apoptosis. We suggest that during thymocyte development, binding of CD8 to MHC class I molecules without T cell receptor engagement induces apoptosis in immature DP thymocytes. Our data are consistent with a model in which thymocytes that do not survive positive selection undergo “death by instruction” instead of death by neglect.
Pattern formation of stationary transcellular ionic currents in Fucus
Authors: Léonetti M. , Dubois-Violette E. , Homblé F.
Published: July 2004

Stationary and nonstationary spatiotemporal pattern formations emerging from the cellular electric activity are a common feature of biological cells and tissues. The nonstationary ones are well explained in the framework of the cable model. Inversely, the formation of the widespread self-organized stationary patterns of transcellular ionic currents remains elusive, despite their importance in cell polarization, apical growth, and morphogenesis. For example, the nature of the breaking symmetry in the Fucus zygote, a model organism for the experimental investigation of embryonic pattern formation, is still an open question. Using an electrodiffusive model, we report here an unexpected property of the cellular electric activity: a phase-space domain that gives rise to stationary patterns of transcellular ionic currents at finite wavelength. The cable model cannot predict this instability. In agreement with experiments, the characteristic time is an ionic diffusive one (<2 min). The critical radius is of the same order of magnitude as the cell radius (30 μm). The generic salient features are a global positive differential conductance, a negative differential conductance for one ion, and a difference between the diffusive coefficients. Although different, this mechanism is reminiscent of Turing instability.
Functionally reproductive diploid and haploid males in an inbreeding hymenopteran with complementary sex determination
Authors: Cowan David P. , Stahlhut Julie K.
Published: July 2004

It has become a matter of orthodoxy that among wasps, ants, bees, and other insects in the order Hymenoptera, only uniparental haploid males that arise from unfertilized eggs are capable of reproduction. This idea is of interest because the best understood and perhaps most widespread sex determination system among these insects [known as single locus complementary sex determination (sl-CSD)] does not depend on ploidy alone and, paradoxically, consistently results in small numbers of diploid biparental males. To date, the reproductive potential of diploid males has been studied in 13 of the perhaps 200,000 hymenopterans world-wide; in each of these instances, the diploid males are genetic dead ends because they are inviable or sterile. The data from these species have resulted in a general conclusion that has been invoked for virtually all species with sl-CSD and has become the basis for assumptions regarding conservation biology, sex ratio analysis, and the evolution of social behavior. Here, we report that in the solitary vespid waspEuodynerus foraminatus, both diploid and haploid males are fertile, which documents normal fertility in diploid males of a hymenopteran with sl-CSD. This wasp has high levels of inbreeding because of frequent brother–sister mating in nature; therefore, diploid males are more frequently produced and thus more likely exposed to selection favoring their fertility. Because inbreeding and diploid male production may be important features of the population biology of many hymenopterans, we sound a cautionary note regarding ideas about the evolutionary ecology of these insects.
A nucleophile-catalyzed cycloisomerization permits a concise synthesis of (+)-harziphilone
Authors: Stark Lucy M. , Pekari Klaus , Sorensen Erik J.
Published: July 2004

Substantial structural transformations of much use in complex chemical synthesis can be achieved by channeling the reactivity of highly unsaturated molecules. This report describes the direct conversion of an acyclic polyunsaturated diketone to the HIV-1 Rev/Rev-responsive element inhibitor harziphilone under mild reaction conditions.
Enhanced (hydrodynamic) transport induced by population growth in reaction–diffusion systems with application to population genetics
Authors: Vlad Marcel Ovidiu , Cavalli-Sforza L. Luca , Ross John
Published: July 2004

We consider a system made up of different physical, chemical, or biological species undergoing replication, transformation, and disappearance processes, as well as slow diffusive motion. We show that for systems with net growth the balance between kinetics and the diffusion process may lead to fast, enhanced hydrodynamic transport. Solitary waves in the system, if they exist, stabilize the enhanced transport, leading to constant transport speeds. We apply our theory to the problem of determining the original mutation position from the current geographic distribution of a given mutation. We show that our theory is in good agreement with a simulation study of the mutation problem presented in the literature. It is possible to evaluate migratory trajectories from measured data related to the current distribution of mutations in human populations.
Apelin, a potent diuretic neuropeptide counteracting vasopressin actions through inhibition of vasopressin neuron activity and vasopressin release
Authors: De Mota Nadia , Reaux-Le Goazigo Annabelle , El Messari Said , Chartrel Nicolas , Roesch Darren , Dujardin Cynthia , Kordon Claude , Vaudry Hubert , Moos Françoise , Llorens-Cortes Catherine
Published: July 2004

Apelin, a recently isolated neuropeptide that is expressed in the supraoptic and the paraventricular nuclei, acts on specific receptors located on vasopressinergic neurons. The increased phasic pattern of these neurons facilitates sustained antidiuresis during dehydration or lactation. Here, we investigated whether apelin interacts with arginine vasopressin (AVP) to maintain body fluid homeostasis. We first characterized the predominant molecular forms of endogenous hypothalamic and plasma apelin as corresponding to apelin 13 and, to a lesser extent, to apelin 17. We then demonstrated that, in lactating rats, apelin was colocalized with AVP in supraoptic nucleus magnocellular neurons and given intracerebroventricularly inhibited the phasic electrical activity of AVP neurons. In lactating mice, intracerebroventricular administration of apelin 17 reduced plasma AVP levels and increased diuresis. Moreover, water deprivation, which increases systemic AVP release and causes depletion of hypothalamic AVP stores, decreased plasma apelin concentrations and induced hypothalamic accumulation of the peptide, indicating that AVP and apelin are conversely regulated to facilitate systemic AVP release and suppress diuresis. Opposite effects of AVP and apelin are likely to occur at the hypothalamic level through autocrine modulation of the phasic electrical activity of AVP neurons. Altogether, these data demonstrate that apelin acts as a potent diuretic neuropeptide counteracting AVP actions through inhibition of AVP neuron activity and AVP release. The coexistence of apelin and AVP in magnocellular neurons, their opposite biological effects, and regulation are likely to play a key role for maintaining body fluid homeostasis.
A demonstration and findings of a statistical approach through reanalysis of inflammatory bowel disease data
Authors: Lo Shaw-Hwa , Zheng Tian
Published: July 2004

We test the backward haplotype transmission association algorithm on genome-scan data previously studied by Rioux
et al
. [Rioux, J. D.,
et al
. (2000)
Am. J. Hum. Genet.
66, 1863–1870]. In their study, multipoint linkage methods were applied to affected sib-pairs with inflammatory bowel disease, and significant linkage evidence points to two susceptibility loci. After we apply our approach to these data with a global search accounting for both joint and marginal effects, very interesting results emerge, many of them intriguing. These results provide compelling support for the application of our approach to other data wherever applicable. Results from this project also make it clear that it is important to reinvestigate available family-based datasets that can be suitably reanalyzed. Given previously collected data in the literature, our approach, with its increased efficiency in using available resources, draws additional crucial information that may lead to novel and surprising results.
A statistical method for identifying differential gene–gene co-expression patterns
Authors: Lai Yinglei , Wu Baolin , Chen Liang , Zhao Hongyu
Published: July 2004

Motivation: To understand cancer etiology, it is important to explore molecular changes in cellular processes from normal state to cancerous state. Because genes interact with each other during cellular processes, carcinogenesis related genes may form differential co-expression patterns with other genes in different cell states. In this study, we develop a statistical method for identifying differential gene–gene co-expression patterns in different cell states.

Results: For efficient pattern recognition, we extend the traditional F-statistic and obtain an Expected Conditional F-statistic (ECF-statistic), which incorporates statistical information of location and correlation. We also propose a statistical method for data transformation. Our approach is applied to a microarray gene expression dataset for prostate cancer study. For a gene of interest, our method can select other genes that have differential gene–gene co-expression patterns with this gene in different cell states. The 10 most frequently selected genes, include hepsin, GSTP1 and AMACR, which have recently been proposed to be associated with prostate carcinogenesis. However, genes GSTP1 and AMACR cannot be identified by studying differential gene expression alone. By using tumor suppressor genes TP53, PTEN and RB1, we identify seven genes that also include hepsin, GSTP1 and AMACR. We show that genes associated with cancer may have differential gene–gene expression patterns with many other genes in different cell states. By discovering such patterns, we may be able to identify carcinogenesis related genes.

Availability: The R-codes for our study are available at http://bioinformatics.med.yale.edu/microarray/BioSupp1.html
Differences in gene expression between B-cell chronic lymphocytic leukemia and normal B cells: a meta-analysis of three microarray studies
Authors: Wang J. , Coombes K. R. , Highsmith W. E. , Keating M. J. , Abruzzo L. V.
Published: July 2004

Motivation: A major focus of current cancer research is to identify genes that can be used as markers for prognosis and diagnosis, and as targets for therapy. Microarray technology has been applied extensively for this purpose, even though it has been reported that the agreement between microarray platforms is poor. A critical question is: how can we best combine the measurements of matched genes across microarray platforms to develop diagnostic and prognostic tools related to the underlying biology?

Results: We introduce a statistical approach within a Bayesian framework to combine the microarray data on matched genes from three investigations of gene expression profiling of B-cell chronic lymphocytic leukemia (CLL) and normal B cells (NBC) using three different microarray platforms, oligonucleotide arrays, cDNA arrays printed on glass slides and cDNA arrays printed on nylon membranes. Using this approach, we identified a number of genes that were consistently differentially expressed between CLL and NBC samples.

Availability: Glass slide cDNA array data are available through the public archives of Stanford University at http://cmgm.stanford.edu/pbrown/. Oligonucleotide array data are available in the supplemental material from Klein ηl. Nylon membrane cDNA microarray data are freely available at our website, http://bioinformatics.mdanderson.org/pubdata.html. Software to batch-process gene annotations (GeneLink) is available at http://bioinformatics.mdanderson.org/GeneLink.html. Image quantification software (ScanAlyze) is available at http://rana.lbl.gov/downloads/ScanAlyze.zip. Statistical software (S-Plus 2000) is available commercially from Insightful Corp., Seattle, WA. Software to determine the co-occurrence of terms in PubMed abstracts (PDQ_MED) is commercially available from Inpharmix Inc., Greenwood, IN.
Systematic benchmarking of microarray data classification: assessing the role of non-linearity and dimensionality reduction
Authors: Pochet Nathalie , De Smet Frank , Suykens Johan A. K. , De Moor Bart L. R.
Published: July 2004

Motivation: Microarrays are capable of determining the expression levels of thousands of genes simultaneously. In combination with classification methods, this technology can be useful to support clinical management decisions for individual patients, e.g. in oncology. The aim of this paper is to systematically benchmark the role of non-linear versus linear techniques and dimensionality reduction methods.

Results: A systematic benchmarking study is performed by comparing linear versions of standard classification and dimensionality reduction techniques with their non-linear versions based on non-linear kernel functions with a radial basis function (RBF) kernel. A total of 9 binary cancer classification problems, derived from 7 publicly available microarray datasets, and 20 randomizations of each problem are examined.

Conclusions: Three main conclusions can be formulated based on the performances on independent test sets. (1) When performing classification with least squares support vector machines (LS-SVMs) (without dimensionality reduction), RBF kernels can be used without risking too much overfitting. The results obtained with well-tuned RBF kernels are never worse and sometimes even statistically significantly better compared to results obtained with a linear kernel in terms of test set receiver operating characteristic and test set accuracy performances. (2) Even for classification with linear classifiers like LS-SVM with linear kernel, using regularization is very important. (3) When performing kernel principal component analysis (kernel PCA) before classification, using an RBF kernel for kernel PCA tends to result in overfitting, especially when using supervised feature selection. It has been observed that an optimal selection of a large number of features is often an indication for overfitting. Kernel PCA with linear kernel gives better results.

Availability: Matlab scripts are available on request.

Supplementary information:  http://www.esat.kuleuven.ac.be/~npochet/Bioinformatics/
BioRAT: extracting biological information from full-length papers
Authors: Corney David P. A. , Buxton Bernard F. , Langdon William B. , Jones David T.
Published: July 2004

Motivation: Converting the vast quantity of free-format text found in journals into a concise, structured format makes the researcher's quest for information easier. Recently, several information extraction systems have been developed that attempt to simplify the retrieval and analysis of biological and medical data. Most of this work has used the abstract alone, owing to the convenience of access and the quality of data. Abstracts are generally available through central collections with easy direct access (e.g. PubMed). The full-text papers contain more information, but are distributed across many locations (e.g. publishers' web sites, journal web sites and local repositories), making access more difficult.

In this paper, we present BioRAT, a new information extraction (IE) tool, specifically designed to perform biomedical IE, and which is able to locate and analyse both abstracts and full-length papers. BioRAT is a Biological Research Assistant for Text mining, and incorporates a document search ability with domain-specific IE.

Results: We show first, that BioRAT performs as well as existing systems, when applied to abstracts; and second, that significantly more information is available to BioRAT through the full-length papers than via the abstracts alone. Typically, less than half of the available information is extracted from the abstract, with the majority coming from the body of each paper. Overall, BioRAT recalled 20.31% of the target facts from the abstracts with 55.07% precision, and achieved 43.6% recall with 51.25% precision on full-length papers.

Availability: The software and documentation can be found at http://bioinf.cs.ucl.ac.uk/biorat
HAPLORE: a program for haplotype reconstruction in general pedigrees without recombination
Authors: Zhang Kui , Sun Fengzhu , Zhao Hongyu
Published: July 2004

Motivation: Haplotype reconstruction is an essential step in genetic linkage and association studies. Although many methods have been developed to estimate haplotype frequencies and reconstruct haplotypes for a sample of unrelated individuals, haplotype reconstruction in large pedigrees with a large number of genetic markers remains a challenging problem.

Methods: We have developed an efficient computer program, HAPLORE (HAPLOtype REconstruction), to identify all haplotype sets that are compatible with the observed genotypes in a pedigree for tightly linked genetic markers. HAPLORE consists of three steps that can serve different needs in applications. In the first step, a set of logic rules is used to reduce the number of compatible haplotypes of each individual in the pedigree as much as possible. After this step, the haplotypes of all individuals in the pedigree can be completely or partially determined. These logic rules are applicable to completely linked markers and they can be used to impute missing data and check genotyping errors. In the second step, a haplotype-elimination algorithm similar to the genotype-elimination algorithms used in linkage analysis is applied to delete incompatible haplotypes derived from the first step. All superfluous haplotypes of the pedigree members will be excluded after this step. In the third step, the expectation-maximization (EM) algorithm combined with the partition and ligation technique is used to estimate haplotype frequencies based on the inferred haplotype configurations through the first two steps. Only compatible haplotype configurations with haplotypes having frequencies greater than a threshold are retained.

Results: We test the effectiveness and the efficiency of HAPLORE using both simulated and real datasets. Our results show that, the rule-based algorithm is very efficient for completely genotyped pedigree. In this case, almost all of the families have one unique haplotype configuration. In the presence of missing data, the number of compatible haplotypes can be substantially reduced by HAPLORE, and the program will provide all possible haplotype configurations of a pedigree under different circumstances, if such multiple configurations exist. These inferred haplotype configurations, as well as the haplotype frequencies estimated by the EM algorithm, can be used in genetic linkage and association studies.

Availability: The program can be downloaded from http://bioinformatics.med.yale.edu

Contact:  hongyu.zhao@yale.edu