bluuebunny/crossref_metadata_2025 huggingface dataset:
PI3P signaling regulates receptor sorting but not transport in the endosomal pathway
Authors: Petiot A. , Fauré J. , Stenmark H. , Gruenberg J.
Published: September 2003

While evidence is accumulating that phosphoinositide signaling plays a crucial role in growth factor and hormone receptor down-regulation, this signaling pathway has also been proposed to regulate endosomal membrane transport and multivesicular endosome biogenesis. Here, we have followed the fate of the down-regulated EGF receptor (EGFR) and bulk transport (fluid phase) markers in the endosomal pathway in vivo and in vitro. We find that bulk transport from early to late endosomes is not affected after inhibition of the phosphatidylinositol-3-phosphate (PI3P) signaling pathway, but that the EGFR then remains trapped in early endosomes. Similarly, we find that hepatocyte growth factor–regulated tyrosine kinase substrate (Hrs) is not directly involved in bulk solute transport, but is required for EGFR sorting. These observations thus show that transport and sorting can be uncoupled in the endosomal pathway. They also show that PI3P signaling does not regulate the core machinery of endosome biogenesis and transport, but controls the sorting of down-regulated receptor molecules in early endosomes via Hrs.
Clustering of multiple specific genes and gene-rich R-bands around SC-35 domains
Authors: Shopland Lindsay S. , Johnson Carol V. , Byron Meg , McNeil John , Lawrence Jeanne B.
Published: September 2003

Typically, eukaryotic nuclei contain 10–30 prominent domains (referred to here as SC-35 domains) that are concentrated in mRNA metabolic factors. Here, we show that multiple specific genes cluster around a common SC-35 domain, which contains multiple mRNAs. Nonsyntenic genes are capable of associating with a common domain, but domain “choice” appears random, even for two coordinately expressed genes. Active genes widely separated on different chromosome arms associate with the same domain frequently, assorting randomly into the 3–4 subregions of the chromosome periphery that contact a domain. Most importantly, visualization of six individual chromosome bands showed that large genomic segments (∼5 Mb) have striking differences in organization relative to domains. Certain bands showed extensive contact, often aligning with or encircling an SC-35 domain, whereas others did not. All three gene-rich reverse bands showed this more than the gene-poor Giemsa dark bands, and morphometric analyses demonstrated statistically significant differences. Similarly, late-replicating DNA generally avoids SC-35 domains. These findings suggest a functional rationale for gene clustering in chromosomal bands, which relates to nuclear clustering of genes with SC-35 domains. Rather than random reservoirs of splicing factors, or factors accumulated on an individual highly active gene, we propose a model of SC-35 domains as functional centers for a multitude of clustered genes, forming local euchromatic “neighborhoods.”
Importance of extra- and intracellular domains of TLR1 and TLR2 in NFκB signaling
Authors: Sandor Frantisek , Latz Eicke , Re Fabio , Mandell Leisa , Repik Galina , Golenbock Douglas T. , Espevik Terje , Kurt-Jones Evelyn A. , Finberg Robert W.
Published: September 2003

Recognition of ligands by toll-like receptor (TLR) 2 requires interactions with other TLRs. TLRs form a combinatorial repertoire to discriminate between the diverse microbial ligands. Diversity results from extracellular and intracellular interactions of different TLRs. This paper demonstrates that TLR1 and TLR2 are required for ara-lipoarabinomannan– and tripalmitoyl cysteinyl lipopeptide–stimulated cytokine secretion from mononuclear cells. Confocal microscopy revealed that TLR1 and TLR2 cotranslationally form heterodimeric complexes on the cell surface and in the cytosol. Simultaneous cross-linking of both receptors resulted in ligand-independent signal transduction. Using chimeric TLRs, we found that expression of the extracellular domains along with simultaneous expression of the intracellular domains of both TLRs was necessary to achieve functional signaling. The domains from each receptor did not need to be contained within a single contiguous protein. Chimeric TLR analysis further defined the toll/IL-1R domains as the area of crucial intracellular TLR1–TLR2 interaction.
The interaction of tropomodulin with tropomyosin stabilizes thin filaments in cardiac myocytes
Authors: Mudry Ryan E. , Perry Cynthia N. , Richards Meredith , Fowler Velia M. , Gregorio Carol C.
Published: September 2003

Actin (thin) filament length regulation and stability are essential for striated muscle function. To determine the role of the actin filament pointed end capping protein, tropomodulin1 (Tmod1), with tropomyosin, we generated monoclonal antibodies (mAb17 and mAb8) against Tmod1 that specifically disrupted its interaction with tropomyosin in vitro. Microinjection of mAb17 or mAb8 into chick cardiac myocytes caused a dramatic loss of the thin filaments, as revealed by immunofluorescence deconvolution microscopy. Real-time imaging of live myocytes expressing green fluorescent protein–α-tropomyosin and microinjected with mAb17 revealed that the thin filaments depolymerized from their pointed ends. In a thin filament reconstitution assay, stabilization of the filaments before the addition of mAb17 prevented the loss of thin filaments. These studies indicate that the interaction of Tmod1 with tropomyosin is critical for thin filament stability. These data, together with previous studies, indicate that Tmod1 is a multifunctional protein: its actin filament capping activity prevents thin filament elongation, whereas its interaction with tropomyosin prevents thin filament depolymerization.
Centrosome positioning in interphase cells
Authors: Burakov Anton , Nadezhdina Elena , Slepchenko Boris , Rodionov Vladimir
Published: September 2003

The position of the centrosome is actively maintained at the cell center, but the mechanisms of the centering force remain largely unknown. It is known that centrosome positioning requires a radial array of cytoplasmic microtubules (MTs) that can exert pushing or pulling forces involving MT dynamics and the activity of cortical MT motors. It has also been suggested that actomyosin can play a direct or indirect role in this process. To examine the centering mechanisms, we introduced an imbalance of forces acting on the centrosome by local application of an inhibitor of MT assembly (nocodazole), and studied the resulting centrosome displacement. Using this approach in combination with microinjection of function-blocking probes, we found that a MT-dependent dynein pulling force plays a key role in the positioning of the centrosome at the cell center, and that other forces applied to the centrosomal MTs, including actomyosin contractility, can contribute to this process.
Long continuous actin bundles in Drosophila bristles are constructed by overlapping short filaments
Authors: Guild Gregory M. , Connelly Patricia S. , Ruggiero Linda , Vranich Kelly A. , Tilney Lewis G.
Published: September 2003

The actin bundles essential for Drosophila bristle elongation are hundreds of microns long and composed of cross-linked unipolar filaments. These long bundles are built from much shorter modules that graft together. Using both confocal and electron microscopy, we demonstrate that newly synthesized modules are short (1–2 μm in length); modules elongate to ∼3 μm by growing over the surface of longitudinally adjacent modules to form a graft; the grafted regions are initially secured by the forked protein cross-bridge and later by the fascin cross-bridge; actin bundles are smoothed by filament addition and appear continuous and without swellings; and in the absence of grafting, dramatic alterations in cell shape occur that substitutes cell width expansion for elongation. Thus, bundle morphogenesis has several components: module formation, elongation, grafting, and bundle smoothing. These actin bundles are much like a rope or cable, made by overlapping elements that run a small fraction of the overall length, and stiffened by cross-linking.
Erythropoietin Selectively Attenuates Cytokine Production and Inflammation in Cerebral Ischemia by Targeting Neuronal Apoptosis
Authors: Villa Pia , Bigini Paolo , Mennini Tiziana , Agnello Davide , Laragione Teresa , Cagnotto Alfredo , Viviani Barbara , Marinovich Marina , Cerami Anthony , Coleman Thomas R. , Brines Michael , Ghezzi Pietro
Published: September 2003

Ischemic brain injury resulting from stroke arises from primary neuronal losses and by inflammatory responses. Previous studies suggest that erythropoietin (EPO) attenuates both processes. Although EPO is clearly antiapoptotic for neurons after experimental stroke, it is unknown whether EPO also directly modulates EPO receptor (EPO-R)–expressing glia, microglia, and other inflammatory cells. In these experiments, we show that recombinant human EPO (rhEPO; 5,000 U/kg body weight, i.p.) markedly reduces astrocyte activation and the recruitment of leukocytes and microglia into an infarction produced by middle cerebral artery occlusion in rats. In addition, ischemia-induced production of the proinflammatory cytokines tumor necrosis factor, interleukin 6, and monocyte chemoattractant protein 1 concentration is reduced by >50% after rhEPO administration. Similar results were also observed in mixed neuronal-glial cocultures exposed to the neuronal-selective toxin trimethyl tin. In contrast, rhEPO did not inhibit cytokine production by astrocyte cultures exposed to neuronal homogenates or modulate the response of human peripheral blood mononuclear cells, rat glial cells, or the brain to lipopolysaccharide. These findings suggest that rhEPO attenuates ischemia-induced inflammation by reducing neuronal death rather than by direct effects upon EPO-R–expressing inflammatory cells.
Characterization of the CD4+ T Cell Response to Epstein-Barr Virus during Primary and Persistent Infection
Authors: Amyes Elisabeth , Hatton Chris , Montamat-Sicotte Damien , Gudgeon Nancy , Rickinson Alan B. , McMichael Andrew J. , Callan Margaret F.C.
Published: September 2003

The CD8+ T cell response to Epstein-Barr virus (EBV) is well characterized. Much less is known about the evolution of the CD4+ T cell response. Here we show that EBV stimulates a primary burst of effector CD4+ T cells and this is followed by a period of down-regulation. A small population of EBV-specific effector CD4+ T cells survives during the lifelong persistent phase of infection. The EBV-specific effector CD4+ T cells accumulate within a CD27+ CD28+ differentiation compartment during primary infection and remain enriched within this compartment throughout the persistent phase of infection. Analysis of CD4+ T cell responses to individual epitopes from EBV latent and lytic cycle proteins confirms the observation that the majority of the effector cells express both CD27 and CD28, although CD4+ T cells specific for lytic cycle antigens have a greater tendency to express CD45RA than those specific for the latent antigens. In clear contrast, effector CD4+ T cells specific for cytomegalovirus (CMV) accumulate within the CD27− CD28+ and CD27− CD28− compartments. There are striking parallels in terms of the differentiation of CD8+ T cells specific for EBV and CMV. The results challenge current ideas on the definition of memory subsets.
CD4+CD25+ T Cells Regulate Virus-specific Primary and Memory CD8+ T Cell Responses
Authors: Suvas Susmit , Kumaraguru Uday , Pack Christopher D. , Lee Sujin , Rouse Barry T.
Published: September 2003

Naturally occurring CD4+CD25+ regulatory T cells appear important to prevent activation of autoreactive T cells. This article demonstrates that the magnitude of a CD8+ T cell–mediated immune response to an acute viral infection is also subject to control by CD4+CD25+ T regulatory cells (Treg). Accordingly, if natural Treg were depleted with specific anti-CD25 antibody before infection with HSV, the resultant CD8+ T cell response to the immunodominant peptide SSIEFARL was significantly enhanced. This was shown by several in vitro measures of CD8+ T cell reactivity and by assays that directly determine CD8+ T cell function, such as proliferation and cytotoxicity in vivo. The enhanced responsiveness in CD25-depleted animals was between three- and fourfold with the effect evident both in the acute and memory phases of the immune response. Surprisingly, HSV infection resulted in enhanced Treg function with such cells able to suppress CD8+ T cell responses to both viral and unrelated antigens. Our results are discussed both in term of how viral infection might temporarily diminish immunity to other infectious agents and their application to vaccines. Thus, controlling suppressor effects at the time of vaccination could result in more effective immunity.
IL-1 Plays an Important Role in Lipid Metabolism by Regulating Insulin Levels under Physiological Conditions
Authors: Matsuki Taizo , Horai Reiko , Sudo Katsuko , Iwakura Yoichiro
Published: September 2003

IL-1 is a proinflammatory cytokine that plays important roles in inflammation. However, the role of this cytokine under physiological conditions is not known completely. In this paper, we analyzed the role of IL-1 in maintaining body weight because IL-1 receptor antagonist–deficient (IL-1Ra−/−) mice, in which excess IL-1 signaling may be induced, show a lean phenotype. Body fat accumulation was impaired in IL-1Ra−/− mice, but feeding behavior, expression of hypothalamic factors involved in feeding control, energy expenditure, and heat production were normal. When IL-1Ra−/− mice were treated with monosodium glutamate (MSG), which causes obesity in wild-type mice by ablating cells in the hypothalamic arcuate nucleus, they were resistant to obesity, indicating that excess IL-1 signaling antagonizes the effect of MSG-sensitive neuron deficiency. IL-1Ra−/− mice showed decreased weight gain when they were fed the same amount of food as wild-type mice, and lipid accumulation remained impaired even when they were fed a high-fat diet. Interestingly, serum insulin levels and lipase activity were low in IL-1Ra−/− mice, and the insulin levels were low in contrast to wild-type mice after MSG treatment. These observations suggest that IL-1 plays an important role in lipid metabolism by regulating insulin levels and lipase activity under physiological conditions.
The Proinflammatory Mediators C3a and C5a Are Essential for Liver Regeneration
Authors: Strey Christoph W. , Markiewski Maciej , Mastellos Dimitrios , Tudoran Ruxandra , Spruce Lynn A. , Greenbaum Linda E. , Lambris John D.
Published: September 2003

Complement has been implicated in liver repair after toxic injury. Here, we demonstrate that complement components are essential for liver regeneration, and mediate their effect by interacting with key signaling networks that promote hepatocyte proliferation. C3- or C5-deficient mice exhibited high mortality, parenchymal damage, and impaired liver regeneration after partial hepatectomy. Mice with dual C3 and C5 deficiency had a more exacerbated phenotype that was reversed by combined C3a and C5a reconstitution. Interception of C5a receptor signaling resulted in suppression of IL-6/TNFα induction and lack of C3 and C5a receptor stimulation attenuated nuclear factor–κB/STAT-3 activation after hepatectomy. These data indicate that C3a and C5a, two potent inflammatory mediators of the innate immune response, contribute essentially to the early priming stages of hepatocyte regeneration.
Normal B Cell Homeostasis Requires B Cell Activation Factor Production by Radiation-resistant Cells
Authors: Gorelik Leonid , Gilbride Kevin , Dobles Max , Kalled Susan L. , Zandman Daniel , Scott Martin L.
Published: September 2003

The cellular source of B cell activation factor (BAFF) required for peripheral B cell survival/maturation is unknown. To determine the nature of BAFF-producing cells we established and analyzed reciprocal bone marrow (BM) chimeras with wild-type (WT) and BAFF-deficient mice. The results revealed that BAFF production by radiation-resistant stromal cells is completely sufficient to provide a necessary signal for B cell survival/maturation, as BAFF−/− BM cells transferred into lethally irradiated WT mice gave rise to normal numbers of follicular (FO) and marginal zone (MZ) B cell subpopulations. On the other hand, transfer of WT BM into BAFF−/− lethally irradiated mice resulted only in minimal reconstitution of mature FO B cells and no restoration of MZ B cells. Thus, in the absence of BAFF+/+ stromal cells, BAFF production by BM-derived cells, presumably by macrophages, dendritic cells, and/or neutrophils, was not at all sufficient to support normal B cell homeostasis. Interestingly, immunization of both types of chimeras stimulated high levels of antigen-specific antibody secretion, indicating that either stromal cell– or hematopoietic cell–derived BAFF is sufficient for B cell antibody responses.
Kinetics of Steady-state Differentiation and Mapping of Intrathymic-signaling Environments by Stem Cell Transplantation in Nonirradiated Mice
Authors: Porritt Helen E. , Gordon Kristie , Petrie Howard T.
Published: September 2003

Upon thymus entry, thymic-homing progenitors undergo distinct phases of differentiation as they migrate through the cortex to the capsule, suggesting that the signals that induce these differentiation steps may be stratified in corresponding cortical regions. To better define these regions, we transplanted purified stem cells into nonirradiated congenic recipients and followed their differentiation with respect to both tissue location and time. The earliest progenitors (DN1) remained confined to a very narrow region of the cortex for about the first 10 d of intrathymic residence; this region virtually overlaps the sites of thymic entry, suggesting that DN1 cells move very little during this lengthy period of proliferation and lineage commitment. Movement out of this region into the deeper cortex is asynchronous, and corresponds to the appearance of DN2 cells. Differentiation to the DN3 stage correlates with movement across the midpoint of the cortex, indicating that stromal signals that induce functions such as TCR gene rearrangement reside mainly in the outer half of the cortex. The minimum time to reach the capsule, and thus transit to the DP stage, is ∼13 d, with the average time a few days longer. These findings reveal for the first time the kinetics of steady-state progenitor differentiation in the thymus, as well as defining the boundaries of cortical regions that support different phases of the differentiation process. We also show that the first lineage-positive progeny of transplanted stem cells to appear in the thymus are dendritic cells in the medulla, suggesting that each new wave of new T cell production is preceded by a wave of regulatory cells that home to the medulla and ensure efficient tolerance and selection.
Molecular Diagnosis of Primary Mediastinal B Cell Lymphoma Identifies a Clinically Favorable Subgroup of Diffuse Large B Cell Lymphoma Related to Hodgkin Lymphoma
Authors: Rosenwald Andreas , Wright George , Leroy Karen , Yu Xin , Gaulard Philippe , Gascoyne Randy D. , Chan Wing C. , Zhao Tong , Haioun Corinne , Greiner Timothy C. , Weisenburger Dennis D. , Lynch James C. , Vose Julie , Armitage James O. , Smeland Erlend B. , Kvaloy Stein , Holte Harald , Delabie Jan , Campo Elias , Montserrat Emili , Lopez-Guillermo Armando , Ott German , Muller-Hermelink H. Konrad , Connors Joseph M. , Braziel Rita , Grogan Thomas M. , Fisher Richard I. , Miller Thomas P. , LeBlanc Michael , Chiorazzi Michael , Zhao Hong , Yang Liming , Powell John , Wilson Wyndham H. , Jaffe Elaine S. , Simon Richard , Klausner Richard D. , Staudt Louis M.
Published: September 2003

Using current diagnostic criteria, primary mediastinal B cell lymphoma (PMBL) cannot be distinguished from other types of diffuse large B cell lymphoma (DLBCL) reliably. We used gene expression profiling to develop a more precise molecular diagnosis of PMBL. PMBL patients were considerably younger than other DLBCL patients, and their lymphomas frequently involved other thoracic structures but not extrathoracic sites typical of other DLBCLs. PMBL patients had a relatively favorable clinical outcome, with a 5-yr survival rate of 64% compared with 46% for other DLBCL patients. Gene expression profiling strongly supported a relationship between PMBL and Hodgkin lymphoma: over one third of the genes that were more highly expressed in PMBL than in other DLBCLs were also characteristically expressed in Hodgkin lymphoma cells. PDL2, which encodes a regulator of T cell activation, was the gene that best discriminated PMBL from other DLBCLs and was also highly expressed in Hodgkin lymphoma cells. The genomic loci for PDL2 and several neighboring genes were amplified in over half of the PMBLs and in Hodgkin lymphoma cell lines. The molecular diagnosis of PMBL should significantly aid in the development of therapies tailored to this clinically and pathogenetically distinctive subgroup of DLBCL.
Algebras of pseudodifferential operators on complete manifolds
Authors: Ammann Bernd , Lauter Robert , Nistor Victor
Published: September 2003

In several influential works, Melrose has studied examples of non-compact manifolds

M
0

M_0

whose large scale geometry is described by a Lie algebra of vector fields

V

⊂
Γ
(
M
;
T
M
)

\mathcal V \subset \Gamma (M;TM)

on a compactification of

M
0

M_0

to a manifold with corners

M
M

. The geometry of these manifolds—called “manifolds with a Lie structure at infinity”—was studied from an axiomatic point of view in a previous paper of ours. In this paper, we define and study an algebra

Ψ

1
,
0
,

V

∞

(

M
0

)

\Psi _{1,0,\mathcal V}^\infty (M_0)

of pseudodifferential operators canonically associated to a manifold

M
0

M_0

with a Lie structure at infinity

V

⊂
Γ
(
M
;
T
M
)

\mathcal V \subset \Gamma (M;TM)

. We show that many of the properties of the usual algebra of pseudodifferential operators on a compact manifold extend to the algebras that we introduce. In particular, the algebra

Ψ

1
,
0
,

V

∞

(

M
0

)

\Psi _{1,0,\mathcal V}^\infty (M_0)

is a “microlocalization” of the algebra

Diff

V

∗

(
M
)

\textrm {Diff}^{*}_{\mathcal V}(M)

of differential operators with smooth coefficients on

M
M

generated by

V

\mathcal V

and

C

∞

(
M
)

\mathcal {C}^\infty (M)

. This proves a conjecture of Melrose (see his ICM 90 proceedings paper).
Cell cycle-dependent and cell cycle-independent control of transcription by theDrosophilaE2F/RB pathway
Authors: Dimova Dessislava K. , Stevaux Olivier , Frolov Maxim V. , Dyson Nicholas J.
Published: September 2003

To determine which E2F/RB-family members are functionally important at E2F-dependent promoters, we used RNA interference (RNAi) to selectively remove each component of the dE2F/dDP/RBF pathway, and we examined the genome-wide changes in gene expression that occur when each element is missing. The results reveal a remarkable division of labor between family members. Classic E2F targets, encoding functions needed for cell cycle progression, are expressed in cycling cells and are primarily dependent on dE2F1and RBF1for regulation. Unexpectedly, there is a second program of dE2F/RBF-dependent transcription, in which dE2F2/RBF1or dE2F2/RBF2 complexes repress gene expression in actively proliferating cells. These new E2F target genes encode differentiation factors that are transcribed in developmentally regulated and gender-specific patterns and not in a cell cycle-regulated manner. We propose that dE2F/RBF complexes should not be viewed simply as a cell cycle regulator of transcription. Instead, dE2F/RBF-mediated repression is exerted on genes that encode an assortment of cellular functions, and these effects are reversed on sets of functionally related genes in particular developmental contexts. As a result, dE2F/RBF regulation is used to link gene expression with cell cycle progression at some targets while simultaneously providing stable repression at others.
Phage N4 RNA polymerase II recruitment to DNA by a single-stranded DNA-binding protein
Authors: Carter Richard H. , Demidenko Alexander A. , Hattingh-Willis Susan , Rothman-Denes Lucia B.
Published: September 2003

Transcription of bacteriophage N4 middle genes is carried out by a phage-coded, heterodimeric RNA polymerase (N4 RNAPII), which belongs to the family of T7-like RNA polymerases. In contrast to phage T7-RNAP, N4 RNAPII displays no activity on double-stranded templates and low activity on single-stranded templates. In vivo, at least one additional N4-coded protein (p17) is required for N4 middle transcription. We show that N4 ORF2encodes p17 (gp2). Characterization of purified gp2revealed that it is a single-stranded DNA-binding protein that activates N4 RNAPII transcription on single-stranded DNA templates through specific interaction with N4 RNAPII. On the basis of the properties of the proteins involved in N4 RNAPII transcription and of middle promoters, we propose a model for N4 RNAPII promoter recognition, in which gp2plays two roles, stabilization of a single-stranded region at the promoter and recruitment of N4 RNAPII through gp2-N4 RNAPII interactions. Furthermore, we discuss our results in the context of transcription initiation by mitochondrial RNA polymerases.
The transcription factor Net regulates the angiogenic switch
Authors: Zheng Hong , Wasylyk Christine , Ayadi Abdelkader , Abecassis Joseph , Schalken Jack A , Rogatsch Hermann , Wernert Nicolas , Maira Sauveur-Michel , Multon Marie-Christine , Wasylyk Bohdan
Published: September 2003

Angiogenesis is fundamental to physiological and pathological processes. Despite intensive efforts, little is known about the intracellular circuits that regulate angiogenesis. The transcription factor Net is activated by phosphorylation induced by Ras, an indirect regulator of angiogenesis. Net is expressed at sites of vasculogenesis and angiogenesis during early mouse development, suggesting that it could have a role in blood vessel formation. We show here that down-regulation of Net inhibits angiogenesis and vascular endothelial growth factor (VEGF) expression in vivo, ex vivo, and in vitro. Ras-activated phosphorylated Net (P-Net) stimulates the mouse VEGF promoter through the -80 to -53 region that principally binds Sp1. P-Net and VEGF are coexpressed in angiogenic processes in wild-type mouse tissues and in human tumors. We conclude that Net is a regulator of angiogenesis that can switch to an activator following induction by pro-angiogenic molecules.
Unique Sm core structure of U7 snRNPs: assembly by a specialized SMN complex and the role of a new component, Lsm11, in histone RNA processing
Authors: Pillai Ramesh S. , Grimmler Matthias , Meister Gunter , Will Cindy L. , Lührmann Reinhard , Fischer Utz , Schümperli Daniel
Published: September 2003

A set of seven Sm proteins assemble on the Sm-binding site of spliceosomal U snRNAs to form the ring-shaped Sm core. The U7 snRNP involved in histone RNA 3′ processing contains a structurally similar but biochemically unique Sm core in which two of these proteins, Sm D1 and D2, are replaced by Lsm10 and by another as yet unknown component. Here we characterize this factor, termed Lsm11, as a novel Sm-like protein with apparently two distinct functions. In vitro studies suggest that its long N-terminal part mediates an important step in histone mRNA 3′-end cleavage, most likely by recruiting a zinc finger protein previously identified as a processing factor. In contrast, the C-terminal part, which comprises two Sm motifs interrupted by an unusually long spacer, is sufficient to assemble with U7, but not U1, snRNA. Assembly of this U7-specific Sm core depends on the noncanonical Sm-binding site of U7 snRNA. Moreover, it is facilitated by a specialized SMN complex that contains Lsm10 and Lsm11 but lacks Sm D1/D2. Thus, the U7-specific Lsm11 protein not only specifies the assembly of the U7 Sm core but also fulfills an important role in U7 snRNP-mediated histone mRNA processing.
Trimming embedded resistors: an enabling technology
Authors: Davignon John J.
Published: September 2003

Focuses on embedded passives (EPs), an emerging technology for the PCB industry, which shows potential for reductions in board area (or increased functionality in a given fixed area), improved signal performance, and attractive cost benefits. Notes that industry acceptance of EPs technology, and its ultimate acceptance in the OEM designers' toolbox may be dependent on some key process tools.
Thin‐film embedded resistor and capacitor technologies
Authors: Chinoy Percy , Langlois Marc
Published: September 2003

Printed circuit board designers face formidable challenges of increased functionality in smaller size boards, and reduced EMI in high‐speed circuits. Embedded passives technology can open up valuable space on the board surface while also improving the electrical performance and reliability of high density, high‐speed designs. Shipley has developed a thin‐film, high sheet resistivity (1,000 Ω/□) resistor material sold under the trade name InSite™ in response to this market need. This paper describes the manufacturing process for embedded resistors and discusses measured data on resistance values, uniformity, and thermal effects, and their impact on design rules for resistor size. Preliminary results of Shipley's thin‐film embedded capacitor technology with high capacitance densities (10 and 200 nF/cm2) are also presented.
Matching embedded capacitor dielectrics to applications
Authors: Ulrich Richard
Published: September 2003

All capacitor dielectric materials, whether used for discrete or embedded applications, can be grouped into two general categories: paraelectric and ferroelectric. Ferroelectrics generally exhibit much higher dielectric constants, but are also less stable with regard to temperature, frequency, voltage, time and film thickness. There are dozens of each of these materials that have been used in discrete capacitors and about ten that are either available for use in embedded capacitors or will soon be marketed for that purpose. The commercialized materials can be broken down into four sub‐categories: thick‐film polymers, ferroelectric powder in polymer binders, thin‐film paraelectrics, and thick‐film ferroelectrics. These four classifications are evaluated with regard to their electrical performance, ease of fabrication, and suitability for specific applications.
Cost and production analysis for substrates with embedded passives
Authors: Sandborn Peter A. , Etienne Bevin , Herrmann Jeffrey W. , Chincholkar Mandar M.
Published: September 2003

With the advent of new materials and technologies that enable passive components to be embedded within electronic substrates, one key question that arises is: under what circumstances (and for what type of applications) is it economically viable to consider using embedded passives? The economic issues that must be considered consist of a combination of manufacturing costs and throughputs, and non‐manufacturing life cycle costs. This paper discusses the assessment of manufacturing costs associated with embedding resistors and capacitors in printed circuit boards and provides cost modeling results for an avionics board. The discussion is extended to include optimizing the specific embedded passive content in a board and design for production modeling when embedded passives are present. Life cycle cost issues are also qualitatively discussed.
New non‐reinforced substrates for use as embedded capacitors
Authors: Andresakis John , Yamamoto Takuya , Biunno Nick
Published: September 2003

As CPUs increase in performance, the number of passive components on the surface of circuit boards also increases dramatically. To reduce the number of components, as well as improve the electrical performance (i.e. reduce inductance), designers are increasingly embedding capacitive layers in the PCB. The majority of the products in use utilize reinforced epoxy laminates. These products are relatively easy to handle, but the thickness and Dk limit the effectiveness of the layer to perform as a capacitor. Other materials are being developed that are thinner (and thus increase capacitance), but either have problems with dielectric breakdown strength, handling or offer only a marginal improvement over existing materials. This paper describes new non‐reinforced substrates for use as embedded capacitance layers that address these issues. The material selection process, substrate processing and electrical performance are reviewed.
Status and trends for PWBs with embedded components
Authors: Rapala‐Virtanen Tarja
Published: September 2003

Increasing packaging density and the requirement for high performance electronic devices are driving high density interconnect (HDI) printed wiring board (PWB) technology towards utilization of the inner space of a PWB for component placement. Aspocomp has been manufacturing HDI PWBs at Salo for more than 5 years. The main focus has been on higher packaging density and on accommodating the needs of future chip packages. In volume production, cost and performance have to be balanced. As a result, manufacturing and material yields, process automation, the cost of materials and added value technologies like embedded passives are key considerations in meeting the high volume requirements of the marketplace. This paper describes how these parameters have evolved over time and how it has been possible to achieve the stringent tolerances required in the manufacturing processes.
The Promise of Postmodern Theology
Authors: Sarot Marcel
Published: September 2003

Books reviewed in this article:

Graham Ward (ed.). The Blackwell Companion to Postmodern Theology
Radical Traditions and the Return to Scripture in Religion and Theology
Authors: Pecknold C. C.
Published: September 2003

Books reviewed in this article:

David Weiss Halivni, Revelation Restored: Divine Writ and Critical Responses

Peter Ochs and Nancy Levene, Textual Reasonings: Jewish Philosophy and Text Study at the End of the Twentieth Century

P. Travis Kroeker and Bruce Ward, Remembering the End: Dostoevsky as Prophet to Modernity

Stanley Hauerwas, Wilderness Wanderings: Probing Twentieth Century Theology and Philosophy

David Toole, Waiting for Godot in Sarajevo: Theological Reflections on Nihilism, Tragedy, and Apocalypse

George Lindbeck (ed.) and James J. Buckley, The Church in a Postliberal Age
Emigration from China: A Sending Country Perspective
Authors: Biao Xiang
Published: September 2003

This paper aims to provide a comprehensive overview of the policies pursued by the People's Republic of China (PRC) regarding the emigration of Chinese nationals. Most of the available literature on migration management has focused on receiving countries. With a few exceptions, little attention has been directed at migration management policies pursued in countries of origin. In the case of the PRC, policies regarding overseas Chinese have been fairly well documented and researched, but very little has been written about how the Chinese authorities manage ongoing emigration flows. This gap becomes particularly salient as the importance of the “partnership with the countries of origin” in devising migration policies is being increasingly acknowledged by receiving countries in Europe (Commission of the European Communities, 2000).

Over the last 20 years, there have been significant changes in the Chinese Government's policies and perspectives on emigration. But, just like most other governments, the Chinese authorities do not have a single blanket policy covering all categories of emigrants. Emigration is normally managed on a case‐by‐case basis and the Government's attitude toward the same type of emigration may vary depending on different cases and circumstances. Because of this, this article examines China's major emigration‐related policy spheres one by one. Specifically, six issues will be discussed: (1) exit control; (2) diaspora policy; (3) student migration; (4) labour export; (5) regulations on emigration agencies and, finally (6) the Government's response to human smuggling.

This article shows both the coherence and the fragmentation in China's policies toward emigration. The coherence is due to the fact that all the policies are inherently linked to China's overall economic and social development strategy. The emigration management regime is sometimes fragmented partly because emigration consists of different streams and is handled by different Government departments, partly because some emigration issues (such as regulations on emigration agents) are very new for the Chinese Government and the authorities are still exploring them. Overall, the Chinese authorities increasingly see emigration as a means to enhance China's integration to the world and are keen to avoid conflicts with the international community over migration issues. At the same time, China's emigration policies need to be more balanced, in particular, the emigration of unskilled labour should be given more priority.
Reducing Irregular Migration from China
Authors: Chin James K.
Published: September 2003

With the development of China's economy since 1979, a new type of Chinese migration has emerged, which is more diversified and quite distinct from previous migration patterns. Trafficking in human beings and other forms of irregular migration are one of the most pressing and complex human rights issues today, reaching across borders and affecting most of the countries in the world, with new and serious security implications. As part of the international irregular migration flows toward and into the European Union (EU), the Chinese, particularly from Fujian and Zhejiang provinces, have played a major role since the 1980s. To some extent, it could be said that China provides the largest number of East Asian irregular immigrants to Europe.

Based on fieldwork conducted in southern China over the past seven years, this paper proposes to examine current Chinese irregular migration trends. It will further present the Government's response regarding the migratory modus operandi and policy implications with the aim of offering policy makers an empirical insight into the most active region of emigration in China. Because of the difficulty and sensitivity involved in collecting data on the topic, materials in this paper are mainly based on a content analysis of local Chinese newspapers and my interviews with various people involved in irregular migration activities, such as “snakeheads”, illegal migrants and their family members, and police, local, and government officials at different levels.
Migration of Highly Skilled Chinese to Europe: Trends and Perspective
Authors: Zhang Guochu
Published: September 2003

Since China's economic opening and reforms in 1978, the country has broadened and deepened its exchanges and relations with other countries. This has contributed to the increase in the scale of international migration of highly skilled Chinese abroad. The impact of the migration of highly skilled Chinese on China and the relevant nations particularly deserve attention and study. Following the earlier migration flows mainly to the United States, Japan, Canada, Australia, and New Zealand, the migration of highly skilled Chinese to Europe has become a notable new trend.

Currently, the flow of international migration of highly skilled Chinese personnel is mainly oriented toward Europe and the United States. While studying abroad has been the main form of migration of the skilled, this has now been joined by the migration of technical and professional staff, and the trend is increasing. The main country of destination for Chinese students is the United States, which absorbs more than half of the total, while Australia and Canada receive the largest number of skilled Chinese manpower. The United States also receives a large number of Chinese technical personnel, but its proportion has declined, while the flow to Europe has sharply increased.

This development may be attributed to the global expansion of economic, scientific and technological, as well as cultural and educational exchanges and cooperation. But it is also the result of an increase in the educational investment made by the Chinese people following the continuous increase in China's economic strength and the population's personal income. Of greater importance are the gaps between China and Europe at the scientific, technological, and educational levels and the research and marketing environment. The intervening changes in labour market and immigration policies in European and American countries accelerate the trend further. For all of these and other reasons, the spatial distribution of Chinese students will become more balanced and play a positive role in the promotion of mutually beneficial exchanges between China and other countries.
The New Chinese Migrants in France
Authors: Guerassimoff Carine
Published: September 2003

Like the United Kingdom and the Netherlands, France is one of the major centres of Chinese migration in Europe. Chinese sojourners arrived in France at the beginning of the twentieth century and the 1911 census showed the presence of 238 Chinese in the country. From 1900 to World War I, this little community remained heterogeneous in its socio‐economic and professional composition (Archaimbault, 1952). Changes in this community occurred during World War I when the lack of labourers led the French Government to recruit 140,000 Chinese workers (Wou, 1939). The 2,000 to 4,000 Chinese who remained in France after the war constituted the basis of a Chinese community in France. In the 1920s, they were joined by some 2,000 student labourers (Wang, 2001; Bailey, 1988). From the 1920s to the 1940s, Zhejiang immigration in France rose until World War II and the rise of the communist party in China stopped the movement. Yet, Chinese immigration did not cease. Migrants of Chinese origin arrived essentially from the old French Indochina (Viet Nam‐Laos‐Cambodia) (Le, 1995). Immigration from these countries increased in the 1970s when different conflicts occurred. From the late 1970s to the early 1980s, France also saw the arrival, albeit in smaller numbers, of Chinese from Hong Kong and Taiwan, family members of citizens of the People's Republic of China (PRC). The new wave of Chinese migration from PRC started in the mid‐1980s and grew steadily until now, with some peaks, e.g. in the mid‐1990s.

Recent fieldwork in France approached this community, in particular, those living in France with a precarious administrative status (asylum seekers or clandestine migrants). In general, the situation of the population covered by this fieldwork was still precarious. Although the paper does not include other categories such as students, entrepreneurs, or researchers, it is nevertheless possible to gather some details on the basis of French official data and reports. The following sections deal with the growing Chinese presence in France, and their precarious status. Most recent research tends to show a diversified Chinese migrant population profile; it also shows that they are still primarily active in the French ethnic Chinese market. In the initial stages of migration, the Chinese migrants continue to maintain links with China and sometimes with Chinese communities in Europe.
New Chinese Migration to Germany: Historical Consistencies and New Patterns of Diversification within a Globalized Migration Regime
Authors: Giese Karsten
Published: September 2003

Chinese migration to Germany is not very well documented, even though sojourners arrived in this country as early as the first half of the eighteenth century. There is some research on particular issues in specific historical contexts, such as the discrimination and persecution during the Third Reich (Yü‐Dembski, 1996, 1997), Chinese students in Germany between 1860 and 1945 (Harnisch, 1999), Chinese‐German mixed marriages (Groeling‐Che, 1991), and irregular immigration and human trafficking during the 1980s and 1990s (Giese, 1999a). Yet, no systematic research on the history of Chinese migration or continuous analysis of more recent migration trends and related political issues has been carried out so far. Some of the reasons for this include: Chinese communities have always formed only a small minority among the non‐German population; after World War II, Chinese communities were dispersed over the whole of (West) Germany and they have not created any visible “Chinatown” yet; and, until very recently, there seemed to be virtually no political or social problems related to Chinese migrants, and the few emerging political issues still appear insignificant compared to those related to other ethnic groups. As a result, Chinese immigration and the lives of Chinese migrants — widely ignored as a potential research topic for Modern China Studies in Germany — have not yet received attention from scholars of social sciences.

This article will attempt to offer a comprehensive summary of the history of new Chinese migration to Germany from the early 1970s to the end of the second millennium. Mainly based on official statistics, it will then discuss recent trends in Chinese immigration for different groups of migrants since the 1990s, focusing on policy‐related issues and political implications of these recent and potential future developments.
New Chinese Migrants in Italy
Authors: Ceccagno Antonella
Published: September 2003

Italy joined the group of European nations with a positive migratory balance in 1980, but now the presence of an immigrant workforce is definitely embedded in the Italian development model. The shift from a net emigration to net immigration country occurred when the internal migration from southern Italy, which had provided the factories in northern Italy with the necessary manpower for their economic development, was coming to an end, and productive decentralization was beginning with the re‐emergence of small businesses. Twenty years later, small dynamic businesses that are mainly clustered in industrial districts specializing in local production are a distinctive feature of the Italian economy to the extent that among industrialized countries Italy counts the largest number of small businesses and the lowest number of employees per business (Accornero, 2000). Starting from the 1980s, opportunities for a low‐skilled labour force opened for new migrants mainly in these productive activities. In addition, throughout the 1980s and the 1990s niche opportunities for self‐employment in workshops producing for Italian suppliers were also appearing or expanding.

Among other migrant groups arriving in Italy were those of Chinese origin. The crucial time for the recent migration flow from China to Italy — either directly or via other European countries, such as France and Holland — can be dated from the early 1980s. Since then, a succession of unskilled workers originating almost exclusively from the south‐eastern Chinese province of Zhejiang arrived in the country, after the family‐based chains of emigration that had almost come to a halt during the years of the Cultural Revolution had again been revitalized.

The number of immigrants of Chinese origin has grown rapidly over the last 20 years, as has the number of businesses owned by the Chinese. By today, the Chinese migrant community shows the strongest entrepreneurial aptitude, and, according to recent national data, account for the largest number of small business owners among non‐European Union (EU) immigrants in Italy.

Unlike the situation in most of the western European countries, such as Great Britain and the Netherlands, where the Chinese are active mainly in the catering service, in Italy their main areas of activity are the production of ready‐to‐wear garments, leather garments and bags, and woollen sweaters. Until recently, these seemed to be the only productive sectors open to Chinese immigrants. However, new trends are emerging in the employment patterns of the Chinese in Italy. The two most striking new features are the expansion from performing only simple manufacturing tasks for Italian suppliers to actually managing the entire productive process in the garment sector, and the growing employment in Italian firms, especially in the dynamic industrial districts where migrants of other origins were already working in large numbers.