bluuebunny/crossref_metadata_2025 huggingface dataset:
A short note on the concept of risk management and VaR for asset management firms
Authors: Putnam Bluford H , Sykes Wilford D , Zecher Philip D
Published: October 2002

Value at risk (VaR) is now the most commonly cited risk management tool for asset managers to utilize. Specialized tools are used for particular types of management problems, usually grouped into the fixed income camp of duration and convexity or derived directly from options theory. In general, however, most firms utilize some type of VaR type analysis, if any analysis is done at all. This note points out the problem of using VaR without understanding that the answer one obtains when applying the tool is highly dependent upon the question being asked. That is, simple VaR is very useful for certain circumstances, but not too useful for many of the issues to which it is applied by asset managers. The conclusion is simplistic in that managers must use the correct tools for the question being asked if a useful, and not misleading, answer is to be obtained. VaR often provides elegant answers to the wrong questions. Interestingly, many of the questions VaR is best suited to answer were answerable using Chebyshev' work of 150 years ago.
A Bayesian methodology to explore the effects of memory loss in currency markets
Authors: Putnam Bluford H
Published: October 2002

As time goes by, people tend to establish new norms based on more recent events and information. Old norms and standards are eclipsed by new developments. The same type of behavior appears to operate in financial markets. New and unexpected information can jolt a market, but over time market participants adjust to new patterns of information, of data flow, of market volatility, and even of structural change.

On another level, one can ask the question of how much weight to give new information relative to old information. Market participants do this naturally, as they weigh new information, such as just‐released economic data, compare it to their previously held expectations and then revise their expectations of future data releases and potential market reactions. When the question is viewed in this perspective, it seems quite natural to assume that new pieces of information, such as economic data releases, should be given more weight in assessing expectations of future market behavior than releases of the same type of data several months or even several years previously. That is, the information value of certain specific types of information, such as specific economic data releases, probably decays as time passes.

This study proposes the use of a dynamic Bayesian technology to explore the effects of time decay in the value placed on specific bits of information that are received at regular intervals through time. The methodology that is being proposed is the main focus of this study and, to clarify this methodology, it is applied to the currency markets asking questions about the time decay pattern of certain economic data. The results reported in this example are purely for illustrative purposes, since they are specific to the data studied, the model specification of currency market behavior, and a wide variety of other assumptions embedded in this specific approach to currency analysis.

Nevertheless, the results are interesting, if only because they demonstrate both the basic idea that new information is more valuable than old information and provide a useful and practical method of analyzing the issue of the time decay factor in how markets process information.
Urbanisation and City Size Distribution in China
Authors: Song Shunfeng , Honglin Zhang Kevin
Published: October 2002

China has been experiencing rapid urbanisation since the economic reform starting in 1978. The number of cities increased from 191 in 1978 to 667 in 1999, while the urban share of the national population increased from 18 to 31 per cent. This paper examines China's urbanisation and the evolution of its city system. It uses city-level data from 1991 and 1998 to investigate China's city size distribution and its changes. It also discusses how economic and institutional factors affect the urban system and the patterns of urban growth.
Distribution and Evolution of von Willebrand/Integrin A Domains: Widely Dispersed Domains with Roles in Cell Adhesion and Elsewhere
Authors: Whittaker Charles A. , Hynes Richard O.
Published: October 2002

The von Willebrand A (VWA) domain is a well-studied domain involved in cell adhesion, in extracellular matrix proteins, and in integrin receptors. A number of human diseases arise from mutations in VWA domains. We have analyzed the phylogenetic distribution of this domain and the relationships among ∼500 proteins containing this domain. Although the majority of VWA-containing proteins are extracellular, the most ancient ones, present in all eukaryotes, are all intracellular proteins involved in functions such as transcription, DNA repair, ribosomal and membrane transport, and the proteasome. A common feature seems to be involvement in multiprotein complexes. Subsequent evolution involved deployment of VWA domains by Metazoa in extracellular proteins involved in cell adhesion such as integrin β subunits (all Metazoa). Nematodes and chordates separately expanded their complements of extracellular matrix proteins containing VWA domains, whereas plants expanded their intracellular complement. Chordates developed VWA-containing integrin α subunits, collagens, and other extracellular matrix proteins (e.g., matrilins, cochlin/vitrin, and von Willebrand factor). Consideration of the known properties of VWA domains in integrins and extracellular matrix proteins allows insights into their involvement in protein–protein interactions and the roles of bound divalent cations and conformational changes. These allow inferences about similar functions in novel situations such as protease regulators (e.g., complement factors and trypsin inhibitors) and intracellular proteins (e.g., helicases, chelatases, and copines).
ARF1·GTP, Tyrosine-based Signals, and Phosphatidylinositol 4,5-Bisphosphate Constitute a Minimal Machinery to Recruit the AP-1 Clathrin Adaptor to Membranes
Authors: Crottet Pascal , Meyer Daniel M. , Rohrer Jack , Spiess Martin
Published: October 2002

At the trans-Golgi network, clathrin coats containing AP-1 adaptor complexes are formed in an ARF1-dependent manner, generating vesicles transporting cargo proteins to endosomes. The mechanism of site-specific targeting of AP-1 and the role of cargo are poorly understood. We have developed an in vitro assay to study the recruitment of purified AP-1 adaptors to chemically defined liposomes presenting peptides corresponding to tyrosine-based sorting motifs. AP-1 recruitment was found to be dependent on myristoylated ARF1, GTP or nonhydrolyzable GTP-analogs, tyrosine signals, and small amounts of phosphoinositides, most prominently phosphatidylinositol 4,5-bisphosphate, in the absence of any additional cytosolic or membrane bound proteins. AP-1 from cytosol could be recruited to a tyrosine signal independently of the lipid composition, but the rate of recruitment was increased by phosphatidylinositol 4,5-bisphosphate. The results thus indicate that cargo proteins are involved in coat recruitment and that the local lipid composition contributes to specifying the site of vesicle formation.
Signal-Driven Computations in Speech Processing
Authors: Peña Marcela , Bonatti Luca L. , Nespor Marina , Mehler Jacques
Published: October 2002

Learning a language requires both statistical computations to identify words in speech and algebraic-like computations to discover higher level (grammatical) structure. Here we show that these computations can be influenced by subtle cues in the speech signal. After a short familiarization to a continuous speech stream, adult listeners are able to segment it using powerful statistics, but they fail to extract the structural regularities included in the stream even when the familiarization is greatly extended. With the introduction of subliminal segmentation cues, however, these regularities can be rapidly captured.
A Ni-Fe-Cu Center in a Bifunctional Carbon Monoxide Dehydrogenase/ Acetyl-CoA Synthase
Authors: Doukov Tzanko I. , Iverson Tina M. , Seravalli Javier , Ragsdale Stephen W. , Drennan Catherine L.
Published: October 2002

A metallocofactor containing iron, sulfur, copper, and nickel has been discovered in the enzyme carbon monoxide dehydrogenase/acetyl-CoA (coenzyme A) synthase from
Moorella thermoacetica
(f.
Clostridium thermoaceticum
). Our structure at 2.2 angstrom resolution reveals that the cofactor responsible for the assembly of acetyl-CoA contains a [Fe
4
S
4
] cubane bridged to a copper-nickel binuclear site. The presence of these three metals together in one cluster was unanticipated and suggests a newly discovered role for copper in biology. The different active sites of this bifunctional enzyme complex are connected via a channel, 138 angstroms long, that provides a conduit for carbon monoxide generated at the C-cluster on one subunit to be incorporated into acetyl-CoA at the A-cluster on the other subunit.
Microfluidic Large-Scale Integration
Authors: Thorsen Todd , Maerkl Sebastian J. , Quake Stephen R.
Published: October 2002

We developed high-density microfluidic chips that contain plumbing networks with thousands of micromechanical valves and hundreds of individually addressable chambers. These fluidic devices are analogous to electronic integrated circuits fabricated using large-scale integration. A key component of these networks is the fluidic multiplexor, which is a combinatorial array of binary valve patterns that exponentially increases the processing power of a network by allowing complex fluid manipulations with a minimal number of inputs. We used these integrated microfluidic networks to construct the microfluidic analog of a comparator array and a microfluidic memory storage device whose behavior resembles random-access memory.
WIGNER FUNCTIONS FOR THE LANDAU PROBLEM IN NONCOMMUTATIVE SPACES
Authors: DAYI ÖMER F. , KELLEYANE LARA T.
Published: October 2002

An electron moving on plane in a uniform magnetic field orthogonal to the plane is known as the Landau problem. Wigner functions for the Landau problem when the plane is noncommutative are found employing solutions of the Schrödinger equation as well as solving the ordinary ⋆-genvalue equation in terms of an effective Hamiltonian. Then, we let momenta and coordinates of the phase space be noncommutative and introduce a generalized ⋆-genvalue equation. We solve this equation to find the related Wigner functions and show that under an appropriate choice of noncommutativity relations they are independent of noncommutativity parameter.
Statin-Induced Expression of Decay-Accelerating Factor Protects Vascular Endothelium Against Complement-Mediated Injury
Authors: Mason Justin C. , Ahmed Zahra , Mankoff Rivka , Lidington Elaine A. , Ahmad Saifur , Bhatia Vinay , Kinderlerer Anne , Randi Anna M. , Haskard Dorian O.
Published: October 2002

Complement-mediated vascular injury is important in the pathophysiology of atherosclerosis and myocardial infarction. Because recent evidence shows that statins have beneficial effects on endothelial cell (EC) function independent of lipid lowering, we explored the hypothesis that statins modulate vascular EC resistance to complement through the upregulation of complement-inhibitory proteins. Human umbilical vein and aortic ECs were treated with atorvastatin or simvastatin, and decay-accelerating factor (DAF), membrane cofactor protein, and CD59 expression was measured by flow cytometry. A dose-dependent increase in DAF expression of up to 4-fold was seen 24 to 48 hours after treatment. Statin-induced upregulation of DAF required increased steady-state mRNA and de novo protein synthesis.
l
-Mevalonate and geranylgeranyl pyrophosphate reversed the effect, confirming the role of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibition and suggesting that constitutive DAF expression is negatively regulated by geranylgeranylation. Neither farnesyl pyrophosphate nor squalene inhibited statin-induced DAF expression, suggesting that the effect is independent of cholesterol lowering. Statin-induced DAF upregulation was mediated by the activation of protein kinase Cα and inhibition of RhoA and was independent of phosphatidylinositol-3 kinase and NO activity. The increased DAF expression was functionally effective, resulting in significant reduction of C3 deposition and complement-mediated lysis of antibody-coated ECs. These observations provide evidence for a novel cytoprotective action of statins on vascular endothelium that is independent of the effect on lipids and results in enhanced protection against complement-mediated injury. Modulation of complement regulatory protein expression may contribute to the early beneficial effects of statins in reducing the morbidity and mortality associated with atherosclerosis.
Cooperation Between Secretory Phospholipase A
2
and TNF-Receptor Superfamily Signaling
Authors: Fuentes Lucía , Hernández Marita , Fernández-Avilés Francisco Jesús , Crespo Mariano Sánchez , Nieto María Luisa
Published: October 2002

Atherogenesis is the consequence of a variety of effector mechanisms rather than the result of a single functional molecule. In this connection, type IIA secretory phospholipase A
2
(sPLA
2
) is an acute-phase reactant, which accumulates in atherosclerotic arterial walls, elicits several effects on monocytes, and has been related to the development of atherosclerosis. CD40/CD40 ligand pair is also a strong proatherogenic system. sPLA
2
produced an increase of the surface expression of CD40 in THP-1 monocytes and enhanced the effect of CD40 ligation on the expression of both Fas and FasL, thus indicating the existence of a positive cooperation between sPLA
2
and different elements of the TNF-receptor superfamily. Activation of the CD40/CD40L dyad with anti-CD40 antibody produced a small release of arachidonic acid and lacked any significant effect on the induction of cyclooxygenase-2, whereas the secretion of the chemokine MCP-1 and the surface display of CD11b, the α chain of the integrin Mac-1, were upregulated. Engagement of CD40 did not influence the survival of THP-1 monocytes, but coincubation of THP-1 monocytes pretreated with anti-CD40 antibody and Jurkat cells induced a significant increase of the number of Jurkat cells showing binding of annexin-V, and nuclear condensation and fragmentation, thus indicating that this treatment might trigger a juxtacrine/paracrine mechanism of apoptotic death in sensitive cell types. This data indicates the existence of overlapping routes for the response to CD40, TNF-α, and sPLA
2
, thus allowing the development of distinct patterns of response in monocytic cells.
Microchimerism and human autoimmune diseases
Authors: Nelson J L
Published: October 2002

Cells traffic in both directions between the fetus and the mother during pregnancy. Recent studies indicate that a low level of fetal cells commonly persists in the maternal circulation for years after pregnancy completion.The harboringof DNA or cells from another individual at low levels is called microchimerism. Chronic graft-vs-host disease is a condition of human chimerism that shares similaritiesto some autoimmune diseasesand for which the specific HLA genes of donor and host are known to be of central importance. Considered together with the female predilection to autoimmunity, these observations led to the hypothesis that microchimerism and HLA genes of host and non-host cells are involved in autoimmune disease. The hypothesis also extends to men and females who have not been pregnant because there are other sources of microchimerism. Maternal cells are now know to persist in her progeny and microchimerism can also derive from a twin or from a blood transfusion. Studies of systemic sclerosis, primary biliary cirrhosis, Sjögrens syndrome, polymorpyhic eruption of pregnancy, myositis and thyroid disease have both lent support and raised doubts about the role of microchimerism in autoimmune disease.
The evolution of left–right asymmetry in chordates
Authors: Boorman Clive J. , Shimeld Sebastian M.
Published: October 2002

The internal organs of all vertebrates are asymmetrically organised across the left–right axis. The development of this asymmetry is controlled by a molecular pathway that includes the signalling molecule Nodal and the transcription factor Pitx2, proteins encoded by genes that are predominantly expressed on the left side of all vertebrate embryos studied to date. Vertebrates share Phylum Chordata with two other groups of animals, amphioxus and the urochordates (including ascidians). Both these taxa develop left–right asymmetries, and recent studies have begun to address the degree of conservation of nodal and Pitx2 in this process. Pitx2 is a member of the Pitx homeobox gene family, and in both amphioxus and ascidians Pitx gene expression is predominantly left sided. These studies suggest that left–right asymmetry in all chordates is regulated by a conserved developmental pathway, and that this pathway evolved before the separation of the lineages leading to living chordates. BioEssays 24:1004–1011, 2002. © 2002 Wiley‐Periodicals, Inc.
Screening for symptoms of eating disorders: Reliability of the SCOFF screening tool with written compared to oral delivery
Authors: Perry Lin , Morgan John , Reid Fiona , Brunton Joan , O'Brien Aileen , Luck Amy , Lacey Hubert
Published: October 2002

Objective

The validity of the SCOFF delivered orally as a screening tool for eating disorders has previously been established, but clinical screening for eating disorders also occurs via written format, for example, in occupational health settings. The objective was to compare responses to the SCOFF between verbal and written administration.

Method

In a volunteer group of nursing and midwifery students at a South London University SCOFF was delivered orally at interview and via written questionnaire. Order was allocated randomly with repeat administration interrupted by distraction questions.

Results

There were 185 students who participated, providing 178 fully completed responses. Twenty subjects were male. There was overall agreement in the scores of 157 subjects (88.2%), providing a kappa coefficient of 0.811, with agreement in prediction of eating disorder for 167 (93.8%) and a kappa value of 0.824 (both p < 0.001). For 82 subjects administered the SCOFF verbally first followed by the written version, the kappa statistic was 0.752 (p < 0.001). For 96 subjects with SCOFF administered in reverse order (written form first), kappa was 0.862 (p < 0.001).

Discussion

Results demonstrated overall good replicability of the SCOFF administered as a written questionnaire compared to oral interview. Two trends were noted. The first was towards higher scores with written versus oral delivery irrespective of order, possibly indicating enhanced disclosure via written format. The second was of less consistency where verbal preceded written responses. Altogether findings support use of the SCOFF where a concise, valid and reliable screening for eating disorders is required in written form. © 2002 by Wiley Periodicals, Inc. Int J Eat Disord 32: 466–472, 2002.
Specialized mucous glands and their possible adaptive role in the males of some species of rana (amphibia, anura)
Authors: Brizzi Rossana , Delfino Giovanni , Pellegrini Roberta
Published: October 2002

A structural and ultrastructural study was carried out on the cutaneous glands in some species of Rana (R. dalmatina, R. iberica, R. italica, R. “esculenta,” and R. perezi), giving particular attention to the mucous secretory units. Two different types of mucous glands occur in R. dalmatina, R. iberica, and R. italica. Besides the ordinary mucous units, which are randomly distributed over the body surface in both males and females, a further population of mucous glands was observed on the male dorsal skin. The latter is recognizable by the peculiar morphology of the epithelial cells and some characteristics of the secretory product. Specialized mucous glands are absent in both sexes of R. “esculenta” and R. perezi. The possible adaptive role of the specialized mucous glands is discussed in light of the absence of vocal sacs in males of R. dalmatina, R. iberica, and R. italica. Chemosignals released by sexually dimorphic mucous units may replace vocal communication during the breeding season and so play an important role in female attraction and/or territorial announcement. The morphology and possible function of the specialized mucous glands in the three species of Rana are compared with the breeding glands of other frogs and with the hedonic glands of some urodeles (Salamandridae and Plethodontidae), which are known to produce pheromonal substances during courtship. J. Morphol. 254:328–341, 2002. © 2002 Wiley‐Liss, Inc.
Perturbation of β1-Integrin Function in Involuting Mammary Gland Results in Premature Dedifferentiation of Secretory Epithelial Cells
Authors: Faraldo Marisa M. , Deugnier Marie-Ange , Tlouzeau Sylvie , Thiery Jean Paul , Glukhova Marina A.
Published: October 2002

To study the mechanism of β1-integrin function in vivo, we have generated transgenic mouse expressing a dominant negative mutant of β1-integrin under the control of mouse mammary tumor virus (MMTV) promoter (MMTV-β1-cyto). Mammary glands from MMTV-β1-cyto transgenic females present significant growth defects during pregnancy and lactation and impaired differentiation of secretory epithelial cells at the onset of lactation. We report herein that perturbation of β1-integrin function in involuting mammary gland induced precocious dedifferentiation of the secretory epithelium, as shown by the premature decrease in β-casein and whey acidic protein mRNA levels, accompanied by inactivation of STAT5, a transcription factor essential for mammary gland development and up-regulation of nuclear factor-κB, a negative regulator of STAT5 signaling. This is the first study demonstrating in vivo that cell–extracellular matrix interactions involving β1-integrins play an important role in the control of milk gene transcription and in the maintenance of the mammary epithelial cell differentiated state.
An Endogenous RNA Transcript Antisense to CNGα1 Cation Channel mRNA
Authors: Cheng Chin-Hung , Yew David Tai-Wai , Kwan Hiu-Yee , Zhou Qing , Huang Yu , Liu Yong , Chan Wing-Yee , Yao Xiaoqiang
Published: October 2002

CNG channels are cyclic nucleotide-gated Ca2+-permeable channels that are suggested to be involved in the activity-dependent alterations of synaptic strength that are thought to underlie information storage in the CNS. In this study, we isolated an endogenous RNA transcript antisense to CNGα1 mRNA. This transcript was capable of down-regulating the expression of sense CNGα1 in theXenopus oocyte expression system. RT-PCR, Northern blot, and in situ hybridization analyses showed that the transcript was coexpressed with CNGα1 mRNA in many regions of human brain, notably in those regions that were involved in long-term potentiation and long-term depression, such as hippocampal CA1 and CA3, dentate gyrus, and cerebellar Purkinje layer. Comparison of expression patterns between adult and fetal cerebral cortex revealed that there were concurrent developmental changes in the expression levels of anti-CNG1 and CNGα1. Treatment of human glioma cell T98 with thyroid hormone T3caused a significant increase in anti-CNG1 expression and a parallel decrease in sense CNGα1 expression. These data suggest that the suppression of CNGα1 expression by anti-CNG1 may play an important role in neuronal functions, especially in synaptic plasticity and cortical development. Endogenous antisense RNA-mediated regulation may represent a new mechanism through which the activity of ion channels can be regulated in the human CNS.
Ischemic Protection and Myofibrillar Cardiomyopathy
Authors: Hahn Harvey S. , Yussman Martin G. , Toyokawa Tsuyoshi , Marreez Yehia , Barrett Thomas J. , Hilty K. Chad , Osinska Hanna , Robbins Jeffrey , Dorn Gerald W.
Published: October 2002

To delineate the in vivo cardiac functions requiring normal δ protein kinase C (PKC) activity, we pursued loss-of-function through transgenic expression of a δPKC-specific translocation inhibitor protein fragment, δV1, in mouse hearts. Initial results using the mouse α-myosin heavy chain (αMHC) promoter resulted in a lethal heart failure phenotype. Viable δV1 mice were therefore obtained using novel attenuated mutant αMHC promoters lacking one or the other thyroid response element (TRE-1 and -2). In transgenic mouse hearts, δV1 decorated cytoskeletal elements and inhibited ischemia-induced δPKC translocation. At high levels, δV1 expression was uniformly lethal, with depressed cardiac contractile function, increased expression of fetal cardiac genes, and formation of intracardiomyocyte protein aggregates. Ultrastructural and immunoconfocal analyses of these aggregates revealed focal cytoskeletal disruptions and localized concentrations of desmin and αB-crystallin. In individual cardiomyocytes, cytoskeletal abnormalities correlated with impaired contractile function. Whereas desmin and αB-crystallin protein were increased ≈4-fold in δV1 hearts, combined overexpression of these proteins at these levels was not sufficient to cause any detectable cardiac pathology. At low levels, δV1 expression conferred striking resistance to postischemic dysfunction, with no measurable effects on basal cardiac structure, function, or gene expression. Intermediate expression of δV1 conferred modest basal contractile depression with less ischemic protection, associated with abnormal cardiac gene expression, and a histological picture of infrequent cardiomyocyte cytoskeletal deformities. These results validate an approach of δPKC inhibition to protect against myocardial ischemia, but indicate that there is a threshold level of δPKC activation that is necessary to maintain normal cardiomyocyte cytoskeletal integrity.
Molecular control of lymphangiogenesis
Authors: Baldwin Megan E. , Stacker Steven A. , Achen Marc G.
Published: October 2002

The lymphatic vasculature plays a critical role in the regulation of body fluid volume and immune function. Extensive research into the molecular mechanisms that control blood vessel growth has led to identification of molecules that also regulate development and growth of the lymphatic vessels. This is generating a great deal of interest in the molecular control of the lymphatics in the context of embryogenesis, lymphatic disorders and tumor metastasis. Studies in animal models carried out over the past three years have shown that the soluble protein growth factors, vascular endothelial growth factor (VEGF)‐C and VEGF‐D, and their cognate receptor tyrosine kinase, VEGF receptor‐3 (VEGFR‐3), are critical regulators of lymphangiogenesis. Furthermore, disfunction of VEGFR‐3 has recently been shown to cause lymphedema. The capacity to induce lymphangiogenesis by manipulation of the VEGF‐C/VEGF‐D/VEGFR‐3 signaling pathway offers new opportunities to understand the function of the lymphatic system and to develop novel treatments for lymphatic disorders. BioEssays 24:1030–1040, 2002. © 2002 Wiley‐Periodicals, Inc.
Adolescent risk: The costs of affluence
Authors: Luthar Suniya S. , Latendresse Shawn J.
Published: October 2002

Within the context of a developmental psychopathology model emphasizing person‐context transactions across the life span, adjustment disturbances among youth in upper‐class suburbia are discussed. Potential reasons for these problems, involving achievement pressure and disconnection from parents, are explored.
Fibronectin Polymerization Regulates the Composition and Stability of Extracellular Matrix Fibrils and Cell-Matrix Adhesions
Authors: Sottile Jane , Hocking Denise C.
Published: October 2002

Remodeling of extracellular matrices occurs during development, wound healing, and in a variety of pathological processes including atherosclerosis, ischemic injury, and angiogenesis. Thus, identifying factors that control the balance between matrix deposition and degradation during tissue remodeling is essential for understanding mechanisms that regulate a variety of normal and pathological processes. Using fibronectin-null cells, we found that fibronectin polymerization into the extracellular matrix is required for the deposition of collagen-I and thrombospondin-1 and that the maintenance of extracellular matrix fibronectin fibrils requires the continual polymerization of a fibronectin matrix. Further, integrin ligation alone is not sufficient to maintain extracellular matrix fibronectin in the absence of fibronectin deposition. Our data also demonstrate that the retention of thrombospondin-1 and collagen I into fibrillar structures within the extracellular matrix depends on an intact fibronectin matrix. An intact fibronectin matrix is also critical for maintaining the composition of cell–matrix adhesion sites; in the absence of fibronectin and fibronectin polymerization, neither α5β1 integrin nor tensin localize to fibrillar cell–matrix adhesion sites. These data indicate that fibronectin polymerization is a critical regulator of extracellular matrix organization and stability. The ability of fibronectin polymerization to act as a switch that controls the organization and composition of the extracellular matrix and cell–matrix adhesion sites provides cells with a means of precisely controlling cell-extracellular matrix signaling events that regulate many aspects of cell behavior including cell proliferation, migration, and differentiation.
Distinct Nongenomic Signal Transduction Pathways Controlled by 17β-Estradiol Regulate DNA Synthesis and Cyclin D1Gene Transcription in HepG2 Cells
Authors: Marino Maria , Acconcia Filippo , Bresciani Francesco , Weisz Alessandro , Trentalance Anna
Published: October 2002

Estrogens induce cell proliferation in target tissues by stimulating progression through the G1 phase of the cell cycle. Activation of cyclin D1gene expression is a critical feature of this hormonal action. The existence of rapid/nongenomic estradiol-regulated protein kinase C (PKC-α) and extracellular signal-regulated kinase (ERK) signal transduction pathways, their cross talk, and role played in DNA synthesis and cyclin D1gene transcription have been studied herein in human hepatoma HepG2 cells. 17β-Estradiol was found to rapidly activate PKC-α translocation and ERK-2/mitogen-activated protein kinase phosphorylation in this cell line. These actions were independent of each other, preceding the increase of thymidine incorporation into DNA and cyclin D1expression, and did not involve DNA binding by estrogen receptor. The results obtained with specific inhibitors indicated that PKC-α pathway is necessary to mediate the estradiol-induced G1-S progression of HepG2 cells, but it does not exert any effect(s) on cyclin D1gene expression. On the contrary, ERK-2 cascade was strongly involved in both G1-S progression and cyclin D1gene transcription. Deletion of its activating protein-1 responsive element motif resulted in attenuation of cyclin D1promoter responsiveness to estrogen. These results indicate that estrogen-induced cyclin D1transcription can occur in HepG2 cells independently of the transcriptional activity of estrogen receptor, sustaining the pivotal role played by nongenomic pathways of estrogen action in hormone-induced proliferation.
Radiation-induced Activation of Nuclear Factor-κB Involves Selective Degradation of Plasma Membrane-associated IκBα
Authors: Russell Jeffery S. , Tofilon Philip J.
Published: October 2002

In contrast to nuclear factor-κB (NF-κB) activation by tumor necrosis factor-α (TNF-α), the specific processes involved in the activation of this transcription factor by ionizing radiation (IR) have not been completely defined. According to the classical paradigm, a critical event in NF-κB activation is the degradation of IκBα. Data presented herein show that, in contrast to treatment with TNF-α, IR-induced NF-κB activation was not accompanied by degradation of IκBα in the U251 glioblastoma cell line as determined in whole cell lysates. However, treatment with the proteosome inhibitor MG-132 inhibited NF-κB activation induced by IR, suggesting that IκBα degradation was a critical event in this process. To reconcile these results, U251 cell lysates were separated into soluble and insoluble fractions and IκBα levels evaluated. Although IκBα was found in both subcellular fractions, treatment with IR resulted in the degradation of IκBα only in the insoluble fraction. Further subcellular fractionation suggested that the IR-sensitive, insoluble pool of IκBα was associated with the plasma membrane. These data suggest that the subcellular location of IκBα is a critical determinant in IR-induced NF-κB activation.
Heparin and osteoporosis during pregnancy: 2002 update
Authors: Ruiz-Irastorza G , Khamashta M A , Hughes G RV
Published: October 2002

Althoughsignificant bone mass loss is rare duringpregnancy,some situationsmay increasethe risk of symptomaticosteoporosis.Heparin may be necessaryfor a number of pregnantwomen with systemic lupus erythematosus and antiphospholipid syndrome. The osteopenic effect of heparin is low even during pregnancy, and recent data point to a more favourable profile of low-molecular-weight heparins as compared with unfractionated heparin. Lactation results in a significant increase of calcium demands and may be a higher risk period for women at risk for osteoporosis.
Sex ratio and rheumatic disease: excerpts from an Institute of Medicine report
Authors: Lockshin Md
Published: October 2002

Some autoimmune diseases have high female/male (F/M) ratios. Definitions and classi”cations of autoimmune diseases differ, as do the F/M ratios themselves. The sex ratio of lupus is the single most prominent, little explored clinical fact that may lead to understanding of how lupus and other autoimmune diseases occur.

The objective of this study was to evaluate evidence for causes of high F/M ratios of autoimmune and non-immunologic diseases. This was done by a literature review.

Some thyroid, rheumatic and hepatic diseases consistently have high F/M ratios; other autoimmune diseases have low ratios. Because F/M ratios reflect disease incidence, not disease severity, an intrinsic biologic cause for the F/M ratios (such as estrogen) would be likely to act through a threshold or permissive mechanism rather than through quantitative immunomodulation. Sex differences related to environmental exposure, X-inactivation, imprinting, X or Y chromosome genes and intrauterine influences are other possible explanations for sex differences of incidence.

The epidemiology of the sex discrepant autoimmune diseases, young, female, suggests that an explanation for sex discrepancy lies in differential exposure, vulnerable periods or thresholds, rather than in quantitative aspects of immunomodulation.
Mechanisms of monocrotophos resistance in cotton bollworm, Helicoverpa armigera (Hübner)
Authors: Ren Xiaoxia , Han Zhaojun , Wang Yinchang
Published: October 2002

Insensitive acetylcholinesterase was identified as a resistance mechanism by comparing biochemical analysis with a laboratory selected monocrotophos resistant cotton bollworm (RR: 200) and the susceptible strain. The cDNA encoding AChE was cloned by the method of RACE (rapid amplification of cDNA ends). The complete AChE gene deduced from the cDNA consisted of a putative signal peptide of 32 amino acid residues, a mature protein of 615 residues, 5′ untranslated regions (UTR) of 315 bp and 3′ UTR of 324 bp. The coding sequence had a high degree of homology to the AChE from other insect species reported in the GenBank. After comparing analysis of the entire AChE gene sequence from 5 resistant and 6 susceptible cotton bollworm individuals, nine mutations were identified. One of them, the Ala/Thr mutation, is likely to be responsible for the AChE insensitivity to monocrotophos. Arch. Insect Biochem. Physiol. 51:103–110, 2002. © 2002 Wiley‐Liss, Inc.
An enhanced role model for alleviating the role‐binding anomaly
Authors: Lee Joon‐Sang , Bae Doo‐Hwan
Published: October 2002

Roles and role models have received much attention as useful concepts for developing highly reusable and dynamically evolvable systems. Role models belong to the category of collaboration‐based development techniques, but most of the existing approaches to role models do not explicitly incorporate the core principle of collaboration‐based developments as an essential property of their primary design goals. Consequently, the existing approaches still suffer from a problematic phenomenon that the structural and behavioral constraints defined in a role system can be violated during the role‐binding stage. We call such a problematic phenomenon the role‐binding anomaly. In order to alleviate the role‐binding anomaly, we propose an enhanced role model, in which all role instances and core objects can exist by themselves, namely, they can be developed, executed, and tested independently. Roles and core classes can be bound to each other at the instance level. In addition, the role system describes and encapsulates the behavior for dynamic reconfigurations among role instances. The enhanced role model is designed so as to be meaningful with respect to software engineering principles, rather than dynamic evolution. It also facilitates role model implementation using general programming languages (i.e. not supporting dynamic specialization) such as Java. To illustrate how the proposed role model makes such benefits, we develop a set of Java classes necessary for implementing the enhanced role model in the form of a Java package role, and present a simplified automatic teller machine system as an example application. Copyright © 2002 John Wiley & Sons, Ltd.
Developing a Lisp‐based preprocessor for TEX documents
Authors: Iwasaki Hideya
Published: October 2002

TEX allows users to define a macro that abstracts a sequence of typesetting commands. However, defining macros is not easy for most users, because the mechanism of macro expansion in TEX is complicated. As a remedy for this situation, a new system that enables users to define macros for TEX documents as Lisp programs has been developed. The system acts as a preprocessor for TEX; given a document that contains Lisp programs as S‐expressions, the system expands each S‐expression on the basis of Lisp's evaluation rules, thus generating an ordinary TEX document. The system is very flexible and easy‐to‐use, thanks to the underlying language's general‐purpose data structure, i.e. the S‐expression, applicative order evaluation, and rich set of predefined functions. This paper also demonstrates that the proposed system is really effective for practical use by giving some concrete examples of Lisp macros, some of which are difficult to define in terms of TEX commands. The system is currently implemented on the Emacs Lisp, and a user‐friendly environment is thus available in the Emacs text editor. Copyright © 2002 John Wiley & Sons, Ltd.
Identity processes and the positive youth development of African Americans: An explanatory framework
Authors: Swanson Dena Phillips , Spencer Margaret Beale , dell'Angelo Tabitha , Harpalani Vinay , Spencer Tirzah R.
Published: October 2002

This chapter presents Spencer's phenomenological variant of ecological systems theory, or PVEST (1995), as a conceptual framework for examining positive youth development. Contextual factors affecting racial and gender identity of African American youth are discussed, with the focus on the influence of schools and religious institutions.
Can Agricultural Labour Adjustment Occur Primarily through Creation of Rural Non-farm Jobs in China?
Authors: Gale Johnson D.
Published: October 2002

If China's rural families are to participate fully in the future economic growth there must be a large reduction in the number of farm workers. In order to accommodate the reduction needed over the next three decades, there will need to be 12-15 million new non-farm jobs created every year. Township and village enterprises have provided roughly 100 million new jobs since 1985, but in recent years there has been little increase in such jobs. One problem is that these enterprises are very small-industrial enterprises average about 11 workers. As the Chinese economy becomes more competitive, such small enterprises have had increasing difficulty in maintaining employment, let alone providing millions of new jobs each year. Where can the new jobs be provided? Due to continuing restrictions on migration, it is unlikely that many will become available in cities. An alternative is proposed, namely to promote the development of enterprises in one or two towns or small cities in each county. The worker could then continue to live in the villages and commute to their jobs on a daily basis. The advantage of this alternative is that it requires far less capital than if the same number of workers migrated with their families to cities.
What Explains China's Rising Urbanisation in the Reform Era?
Authors: Zhang Kevin Honglin
Published: October 2002

China has been transforming from a rural to an urban economy over the past century, especially since 1978 when economic reforms were initiated and rapid economic growth began. This paper attempts to investigate what factors contributed to the rising urbanisation in the period 1978-2000, based on time-series and cross-section analyses. We find that the main driving-forces behind urbanisation, besides changes in urban policy, are economic growth, structural changes and especially inflows of foreign direct investment (FDI). The causal link runs from economic growth to urbanisation and not vice versa. FDI inflows contribute greatly to the coast-inland differences in the rate of urbanisation. Geographical and historical factors have a significant impact on regional urbanisation levels and a high initial level of urbanisation curtails a province's subsequent urban growth.
A Primordial Origin of the Laplace Relation Among the Galilean Satellites
Authors: Peale S. J. , Lee Man Hoi
Published: October 2002

Understanding the origin of the orbital resonances of the Galilean satellites of Jupiter will constrain the longevity of the extensive volcanism on Io, may explain a liquid ocean on Europa, and may guide studies of the dissipative properties of stars and Jupiter-like planets. The differential migration of the newly formed Galilean satellites due to interactions with a circumjovian disk can lead to the primordial formation of the Laplace relation
n
1
– 3
n
2
+ 2
n
3
= 0, where the

n
i

are the mean orbital angular velocities of Io, Europa, and Ganymede, respectively. This contrasts with the formation of the resonances by differential expansion of the orbits from tidal torques from Jupiter.
Absence of Calsequestrin 2 Causes Severe Forms of Catecholaminergic Polymorphic Ventricular Tachycardia
Authors: Postma Alex V. , Denjoy Isabelle , Hoorntje Theo M. , Lupoglazoff Jean-Marc , Da Costa Antoine , Sebillon Pascale , Mannens Marcel M.A.M. , Wilde Arthur A.M. , Guicheney Pascale
Published: October 2002

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare arrhythmogenic disorder characterized by syncopal events and sudden cardiac death at a young age during physical stress or emotion, in the absence of structural heart disease. We report the first nonsense mutations in the cardiac calsequestrin gene,
CASQ2
, in three CPVT families. The three mutations, a nonsense R33X, a splicing 532+1 G>A, and a 1-bp deletion, 62delA, are thought to induce premature stop codons. Two patients who experienced syncopes before the age of 7 years were homozygous carriers, suggesting a complete absence of calsequestrin 2. One patient was heterozygous for the stop codon and experienced syncopes from the age of 11 years. Despite the different mutations, there is little phenotypic variation of CPVT for the CASQ2 mutations. Of the 16 heterozygous carriers of these various mutations, 14 were devoid of clinical symptoms or ECG anomalies, whereas 2 of them had ventricular arrhythmias at ECG on exercise tests. In line with this, the diagnosis of the probands was difficult because of the absence of a positive family history. In conclusion, these additional three CASQ2 CPVT families suggest that CASQ2 mutations are more common than previously thought and produce a severe form of CPVT. The full text of this article is available at http://www.circresaha.org.
Cloning, expression, and regulation by androgens of a putative member of the oxytocinase family of proteins in the rat prostate
Authors: Arenas María Isabel , Pérez‐Márquez Julio
Published: October 2002

BACKGROUND

Proteases are relevant in the physiology of the prostate, and its expression is regulated by androgens.

METHODS

Isolation of a novel cDNA from the rat prostate was done by reverse transcriptase‐polymerase chain reaction and rapid amplification of cDNA ends. By Northern blot, we analyzed the RNA expression in different tissues and in the prostate after orchidectomy and androgen treatment. By using in situ hybridization, we studied the cellular localization of the RNA.

RESULTS

The cDNA codes a putative novel form of the vp‐165 aminopeptidase family of proteins that we named short‐vp. The short‐vp probe labels one mRNA of 1.3 kb in the prostate, brain, testis, heart, and kidney. In the prostate, the levels of short‐vp mRNA decrease after orchidectomy and increase with testosterone treatment. The short‐vp mRNA is expressed by the prostatic epithelial cells.

CONCLUSION

We isolated one putative member of the oxytocinase family of proteins that is expressed in various tissues and by the epithelial cells of the prostate. The expression of short‐vp mRNA in the prostate depends on androgen levels. Prostate 53: 218–224, 2002. © 2002 Wiley‐Liss, Inc.
A Novel Conserved RNA-binding Domain Protein, RBD-1, Is Essential For Ribosome Biogenesis
Authors: Björk Petra , Baurén Göran , Jin ShaoBo , Tong Yong-Guang , Bürglin Thomas R. , Hellman Ulf , Wieslander Lars
Published: October 2002

Synthesis of the ribosomal subunits from pre-rRNA requires a large number of trans-acting proteins and small nucleolar ribonucleoprotein particles to execute base modifications, RNA cleavages, and structural rearrangements. We have characterized a novel protein, RNA-binding domain-1 (RBD-1), that is involved in ribosome biogenesis. This protein contains six consensus RNA-binding domains and is conserved as to sequence, domain organization, and cellular location from yeast to human. RBD-1 is essential in Caenorhabditis elegans. In the dipteran Chironomus tentans, RBD-1 (Ct-RBD-1) binds pre-rRNA in vitro and anti-Ct-RBD-1 antibodies repress pre-rRNA processing in vivo. Ct-RBD-1 is mainly located in the nucleolus in an RNA polymerase I transcription-dependent manner, but it is also present in discrete foci in the interchromatin and in the cytoplasm. In cytoplasmic extracts, 20–30% of Ct-RBD-1 is associated with ribosomes and, preferentially, with the 40S ribosomal subunit. Our data suggest that RBD-1 plays a role in structurally coordinating pre-rRNA during ribosome biogenesis and that this function is conserved in all eukaryotes.
Direct Observation of Internal Spin Structure of Magnetic Vortex Cores
Authors: Wachowiak A. , Wiebe J. , Bode M. , Pietzsch O. , Morgenstern M. , Wiesendanger R.
Published: October 2002

Thin film nanoscale elements with a curling magnetic structure (vortex) are a promising candidate for future nonvolatile data storage devices. Their properties are strongly influenced by the spin structure in the vortex core. We have used spin-polarized scanning tunneling microscopy on nanoscale iron islands to probe for the first time the internal spin structure of magnetic vortex cores. Using tips coated with a layer of antiferromagnetic chromium, we obtained images of the curling in-plane magnetization around and of the out-of-plane magnetization inside the core region. The experimental data are compared with micromagnetic simulations. The results confirm theoretical predictions that the size and the shape of the vortex core as well as its magnetic field dependence are governed by only two material parameters, the exchange stiffness and the saturation magnetization that determines the stray field energy.