bluuebunny/crossref_metadata_2025 huggingface dataset:
Are all the equations of the Kadomtsev–Petviashvili hierarchy integrable?
Authors: Dorizzi B. , Grammaticos B. , Ramani A. , Winternitz P.
Published: July 2002

The Kadomtsev–Petviashvili (KP) hierarchy is an infinite set of nonlinear partial differential equations in which the number of independent variables increases indefinitely as one proceeds down the hierarchy. Since these equations were obtained as part of a group theoretical approach to soliton equations it would appear that the KP hierarchy provides integrable scalar equations with an arbitrary number of independent variables. It is shown, by investigating a specific equation in 3+1 dimensions, that the higher equations in the KP hierarchy are only integrable in a conditional sense. The equation under study, taken in isolation, does not pass certain well-known and reliable integrability tests. Thus, applying Painlevé analysis, we find that solutions exist, allowing movable critical points. Furthermore, solitary wave solutions are shown to exist that do not behave like solitons in multiple collisions. On the other hand, if the dependence of a solution on the first 2+1 variables is restricted by the fact that it should also satisfy the KP equation itself, then the integrability conditions in the other dimensions are satisfied. ‘‘Conditional integrability’’ thus means that linear techniques will provide only those solutions of equations in the hierarchy that simultaneously satisfy lower equations in the same hierarchy.
GR via characteristic surfaces
Authors: Frittelli Simonetta , Kozameh Carlos , Newman Ezra T.
Published: July 2002

We reformulate the Einstein equations as equations for families of surfaces on a four-manifold. These surfaces eventually become characteristic surfaces for an Einstein metric (with or without sources). In particular they are formulated in terms of two functions on R4×S2, i.e., the sphere bundle over space–time, one of the functions playing the role of a conformal factor for a family of associated conformal metrics, the other function describing an S2’s worth of surfaces at each space–time point. It is from these families of surfaces themselves that the conformal metric, conformal to an Einstein metric, is constructed; the conformal factor turns them into Einstein metrics. The surfaces are null surfaces with respect to this metric.
The lubrication force between two viscous drops
Authors: Davis Robert H. , Schonberg Jeffrey A. , Rallison John M.
Published: July 2002

The hydrodynamic force resisting the relative motion of two unequal drops moving along their line of centers is determined for Stokes flow conditions. The drops are assumed to be in near-contact and to have sufficiently high interfacial tension that they remain spherical. The squeeze flow in the narrow gap between the drops is analyzed using lubrication theory, and the flow within the drops near the axis of symmetry is analyzed using a boundary integral technique. The two flows are coupled through the nonzero tangential stress and velocity at the interface. Depending on the ratio of drop viscosity to that of the continuous phase, and also on the ratio of the distance between the drops to their reduced radius, three possible flow situations arise, corresponding to nearly rigid drops, drops with partially mobile interfaces, and drops with fully mobile interfaces. The results for the resistance functions are in good agreement with an earlier series solution using bispherical coordinates. These results have important implications for droplet collisions and coalescence.
Compressibility effects in free shear layers
Authors: Elliott G. S. , Samimy M.
Published: July 2002

High Reynolds number compressible free shear layers were studied experimentally to explore the effects of compressibility on the turbulence field. Previous preliminary results reported by the authors showed that the level and the lateral extent of turbulence fluctuations are reduced as the compressibility, which is characterized by a convective Mach number, is increased. The two convective Mach numbers used in the previous study were relatively close, Mc=0.51 and 0.64, and as a result the conclusions were not concrete. The present results with Mc=0.86 strongly support the earlier results, showing even higher reductions in the level and the lateral extent of Reynolds stresses. The higher-order moments of turbulence fluctuations such as skewness and flatness are reported, which show that the intermittency resulting from the excursion of large-scale structures into the free streams at the edge of shear layers was significantly reduced (both in the level and the extent) because of increased Mc. In the developing region of shear layers, development of mean flow and turbulence fluctuation profiles are reported that have similar trends seen in incompressible shear layers.
From Reynolds’s stretching and folding to mixing studies using horseshoe maps
Authors: Ottino J. M. , Jana S. C. , Chakravarthy V. S.
Published: July 2002

Osborne Reynolds’s seminal idea of stretching and folding being the basis of fluid mixing has a direct bearing on the interpretation of mixing processes involving dynamical systems tools, in particular, horseshoe maps. Horseshoes offer the only direct, mathematically rigorous, experimental verification of chaos in a flow. In this work these ideas are formalized and developed, with the goal of exploiting the concepts in experimental mixing studies, particularly in the case of alternating doubly symmetric flows. Methods to represent and to identify horseshoes are developed. Application examples to three different flows—focusing primarily on errors arising from imperfect placement and reconstruction—are presented.
On the formulation of the dynamic mixed subgrid-scale model
Authors: Vreman Bert , Geurts Bernard , Kuerten Hans
Published: July 2002

The dynamic mixed subgrid-scale model of Zang et al. [Phys. Fluids A 5, 3186 (1993)] (DMM1) is modified with respect to the incorporation of the similarity model in order to remove a mathematical inconsistency. Compared to DMM1, the magnitude of the dynamic model coefficient of the modified model (DMM2) is increased considerably, while it is still significantly smaller than as occurs in the dynamic subgrid-scale eddy-viscosity model of Germano [J. Fluid Mech. 238, 325 (1992)] (DSM). Large eddy simulations (LES) for the weakly compressible mixing layer are conducted using these three models and results are compared with direct numerical simulation (DNS) data. LES based on DMM1 gives a significant improvement over LES using DSM, while even better agreement is achieved with DMM2.
The effect of surfactant on the rise of a spherical bubble at high Reynolds and Peclet numbers
Authors: Bel Fdhila R. , Duineveld P. C.
Published: July 2002

Experiments and numerical simulations of rising spherical bubbles in quiescent surfactant solutions are presented. The rise velocities versus the concentration in the bulk are measured using three surfactants, Triton X100, Brij30 and SDS for different bubble sizes, between 0.4 and 1 mm equivalent radius. We also present a brief description of the finite-difference numerical method developed to solve the full Navier-Stokes equations around the contaminated bubble for Reynolds numbers ranging from 50 to 200. The distributions of the tangential velocity, the vorticity, the pressure and the surfactant concentration on the bubble surface are calculated. In the case of high Peclet numbers surfactant molecules, which adsorb on the surface are convected and collected at the rear part of the bubble forming a stagnant cap where the no-slip condition holds. The concentration on the bubble interface is obtained for surfactants having a desorption rate much slower than the convective rate. The sudden increase of the shear stress and pressure at the leading edge of the cap contributes mainly to decrease the rise velocity. This rapid slowdown of the bubble occurs when nearly half of the bubble surface is covered by the surfactant layer, and this is due to the particularly high values obtained for the shear stress and the pressure at the leading edge of this cap-angle. Measured and calculated rise velocities for bubbles of 0.4 mm equivalent radius show good agreement when the sorption kinetics controls the surfactant exchange between the bulk and the surface. Calculated critical concentrations needed to cover completely the bubble agree with the measurements even for larger bubbles.
Instability of vortical and acoustic modes in supersonic round jets
Authors: Luo K. H. , Sandham N. D.
Published: July 2002

The stability of “top-hat” and fully developed jet profiles is investigated by an inviscid linear stability theory for compressible flow. The study covers a wide range of the Mach number and the temperature ratio. Two types of instabilities are found: vortical and acoustic, each of which can be subdivided into non-radiating (subsonic) and radiating (supersonic) modes. The vortical mode is the continuation of the Kelvin-Helmholtz instability from incompressible flow. The acoustic mode is a compressible flow phenomenon, which becomes important at large Mach numbers. Temperature-ratio effects can be destabilizing or stabilizing, depending on the Mach number and mode of instability. A spectrum of unstable acoustic modes, including axisymmetric ones, are found to exist in the fully developed jet. For this jet, acoustic axisymmetric waves become more unstable than both vortical and acoustic helical waves at Mach numbers over about 3. Strong evidence of a resonance mechanism for acoustic modes is seen in the growth rate curves at high Mach numbers, where a spectrum of local peaks and valleys appears at regularly distributed frequencies.
Transfer of energy to two-dimensional large scales in forced, rotating three-dimensional turbulence
Authors: Smith Leslie M. , Waleffe Fabian
Published: July 2002

Forced turbulence in a rotating frame is studied using numerical simulations in a triply periodic box. The random forcing is three dimensional and localized about an intermediate wavenumber kf. The results show that energy is transferred to scales larger than the forcing scale when the rotation rate is large enough. The scaling of the energy spectrum approaches E(k)∝k−3 for k<kf. Almost all of the energy for k<kf lies in the two-dimensional (2D) plane perpendicular to the rotation z-axis, and thus the large-scale motions are quasi-2D with E(k)≈E(kh,kz=0), where kh and kz are, respectively, the horizontal and vertical components of the wavevector. The large scales consist of cyclonic vortices. Possible mechanisms responsible for the two-dimensionalization are discussed. The development of the 2D spectrum E(kh,kz=0)∝kh−3 is analogous to the dynamics of β-plane turbulence leading to the Rhines spectrum E(ky,kx=0)∝ky−5.
Velocity field for Taylor–Couette flow with an axial flow
Authors: Wereley Steven T. , Lueptow Richard M.
Published: July 2002

The flow in the gap between an inner rotating cylinder concentric with an outer stationary cylinder with an imposed pressure-driven axial flow was studied experimentally using particle image velocimetry (PIV) in a meridional plane of the annulus. The radius ratio was η=0.83 and the aspect ratio was Γ=47. Velocity vector fields for nonwavy toroidal and helical vortices show the axial flow winding around vortices. When the axially averaged axial velocity profile is removed from the velocity field in a meridional plane, the velocity field looks much like it would with no imposed axial flow except that the vortices translate axially and the distortion of the azimuthal velocity contours in meridional plane related to the vortices is shifted axially by the axial flow. The velocity vector fields for wavy vortices also show axial flow winding around the vortices. Again, removing the axial velocity profile results in a flow that appears similar to that with no axial flow. The path of the vortices is generally axial, but the vortices periodically move retrograde to the imposed axial flow due to the waviness of the vortices. The axial velocity of helical vortices, both nonwavy and wavy, is twice the rotational frequency of the inner cylinder indicating a coupling between the axial translation of the vortices and the cylinder rotation. Little fluid transport between vortices occurs for nonwavy vortices, but there is substantial transport between vortices for wavy vortex flow, much like supercritical cylindrical Couette flow with no axial flow.
Spatial stability of similarity solutions for viscous flows in channels with porous walls
Authors: Ferro Sergio , Gnavi Graciela
Published: July 2002

The spatial stability of similarity solutions for an incompressible fluid flowing along a channel with porous walls and driven by constant uniform suction along the walls is analyzed. This work extends the results of Durlofsky and Brady [Phys. Fluids 27, 1068 (1984)] to a wider class of similarity solutions, and examines the spatial stability of small amplitude perturbations of arbitrary shape, generated at the entrance of the channel. It is found that antisymmetric perturbations are the best candidates to destabilize the solutions. Temporally stable asymmetric solutions with flow reversal presented by Zaturska, Drazin, and Banks [Fluid Dyn. Res. 4, 151 (1988)] are found to be spatially unstable. The perturbed similarity solutions are also compared with fully bidimensional ones obtained with a finite difference code. The results confirm the importance of similarity solutions and the validity of the stability analysis in a region whose distance to the center of the channel is more than three times the channel half-width.
Effective constants for wave propagation through partially saturated porous media
Authors: Berryman James G. , Thigpen Lewis
Published: July 2002

The multipole scattering coefficients for elastic wave scattering from a spherical inhomogeneity in a fluid-saturated porous medium have been calculated. These coefficients may be used to obtain estimates of the effective macroscopic constants for long-wavelength propagation of elastic waves through partially saturated media. If the volume average of the single scattering from spherical bubbles of gas and liquid is required to vanish, the resulting equations determine the effective bulk modulus, density, and viscosity of the multiphase fluid filling the pores. The formula for the effective viscosity during compressional wave excitation is apparently new.
Water interaction with the superconducting YBa2Cu3O7 phase
Authors: Yan M. F. , Barns R. L. , O’Bryan H. M. , Gallagher P. K. , Sherwood R. C. , Jin S.
Published: July 2002

We show that the superconducting YBa2Cu3O7 phase is highly sensitive to water and water vapor. This is probably due to the presence of nonequilibrium Cu3+ ions in this compound. In particular, the YBa2Cu3O7 phase decomposes in water to CuO, Ba(OH)2 and Y2BaCuO5 and evolves oxygen. Samples with a reduced oxygen content, e.g., YBa2Cu3O6.0, also decompose in an aqueous ambient. The superconductivity of YBa2Cu3O7 samples is greatly degraded by the interaction with water and humid air. This effect should not preclude practical application of these materials since it should be possible to protect them with coatings of metal, glass, or plastic.
Wild-type PrP and a mutant associated with prion disease are subject to retrograde transport and proteasome degradation
Authors: Ma Jiyan , Lindquist Susan
Published: July 2002

The cytoplasm seems to provide an environment that favors
conversion of the prion protein (PrP) to a form with the physical
characteristics of the PrP
Sc
conformation, which is
associated with transmissible spongiform encephalopathies.
However, it is not clear whether PrP would ever exist in the cytoplasm
under normal circumstances. We report that PrP accumulates in the
cytoplasm when proteasome activity is compromised. The accumulated PrP
seems to have been subjected to the normal proteolytic cleavage events
associated with N- and C-terminal processing in the endoplasmic
reticulum, suggesting that it arrives in the cytoplasm through
retrograde transport. In the cytoplasm, PrP forms aggregates, often in
association with Hsc70. With prolonged incubation, these aggregates
accumulate in an “aggresome”-like state, surrounding the
centrosome. A mutant (D177N), which is associated with a heritable and
transmissible form of the spongiform encephalopathies, is less
efficiently trafficked to the surface than wild-type PrP and
accumulates in the cytoplasm even without proteasome inhibition. These
results demonstrate that PrP can accumulate in the cytoplasm and is
likely to enter this compartment through normal protein quality-control
pathways. Its potential to accumulate in the cytoplasm has implications
for pathogenesis.
Activation of β-catenin signaling in differentiated mammary secretory cells induces transdifferentiation into epidermis and squamous metaplasias
Authors: Miyoshi Keiko , Shillingford Jonathan M. , Le Provost Fabienne , Gounari Fotini , Bronson Roderick , von Boehmer Harald , Taketo Makoto M. , Cardiff Robert D. , Hennighausen Lothar , Khazaie Khashayarsha
Published: July 2002

Mammary anlagen are formed in the embryo as a derivative of the
epidermis, a process that is controlled by Lef-1 and therefore possibly
by β-catenin. To investigate the role of β-catenin signaling in
mammary alveolar epithelium, we have stabilized endogenous
β-catenin in differentiating alveolar epithelium through the deletion
of exon 3 (amino acids 5–80) of the
β-catenin
gene.
This task was accomplished in mice carrying a floxed β-catenin gene
and a Cre transgene under control of the mammary-specific whey acidic
protein (WAP) gene promoter or the mouse mammary tumor virus-long
terminal repeat (MMTV-LTR). Stabilized β-catenin was obtained during
the first pregnancy, and its presence resulted in the
dedifferentiation of alveolar epithelium followed by a
transdifferentiation into epidermal and pilar structures. Extensive
squamous metaplasia, but no adenocarcinomas, developed upon β-catenin
activation during pregnancy and persisted throughout involution. These
data demonstrate that the activation of β-catenin signaling induces a
program that results in loss of mammary epithelial cell differentiation
and induction of epidermal structures.
Profile of the genes expressed in the human peripheral retina, macula, and retinal pigment epithelium determined through serial analysis of gene expression (SAGE)
Authors: Sharon Dror , Blackshaw Seth , Cepko Constance L. , Dryja Thaddeus P.
Published: July 2002

We used the serial analysis of gene expression (SAGE)
technique to catalogue and measure the relative levels of expression of
the genes expressed in the human peripheral retina, macula, and
retinal pigment epithelium (RPE) from one or both of two humans, aged
88 and 44 years. The cone photoreceptor contribution to all
transcription in the retina was found to be similar in the macula
versus the retinal periphery, whereas the rod contribution was greater
in the periphery versus the macula. Genes encoding structural proteins
for axons were found to be expressed at higher levels in the macula
versus the retinal periphery, probably reflecting the large proportion
of ganglion cells in the central retina. In comparison with the younger
eye, the peripheral retina of the older eye had a substantially higher
proportion of mRNAs from genes encoding proteins involved in iron
metabolism or protection against oxidative damage and a substantially
lower proportion of mRNAs from genes encoding proteins involved in rod
phototransduction. These differences may reflect the difference in age
between the two donors or merely interindividual variation. The RPE
library had numerous previously unencountered tags, suggesting
that this cell type has a large, idiosyncratic repertoire of expressed
genes. Comparison of these libraries with 100 reported nonocular SAGE
libraries revealed 89 retina-specific or enriched genes expressed at
substantial levels, of which 14 are known to cause a retinal disease
and 53 are RPE-specific genes. We expect that these libraries will
serve as a resource for understanding the relative expression levels of
genes in the retina and the RPE and for identifying additional disease
genes.
Synaptophysin regulates activity-dependent synapse formation in cultured hippocampal neurons
Authors: Tarsa Leila , Goda Yukiko
Published: July 2002

Synaptophysin is an abundant synaptic vesicle protein without a definite synaptic function. Here, we examined a role for synaptophysin in synapse formation in mixed genotype micro-island cultures of wild-type and synaptophysin-mutant hippocampal neurons. We show that synaptophysin-mutant synapses are poor donors of presynaptic terminals in the presence of competing wild-type inputs. In homogenotypic cultures, however, mutant neurons display no apparent deficits in synapse formation compared with wild-type neurons. The reduced extent of synaptophysin-mutant synapse formation relative to wild-type synapses in mixed genotype cultures is attenuated by blockers of synaptic transmission. Our findings indicate that synaptophysin plays a previously unsuspected role in regulating activity-dependent synapse formation.
Insulin-stimulated phosphorylation of lipin mediated by the mammalian target of rapamycin
Authors: Huffman Todd A. , Mothe-Satney Isabelle , Lawrence John C.
Published: July 2002

The phosphorylation of a previously uncharacterized protein of apparent
M
r
≈ 140,000 was found to be increased when rat adipocytes were incubated with insulin. The sequences of peptides generated by digesting the protein with trypsin matched perfectly with sequences in mouse lipin. Lipin is the product of the gene that is mutated in fatty liver dystrophy (
fld
) mice [Peterfy, M., Phan, J., Xu, P. & Reue, K (2001)
Nat. Genet.
27, 121–124], which exhibit several phenotypic abnormalities including hyperlipidemia, defects in adipocyte differentiation, impaired glucose tolerance, and slow growth. When immunoblots were prepared with lipin antibodies, both endogenous adipocyte lipin and recombinant lipin overexpressed in HEK293 cells appeared as bands ranging in apparent
M
r
from 120,000 to 140,000. Incubating adipocytes with insulin decreased the electrophoretic mobility and stimulated the phosphorylation of both Ser and Thr residues in lipin. The effects of insulin were abolished by inhibitors of phosphatidylinositol 3-OH kinase, and by rapamycin, a specific inhibitor of the mammalian target of rapamcyin (mTOR). The inhibition by rapamycin was blocked by FK506, which competitively inhibits those effects of rapamycin that are mediated by inhibition of mTOR. Moreover, amino acids, which activate mTOR, mimicked insulin by increasing lipin phosphorylation in a rapamycin-sensitive manner. Thus, lipin represents a target of the mTOR pathway, and potentially links this nutrient-sensing pathway to adipocyte development.
TRM1, a YY1-like suppressor of
rbcS-m3
expression in maize mesophyll cells
Authors: Xu Tao , Purcell Marc , Zucchi Paola , Helentjaris Tim , Bogorad Lawrence
Published: July 2002

The genes
rbcS
and
rbcL
encode,
respectively, the small and large subunits of the photosynthetic carbon
dioxide fixation enzyme ribulose bisphosphate carboxylase/oxygenase.
There is a single
rbcL
gene in each chloroplast
chromosome; a family of
rbcS
genes is located in the
nuclear genome. These two genes are not expressed in mesophyll cells
but are in adjacent bundle-sheath cells of leaves of the C4 plant
Zea mays
. Two regions of the maize gene
rbcS-m3
are required for suppressing expression in
mesophyll cells. One region is just beyond the translation termination
site in the 3′ region, and the other is several hundred base pairs
upstream of the transcription start site. A binding site for a protein
with limited homology to the viral, yeast, and mammalian transcription
repressor-activator YY1 (Yin-Yang I), has now been identified in the 3′
region. A maize gene for a protein with zinc fingers homologous to
those of YY1 has been isolated, characterized, and expressed in
Escherichia coli
. The gene is designated
trm1
(transcription repressor-maize 1). The protein TRM1
binds to the YY1-like site and, in addition, TRM1 binds to two sequence
regions in the 5′ region of the gene that have no homology to the YY1
site. Mutagenesis or deletion of any of these three sequences
eliminates repression of
rbcS-m3
reporter genes in
mesophyll cells.
Latitudinal gradients of species richness in the deep-sea benthos of the North Atlantic
Authors: Rex Michael A. , Stuart Carol T. , Coyne Gina
Published: July 2002

Latitudinal species diversity gradients (LSDGs) in the Northern Hemisphere are the most well established biogeographic patterns on Earth. Despite long-standing interest in LSDGs as a central problem in ecology, their explanation remains uncertain. In terrestrial as well as coastal and pelagic marine ecosystems, these poleward declines in diversity typically have been represented and interpreted in terms of species richness, the number of coexisting species. Newly discovered LSDGs in the bathyal (500–4,000 m) benthos of the North Atlantic may help to resolve the underlying causes of these large-scale trends because the deep sea is such a physically distinct environment. However, a major problem in comparing surface and deep-sea LSDGs is that the latter have been measured differently, by using species diversity indices that are affected by both species richness and the evenness of relative abundance. Here, we demonstrate that deep-sea isopods, gastropods, and bivalves in the North Atlantic do exhibit poleward decreases in species richness, just as those found in other environments. A comprehensive systematic revision of the largest deep-sea gastropod family (Turridae) has provided a unique database on geographic distributions that is directly comparable to those used to document LSDGs in surface biotas. This taxon also shows a poleward decline in the number of species. Seasonal organic enrichment from sinking phytodetritus is the most plausible ecological explanation for deep-sea LSDGs and is the environmental factor most consistently associated with depressed diversity in a variety of bathyal habitats.
A common mutation in the 5,10-methylenetetrahydrofolate reductase gene affects genomic DNA methylation through an interaction with folate status
Authors: Friso Simonetta , Choi Sang-Woon , Girelli Domenico , Mason Joel B. , Dolnikowski Gregory G. , Bagley Pamela J. , Olivieri Oliviero , Jacques Paul F. , Rosenberg Irwin H. , Corrocher Roberto , Selhub Jacob
Published: July 2002

DNA methylation, an essential epigenetic feature of DNA that modulates gene expression and genomic integrity, is catalyzed by methyltransferases that use the universal methyl donor
S
-adenosyl-
l
-methionine. Methylenetetrahydrofolate reductase (MTHFR) catalyzes the synthesis of 5-methyltetrahydrofolate (5-methylTHF), the methyl donor for synthesis of methionine from homocysteine and precursor of
S
-adenosyl-
l
-methionine. In the present study we sought to determine the effect of folate status on genomic DNA methylation with an emphasis on the interaction with the common
C677T
mutation in the
MTHFR
gene. A liquid chromatography/MS method for the analysis of nucleotide bases was used to assess genomic DNA methylation in peripheral blood mononuclear cell DNA from 105 subjects homozygous for this mutation (
T
/
T
) and 187 homozygous for the wild-type (
C
/
C
)
MTHFR
genotype. The results show that genomic DNA methylation directly correlates with folate status and inversely with plasma homocysteine (tHcy) levels (
P
< 0.01).
T
/
T
genotypes had a diminished level of DNA methylation compared with those with the
C
/
C
wild-type (32.23 vs.62.24 ng 5-methylcytosine/μg DNA,
P
< 0.0001). When analyzed according to folate status, however, only the
T
/
T
subjects with low levels of folate accounted for the diminished DNA methylation (
P
< 0.0001). Moreover, in
T
/
T
subjects DNA methylation status correlated with the methylated proportion of red blood cell folate and was inversely related to the formylated proportion of red blood cell folates (
P
< 0.03) that is known to be solely represented in those individuals. These results indicate that the
MTHFR C677T
polymorphism influences DNA methylation status through an interaction with folate status.
CD8+T cells are not necessary for 1α,25-dihydroxyvitamin D3to suppress experimental autoimmune encephalomyelitis in mice
Authors: Meehan Terrence F. , DeLuca Hector F.
Published: July 2002

In addition to its role in calcium and phosphorous homeostasis, 1α,25-dihydroxyvitamin D3[1,25-(OH)2D3] appears to be a modulator of the immune system. Administration of 1,25-(OH)2D3prevents disease in several autoimmune animal models, including experimental autoimmune encephalomyelitis (EAE). The vitamin D receptor is believed to mediate this activity. Among cells of the immune system, CD8+T cells have the highest levels of the vitamin D receptor. Because CD8+T cells have been implicated as both suppressors and effectors of the inflammation associated with multiple sclerosis and EAE, we examined the question of whether the 1,25-(OH)2D3suppression of EAE occurs through a CD8+T cell-dependent mechanism. To test this hypothesis, mice that are homozygous knockouts for the α chain of the CD8 receptor and have been characterized as lacking functional CD8+T cells (CD8+−/−) were provided 1,25-(OH)2D3in their diet before EAE induction. Although CD8+−/− mice fed the same diet lacking 1,25-(OH)2D3have a high incidence of EAE, EAE did not occur in CD8+−/− mice fed the diet containing 1,25-(OH)2D3. We conclude that CD8+T cells neither are needed nor do they play a role in the prevention of EAE by 1,25-(OH)2D3.
Iron uptake from plasma transferrin by the duodenum is impaired in the
Hfe
knockout mouse
Authors: Trinder Debbie , Olynyk John K. , Sly William S. , Morgan Evan H.
Published: July 2002

Hereditary hemochromatosis (HH) is a disorder of iron metabolism in which enhanced iron absorption of dietary iron causes increased iron accumulation in the liver, heart, and pancreas. Most individuals with HH are homozygous for a C282Y mutation in the
HFE
gene. The function of HFE protein is unknown, but it is hypothesized that it acts in association with β
2
-microglobulin and transferrin receptor 1 to regulate iron uptake from plasma transferrin by the duodenum, the proposed mechanism by which body iron levels are sensed. The aim of this study was to test this hypothesis by comparing clearance of transferrin-bound iron in
Hfe
knockout (KO) mice with that observed in C57BL/6 control mice. The mice were fed either an iron-deficient, control, or iron-loaded diet for 6 weeks to alter body iron status. The mice then were injected i.v. with
59
Fe-transferrin, and blood samples were taken over 2 h to determine the plasma
59
Fe turnover. After 2 h, the mice were killed and the amount of radioactivity in the duodenum, liver, and kidney was measured. In both
Hfe
KO and C57BL/6 mice, plasma iron turnover and iron uptake from plasma transferrin by the duodenum, liver, and kidney correlated positively with plasma iron concentration. However, duodenal iron uptake from plasma transferrin was decreased in the
Hfe
KO mice compared with the control mice. Despite this difference in duodenal uptake, the
Hfe
KO mice showed no decrease in iron uptake by the liver and kidney or alteration in the plasma iron turnover when compared with C57BL/6 mice. These data support the hypothesis that HFE regulates duodenal uptake of transferrin-bound iron from plasma, and that this mechanism of sensing body iron status, as reflected in plasma iron levels, is impaired in HH.
Pattern of mutation in the genome of influenza A virus on adaptation to increased virulence in the mouse lung: Identification of functional themes
Authors: Brown E. G. , Liu H. , Kit L. Chang , Baird S. , Nesrallah M.
Published: July 2002

The genetic basis for virulence in influenza virus is largely
unknown. To explore the mutational basis for increased virulence in the
lung, the H3N2 prototype clinical isolate, A/HK/1/68, was adapted
to the mouse. Genomic sequencing provided the first demonstration, to
our knowledge, that a group of 11 mutations can convert an avirulent
virus to a virulent variant that can kill at a minimal dose. Thirteen
of the 14 amino acid substitutions (93%) detected among clonal
isolates were likely instrumental in adaptation because of their
positive selection, location in functional regions, and/or
independent occurrence in other virulent influenza viruses. Mutations
in virulent variants repeatedly involved nuclear localization signals
and sites of protein and RNA interaction, implicating them as novel
modulators of virulence. Mouse-adapted variants with the same
hemagglutinin mutations possessed different pH optima of fusion,
indicating that fusion activity of hemagglutinin can be modulated by
other viral genes. Experimental adaptation resulted in the selection of
three mutations that were in common with the virulent human H5N1
isolate A/HK/156/97 and that may be instrumental in its extreme
virulence. Analysis of viral adaptation by serial passage appears to
provide the identification of biologically relevant mutations.
Regulation of oxidative stress-induced calcium release by phosphatidylinositol 3-kinase and Bruton's tyrosine kinase in B cells
Authors: Qin Suofu , Stadtman Earl R. , Chock P. Boon
Published: July 2002

Hydrogen peroxide stimulates a tyrosine kinase-dependent calcium release from intracellular stores, which is assumed to be achieved through the activation of phospholipase Cγ2 (PLCγ2) via a tyrosine phosphorylation mechanism in B cells. Here we show that H2O2induces both tyrosine phosphorylation on PLCγ2 and the activation of phosphatidylinositol 3-kinase (PI3K) in B cells, and that the phosphatidylinositol 3-kinase inhibitor, Wortmannin, partially inhibited the H2O2-induced calcium release without affecting tyrosine phosphorylation on PLCγ2. Overexpression of human Bruton's tyrosine kinase (Btk), which was activated by H2O2, almost completely overcame the inhibition of calcium release by Wortmannin. The reversal of Wortmannin's inhibition by enhancing Btk concentration seemed unique to the H2O2-mediated effect, because Btk failed to overcome the inhibition of Wortmannin on B cell receptor-triggered calcium mobilization. Immunoblot analysis revealed that Btk formed stable complexes with several tyrosine-phosphorylated proteins, including PLCγ2, only in Btk-overexpressed cells on H2O2stimulation. Together, our data are consistent with the notion that PIP3 and/or a high concentration of Btk target the activated PLCγ2 to its substrate site for maximal catalytic efficiency.
Oxygen deprivation causes suspended animation in the zebrafish embryo
Authors: Padilla Pamela A. , Roth Mark B.
Published: July 2002

Continuous exposure to oxygen is essential for nearly all vertebrates. We found that embryos of the zebrafish
Danio rerio
can survive for 24 h in the absence of oxygen (anoxia, 0% O
2
). In anoxia, zebrafish entered a state of suspended animation where all microscopically observable movement ceased, including cell division, developmental progression, and motility. Animals that had developed a heartbeat before anoxic exposure showed no evidence of a heartbeat until return to terrestrial atmosphere (normoxia, 20.8% O
2
). In analyzing cell-cycle changes of rapidly dividing blastomeres exposed to anoxia, we found that no cells arrested in mitosis. This is in sharp contrast to similarly staged normoxic embryos that consistently contain more than 15% of cells in mitosis. Flow cytometry analysis revealed that blastomeres arrested during the S and G
2
phases of the cell cycle. This work indicates that survival of oxygen deprivation in vertebrates involves the reduction of diverse processes, such as cardiac function and cell-cycle progression, thus allowing energy supply to be matched by energy demands.
Excess “read-through” acetylcholinesterase attenuates but the “synaptic” variant intensifies neurodeterioration correlates
Authors: Sternfeld Meira , Shoham Shai , Klein Omer , Flores-Flores Cesar , Evron Tamah , Idelson Gregory H. , Kitsberg Dani , Patrick James W. , Soreq Hermona
Published: July 2002

Acute stress increases the risk for neurodegeneration, but the molecular signals regulating the shift from transient stress responses to progressive disease are not yet known. The “read-through” variant of acetylcholinesterase (AChE-R) accumulates in the mammalian brain under acute stress. Therefore, markers of neurodeterioration were examined in transgenic mice overexpressing either AChE-R or the “synaptic” AChE variant, AChE-S. Several observations demonstrate that excess AChE-R attenuates, whereas AChE-S intensifies, neurodeterioration. In the somatosensory cortex, AChE-S transgenics, but not AChE-R or control FVB/N mice, displayed a high density of curled neuronal processes indicative of hyperexcitation. In the hippocampus, AChE-S and control mice, but not AChE-R transgenics, presented progressive accumulation of clustered, heat shock protein 70–immunopositive neuronal fragments and displayed a high incidence of reactive astrocytes. Our findings suggest that AChE-R serves as a modulator that may play a role in preventing the shift from transient, acute stress to progressive neurological disease.
A repressible female-specific lethal genetic system for making transgenic insect strains suitable for a sterile-release program
Authors: Heinrich Jörg C. , Scott Maxwell J.
Published: July 2002

We have developed a tetracycline-repressible female-specific lethal genetic system in the vinegar fly
Drosophila melanogaster
. One component of the system is the tetracycline-controlled transactivator gene under the control of the fat body and female-specific transcription enhancer from the yolk protein 1 gene. The other component consists of the proapoptotic gene
hid
under the control of a tetracycline-responsive element. Males and females of a strain carrying both components are viable on medium supplemented with tetracycline, but only males survive on normal medium. A strain with such properties would be ideal for a sterile-insect release program, which is most effective when only males are released in the field.
Image metrics in the statistical analysis of DNA microarray data
Authors: Brown Carl S. , Goodwin Paul C. , Sorger Peter K.
Published: July 2002

DNA microarrays represent an important new method for determining the complete expression profile of a cell. In “spotted” microarrays, slides carrying spots of target DNA are hybridized to fluorescently labeled cDNA from experimental and control cells and the arrays are imaged at two or more wavelengths. In this paper, we perform statistical analysis on images of microarrays and show that quantitating the amount of fluorescent DNA bound to microarrays is subject to considerable uncertainty because of large and small-scale intensity fluctuations within spots, nonadditive background, and fabrication artifacts. Pixel-by-pixel analysis of individual spots can be used to estimate these sources of error and establish the precision and accuracy with which gene expression ratios are determined. Simple weighting schemes based on these estimates are effective in improving significantly the quality of microarray data as it accumulates in a multiexperiment database. We propose that error estimates from image-based metrics should be one component in an explicitly probabilistic scheme for the analysis of DNA microarray data.
An inherited
p53
mutation that contributes in a tissue-specific manner to pediatric adrenal cortical carcinoma
Authors: Ribeiro Raul C. , Sandrini Fabiano , Figueiredo Bonald , Zambetti Gerard P. , Michalkiewicz Edson , Lafferty Antony R. , DeLacerda Luiz , Rabin Mark , Cadwell Craig , Sampaio Gilberto , Cat Israil , Stratakis Constantine A. , Sandrini Romolo
Published: July 2002

The incidence of pediatric adrenal cortical carcinoma (ACC) in southern Brazil is 10–15 times higher than that of pediatric ACC worldwide. Because childhood ACC is associated with Li-Fraumeni syndrome, we examined the cancer history and
p53
status of 36 Brazilian patients and their families. Remarkably, 35 of 36 patients had an identical germ-line point mutation of
p53
encoding an R337H amino acid substitution. Differences within intragenic polymorphic markers demonstrated that at least some mutant alleles arose independently, thus eliminating a founder effect. In tumor cells, the wild-type allele was deleted, and mutant p53 protein accumulated within the nuclei. Although these features are consistent with Li-Fraumeni syndrome-associated adrenal tumors, there was no history of increased cancer incidence among family members. Therefore, this inherited R337H
p53
mutation represents a low-penetrance
p53
allele that contributes in a tissue-specific manner to the development of pediatric ACC.
HIN-1, a putative cytokine highly expressed in normal but not cancerous mammary epithelial cells
Authors: Krop Ian E. , Sgroi Dennis , Porter Dale A. , Lunetta Kathryn L. , LeVangie Rebbecca , Seth Pankaj , Kaelin Carolyn M. , Rhei Esther , Bosenberg Marcus , Schnitt Stuart , Marks Jeffrey R. , Pagon Zrinka , Belina Drazen , Razumovic Jasminka , Polyak Kornelia
Published: July 2002

To identify molecular alterations implicated in the initiating
steps of breast tumorogenesis, we compared the gene expression profiles
of normal and ductal carcinoma
in situ
(DCIS) mammary
epithelial cells by using serial analysis of gene expression (SAGE).
Through the pair-wise comparison of normal and DCIS SAGE libraries, we
identified several differentially expressed genes. Here, we report the
characterization of one of these genes, HIN-1 (high in normal-1). HIN-1
expression is significantly down regulated in 94% of human breast
carcinomas and in 95% of preinvasive lesions, such as ductal and
lobular carcinoma
in situ
. This decrease in HIN-1
expression is accompanied by hypermethylation of its promoter in the
majority of breast cancer cell lines (>90%) and primary tumors
(74%). HIN-1 is a putative cytokine with no significant homology to
known proteins. Reintroduction of HIN-1 into breast cancer cells
inhibits cell growth. These results indicate that HIN-1 is a candidate
tumor suppressor gene that is inactivated at high frequency in the
earliest stages of breast tumorogenesis.
Experimental infection model for Sin Nombre hantavirus in the deer mouse (
Peromyscus maniculatus
)
Authors: Botten Jason , Mirowsky Katy , Kusewitt Donna , Bharadwaj Mausumi , Yee Joyce , Ricci Roy , Feddersen Richard M. , Hjelle Brian
Published: July 2002

The relationship between hantaviruses and their reservoir hosts is not well understood. We successfully passaged a mouse-adapted strain of Sin Nombre virus from deer mice (
Peromyscus maniculatus
) by i.m. inoculation of 4- to 6-wk-old deer mouse pups. After inoculation with 5 ID
50
, antibodies to the nucleocapsid (N) antigen first became detectable at 14 d whereas neutralizing antibodies were detectable by 7 d. Viral N antigen first began to appear in heart, lung, liver, spleen, and/or kidney by 7 d, whereas viral RNA was present in those tissues as well as in thymus, salivary gland, intestine, white fat, and brown fat. By 14 d nearly all tissues examined displayed both viral RNA and N antigen. We noted no consistent histopathologic changes associated with infection, even when RNA load was high. Viral RNA titers peaked on 21 d in most tissues, then began to decline by 28 d. Infection persisted for at least 90 d. The RNA titers were highest in heart, lung, and brown fat. Deer mice can be experimentally infected with Sin Nombre virus, which now allows provocative examination of the virus-host relationship. The prominent involvement of heart, lung, and brown fat suggests that these sites may be important tissues for early virus replication or for maintenance of the virus in nature.
A model for melanosome biogenesis based on the purification and analysis of early melanosomes
Authors: Kushimoto Tsuneto , Basrur Venkatesha , Valencia Julio , Matsunaga Jun , Vieira Wilfred D. , Ferrans Victor J. , Muller Jacqueline , Appella Ettore , Hearing Vincent J.
Published: July 2002

Melanosome biogenesis and function were studied after purification of early stage melanosomes and characterization of specific proteins sorted to that organelle. Melanosomes were isolated from highly pigmented human MNT1 melanoma cells after disruption and initial separation by sucrose density gradient centrifugation. Low-density sucrose fractions were found by electron microscopy to be enriched in stage I and stage II melanosomes, and these fractions were further separated and purified by free flow electrophoresis. Tyrosinase and dopachrome tautomerase (DCT) activities were found exclusively in stage II melanosomes, even though DCT (and to some extent tyrosinase) proteins were sorted to stage I melanosomes. Western immunoblotting revealed that these catalytic proteins, as well as TYRP1, MART1, and GP100, were cleaved and inactivated in stage I melanosomes. Proteolytic cleavage was critical for the refolding of GP100 within the melanosomal milieu, and subsequent reorganization of amorphous stage I melanosomes into fibrillar, ovoid, and highly organized stage II melanosomes appears to stabilize the catalytic functions of melanosomal enzymes and allows melanin biosynthesis to begin. These results provide a better understanding of the structural features seen during melanosome biogenesis, and they yield further clues as to the physiological regulation of pigmentation.
Cloning of a type I cytokine receptor most related to the IL-2 receptor β chain
Authors: Ozaki Katsutoshi , Kikly Kristine , Michalovich David , Young Peter R. , Leonard Warren J.
Published: July 2002

We have identified a type I cytokine receptor, which we have termed
novel interleukin receptor (NILR), that is most related to the IL-2
receptor β chain (IL-2Rβ) and physically adjacent to the IL-4
receptor α chain gene on chromosome 16. NILR mRNA is most highly
expressed in thymus and spleen, and is induced by phytohemagglutinin in
human peripheral blood mononuclear cells. NILR protein was detected on
human T cell lymphotropic virus type I-transformed T cell lines, Raji B
cells, and YT natural killer-like cells. Artificial homodimerization of
the NILR cytoplasmic domain confers proliferation to Ba/F3 murine
pro-B cells but not to 32D myeloid progenitor cells or CTLL-2 murine
helper T cells. In these latter cells, heterodimerization of IL-2Rβ
and the common cytokine receptor γ chain (γ
c
)
cytoplasmic domains allows potent proliferation, whereas such
heterodimerization of NILR with γ
c
does not. This finding
suggests that NILR has signaling potential but that a full
understanding of its signaling partner(s) is not yet clear. Like
IL-2Rβ, NILR associates with Jak1 and mediates Stat5 activation.