bluuebunny/crossref_metadata_2025 huggingface dataset:
Kinetics of Core Histones in Living Human Cells
Authors: Kimura Hiroshi , Cook Peter R.
Published: July 2002

Histones H2A and H2B form part of the same nucleosomal structure as H3 and H4. Stable HeLa cell lines expressing histones H2B, H3, and H4 tagged with green fluorescent protein (GFP) were established; the tagged molecules were assembled into nucleosomes. Although H2B-GFP was distributed like DNA, H3-GFP and H4-GFP were concentrated in euchromatin during interphase and in R-bands in mitotic chromosomes. These differences probably result from an unregulated production of tagged histones and differences in exchange. In both single cells and heterokaryons, photobleaching revealed that H2B-GFP exchanged more rapidly than H3-GFP and H4-GFP. About 3% of H2B exchanged within minutes, whereas ∼40% did so slowly (t1/2 ∼ 130 min). The rapidly exchanging fraction disappeared in 5,6-dichloro-1-β-d-ribofuranosylbenzimidazole and so may represent H2B in transcriptionally active chromatin. The slowly exchanging fraction was probably associated with chromatin domains surrounding active units. H3-GFP and H4-GFP were assembled into chromatin when DNA was replicated, and then >80% remained bound permanently. These results reveal that the inner core of the nucleosome is very stable, whereas H2B on the surface of active nucleosomes exchanges continually.
Nuclear pore complexes form immobile networks and have a very low turnover in live mammalian cells
Authors: Daigle Nathalie , Beaudouin Joël , Hartnell Lisa , Imreh Gabriela , Hallberg Einar , Lippincott-Schwartz Jennifer , Ellenberg Jan
Published: July 2002

The nuclear pore complex (NPC) and its relationship to the nuclear envelope (NE) was characterized in living cells using POM121–green fluorescent protein (GFP) and GFP-Nup153, and GFP–lamin B1. No independent movement of single pore complexes was found within the plane of the NE in interphase. Only large arrays of NPCs moved slowly and synchronously during global changes in nuclear shape, strongly suggesting mechanical connections which form an NPC network. The nuclear lamina exhibited identical movements. NPC turnover measured by fluorescence recovery after photobleaching of POM121 was less than once per cell cycle. Nup153 association with NPCs was dynamic and turnover of this nucleoporin was three orders of magnitude faster. Overexpression of both nucleoporins induced the formation of annulate lamellae (AL) in the endoplasmic reticulum (ER). Turnover of AL pore complexes was much higher than in the NE (once every 2.5 min). During mitosis, POM121 and Nup153 were completely dispersed and mobile in the ER (POM121) or cytosol (Nup153) in metaphase, and rapidly redistributed to an immobilized pool around chromatin in late anaphase. Assembly and immobilization of both nucleoporins occurred before detectable recruitment of lamin B1, which is thus unlikely to mediate initiation of NPC assembly at the end of mitosis.
A Critical Role for Lymphotoxin in Experimental Allergic Encephalomyelitis
Authors: Suen Winnie E. , Bergman Cheryl M. , Hjelmström Peter , Ruddle Nancy H.
Published: July 2002

The lymphotoxin (LT)/tumor necrosis factor (TNF) family has been implicated in the neurologic inflammatory diseases multiple sclerosis (MS) and experimental allergic encephalomyelitis (EAE). To determine the role of individual family members in EAE, C57BL/6 mice, LT-α–deficient (LT-α−/− mice), or LT-β–deficient (LT-β−/− mice), and their wild-type (WT) littermates were immunized with rat myelin oligodendrocyte glycoprotein (MOG) peptide 35-55. C57BL/6 and WT mice developed chronic, sustained paralytic disease with average maximum clinical scores of 3.5 and disease indices (a measure of day of onset and sustained disease scores) ranging from 367 to 663 with central nervous system (CNS) inflammation and demyelination. LT-α−/− mice were primed so that their splenic lymphocytes proliferated in response to MOG 35-55 and the mice produced anti-MOG antibody. However, LT-α−/− mice were quite resistant to EAE with low average clinical scores (<1), an average disease index of 61, and the negligible CNS inflammation and demyelination. WT T cells transferred EAE to LT-α−/− recipients. LT-β−/− mice were susceptible to EAE, though less than WT, with an average maximum clinical score of 1.9 and disease index of 312. These data implicate T cell production of LT-α in MOG EAE and support a major role for LT-α3, a minor role for the LT-α/β complex, and by inference, no role for TNF-α.
Selective Histocompatibility Leukocyte Antigen (Hla)-A2 Loss Caused by Aberrant Pre-mRNA Splicing in 624mel28 Melanoma Cells
Authors: Wang Zhigang , Marincola Francesco M. , Rivoltini Licia , Parmiani Giorgio , Ferrone Soldano
Published: July 2002

Histocompatibility leukocyte antigen (HLA)-A2 is used as a restricting element to present several melanoma-associated antigen (MAA)-derived peptides to cytotoxic T lymphocytes (CTLs). HLA-A2 antigen is selectively lost in primary melanoma lesions and more frequently in metastases. Only scanty information is available about the molecular mechanisms underlying this abnormality, in spite of its potentially negative impact on the clinical course of the disease and on the outcome of T cell–based immunotherapy. Therefore, in this study we have shown that the selective HLA-A2 antigen loss in melanoma cells 624MEL28 is caused by a splicing defect of HLA-A2 pre-mRNA because of a base substitution at the 5′ splice donor site of intron 2 of the HLA-A2 gene. As a result, HLA-A2 transcripts are spliced to two aberrant forms, one with exon 2 skipping and the other with intron 2 retention. The latter is not translated because of an early premature stop codon in the retained intron. In contrast, the transcript with exon 2 skipping is translated to a truncated HLA-A2 heavy chain without the α1 domain. Such a polypeptide is synthesized in vitro but is not detectable in cells, probably because of the low steady state level of the corresponding mRNA and the low translation efficiency. These results indicate that a single mutational event in an HLA class I gene is sufficient for loss of the corresponding allele. This may account, at least in part, for the high frequency of selective HLA class I allele loss in melanoma cells. Our conclusion emphasizes the need to implement active specific immunotherapy with a combination of peptides presented by various HLA class I alleles. This strategy may counteract the ability of melanoma cells with selective HLA class I allele loss to escape from immune recognition.
Suppression of T and B Lymphocyte Activation by a Yersinia pseudotuberculosis Virulence Factor, Yoph
Authors: Yao Tony , Mecsas Joan , Healy James I. , Falkow Stanley , Chien Yueh-hsiu
Published: July 2002

The acquired immune responses are crucial to the survival of Yersinia-infected animals. Mice lacking T cells are sensitive to Yersinia infection, and a humoral response to Yersinia can be protective. Diverse mechanisms for Yersinia to impair and evade the host innate immune defense have been suggested, but the effects of Yersinia on lymphocytes are not known. Here, we demonstrate that after a transient exposure to Y. pseudotuberculosis, T and B cells are impaired in their ability to be activated through their antigen receptors. T cells are inhibited in their ability to produce cytokines, and B cells are unable to upregulate surface expression of the costimulatory molecule, B7.2, in response to antigenic stimulation. The block of lymphocyte activation results from the inhibition of early phosphorylation events of the antigen receptor signaling complex. Through the use of Y. pseudotuberculosis mutants, we show that the inhibitory effect in both T cells and B cells is dependent on the production of Yersinia outermembrane protein (Yop) H, a tyrosine phosphatase. Our results suggest a mechanism by which the pathogenic bacteria may modulate a wide range of T and B cell–mediated immune responses.
Age-Associated Characteristics of Murine Hematopoietic Stem Cells
Authors: Sudo Kazuhiro , Ema Hideo , Morita Yohei , Nakauchi Hiromitsu
Published: July 2002

Little is known of age-associated functional changes in hematopoietic stem cells (HSCs). We studied aging HSCs at the clonal level by isolating CD34−/lowc-Kit+Sca-1+ lineage marker–negative (CD34−KSL) cells from the bone marrow of C57BL/6 mice. A population of CD34−KSL cells gradually expanded as age increased. Regardless of age, these cells formed in vitro colonies with stem cell factor and interleukin (IL)-3 but not with IL-3 alone. They did not form day 12 colony-forming unit (CFU)-S, indicating that they are primitive cells with myeloid differentiation potential. An in vivo limiting dilution assay revealed that numbers of multilineage repopulating cells increased twofold from 2 to 18 mo of age within a population of CD34−KSL cells as well as among unseparated bone marrow cells. In addition, we detected another compartment of repopulating cells, which differed from HSCs, among CD34−KSL cells of 18-mo-old mice. These repopulating cells showed less differentiation potential toward lymphoid cells but retained self-renewal potential, as suggested by secondary transplantation. We propose that HSCs gradually accumulate with age, accompanied by cells with less lymphoid differentiation potential, as a result of repeated self-renewal of HSCs.
Absence of Monocyte Chemoattractant Protein 1 in Mice Leads to Decreased Local Macrophage Recruitment and Antigen-Specific T Helper Cell Type 1 Immune Response in Experimental Autoimmune Encephalomyelitis
Authors: Huang DeRen , Wang Jintang , Kivisakk Pia , Rollins Barrett J. , Ransohoff Richard M.
Published: July 2002

Monocyte chemoattractant protein (MCP)-1 plays a critical role in innate immunity by directing the migration of monocytes into inflammatory sites. Recent data indicated a function for this chemokine in adaptive immunity as a regulator of T cell commitment to T helper cell type 2 (Th2) effector function. Studies in a Th1-dependent animal model, experimental autoimmune encephalomyelitis (EAE), showed that MCP-1 was highly expressed in the central nervous system (CNS) of affected rodents, and MCP-1 antibodies could block relapses of the disease. Mice deficient for the major MCP-1 receptor, CC chemokine receptor (CCR)2, did not develop EAE after active immunization but generated effector cells that could transfer the disease to naive wild-type recipients. We analyzed EAE in mice deficient for MCP-1 to define the relevant ligand for CCR2, which responds to murine MCP-1, MCP-2, MCP-3, and MCP-5. We found that C57BL/6 MCP-1–null mice were markedly resistant to EAE after active immunization, with drastically impaired recruitment of macrophages to the CNS, yet able to generate effector T cells that transferred severe disease to naive wild-type recipients. By contrast, adoptive transfer of primed T cells from wild-type mice into naive MCP-1–null recipients did not mediate clinical EAE. On the SJL background, disruption of the MCP-1 gene produced a milder EAE phenotype with diminished relapses that mimicked previous findings using anti–MCP-1 antibodies. There was no compensatory upregulation of MCP-2, MCP-3, or MCP-5 in MCP-1–null mice with EAE. These results indicated that MCP-1 is the major CCR2 ligand in mice with EAE, and provided an opportunity to define the role of MCP-1 in EAE. Compared with wild-type littermates, MCP-1−/− mice exhibited reduced expression of interferon γ in draining lymph node and CNS and increased antigen-specific immunoglobulin G1 antibody production. Taken together, these data demonstrate that MCP-1 is crucial for Th1 immune responses in EAE induction and that macrophage recruitment to the inflamed CNS target organ is required for primed T cells to execute a Th1 effector program in EAE.
The Contribution of Accessory Toxins of Vibrio cholerae O1 El Tor to the Proinflammatory Response in a Murine Pulmonary Cholera Model
Authors: Fullner Karla Jean , Boucher John C. , Hanes Martha A. , Haines G. Kenneth , Meehan Brian M. , Walchle Cynthia , Sansonetti Philippe J. , Mekalanos John J.
Published: July 2002

The contribution of accessory toxins to the acute inflammatory response to Vibrio cholerae was assessed in a murine pulmonary model. Intranasal administration of an El Tor O1 V. cholerae strain deleted of cholera toxin genes (ctxAB) caused diffuse pneumonia characterized by infiltration of PMNs, tissue damage, and hemorrhage. By contrast, the ctxAB mutant with an additional deletion in the actin-cross-linking repeats-in-toxin (RTX) toxin gene (rtxA) caused a less severe pathology and decreased serum levels of proinflammatory molecules interleukin (IL)-6 and murine macrophage inflammatory protein (MIP)-2. These data suggest that the RTX toxin contributes to the severity of acute inflammatory responses. Deletions within the genes for either hemagglutinin/protease (hapA) or hemolysin (hlyA) did not significantly affect virulence in this model. Compound deletion of ctxAB, hlyA, hapA, and rtxA created strain KFV101, which colonized the lung but induced pulmonary disease with limited inflammation and significantly reduced serum titers of IL-6 and MIP-2. 100% of mice inoculated with KFV101 survive, compared with 20% of mice inoculated with the ctxAB mutant. Thus, the reduced virulence of KFV101 makes it a prototype for multi-toxin deleted vaccine strains that could be used for protection against V. cholerae without the adverse effects of the accessory cholera toxins.
Gat1 (Gaba:Na+:Cl−) Cotransport Function
Authors: Hilgemann Donald W. , Lu Chin-Chih
Published: July 2002

We have developed an alternating access transport model that accounts well for GAT1 (GABA:Na+:Cl−) cotransport function in Xenopus oocyte membranes. To do so, many alternative models were fitted to a database on GAT1 function, and discrepancies were analyzed. The model assumes that GAT1 exists predominantly in two states, Ein and Eout. In the Ein state, one chloride and two sodium ions can bind sequentially from the cytoplasmic side. In the Eout state, one sodium ion is occluded within the transporter, and one chloride, one sodium, and one γ-aminobutyric acid (GABA) molecule can bind from the extracellular side. When Ein sites are empty, a transition to the Eout state opens binding sites to the outside and occludes one extracellular sodium ion. This conformational change is the major electrogenic GAT1 reaction, and it rate-limits forward transport (i.e., GABA uptake) at 0 mV. From the Eout state, one GABA can be translocated with one sodium ion to the cytoplasmic side, thereby forming the *Ein state. Thereafter, an extracellular chloride ion can be translocated and the occluded sodium ion released to the cytoplasm, which returns the transporter to the Ein state. GABA–GABA exchange can occur in the absence of extracellular chloride, but a chloride ion must be transported to complete a forward transport cycle. In the reverse transport cycle, one cytoplasmic chloride ion binds first to the Ein state, followed by two sodium ions. One chloride ion and one sodium ion are occluded together, and thereafter the second sodium ion and GABA are occluded and translocated. The weak voltage dependence of these reactions determines the slopes of outward current–voltage relations. Experimental results that are simulated accurately include (a) all current–voltage relations, (b) all substrate dependencies described to date, (c) cis–cis and cis–trans substrate interactions, (d) charge movements in the absence of transport current, (e) dependencies of charge movement kinetics on substrate concentrations, (f) pre–steady state current transients in the presence of substrates, (g) substrate-induced capacitance changes, (h) GABA–GABA exchange, and (i) the existence of inward transport current and GABA–GABA exchange in the nominal absence of extracellular chloride.
Sequential Choice in Group Settings: Taking the Road Less Traveled and Less Enjoyed
Authors: Ariely Dan , Levav Jonathan
Published: July 2002

Many individual decisions take place in a group context wherein group members voice their choices sequentially. In this article we examine the impact of this dynamic decision process on individuals' choices and satisfaction with their outcomes. We propose that choices reflect a balancing of two classes of goals: goals that are strictly individual and goals that are triggered by the existence of the group. The latter sometimes results in choices that undermine personal satisfaction and increase regret. We find support for goal balancing in three studies in which we tracked consumers' orders of dishes and drinks. In the Lunch study we found that real groups (tables) choose more varied dishes than would be expected by random sampling of the population of all individual choices across all tables. The Beer study demonstrates that this group-level variety seeking is attributable to the interaction—implicit or explicit—among group members, and can be dissipated when the group is forced to “disband” and its members make strictly individual choices. Finally, the Wine study demonstrated that individual choices in a group context are also aimed at satisfying goals of information gathering and self-presentation in the form of uniqueness.
The rapid evolution of scholarly communication
Authors: Odlyzko Andrew
Published: July 2002

Traditional journals, even those available electronically, are changing slowly. However, there is rapid evolution in scholarly communication. Usage is moving to electronic formats. In some areas, it appears that electronic versions of papers are being read about as often as the printed journal versions. Although there are serious difficulties in comparing figures from different media, the growth rates in usage of electronic scholarly information are sufficiently high that if they continue for a few years, there will be no doubt that print versions will be eclipsed. Further, much of the electronic information that is accessed is outside the formal scholarly publication process. There is also vigorous growth in forms of electronic communication that take advantage of the unique capabilities of the web, and which simply do not fit into the traditional journal publishing format. This paper presents some statistics on usage of print and electronic information. It also discusses some preliminary evidence about the changing patterns of usage. It appears that much of the online usage comes from new readers (esoteric research papers assigned in undergraduate classes, for example) and often from places that do not have access to print journals. Also, the reactions to even slight barriers to usage suggest that even high‐quality scholarly papers are not irreplaceable. Readers are faced with a ‘river of knowledge’ that allows them to select among a multitude of sources, and to find near substitutes when necessary. To stay relevant, scholars, publishers and librarians will have to make even greater efforts to make their material easily accessible.
Eigenvalue asymptotics and exponential decay of eigenfunctions for Schrödinger operators with magnetic fields
Authors: Shen Zhongwei
Published: July 2002

We consider the Schrödinger operator with magnetic field,
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="upper H equals left-parenthesis StartFraction 1 Over i EndFraction nabla minus ModifyingAbove a With right harpoon with barb up left-parenthesis x right-parenthesis right-parenthesis squared plus upper V left-parenthesis x right-parenthesis in double-struck upper R Superscript n Baseline period">

H
=
(

1
i

∇
−

a
⇀

(
x
)

)

2

+
V
(
x
)
 in 

R

n

.

\begin{equation*}H=(\frac {1}{i}\nabla -{\overset {\rightharpoonup }{a}}(x))^{2}+V(x) \text { in } \mathbb {R}^{n}. \end{equation*}

Assuming that

V
≥
0

V\ge 0

and

|

curl

a
⇀

|

+
V
+
1

|\text {curl}\, \overset {\rightharpoonup }{a}|+V+1

is locally in certain reverse Hölder class, we study the eigenvalue asymptotics and exponential decay of eigenfunctions.
On Matroids Representable over 𝐺𝐹(3) and Other Fields
Authors: Whittle Geoff
Published: July 2002

The matroids that are representable over

G
F
(
3
)

GF(3)

and some other fields depend on the choice of field. This paper gives matrix characterisations of the classes that arise. These characterisations are analogues of the characterisation of regular matroids as the ones that can be represented over the rationals by a totally-unimodular matrix. Some consequences of the theory are as follows. A matroid is representable over

G
F
(
3
)

GF(3)

and

G
F
(
5
)

GF(5)

if and only if it is representable over

G
F
(
3
)

GF(3)

and the rationals, and this holds if and only if it is representable over

G
F
(
p
)

GF(p)

for all odd primes

p
p

. A matroid is representable over

G
F
(
3
)

GF(3)

and the complex numbers if and only if it is representable over

G
F
(
3
)

GF(3)

and

G
F
(
7
)

GF(7)

. A matroid is representable over

G
F
(
3
)

GF(3)

,

G
F
(
4
)

GF(4)

and

G
F
(
5
)

GF(5)

if and only if it is representable over every field except possibly

G
F
(
2
)

GF(2)

. If a matroid is representable over

G
F
(
p
)

GF(p)

for all odd primes

p
p

, then it is representable over the rationals.
Hyperbolic groups and free constructions
Authors: Kharlampovich O. , Myasnikov A.
Published: July 2002

It is proved that the property of a group to be hyperbolic is preserved under HHN-extensions and amalgamated free products provided the associated (amalgamated) subgroups satisfy certain conditions. Some more general results about the preservation of hyperbolicity under graph products are also obtained. Using these results we describe the

Q

\mathbf {Q}

-completion

(

Q

(\mathbf {Q}

is the field of rationals)

G

Q

G^{\mathbf {Q}}

of a torsion-free hyperbolic group

G
G

as a union of an effective chain of hyperbolic subgroups, and solve the conjugacy problem in

G

Q

G^{\mathbf {Q}}

.
Tensor product Gauss-Lobatto points are Fekete points for the cube
Authors: Bos L. , Taylor M. , Wingate B.
Published: July 2002

Tensor products of Gauss-Lobatto quadrature points are frequently used as collocation points in spectral element methods. Unfortunately, it is not known if Gauss-Lobatto points exist in non-tensor-product domains like the simplex. In this work, we show that the

n
n

-dimensional tensor-product of Gauss-Lobatto quadrature points are also Fekete points. This suggests a way to generalize spectral methods based on Gauss-Lobatto points to non-tensor-product domains, since Fekete points are known to exist and have been computed in the triangle and tetrahedron. In one dimension this result was proved by Fejér in 1932, but the extension to higher dimensions in non-trivial.
Grx5 Is a Mitochondrial Glutaredoxin Required for the Activity of Iron/Sulfur Enzymes
Authors: Rodrı́guez-Manzaneque Marı́a Teresa , Tamarit Jordi , Bellı́ Gemma , Ros Joaquim , Herrero Enrique
Published: July 2002

Yeast cells contain a family of three monothiol glutaredoxins: Grx3, 4, and 5. Absence of Grx5 leads to constitutive oxidative damage, exacerbating that caused by external oxidants. Phenotypic defects associated with the absence of Grx5 are suppressed by overexpression ofSSQ1 and ISA2, two genes involved in the synthesis and assembly of iron/sulfur clusters into proteins. Grx5 localizes at the mitochondrial matrix, like other proteins involved in the synthesis of these clusters, and the mature form lacks the first 29 amino acids of the translation product. Absence of Grx5 causes: 1) iron accumulation in the cell, which in turn could promote oxidative damage, and 2) inactivation of enzymes requiring iron/sulfur clusters for their activity. Reduction of iron levels in grx5 null mutants does not restore the activity of iron/sulfur enzymes, and cell growth defects are not suppressed in anaerobiosis or in the presence of disulfide reductants. Hence, Grx5 forms part of the mitochondrial machinery involved in the synthesis and assembly of iron/sulfur centers.
Associations among 5-Year Changes in Weight, Physical Activity, and Cardiovascular Disease Risk Factors in Mexican Americans
Authors: Rainwater David L. , Mitchell Braxton D. , Comuzzie Anthony G. , VandeBerg John L. , Stern Michael P. , MacCluer Jean W.
Published: July 2002

Recent changes in lifestyle have led to a global epidemic of obesity. To determine the associations of these changes with cardiovascular disease (CVD) risk, the authors correlated changes in CVD risk factors with changes in weight and physical activity in a population-based sample of 539 Mexican Americans in the San Antonio Heart Study in 1992–1999 who were examined twice approximately 5 years apart. Average weight change during that interval was 2.7 kg. While change in physical activity (expressed as percent change) was associated modestly only with change in low density lipoprotein cholesterol median diameter (p = 0.017), weight change was strongly and positively associated with unfavorable changes in lipid and lipoprotein traits, insulin levels, and blood pressure, explaining 2–10% of the variation in the risk factor changes during the interval. The unfavorable associations with weight gain tended to be more pronounced in lean compared with obese individuals and in men compared with women. However, the associations were significant for most CVD risk factors in all groups. In Mexican Americans, a population at high risk for obesity, weight change was positively correlated with metabolic variables associated with risk of CVD. Therefore, increasing adiposity in this population may tend to slow, or even reverse, the decline in CVD morbidity and mortality. Am J Epidemiol 2000;152:974–82.
Genetic network inference: from co-expression clustering to

reverse engineering
Authors: D’haeseleer Patrik , Liang Shoudan , Somogyi Roland
Published: July 2002

motivation: Advances in molecular biological, analytical and computational technologies are enabling us to systematically investigate the complex molecular processes underlying biological systems. In particular, using high-throughput gene expression assays, we are able to measure the output of the gene regulatory network. We aim here to review datamining and modeling approaches for conceptualizing and unraveling the functional relationships implicit in these datasets. Clustering of co-expression profiles allows us to infer shared regulatory inputs and functional pathways. We discuss various aspects of clustering, ranging from distance measures to clustering algorithms and multiple-cluster memberships. More advanced analysis aims to infer causal connections between genes directly, i.e. who is regulating whom and how. We discuss several approaches to the problem of reverse engineering of genetic networks, from discrete Boolean networks, to continuous linear and non-linear models. We conclude that the combination of predictive modeling with systematic experimental verification will be required to gain a deeper insight into living organisms, therapeutic targeting and bioengineering.

Contact: patrik@cs.unm.edu; sliang@mail.arc.nasa.gov; rsomogyi@incyte.com
SACS—Self-maintaining database of antibody crystal
structure information
Authors: Allcorn Lee C. , Martin Andrew C. R.
Published: July 2002

Motivation: The rapid increase in the number of structures in the Protein Databank (PDB) makes it difficult to find all structures in a given protein class. Automatically-maintained web-based summaries are one solution to this problem.

Results: Summary of Antibody Crystal Structures (SACS), a self-maintaining web-site containing summary information on antibody structures in the PDB, is described. Mirrored PDB data are processed automatically using a Make-based system to identify new antibody structures. The PDB header records and sequence data are then parsed to identify a number of features of the structure and the data are stored using eXtensible Markup Language (XML). eXtensible Stylesheet Language: Transformations (XSLT), a new style sheet language for XML, is used to generate Hypertext Markup Language (HTML) pages containing either a one-line summary of every structure or a more detailed page describing a single antibody.

Availability: The pages are accessible at http://www.bioinf.org.uk/abs/sacs/or http://www.rubic.rdg.ac.uk/abs/sacs/

Contact: a.c.r.martin@reading.ac.uk; andrew@bioinf.org.uk

* To whom correspondence should be addressed.
LigBase: a database of families of aligned ligand binding sites
in known protein sequences and structures
Authors: Stuart Ashley C. , Ilyin Valentin A. , Sali Andrej
Published: July 2002

Summary: A database comprising all ligand-binding sites of known structure aligned with all related protein sequences and structures is described. Currently, the database contains approximately 50000 ligand-binding sites for small molecules found in the Protein Data Bank (PDB). The structure–structure alignments are obtained by the Combinatorial Extension (CE) program (Shindyalov and Bourne, Protein Eng. , 11, 739–747, 1998) and sequence–structure alignments are extracted from the ModBase database of comparative protein structure models for all known protein sequences (Sanchez et al. , Nucleic Acids Res. , 28, 250–253, 2000). It is possible to search for binding sites in LigBase by a variety of criteria. LigBase reports summarize ligand data including relevant structural information from the PDB file, such as ligand type and size, and contain links to all related protein sequences in the TrEMBL database. Residues in the binding sites are graphically depicted for comparison with other structurally defined family members. LigBase provides a resource for the analysis of families of related binding sites.

Availability: LigBase is accessible on the web at http://guitar.rockefeller.edu/ligbase.

Contact: ash@guitar.rockefeller.edu; sali@rockefeller.edu

* To whom correspondence should be addressed.
The Sulfinator: predicting tyrosine sulfation sites in
protein sequences
Authors: Monigatti Flavio , Gasteiger Elisabeth , Bairoch Amos , Jung Eva
Published: July 2002

Summary: Protein tyrosine sulfation is an important post-translational modification of proteins that go through the secretory pathway. No clear-cut acceptor motif can be defined that allows the prediction of tyrosine sulfation sites in polypeptide chains. The Sulfinator is a software tool that can be used to predict tyrosine sulfation sites in protein sequences with an overall accuracy of 98%. Four different Hidden Markov Models were constructed, each of them specialized to recognize sulfated tyrosine residues depending on their location within the sequence: near the N-terminus, near the C-terminus, in the center of a window with a size of at least 25 amino acids, as well as in windows containing several tyrosine residues.

Availability: The Sulfinator is accessible at (http://www.expasy.org/tools/sulfinator/).

Supplementary information: Sulfinator documentation is accessible at (http://www.expasy.org/tools/sulfinator/sulfinator-doc.html).

Abbreviations: SWP: SWISS-PROT accession number.

* To whom correspondence should be addressed.
THE EFFECT OF OPEN SPACES ON A HOME'S SALE PRICE
Authors: Lutzenhiser Margot , Netusil Noelwah R.
Published: July 2002

The relationship between a home's sale price and its proximity to different open spaces types is explored using a data set comprised of single‐family home sales in the city of Portland, within Multnomah County, between 1990 and 1992. Homes located within 1,500 feet of a natural area park, where more than 50% of the park is preserved in native and/or natural vegetation, are found to experience, on average, the largest increase in sale price. The open space size that maximizes a home's sale price is calculated for each open space type. Natural area parks require the largest acreage to maximize sale price, and specialty parks are found to have the largest potential effect on a home's sale price. A zonal approach is used to examine the relationship between a home's sale price and its distance to an open space. Natural area parks and specialty parks are found to have a positive and statistically significant effect on a home's sale price for each zone studied. Homes located adjacent to golf courses (within 200 feet) are estimated to experience the largest increase in sale price due to open space proximity although the effect drops off quickly as distance from the golf course increases.
WHAT ATTRACTS FOREIGN MULTINATIONAL CORPORATIONS TO CHINA?
Authors: Zhang Kevin Honglin
Published: July 2002

After adopting the open‐door policy, China experienced a boom of inward foreign direct investment (FDI) by multinational corporations. This article attempts to assess effects of location characteristics and government policies on FDI flows during the period 1987–98. A model of FDI determinants is specified and estimated with cross‐section and panel data. The estimates indicate that China's huge market size, liberalized FDI regime, and improving infrastructure are attractive to multinationals. The regional distribution of FDI within China is influenced largely by FDI incentives and historical‐cultural links with foreign investors, along with other location factors.
Automation, Transfer Machinery, and Mass Production in the U.S.
Automobile Industry in the Post–World War II Era
Authors: Hounshell David A.
Published: July 2002

First experimented with in the 1920s and 1930s in the production of
automobile engines, transfer machines became dominant in U.S. engine plants
in the 1940s and 1950s, as automakers invested heavily in this equipment to
meet pent-up demand following the war. Transfer machines thus became
identified with “Detroit automation”. But with the advent of a “horsepower
race”, firms found that transfer machines could not accommodate even minor
changes in design. Late in the 1950s the industry developed and applied
“building-block automation” to transfer machines to attain greater
flexibility. Examining these developments contributes to our understanding
of both specific industries and the general history of mass production and
its alternatives.
The Chocolates of Sucre: Stories of a Bolivian Industry
Authors: Eversole Robyn
Published: July 2002

Chocolate is a Sucre trademark, one of the few products that this Bolivian city regularly markets to other parts of the country. Despite Sucre's long history of chocolate production, however, the city's chocolate industry at the turn of the twenty-first century remains small, unable to export, and generally uncompetitive with products from neighboring countries. Yet Sucre's chocolate-making enterprises have not disappeared; they continue to produce on a small scale in the face of mass-produced, imported brands. In this article, the history of Sucre's chocolate industry is examined to shed light on larger issues of industrial development and “underdevelopment” in Sucre and on the roots of the city's strong artisan identity.
Cold War Armory: Military Contracting in Silicon Valley
Authors: Heinrich Thomas
Published: July 2002

Silicon Valley is frequently portrayed as a manifestation of postindustrial entrepreneurship, where ingenious inventor-businessmen and venture capitalists forged a dynamic, high-tech economy unencumbered by government's “heavy hand.” Closer examination reveals that government played a major role in launching and sustaining some of the region's core industries through military contracting. Focusing on leading firms in the microwave electronics, missile, satellite, and semiconductor industries, this article argues that demand for customized military technology encouraged contractors to embark on a course of flexible specialization, batch production, and continuous innovation. Thriving throughout much of the Cold War, major military contractors fell on hard times when defense markets started to shrink in the late 1980s, because specialized design and production capabilities were rarely applicable to civilian product lines. But Pentagon funding for research and development helped lay the technological groundwork for a new generation of startups, contributing to Silicon Valley's economic renaissance in the 1990s.
Blood vessel maturation in a 3‐dimensional spheroidal coculture model: direct contact with smooth muscle cells regulates endothelial cell quiescence and abrogates VEGF responsiveness
Authors: KORFF THOMAS , KIMMINA SARAH , MARTINY‐BARON GEORG , AUGUSTIN HELLMUT G.
Published: July 2002

Paracrine interactions between endothelial cells (EC) and mural cells act as critical regulators of vessel wall assembly, vessel maturation and define a plasticity window for vascular remodeling. The present study was aimed at studying blood vessel maturation processes in a novel 3‐dimensional spheroidal coculture system of EC and smooth muscle cells (SMC). Coculture spheroids differentiate spontaneously in a calciumdependent manner to organize into a core of SMC and a surface layer of EC, thus mimicking the physiological assembly of blood vessels with surface lining EC and underlying mural cells. Coculture of EC with SMC induces a mature, quiescent EC phenotype as evidenced by 1) a significant increase in the number of junctional complexes of the EC surface layer, 2) a down‐regulation of PDGF‐B expression by cocultured EC, and 3) an increased resistance of EC to undergo apoptosis. Furthermore, EC cocultured with SMC become refractory to stimulation with VEGF (lack of CD34 expression on VEGF stimulation;inability to form capillary‐like sprouts in a VEGF‐dependent manner in a 3‐dimensional in gel angiogenesis assay). In contrast, costimulation with VEGF and Ang‐2 induced sprouting angiogenesis originating from coculture spheroids consistent with a model of Ang‐2‐mediated vessel destabilization resulting in VEGF responsiveness. Ang‐2 on its own was able to stimulate endothelial cells in the absence of Ang‐1 producing SMC, inducing lateral sheet migration as well as in gel sprouting angiogenesis. Taken together, the data establish the spheroidal EC/SMC system as a powerful cell culture model to study paracrine interactions in the vessel wall and provide functional evidence for smooth muscle cell‐mediated quiescence effects on endothelial cells.—Korff, T., Kimmina, S., Martiny‐Baron, G., Augustin, H. G. Blood vessel maturation in a 3‐dimensional spheroidal coculture model: direct contact with smooth muscle cells regulates endothelial cell quiescence and abrogates VEGF responsiveness. FASEB J. 15, 447‐457 (2001)
Nitrite–dependent nitric oxide production pathway: implications for involvement of active nitrogen species in photoinhibitionin vivo
Authors: Yamasaki Hideo
Published: July 2002

Air pollution studies have shown that nitric oxide (NO), a gaseous free radical, is a potent photosynthetic inhibitor that reduces CO2uptake activity in leaves. It is now recognized that NO is not only an air pollutant but also an endogenously produced metabolite, which may play a role in regulating plant cell functions. Although many studies have suggested the presence of mammalian–type NO synthase (NOS) in plants, the source of NO is still not clear. There has been a number of studies indicating that plant cells possess a nitrite–dependent NO production pathway which can be distinguished from the NOS–mediated reaction. Nitrate reductase (NR) has been recently found to be capable of producing NO through oneelectron reduction of nitrite using NAD(P)H as an electron donor. This review focuses on current understanding of the mechanism for the nitrite–dependent NO production in plants. Impacts of NO produced by NR on photosynthesis are discussed in association with photo–oxidative stress in leaves.
Monte Carlo calculation of nine megavoltage photon beam spectra using the BEAM code
Authors: Sheikh‐Bagheri Daryoush , Rogers D. W. O.
Published: July 2002

A recent paper analyzed the sensitivity to various simulation parameters of the Monte Carlo simulations of nine beams from three major manufacturers of commercial medical linear accelerators, ranging in energy from 4–25 MV. In this work the nine models are used: to calculate photon energy spectra and average energy distributions and compare them to those published by Mohan et al. [Med. Phys. 12, 592–597 (1985)]; to separate the spectra into primary and scatter components from the primary collimator, the flattening filter and the adjustable collimators; and to calculate the contaminant‐electron fluence spectra and the electron contribution to the depth‐dose curves. Notwithstanding the better precision of the calculated spectra, they are similar to those calculated by Mohan et al. The three photon spectra at 6 MV from the machines of three different manufacturers show differences in their shapes as well as in the efficiency of bremsstrahlung production in the corresponding target and filter combinations. The contribution of direct photons to the photon energy fluence in a field varies between 92% and 97%, where the primary collimator contributes between 0.6% and 3.4% and the flattening filter contributes between 0.6% and 4.5% to the head‐scatter energy fluence. The fluence of the contaminant electrons at 100 cm varies between and per incident electron on target, and the corresponding spectrum for each beam is relatively invariant inside a field. On the surface the dose from electron contamination varies between 5.7% and 11% of maximum dose and, at the depth of maximum dose, between 0.16% and 2.5% of maximum dose. The photon component of the percentage depth‐dose at 10 cm depth is compared with the general formula provided by AAPM's task group 51 and confirms the claimed accuracy of 2%.
Autoresonant (nonstationary) excitation of pendulums, Plutinos, plasmas, and other nonlinear oscillators
Authors: Fajans J. , Frièdland L.
Published: July 2002

A weakly driven pendulum cannot be strongly excited by a fixed frequency drive. The only way to strongly excite the pendulum is to use a drive whose frequency decreases with time. Feedback is often used to control the rate at which the frequency decreases. Feedback need not be employed, however; the drive frequency can simply be swept downwards. With this method, the drive strength must exceed a threshold proportional to the sweep rate raised to the 3/4 power. This threshold has been discovered only recently, and holds for a very broad class of driven nonlinear oscillators. The threshold may explain the abundance of 3:2 resonances and dearth of 2:1 resonances observed between the orbital periods of Neptune and the Plutinos (Pluto and many of the Kuiper Belt objects), and has been extensively investigated in the Diocotron system in pure-electron plasmas.
Dynamic light scattering
Authors: Goldburg W. I.
Published: July 2002

By scattering light from small particles, their geometrical structure and their state of motion can be measured. An experiment is described for measuring the diffusivity of small particles undergoing Brownian motion using the technique called photon correlation spectroscopy or dynamic light scattering. The necessary experimental apparatus and the related theory are discussed. Photon correlation spectroscopy is a powerful tool for studying the dynamical behavior of fluids near critical points, and a discussion is given of this phenomenon. The same experimental technique also can be used to study laminar or turbulent flows, and the associated theory is introduced to enable such experiments to be interpreted.
Behavior of first guided wave on finite cylindrical shells of various lengths: Experimental investigation
Authors: Haumesser Lionel , Baillard André , Décultot Dominique , Maze Gérard
Published: July 2002

Acoustic backscattering from elastic cylindrical shells of finite lengths, immersed in water, is investigated. These objects, characterized by the ratio of length over diameter (L/2a=9.76, 4.88, 2.44, a: outer radius), are excited by an obliquely incident plane acoustic wave. In the three cases studied here, the radii ratio b/a (b: inner radius) is fixed at 0.97. The investigated dimensionless frequency range extends over 10⩽k1a⩽50 (k1: wave number in water). The first guided wave, T0, is of particular interest here. The influence of the shell’s length on the backscattered pressure is experimentally observed in the time-angle and frequency-angle representations. In support of this experimental study, a time-domain representation is used by extending a theoretical model that provides a geometrical description of the helical propagation of the surface waves around the shell [Bao, J. Acoust. Soc. Am. 94, 1461–1466 (1993)]. Theoretical results on cylindrical shells considered as infinitely long, with identical characteristics, are compared with both experimental representations.
System identification of feedback in hearing aids
Authors: Hellgren Johan , Lunner Thomas , Arlinger Stig
Published: July 2002

The feedback problems of behind the ear (BTE), in the ear (ITE), and in the ear canal (ITEC) hearing aid categories have been investigated. All possible feedback paths (acoustical via vent, via tubing wall, mechanical, etc.) were converted to a single transfer function from the ear canal to the hearing aid microphone, here called the acoustic feedback equivalent (AFE). The attenuation of the AFE represents the maximum gain that can be used without the hearing aid starting to howl. Magnitude and phase responses of the AFE were identified on ten human subjects and on a Knowles ear manikin (KEMAR). The acoustic feedback via vent and leak between earmould and ear canal dominated the AFE. The transfer function from a reference point under the ear to the position of microphone of the different hearing aid categories was identified and used together with the AFE to calculate the maximum real ear aided gain (REAG) for the hearing aid categories. A model of the AFE, consisting of a fourth-order filter together with a delay, showed good agreement with the measured data.
Discrimination of amplitude-modulation phase spectrum
Authors: Lorenzi Christian , Berthommier Frédéric , Demany Laurent
Published: July 2002

Listeners were asked to discriminate between two amplitude-modulation functions imposed on white noise and consisting of the sum of two sinusoids. The frequency ratio of the sinusoids constituting each function was 2 or 3. In one function, the sinusoids had a constant relative phase. In the other function, their phase relation was continuously and cyclically changing, at a slow rate. For all listeners, the two functions with a frequency ratio of 2 were easily discriminated. However, discrimination was impossible when the frequency ratio was 3. Simulations were performed using an envelope-detector model and various decision statistics. The max/min statistic predicted discrimination above chance level when the frequency ratio was 3. It seems, therefore, that listeners are unable to use this statistic. In contrast, the crest factor and skewness of the envelope accounted well for the discrimination data.
On the determination of yield surfaces in Herschel–Bulkley fluids
Authors: Burgos Gilmer R. , Alexandrou Andreas N. , Entov Vladimir
Published: July 2002

Herschel–Bulkley fluids are materials that behave as rigid solids when the local stress τ is lower than a finite yield stress τ0, and flow as nonlinearly viscous fluids for τ>τ0. The flow domain then is characterized by two distinct areas, τ<τ0 and τ>τ0. The surface τ=τ0 is known as the yield surface. In this paper, by using analytic solutions for antiplane shear flow in a wedge between two rigid walls, we discuss the ability of regularized Herschel–Bulkley models such as the Papanastasiou, the bi-viscosity and the Bercovier and Engelman models in determining the topography of the yield surface. Results are shown for different flow parameters and compared to the exact solutions. It is concluded that regularized models with a proper choice of the regularizing parameters can be used to both predict the bulk flow and describe the unyielded zones. The Papanastasiou model predicts well the yield surface, while both the Papanastasiou and the bi-viscosity models predict well the stress field away from τ=τ0. The Bercovier and Engelman model is equivalent to the Papanastasiou model provided a proper choice of the regularization parameter δ is made. It is also demonstrated that in some cases the yield surface can be effectively recovered using an extrapolation procedure based upon an analytical representation of the solution.