bluuebunny/crossref_metadata_2025 huggingface dataset:
Natural Resistance to Infection with Intracellular Pathogens: The Nramp1 Protein Is Recruited to the Membrane of the Phagosome
Authors: Gruenheid Samantha , Pinner Elhanan , Desjardins Michel , Gros Philippe
Published: July 2002

The Nramp1 (natural-resistance-associated macrophage protein 1) locus (Bcg, Ity, Lsh) controls the innate resistance or susceptibility of mice to infection with a group of unrelated intracellular parasites which includes Salmonella, Leishmania, and Mycobacterium. Nramp1 is expressed exclusively in professional phagocytes and encodes an integral membrane protein that shares structural characteristics with ion channels and transporters. Its function and mechanism of action remain unknown. The intracellular localization of the Nramp1 protein was analyzed in control 129/sv and mutant Nramp1−/− macrophages by immunofluorescence and confocal microscopy and by biochemical fractionation. In colocalization studies with a specific anti-Nramp1 antiserum and a panel of control antibodies directed against known cellular structures, Nramp1 was found not to be expressed at the plasma membrane but rather localized to the late endocytic compartments (late endosome/lysosome) of resting macrophages in a Lamp1 (lysosomal-associated membrane protein 1)-positive compartment. Double immunofluorescence studies and direct purification of latex bead–containing phagosomes demonstrated that upon phagocytosis, Nramp1 is recruited to the membrane of the phagosome and remains associated with this structure during its maturation to phagolysosome. After phagocytosis, Nramp1 is acquired by the phagosomal membrane with time kinetics similar to Lamp1, but clearly distinct from those of the early endosomal marker Rab5. The targeting of Nramp1 from endocytic vesicles to the phagosomal membrane supports the hypothesis that Nramp1 controls the replication of intracellular parasites by altering the intravacuolar environment of the microbe-containing phagosome.
Intrinsic and Extrinsic Control of Hemopoietic Stem Cell Numbers: Mapping of a Stem Cell Gene
Authors: Haan Gerald de , Zant Gary Van
Published: July 2002

We evaluated in vivo interactions between extrinsic (growth factor induced) and intrinsic (genetically determined) effectors of mouse primitive hemopoietic stem cell proliferation and numbers. Accordingly, stem cell frequency and cell cycle kinetics were assessed in eight strains of inbred mice using the cobblestone area–forming cell (CAFC) assay. A strong inverse correlation was observed between mouse lifespan and the number of autonomously cycling progenitors (CAFC day 7) in the femur. The population size of primitive stem cells (CAFC day 35) varied widely (up to sevenfold) among strains, unlike total CAFC day 7 numbers (cycling and quiescent), which were similar. Administration of the early acting cytokine flt-3 ligand to these strains resulted in activation of quiescent primitive stem cells exclusively in strains with high endogenous stem cell numbers (DBA and AKR), but was unrelated to strain-specific progenitor cell cycling. To map loci affecting stem cell frequency, we quantified stem cells in BXD recombinant inbred mice (offspring of C57BL/6 and DBA/2). The resulting strain distribution pattern showed high concordance with a marker that mapped to chromosome 18 (19 cM). Linkage with this genomic interval was associated with a likelihood of odds score of 3.3, surpassing the level required for significance. Interestingly, this segment, containing the EGR-1 gene, shows synteny with human chromosome 5q, a region strongly associated with various hematological malignancies. Our findings indicate that a gene mapping to this region is mutated in either C57BL/6 or DBA/2 (and possibly AKR) mice. These studies in apparently healthy mice may facilitate the identification of a gene implicated in human 5q-syndromes.
Vav Regulates Peptide-specific Apoptosis in Thymocytes
Authors: Kong Young-Yun , Fischer Klaus-Dieter , Bachmann Martin F. , Mariathasan Sanjeev , Kozieradzki Ivona , Nghiem Mai P. , Bouchard Dennis , Bernstein Alan , Ohashi Pamela S. , Penninger Josef M.
Published: July 2002

The protooncogene Vav functions as a GDP/GTP exchange factor (GEF) for Rho-like small GTPases involved in cytoskeletal reorganization and cytokine production in T cells. Gene-targeted mice lacking Vav have a severe defect in positive and negative selection of T cell antigen receptor transgenic thymocytes in vivo, and vav−/− thymocytes are completely resistant to peptide-specific and anti-CD3/anti-CD28–mediated apoptosis. Vav acts upstream of mitochondrial pore opening and caspase activation. Biochemically, Vav regulates peptide-specific Ca2+ mobilization and actin polymerization. Peptide-specific cell death was blocked both by cytochalasin D inhibition of actin polymerization and by inhibition of protein kinase C (PKC). Activation of PKC with phorbol ester restored peptide-specific apoptosis in vav−/− thymocytes. Vav was found to bind constitutively to PKC-θ in thymocytes. Our results indicate that peptide-triggered thymocyte apoptosis is mediated via Vav activation, changes in the actin cytoskeleton, and subsequent activation of a PKC isoform.
Immune Adherence–mediated Opsonophagocytosis:  The Mechanism of Leishmania Infection
Authors: Domínguez Mercedes , Toraño Alfredo
Published: July 2002

To mimic the sandfly pool feeding process and characterize the cellular and biochemical events that occur during the early stages of promastigote–host interaction, we developed an ex vivo model of human blood infection with Leishmania promastigotes. Within 30 s of blood contact, Leishmania promastigotes bind natural anti–Leishmania antibodies, which then activate the classical complement pathway and opsonization by the third component of complement. The opsonized promastigotes undergo an immune adherence reaction and bind quantitatively to erythrocyte CR1 receptors; opsonized Leishmania amastigotes also bind to erythrocytes. Progression of infection implies promastigote transfer from erythrocytes to acceptor blood leukocytes. After 10 min of ex vivo infection, 25% of all leukocytes contain intracellular parasites, indicating that blood cells are the early targets for the invading promastigotes. We propose that adaptation to the immune adherence mechanism aids Leishmania survival, promoting rapid promastigote phagocytosis by leukocytes. This facilitates host colonization and may represent the parasite's earliest survival strategy. In light of this mechanism, it is unlikely that infection-blocking vaccines can be developed.
CD34+ Hematopoietic Stem Cells Exert Accessory Function in Lipopolysaccharide-induced  T Cell Stimulation and CD80 Expression on Monocytes
Authors: Mattern Taila , Girroleit Gundolf , Flad Hans-Dieter , Rietschel Ernst T. , Ulmer Artur J.
Published: July 2002

CD34+ hematopoietic stem cells, which circulate in peripheral blood with very low frequency, exert essential accessory function during lipopolysaccharide (LPS)-induced human T lymphocyte activation, resulting in interferon γ production and proliferation. In contrast, stimulation of T cells by “conventional” recall antigens is not controlled by blood stem cells. These conclusions are based on the observation that depletion of CD34+ blood stem cells results in a loss of LPS-induced T cell stimulation as well as reduced expression of CD80 antigen on monocytes. The addition of CD34-enriched blood stem cells resulted in a recovery of reactivity of T cells and monocytes to LPS. Blood stem cells could be replaced by the hematopoietic stem cell line KG-1a. These findings may be of relevance for high risk patients treated with stem cells or stem cell recruiting compounds and for patients suffering from endotoxin-mediated diseases.
Mice Transgenic for Baff Develop Lymphocytic Disorders along with Autoimmune Manifestations
Authors: Mackay Fabienne , Woodcock Stephen A. , Lawton Pornsri , Ambrose Christine , Baetscher Manfred , Schneider Pascal , Tschopp Jurg , Browning Jeffrey L.
Published: July 2002

The cause of many autoimmune and inflammatory diseases is unresolved, although dysregulated production of tumor necrosis factor (TNF) family members appears to be important in many cases. BAFF, a new member of the TNF family, binds to B cells and costimulates their growth in vitro. Mice transgenic for BAFF have vastly increased numbers of mature B and effector T cells, and develop autoimmune-like manifestations such as the presence of high levels of rheumatoid factors, circulating immune complexes, anti–DNA autoantibodies, and immunoglobulin deposition in the kidneys. This phenotype is reminiscent of certain human autoimmune disorders and suggests that dysregulation of BAFF expression may be a critical element in the chain of events leading to autoimmunity.
Expression of Cd28 and Cd86 by Human Eosinophils and Role in the Secretion of Type 1 Cytokines (Interleukin 2 and Interferon γ)
Authors: Woerly Gaëtane , Roger Nadine , Loiseau Sylvie , Dombrowicz David , Capron André , Capron Monique
Published: July 2002

Eosinophils are the source of various immunoregulatory cytokines, but the membrane molecules involved in their secretion have not been clearly identified. Here we show that peripheral blood eosinophils from hypereosinophilic patients could express membrane CD86 but not CD80. The T cell costimulatory molecule CD28 is also detected on the eosinophil surface. CD28 ligation but not CD86 ligation resulted in interleukin (IL)-2 and interferon (IFN)-γ secretion by eosinophils, whereas IL-4, IL-5, and IL-10 were not detected. In contrast to T cells requiring two signals for effective stimulation, CD28 ligation alone was sufficient for optimal eosinophil activation. Eosinophil-derived IL-2 and IFN-γ were biologically active, as supernatants from anti-CD28–treated cells were able to induce CTLL-2 proliferation and major histocompatibility complex class II expression on the colon carcinoma cell line Colo 205, respectively. Addition of secretory immunoglobulin (Ig)A–anti-IgA complexes, which could induce the release of IL-10, very significantly inhibited both CD28-mediated IL-2 and IFN-γ release. These results suggest that the release of type 1 (IFN-γ and IL-2) versus type 2 cytokines by eosinophils is not only differential but also dependent on cross-regulatory signals. They confirm that through activation of costimulatory molecules, eosinophils could function as an immunoregulatory cell involved in the release of both type 1 and type 2 cytokines.
Baff Mediates Survival of Peripheral Immature B Lymphocytes
Authors: Batten Marcel , Groom Joanna , Cachero Teresa G. , Qian Fang , Schneider Pascal , Tschopp Jurg , Browning Jeffrey L. , Mackay Fabienne
Published: July 2002

B cell maturation is a very selective process that requires finely tuned differentiation and survival signals. B cell activation factor from the TNF family (BAFF) is a TNF family member that binds to B cells and potentiates B cell receptor (BCR)-mediated proliferation. A role for BAFF in B cell survival was suggested by the observation of reduced peripheral B cell numbers in mice treated with reagents blocking BAFF, and high Bcl-2 levels detected in B cells from BAFF transgenic (Tg) mice. We tested in vitro the survival effect of BAFF on lymphocytes derived from primary and secondary lymphoid organs. BAFF induced survival of a subset of splenic immature B cells, referred to as transitional type 2 (T2) B cells. BAFF treatment allowed T2 B cells to survive and differentiate into mature B cells in response to signals through the BCR. The T2 and the marginal zone (MZ) B cell compartments were particularly enlarged in BAFF Tg mice. Immature transitional B cells are targets for negative selection, a feature thought to promote self-tolerance. These findings support a model in which excessive BAFF-mediated survival of peripheral immature B cells contributes to the emergence and maturation of autoreactive B cells, skewed towards the MZ compartment. This work provides new clues on mechanisms regulating B cell maturation and tolerance.
Hla-Dm Recognizes the Flexible Conformation of Major Histocompatibility Complex Class II
Authors: Chou Chih-Ling , Sadegh-Nasseri Scheherazade
Published: July 2002

DM facilitates formation of high affinity complexes of peptide–major histocompatibility complex (MHC) by release of class II MHC–associated invariant chain peptide (CLIP). This has been proposed to occur through discrimination of complex stability. By probing kinetic and conformational intermediates of the wild-type and mutant human histocompatibility leukocyte antigen (HLA)-DR1–peptide complexes, and examining their reactivities with DM, we propose that DM interacts with the flexible hydrophobic pocket 1 of DR1 and converts the molecule into a conformation that is highly peptide receptive. A more rigid conformation, generated upon filling of pocket 1, is less susceptible to DM effects. Thus, DM edits peptide–MHC by recognition of the flexibility rather than stability of the complex.
The Rho Family Guanine Nucleotide Exchange Factor Vav-2 Regulates the Development of Cell-Mediated Cytotoxicity
Authors: Billadeau Daniel D. , Mackie Stacy M. , Schoon Renee A. , Leibson Paul J.
Published: July 2002

Previous pharmacologic and genetic studies have demonstrated a critical role for the low molecular weight GTP-binding protein RhoA in the regulation of cell-mediated killing by cytotoxic lymphocytes. However, a specific Rho family guanine nucleotide exchange factor (GEF) that activates this critical regulator of cellular cytotoxicity has not been identified. In this study, we provide evidence that the Rho family GEF, Vav-2, is present in cytotoxic lymphocytes, and becomes tyrosine phosphorylated after the cross-linking of activating receptors on cytotoxic lymphocytes and during the generation of cell-mediated killing. In addition, we show that overexpression of Vav-2 in cytotoxic lymphocytes enhances cellular cytotoxicity, and this enhancement requires a functional Dbl homology and Src homology 2 domain. Interestingly, the pleckstrin homology domain of Vav-2 was found to be required for enhancement of killing through some, but not all activating receptors on cytotoxic lymphocytes. Lastly, although Vav and Vav-2 share significant structural homology, only Vav is able to enhance nuclear factor of activated T cells–activator protein 1–mediated gene transcription downstream of the T cell receptor. These data demonstrate that Vav-2, a Rho family GEF, differs from Vav in the control of certain lymphocyte functions and participates in the control of cell-mediated killing by cytotoxic lymphocytes.
Immunoglobulin Heavy Chain Variable Region Gene Replacement as a Mechanism for Receptor Revision in Rheumatoid Arthritis Synovial Tissue B Lymphocytes
Authors: Itoh Kenji , Meffre Eric , Albesiano Emilia , Farber Andrew , Dines David , Stein Peter , Asnis Stanley E. , Furie Richard A. , Jain Rita I. , Chiorazzi Nicholas
Published: July 2002

Mature B cells can alter their antibody repertoires by several mechanisms, including immunoglobulin heavy chain variable region (VH) replacement. This process changes the antigen combining site by replacing a portion of the original VH/diversity/heavy chain joining region (VHDJH) rearrangement with a corresponding portion of a new VH segment. This exchange can involve cryptic heptamer-like sequences embedded in the coding regions of VH genes.

While studying the B lymphocytes that expand in the synovial tissues of patients with rheumatoid arthritis (RA), clones with VHDJH variants that were apparently generated by VH replacement were identified with surprising frequency (∼8%). Examples of multiple independent VH replacement events occurring in distinct progeny clones were also identified. These secondary VH rearrangements were documented at both the cDNA and genomic DNA levels and involved several heptamer-like sequences at four distinct locations within VH (three sites in framework region 3 and one in complementarity determining region 2). The identification of blunt-ended double-stranded DNA breaks at the embedded heptamers and the demonstration of recombinase activating gene (RAG) expression suggested that these rearrangements could occur in the synovial tissues, presumably in pseudo-germinal centers, and that they could be mediated by RAG in a recognition signal sequence–specific manner. The presence of VH mutations in the clones that had undergone replacement indicated that these B cells were immunocompetent and could receive and respond to diversification signals. A relationship between these secondary VH gene rearrangements and the autoimmunity characteristic of RA should be considered.
Subspecialization of Cxcr5+ T Cells
Authors: Kim Chang H. , Rott Lusijah S. , Clark-Lewis Ian , Campbell Daniel J. , Wu Lijun , Butcher Eugene C.
Published: July 2002

The T helper (Th) cell pool is composed of specialized cells with heterogeneous effector functions. Apart from Th1 and 2 cells, CXCR5+ T cells have been suggested to be another type of effector T cell specialized for B cell help. We show here that CXCR5+ T cells are heterogeneous, and we identify subsets of CXCR5+ CD4 T cells that differ in function and microenvironmental localization in secondary lymphoid tissues. CD57+CXCR5 T cells, hereafter termed germinal center Th (GC-Th) cells, are localized only in GCs, lack CCR7, and are highly responsive to the follicular chemokine B lymphocyte chemoattractant but not to the T cell zone EBI1-ligand chemokine. Importantly, GC-Th cells are much more efficient than CD57−CXCR5+ T cells or CXCR5− T cells in inducing antibody production from B cells. Consistent with their function, GC-Th cells produce elevated levels of interleukin 10 upon stimulation which, with other cytokines and costimulatory molecules, may help confer their B cell helper activity. Our results demonstrate that CXCR5+ T cells are functionally heterogeneous and that the GC-Th cells, a small subset of CXCR5+ T cells, are the key helpers for B cell differentiation and antibody production in lymphoid tissues.
Constitutive Nuclear Factor κB Activity Is Required for Survival of Activated B Cell–like Diffuse Large B Cell Lymphoma Cells
Authors: Davis R. Eric , Brown Keith D. , Siebenlist Ulrich , Staudt Louis M.
Published: July 2002

Gene expression profiling has revealed that diffuse large B cell lymphoma (DLBCL) consists of at least two distinct diseases. Patients with one DLBCL subtype, termed activated B cell–like (ABC) DLBCL, have a distinctly inferior prognosis. An untapped potential of gene expression profiling is its ability to identify pathogenic signaling pathways in cancer that are amenable to therapeutic attack. The gene expression profiles of ABC DLBCLs were notable for the high expression of target genes of the nuclear factor (NF)-κB transcription factors, raising the possibility that constitutive activity of the NF-κB pathway may contribute to the poor prognosis of these patients. Two cell line models of ABC DLBCL had high nuclear NF-κB DNA binding activity, constitutive IκB kinase (IKK) activity, and rapid IκBα degradation that was not seen in cell lines representing the other DLBCL subtype, germinal center B-like (GCB) DLBCL. Retroviral transduction of a super-repressor form of IκBα or dominant negative forms of IKKβ was toxic to ABC DLBCL cells but not GCB DLBCL cells. DNA content analysis showed that NF-κB inhibition caused both cell death and G1-phase growth arrest. These findings establish the NF-κB pathway as a new molecular target for drug development in the most clinically intractable subtype of DLBCL and demonstrate that the two DLBCL subtypes defined by gene expression profiling utilize distinct pathogenetic mechanisms.
Active Immunization Against the Vascular Endothelial Growth Factor Receptor flk1 Inhibits Tumor Angiogenesis and Metastasis
Authors: Li Yiwen , Wang Mei-Nai , Li Hongli , King Karen D. , Bassi Rajiv , Sun Haijun , Santiago Angel , Hooper Andrea T. , Bohlen Peter , Hicklin Daniel J.
Published: July 2002

The vascular endothelial growth factor (VEGF) receptor fetal liver kinase 1 (flk1; VEGFR-2, KDR) is an endothelial cell–specific receptor tyrosine kinase that mediates physiological and pathological angiogenesis. We hypothesized that an active immunotherapy approach targeting flk1 may inhibit tumor angiogenesis and metastasis. To test this hypothesis, we first evaluated whether immune responses to flk1 could be elicited in mice by immunization with dendritic cells pulsed with a soluble flk1 protein (DC-flk1). This immunization generated flk1-specific neutralizing antibody and CD8+ cytotoxic T cell responses, breaking tolerance to self-flk1 antigen. Tumor-induced angiogenesis was suppressed in immunized mice as measured in an alginate bead assay. Development of pulmonary metastases was strongly inhibited in DC-flk1–immunized mice challenged with B16 melanoma or Lewis lung carcinoma cells. DC-flk1 immunization also significantly prolonged the survival of mice challenged with Lewis lung tumors. Thus, an active immunization strategy that targets an angiogenesis-related antigen on endothelium can inhibit angiogenesis and may be a useful approach for treating angiogenesis-related diseases.
A note on fixed point theorems for semi-continuous correspondences on [0,1]
Authors: Wu Zhou
Published: July 2002

This paper presents a fixed point theorem for correspondences on [0,1]. Some examples comparing it to related work and also some simple applications to game theory are included.
Jones index theory by Hilbert C*-bimodules and K-theory
Authors: Kajiwara Tsuyoshi , Watatani Yasuo
Published: July 2002

In this paper we introduce the notion of Hilbert

C

∗

{\mathrm {C}}^{*}

-bimodules, replacing the associativity condition of two-sided inner products in Rieffel’s imprimitivity bimodules by a Pimsner-Popa type inequality. We prove Schur’s Lemma and Frobenius reciprocity in this setting. We define minimality of Hilbert

C

∗

{\mathrm {C}}^{*}

-bimodules and show that tensor products of minimal bimodules are also minimal. For an

A
A

-

A
A

bimodule which is compatible with a trace on a unital

C

∗

{\mathrm {C}}^{*}

-algebra

A
A

, its dimension (square root of Jones index) depends only on its

K
K

KK

-class. Finally, we show that the dimension map transforms the Kasparov products in

K
K
(
A
,
A
)

KK(A,A)

to the product of positive real numbers, and determine the subring of

K
K
(
A
,
A
)

KK(A,A)

generated by the Hilbert

C

∗

{\mathrm {C}}^{*}

-bimodules for a

C

∗

{\mathrm {C}}^{*}

-algebra generated by Jones projections.
Extremal functions for Moser’s inequality
Authors: Lin Kai-Ching
Published: July 2002

Let

Ω
\Omega

be a bounded smooth domain in

R

n

R^{n}

, and

u
(
x
)

u(x)

a

C

1

C^{1}

function with compact support in

Ω
\Omega

. Moser’s inequality states that there is a constant

c

o

c_{o}

, depending only on the dimension

n
n

, such that
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="StartFraction 1 Over StartAbsoluteValue normal upper Omega EndAbsoluteValue EndFraction integral Underscript normal upper Omega Endscripts e Superscript n omega Super Subscript n minus 1 Super Superscript StartFraction 1 Over n minus 1 EndFraction Superscript u Super Superscript StartFraction n Over n minus 1 EndFraction Superscript Baseline d x less-than-or-equal-to c Subscript o Baseline comma">

1

|

Ω

|

∫

Ω

e

n

ω

n
−
1

1

n
−
1

u

n

n
−
1

d
x
≤

c

o

,

\begin{equation*} \frac {1}{|\Omega |} \int _{\Omega } e^{n \omega _{n-1}^{\frac {1}{n-1}} u^{\frac {n}{n-1}}}\, dx \leq c_{o} , \end{equation*}

where

|

Ω

|

|\Omega |

is the Lebesgue measure of

Ω
\Omega

, and

ω

n
−
1

\omega _{n-1}

the surface area of the unit ball in

R

n

R^{n}

. We prove in this paper that there are extremal functions for this inequality. In other words, we show that the
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="sup left-brace StartFraction 1 Over StartAbsoluteValue normal upper Omega EndAbsoluteValue EndFraction integral Underscript normal upper Omega Endscripts e Superscript n omega Super Subscript n minus 1 Super Superscript StartFraction 1 Over n minus 1 EndFraction Superscript u Super Superscript StartFraction n Over n minus 1 EndFraction Superscript Baseline d x colon u element-of upper W Subscript o Superscript 1 comma n Baseline comma double-vertical-bar nabla u double-vertical-bar Subscript n Baseline less-than-or-equal-to 1 right-brace">

sup
{

1

|

Ω

|

∫

Ω

e

n

ω

n
−
1

1

n
−
1

u

n

n
−
1

d
x
:
u
∈

W

o

1
,
n

,
‖
∇
u

‖

n

≤
1
}

\begin{equation*} \sup \{\frac {1}{|\Omega |} \int _{\Omega } e^{n \omega _{n-1}^{\frac {1}{n-1}} u^{\frac {n}{n-1}}}\, dx: u \in W_{o}^{1,n}, \|\nabla u\|_{n} \leq 1 \} \end{equation*}

is attained. Earlier results include Carleson-Chang (1986,

Ω
\Omega

is a ball in any dimension) and Flucher (1992,

Ω
\Omega

is any domain in 2-dimensions).
“Best possible” upper and lower bounds for the zeros of the Bessel function 𝐽_{𝜈}(𝑥)
Authors: Qu C. , Wong R.
Published: July 2002

Let

j

ν
,
k

j_{\nu ,k}

denote the

k
k

-th positive zero of the Bessel function

J
ν

(
x
)

J_\nu (x)

. In this paper, we prove that for

ν
>
0

\nu >0

and

k
=
1

k=1

, 2, 3,

…
\ldots

,
\[
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="nu minus StartFraction a Subscript k Baseline Over 2 Superscript 1 slash 3 Baseline EndFraction nu Superscript 1 slash 3 Baseline greater-than j Subscript nu comma k Baseline greater-than nu minus StartFraction a Subscript k Baseline Over 2 Superscript 1 slash 3 Baseline EndFraction nu Superscript 1 slash 3 Baseline plus three twentieths a Subscript k Superscript 2 Baseline StartFraction 2 Superscript 1 slash 3 Baseline Over nu Superscript 1 slash 3 Baseline EndFraction period">

ν
−

a
k

2

1

/

3

ν

1

/

3

>

j

ν
,
k

>
ν
−

a
k

2

1

/

3

ν

1

/

3

+

3
20

a
k
2

2

1

/

3

ν

1

/

3

.

\nu - \frac {a_k}{2^{1/3}} \nu ^{1/3} > j_{\nu ,k} > \nu - \frac {a_k}{2^{1/3}} \nu ^{1/3} + \frac {3}{20} a_k^2 \frac {2^{1/3}}{\nu ^{1/3}} \,.

\]
These bounds coincide with the first few terms of the well-known asymptotic expansion
\[
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="j Subscript nu comma k Baseline tilde nu minus StartFraction a Subscript k Baseline Over 2 Superscript 1 slash 3 Baseline EndFraction nu Superscript 1 slash 3 Baseline plus three twentieths a Subscript k Superscript 2 Baseline StartFraction 2 Superscript 1 slash 3 Baseline Over nu Superscript 1 slash 3 Baseline EndFraction plus midline-horizontal-ellipsis">

j

ν
,
k

∼
ν
−

a
k

2

1

/

3

ν

1

/

3

+

3
20

a
k
2

2

1

/

3

ν

1

/

3

+
⋯

j_{\nu ,k} \sim \nu - \frac {a_k}{2^{1/3}} \nu ^{1/3} + \frac {3}{20} a_k^2 \frac {2^{1/3}}{\nu ^{1/3}} + \cdots

\]
as

ν
→
∞

\nu \to \infty

,

k
k

being fixed, where

a
k

a_k

is the

k
k

-th negative zero of the Airy function

Ai
⁡
(
x
)

\operatorname {Ai}(x)

, and so are “best possible”.
Efficient Runge-Kutta integrators for index-2 differential algebraic equations
Authors: Butcher J. , Chan R.
Published: July 2002

In seeking suitable Runge-Kutta methods for differential algebraic equations, we consider singly-implicit methods to which are appended diagonally-implicit stages. Methods of this type are either similar to those of Butcher and Cash  or else allow for the importation of a final derivative from a previous step. For these two classes, with up to three additional diagonally-implicit stages, we derive methods that satisfy appropriate order conditions for index-2 DAEs.
Advances in aliquot sequences
Authors: Benito Manuel , Varona Juan
Published: July 2002

In this paper we describe some advances in the knowledge of the behavior of aliquot sequences starting with a number less than

10000
10000

. For some starting values, it is shown for the first time that the sequence terminates. The current record for the maximum of a terminating sequence is located in the one starting at 4170; it converges to 1 after 869 iterations getting a maximum of 84 decimal digits at iteration 289.
Foliations with good geometry
Authors: Fenley Sérgio
Published: July 2002

The goal of this article is to show that there is a large class of closed hyperbolic 3-manifolds admitting codimension one foliations with good large scale geometric properties. We obtain results in two directions. First there is an internal result: A possibly singular foliation in a manifold is quasi-isometric if, when lifted to the universal cover, distance along leaves is efficient up to a bounded multiplicative distortion in measuring distance in the universal cover. This means that leaves reflect very well the geometry in the large of the universal cover and are geometrically tight—this is the best geometric behavior. We previously proved that nonsingular codimension one foliations in closed hyperbolic 3-manifolds can never be quasi-isometric. In this article we produce a large class of singular quasi-isometric, codimension one foliations in closed hyperbolic 3-manifolds. The foliations are stable and unstable foliations of pseudo-Anosov flows. Our second result is an external result, relating (nonsingular) foliations in hyperbolic 3-manifolds with their limit sets in the universal cover, that is, showing that leaves in the universal cover have good asymptotic behavior. Let

G

\mathcal G

be a Reebless, finite depth foliation in a closed hyperbolic 3-manifold. Then

G

\mathcal G

is not quasi-isometric, but suppose that

G

\mathcal G

is transverse to a quasigeodesic pseudo-Anosov flow with quasi-isometric stable and unstable foliations—which are given by the internal result. We then show that the lifts of leaves of

G

\mathcal G

to the universal cover extend continuously to the sphere at infinity and we also produce infinitely many examples satisfying the hypothesis. The main tools used to prove these results are first a link between geometric properties of stable/unstable foliations of pseudo-Anosov flows and the topology of these foliations in the universal cover, and second a topological theory of the joint structure of the pseudo-Anosov foliation in the universal cover.
Self-organizing tree growing network for classifying amino acids.
Authors: Wang H C , Dopazo J , Carazo J M
Published: July 2002

SUMMARY: A self-organizing tree growing neural network was applied to classify amino acids and amino acid exchange matrices. AVAILABILITY: SOTA, is freely available by anonymous FTP or at http://www.cnb.uam.es/bioinfo/Software/so ta. CONTACT: carazo@cnb.uam.es
ProPred: prediction of HLA-DR binding sites
Authors: Singh Harpreet , Raghava G. P. S.
Published: July 2002

Summary: ProPred is a graphical web tool for predicting MHC class II binding regions in antigenic protein sequences. The server implement matrix based prediction algorithm, employing amino-acid/position coefficient table deduced from literature. The predicted binders can be visualized either as peaks in graphical interface or as colored residues in HTML interface. This server might be a useful tool in locating the promiscuous binding regions that can bind to several HLA-DR alleles.

Availability: The server is available at http://www.imtech.res.in/raghava/propred/

Contact: raghava@imtech.res.in

Supplementary information: http://www.imtech.res.in/raghava/propred/page3.html

* To whom correspondence should be addressed.
Panel Tests of Okun's Law for Ten Industrial Countries
Authors: Freeman Donald G.
Published: July 2002

Okun's Law is one of the most enduring stylistic facts in macroeconomics. This article uses new developments in trend/cycle decomposition to test Okun's Law for a panel of ten industrial countries, finding that Okun's original estimate for the U.S. of three points of real GDP growth for each one percent reduction in the unemployment rate now averages just under two points of real GDP growth for the sample countries. Pooled estimates for Europe are smaller than estimates for the rest of the sample. Also, this article finds that omission of capital and labor inputs may have biased previous estimates.
Reconciling Automation and Flexibility? Technology and Production in the Postwar British Motor Vehicle Industry
Authors: Zeitlin Jonathan
Published: July 2002

This article contests the view that “stages of development” determine a uniquely appropriate set of production and marketing strategies for a given industry in a given period. Looking closely at the British automobile industry after World War II, it instead presents the argument that opportunities for significant choices between more or less flexible technologies and organizational forms constitute a continuous feature of modern economic history. Moreover, piecemeal borrowing and selective adaptation have been more common than wholesale imitation of any particular system, and modification and hybridization of imported technologies represent not resistance to “foreign” elements, but creative attempts to fit those elements to local conditions.
Masculine Guidance: Boys, Men, and Newspapers, 1930–1939
Authors: Postol Todd Alexander
Published: July 2002

The familiar neighborhood paper boy was a product of the Depression, born of the need to boost revenues and improve readership. Operating funds for newspapers swiftly declined in the wake of the 1929 stock market crash. Circulation managers responded with one of the few resources at their command—inexpensive juvenile labor. Drawing on connections linking men and boys in the marketplace, circulation heads fashioned a gendered managerial philosophy that was distinctive to their industry. This approach, here termed masculine guidance, revitalized daily news delivery and transformed the relationship between middle-class childhood and paid work in the United States.
“Rosie the Realtor” and the Re-Gendering of Real Estate Brokerage, 1930–1960
Authors: Hornstein Jeffrey M.
Published: July 2002

Rapidly increasing numbers of women entered the field of real estate brokerage from the 1930s through the 1950s. “Rosie the Realtor” took advantage of the postwar building boom to create an expanding career niche, capturing residential brokerage as a female domain. In the process, she stretched gendered boundaries in the masculine world of brokerage to the breaking point. Employing a complex and internally antagonistic mix of liberal feminist and conservative ideologies, female realtors created their own professional space, expanding career opportunities for women at the same time that their economic and political practices reinforced the constraints of domesticity.
Induction and apoptotic regression of lung adenocarcinomas by regulation of a K-Ras transgene in the presence and absence of tumor suppressor genes
Authors: Fisher Galen H. , Wellen Shari L. , Klimstra David , Lenczowski Joi M. , Tichelaar Jay W. , Lizak Martin J. , Whitsett Jeffrey A. , Koretsky Alan , Varmus Harold E.
Published: July 2002

To investigate the role of an activated K-Ras gene in the initiation and maintenance of lung adenocarcinomas, we developed transgenic mice that express murine K-Ras4bG12D under the control of doxycycline in type II pneumocytes. Focal proliferative lesions of alveolar type II pneumocytes were observed as early as seven days after induction with doxycycline; after two months of induction, the lungs contained adenomas and adenocarcinomas, with focal invasion of the pleura at later stages. Removal of doxycycline caused a rapid fall in levels of mutant K-Ras RNA and concomitant apoptotic regression of both the early proliferative lesions and the tumors. Tumor burden was dramatically decreased by three days after withdrawal, and tumors were undetectable after one month. When similar experiments were performed with animals deficient in either the p53 gene or the Ink4A/Arf locus, tumors arose more quickly (within one month of exposure to doxycycline) and displayed more obvious histological features of malignancy; nevertheless, these tumors also regressed rapidly when the inducer was removed, implying that continued production of mutant K-Ras is necessary to maintain the viability of tumor cells in the absence as well as the presence of tumor suppressor genes. We also show that the appearance and regression of these pulmonary tumors can be readily monitored in anesthetized transgenic animals by magnetic resonance imaging.
The linear no‐threshold dose‐effect relation: Is it relevant to radiation protection regulation?
Authors: Nussbaum Rudi H.
Published: July 2002

Official radiogenic cancer risk estimates for low‐dose, protracted exposure conditions have been based on linear, no‐threshold downward extrapolation from medium and high‐dose effects among a population of A‐bomb survivors, with the application of a downward correction for an assumed reduced biological effectiveness at low doses and low dose rates (DDREF correction). Neither in the follow‐up of populations exposed to the high‐dose A‐bomb flash, nor from epidemiological data after low‐dose occupational or medical irradiation is there any convincing evidence for this DDREF hypothesis—even less for a zero‐effect threshold dose. To the contrary, for external low‐dose exposures of nuclear workers or general populations, cancer risks per unit dose have been found to be about 1 order of magnitude larger than those derived from the Japanese survivors, with larger discrepancies for persons above 50 years of age, and for x‐rayed fetuses. This may be due to a dose and dose‐rate effect exactly opposite from that postulated by the DDREF assumption, and a dose‐dependent bias due to selection for exceptionally high immune competence among the years A‐bomb survivor cohort. Excess cancer mortality following occupational exposures to ingested fission products and radiation‐associated teratogenic, genetic, and cancer detriment among diverse populations who had ingested small amounts of radioactivity after the precipitation of fallout at great distances from the Chernobyl nuclear explosion, suggest discrepancies of as much as 2 orders of magnitude with official risk estimates. Contrary to widely publicized statements, claiming that current regulations of population exposures are far too restrictive, thus unnecessarily costly for the radiation industries, the aggregate of radiation epidemiological evidence suggests that current standards are inadequate to protect public health.
A statistical development of entropy for the introductory physics course
Authors: Schoepf David C.
Published: July 2002

Many introductory physics texts introduce the statistical basis for the definition of entropy in addition to the Clausius definition, ΔS=q/T. We use a model based on equally spaced energy levels to present a way that the statistical definition of entropy can be developed at the introductory level. In addition to motivating the statistical definition of entropy, we also develop statistical arguments to answer the following questions: (i) Why does a system approach a state of maximum number of microstates? (ii) What is the equilibrium distribution of particles? (iii) What is the statistical basis of temperature? (iv) What is the statistical basis for the direction of spontaneous energy transfer? Finally, a correspondence between the statistical and the classical Clausius definitions of entropy is made.
On the character of acoustic waves at the interface between hard and soft solids and liquids
Authors: Glorieux Christ , Van de Rostyne Kris , Nelson Keith , Gao Weimin , Lauriks Walter , Thoen Jan
Published: July 2002

Laser ultrasonics is used to optically excite and detect acoustic waves at the interface between a liquid and a solid or coated solid. Several case studies show that this technique is feasible to investigate experimentally the theoretically predicted fundamental properties of different aspects of interface waves at liquid–solid interfaces and to characterize the elastic properties of soft solids. The theoretical prediction that the leaky Rayleigh (LR)-type root of the characteristic determinant becomes forbidden when the shear velocity of the solid lies below the bulk velocity of the liquid was experimentally confirmed. The depth profiling and nondestructive testing potential of Scholte waves was experimentally illustrated and explained by the properties of the wave displacement profile.
Nonlinearity of acoustic waves at solid–liquid interfaces
Authors: Glorieux Christ , Van de Rostyne Kris , Gusev Vitalyi , Gao Weimin , Lauriks Walter , Thoen Jan
Published: July 2002

The small-amplitude and finite-amplitude propagation characteristics of laser line source excited and laser detected Scholte waves are investigated. Acoustic waves with Mach numbers up to 0.054 are observed at the interface between water and glass. In our case of a hard solid–liquid interface, the Scholte wave propagates very much like a bulk wave, for which the simple-wave equation holds. The experimental results are well fitted with this model, extended with an attenuation term. An anomalously large (compared with low amplitude viscous effects) attenuation reveals possible leakage of energy from the Scholte wave to bulk waves, through a mechanism of nonlinear mixing between the different wave modes and viscosity induced turbulence.
Speech perception as pattern recognition
Authors: Nearey Terrance M.
Published: July 2002

This work provides theoretical and empirical arguments in favor of an approach to phonetics that is called double-weak. It is so called because it assumes relatively weak constraints both on the articulatory gestures and on the auditory patterns that map phonological elements. This approach views speech production and perception as distinct but cooperative systems. Like the motor theory of speech perception, double-weak theory accepts that phonological units are modified by context in ways that are important to perception. It further agrees that many aspects of such context dependency have their origin in natural articulatory processes. However, double-weak theory sides with proponents of auditory theories of phonetics by accepting that the real-time objects of perception are well-defined auditory patterns. Because speakers find ways to obey “orderly output conditions” (Sussman et al., 1995), listeners are able to successfully decode speech using relatively simple pattern-recognition mechanisms. It is suggested that this situation has arisen through a stylization of gestural patterns to accommodate real-time limits of the perceptual system. Results from a new perceptual experiment, involving a four-dimensional stimulus continuum and a 10-category /hVC/ response set, are shown to be largely compatible with this framework.
High-frequency backscattering enhancements by thick finite cylindrical shells in water at oblique incidence: Experiments, interpretation, and calculations
Authors: Morse Scot F. , Marston Philip L. , Kaduchak Gregory
Published: July 2002

Impulse response backscattering measurements are presented and interpreted for the scattering of obliquely incident plane waves by air-filled finite cylindrical shells immersed in water. The measurements were carried out to determine the conditions for significant enhancements of the backscattering by thick shells at large tilt angles. The shells investigated are made of stainless steel and are slender and have thickness to radius ratios of 7.6% and 16.3%. A broadband PVDF (polyvinylidene fluoride) sheet source is used to obtain the backscattering spectral magnitude as a function of the tilt angle (measured from broadside incidence) of the cylinder. Results are plotted as a function of frequency and angle. These plots reveal large backscattering enhancements associated with elastic excitations at high tilt angles, which extend to end-on incidence in the coincidence frequency region. Similar features are present in approximate calculations for finite cylindrical shells based on full elasticity theory and the Kirchhoff diffraction integral. One feature is identified as resulting from the axial (meridional ray) propagation of the supersonic a0 leaky Lamb wave. A simple approximation is used to describe circumferential coupling loci in frequency-angle space for several surface waves. The resulting loci are used to identify enhancements due to the helical propagation of the subsonic a0− Lamb wave.
Adaptation in the processing of interaural time differences revealed by the auditory localization aftereffect
Authors: Kashino Makio , Nishida Shin’ya
Published: July 2002

Two experiments were conducted involving the auditory localization aftereffect, in which the perceptual lateralization of a test sound having an interaural time difference (ITD) shifts away from that of a prior adapting sound having a different ITD. First, the frequency selectivity of the aftereffect was examined for sinusoids presented through headphones, with various combinations of adapter and test frequencies below 800 Hz, using the method of constant stimuli. The magnitude of the aftereffect was found to be largest when the frequencies of the two tones were similar, and virtually disappeared at a frequency difference of one-half octave. Second, the ITD selectivity of the aftereffect was examined for 400-Hz sinusoids. Subjects’ judgments of lateralization were measured directly in terms of the perceived azimuth of the test tone for various combinations of adapter and test ITDs in the range of ±625 μs. The magnitude of the aftereffect was found to be largest when adapter and test ITDs differed by approximately 250 μs. These results were successfully simulated by an interaural cross-correlation model having gain control. The results are consistent with the idea that the gain of ITD-selective units, located after binaural interaction but before across-frequency integration, is changed by recent input.
Cortical auditory evoked potential correlates of categorical perception of voice-onset time
Authors: Sharma Anu , Dorman Michael F.
Published: July 2002

The goal of this study was to examine the neural encoding of voice-onset time distinctions that indicate the phonetic categories /da/ and /ta/ for human listeners. Cortical Auditory Evoked Potentials (CAEP) were measured in conjunction with behavioral perception of a /da/-/ta/ continuum. Sixteen subjects participated in identification and discrimination experiments. A sharp category boundary was revealed between /da/ and /ta/ around the same location for all listeners. Subjects’ discrimination of a VOT change of equal magnitude was significantly more accurate across the /da/-/ta/ categories than within the /ta/ category. Neurophysiologic correlates of VOT encoding were investigated using the N1 CAEP which reflects sensory encoding of stimulus features and the MMN CAEP which reflects sensory discrimination. The MMN elicited by the across-category pair was larger and more robust than the MMN which occurred in response to the within-category pair. Distinct changes in N1 morphology were related to VOT encoding. For stimuli that were behaviorally identified as /da/, a single negativity (N1) was apparent; however, for stimuli identified as /ta/, two distinct negativities (N1 and N1′) were apparent. Thus the enhanced MMN responses and the morphological discontinuity in N1 morphology observed in the region of the /da/-/ta/ phonetic boundary appear to provide neurophysiologic correlates of categorical perception for VOT.