bluuebunny/crossref_metadata_2025 huggingface dataset:
Enzymatically Modified Nonoxidized Low-Density Lipoprotein Induces Interleukin-8 in Human Endothelial Cells
Authors: Suriyaphol Prapat , Fenske Dominic , Zähringer Ulrich , Han Shan-Rui , Bhakdi Sucharit , Husmann Matthias
Published: November 2002

Background—

Treatment of low-density lipoprotein (LDL) with a protease and cholesterolesterase transforms the lipoprotein to an entity that resembles lipoprotein particles in atherosclerotic lesions, which have a high content of free cholesterol, reflecting extensive de-esterification in the intima. Because de-esterification would occur beneath the endothelium, we examined the effects of enzymatically modified LDL (E-LDL) on cultured endothelial cells.

Methods and Results—

Incubation of endothelial cells with E-LDL provoked selective accumulation of interleukin (IL)-8 mRNA and production of the cytokine. Chemical analyses and depletion experiments indicated that the effect was caused by the presence of free fatty acids in the altered lipoprotein. Reconstitution studies demonstrated that the oleic and linoleic acids associated with E-LDL are particularly effective IL-8 inducers. The effects of E-LDL on endothelial cells could be abrogated with albumin.

Conclusion—

IL-8 is required for rolling monocytes to adhere firmly to the endothelium; thus, the findings reveal a link between subendothelial entrapment of LDL, cleavage of cholesterol esters, and monocyte recruitment into the lesion.
Predictors and outcomes of scleroderma renal crisis: The high‐dose versus low‐dose D‐penicillamine in early diffuse systemic sclerosis trial
Authors: DeMarco Paul J. , Weisman Michael H. , Seibold James R. , Furst Daniel E. , Wong Weng Kee , Hurwitz Eric L. , Mayes Maureen , White Barbara , Wigley Fredrick , Barr Walter , Moreland Larry , Medsger Thomas A. , Steen Virginia , Martin Richard W. , Collier David , Weinstein Arthur , Lally Edward , Varga John , Weiner Steven R. , Andrews Brian , Abeles Micha , Clements Philip J.
Published: November 2002

Objective

The reported frequency of scleroderma M01‐R renal crisis (SRC) in diffuse systemic sclerosis (SSc; scleroderma) is 15–20%. Early use of angiotensin‐converting enzyme (ACE) inhibitors has markedly improved outcome. The present analysis reexamines the prognostic factors for and outcome of SRC in a prospective cohort of patients with early diffuse SSc.

Methods

We retrospectively evaluated the cohort of SSc patients who participated in the High‐Dose Versus Low‐Dose D‐Penicillamine in Early Diffuse SSc trial. Patients with diffuse cutaneous scleroderma were enrolled if their disease duration was <18 months. Because the trial failed to show a difference between treatment groups, the data were pooled.

Results

One hundred thirty‐four SSc patients entered the observation period a mean ± SD of 0.8 ± 0.3 years after onset of SSc. SRC occurred in 18 patients a mean ± SD of 0.9 ± 1.1 years after entry. During a mean ± SD 4.0 ± 1.1 years of followup after entry, 9 of the 18 patients died (mean ± SD 0.6 ± 0.9 years after SRC onset). Baseline characteristics that predicted SRC included a modified Rodnan skin thickness score of ≥20 (P < 0.01), enlarged cardiac silhouette on radiograph (P = 0.04), large joint contractures (wrist, elbow, knee) (P = 0.008), and prednisone use at entry (P = 0.01). Baseline characteristics that did not predict SRC included age, sex, race, Health Assessment Questionnaire score, fist closure, handspread, lung involvement, muscle weakness, erythrocyte sedimentation rate, and platelet count. In 5 of 10 subjects for whom at least 2 sequential skin scores were available, skin scores increased significantly (P = 0.012) in the 6 months before onset of SRC.

Conclusion

SRC occurred in 13% of patients soon (mean 11 months) after entry into the cohort. Predictors of SRC identified in this study included higher than average skin score, prednisone use at study entry, large joint contractures, and heart enlargement. Our data suggest, however, that low‐dose prednisone alone was not associated with the onset of SRC, except in the appropriate clinical setting. Although ACE inhibitors and dialysis are now readily available, SRC continues to be associated with poor survival (in this study, 50% of patients with SRC died).
Linear optimal control applied to instabilities
in spatially developing boundary layers
Authors: HÖGBERG MARKUS , HENNINGSON DAN S.
Published: November 2002

The work presented extends previous research on linear controllers in temporal channel flow to spatially evolving boundary layer flow. The flows studied are those on an
infinite swept wedge described by the Falkner–Skan–Cooke (FSC) velocity profiles,
including the special case of the flow over a flat plate. These velocity profiles are used
as the base flow in the Orr–Sommerfeld–Squire equations to compute the optimal
feedback control through blowing and suction at the wall utilizing linear optimal control theory. The control is applied to a parallel FSC flow with unstable perturbations.
Through an eigenvalue analysis and direct numerical simulations (DNS), it is shown
that instabilities are stabilized by the controller in the parallel case. The localization
of the convolution kernels for control is also shown for the FSC profiles.

Assuming that non-parallel effects are small a technique is developed to apply
the same controllers to a DNS of a spatially evolving flow. The performance of
these controllers is tested in a Blasius flow with both a Tollmien–Schlichting (TS)
wave and an optimal spatial transiently growing perturbation. It is demonstrated
that TS waves are stabilized and that transient growth is lowered by the controller.
Then the control is also applied to a spatial FSC flow with unstable perturbations
leading to saturated cross-flow vortices in the uncontrolled case. It is demonstrated
that the linear controller successfully inhibits the growth of the cross-flow vortices to
a saturated level and thereby delays the possibility of transition through secondary
instabilities. It is also demonstrated that the controller works for relatively high levels
of nonlinearity, and for stationary as well as time-varying perturbations.
A Javanese Handbook for Would-Be Husbands: The Sěrat Candraning Wanita
Authors: Wieringa Edwin P.
Published: November 2002

The Sěrat candraning wanita (Book of descriptions of women) is a voluminous Javanese manuscript written in Yogyakarta in the 1930s. This handbook for would-be husbands is basically an instruction manual, informing its (male) readers how to choose a good wife/sexual partner (based on physiognomy) and how sex works (based on ‘the etiquette of sexual intercourse’). It can be regarded as the swansong of pre-modern Javano-Muslim erotology.
cDNA nucleotide sequence encoding the ZPC protein of Australian hydromyine rodents: a novel sequence of the putative sperm-combining site within the family Muridae
Authors: Swann Christine A. , Hope Rory M. , Breed William G.
Published: November 2002

This comparative study of the cDNA sequence of the zona pellucida C (ZPC) glycoprotein in murid rodents focuses on the nucleotide and amino acid sequence of the putative sperm-combining site. We ask the question: Has divergence evolved in the nucleotide sequence of ZPC in the murid rodents of Australia? Using RT-PCR and (RACE) PCR, the complete cDNA coding region of ZPC in the Australian hydromyine rodents Notomys alexis and Pseudomys australis, and a partial cDNA sequence from a third hydromyine rodent, Hydromys chrysogaster, has been determined. Comparison between the cDNA sequences of the hydromyine rodents reveals that the level of amino acid sequence identity between N. alexis and P. australis is 96%, whereas that between the two species of hydromyine rodents and M. musculus and R. norvegicus is 88% and 87% respectively. Despite being reproductively isolated from each other, the three species of hydromyine rodents have a 100% level of amino acid sequence identity at the putative sperm-combining site. This finding does not support the view that this site is under positive selective pressure. The sequence data obtained in this study may have important conservation implications for the dissemination of immunocontraception directed against M. musculus using ZPC antibodies.
Case study 1: top of the class
Authors: Tavernor Robert
Published: November 2002

Inevitably, as some went up the
pecking order and others down,
the results of the latest Research
Assessment Exercise will have
delighted some schools of
architecture and disappointed
others. Now may be the time for
recriminations and breast-beating.
But it would be dangerous for
architecture's standing in the
academic firmament if it were to
claim separate status or that
research is somehow different for
architects. Instead it is important
that the architecture community
responds positively to the outcome
and understands what it takes to
succeed within the rules. A
fundamental question to be asked
is whether the judgements meted
out were deserved.
Considerations for Antipsychotic Therapy: Implications for the Safe and Appropriate Management of Patients
Authors: Boyd Mary Ann
Published: November 2002

We are pleased to present highlights of the 2001 American Psychiatric Nurses Association symposium entitled “Considerations for Antipsychotic Therapy: Implications for the Safe and Appropriate Management of Patients.” This symposium presented several timely discussions on antipsychotic therapy from the clinical standpoint: decreasing stress and trauma to the psychiatric patient and staff, improving patient long-term health and treatment success, and fostering effective therapeutic relationships.
The evolution of fungus-growing termites and their mutualistic fungal symbionts
Authors: Aanen Duur K. , Eggleton Paul , Rouland-Lefèvre Corinne , Guldberg-Frøslev Tobias , Rosendahl Søren , Boomsma Jacobus J.
Published: November 2002

We have estimated phylogenies of fungus-growing termites and their associated mutualistic fungi of the genus
Termitomyces
using Bayesian analyses of DNA sequences. Our study shows that the symbiosis has a single African origin and that secondary domestication of other fungi or reversal of mutualistic fungi to a free-living state has not occurred. Host switching has been frequent, especially at the lower taxonomic levels, and nests of single termite species can have different symbionts. Data are consistent with horizontal transmission of fungal symbionts in both the ancestral state of the mutualism and most of the extant taxa. Clonal vertical transmission of fungi, previously shown to be common in the genus
Microtermes
(via females) and in the species
Macrotermes bellicosus
(via males) [Johnson, R. A., Thomas, R. J., Wood, T. G. & Swift, M. J. (1981)
J. Nat. Hist.
15, 751–756], is derived with two independent origins. Despite repeated host switching, statistical tests taking phylogenetic uncertainty into account show a significant congruence between the termite and fungal phylogenies, because mutualistic interactions at higher taxonomic levels show considerable specificity. We identify common characteristics of fungus-farming evolution in termites and ants, which apply despite the major differences between these two insect agricultural systems. We hypothesize that biparental colony founding may have constrained the evolution of vertical symbiont transmission in termites but not in ants where males die after mating.
Motion perception of saccade-induced retinal translation
Authors: Castet Eric , Jeanjean Sébastien , Masson Guillaume S.
Published: November 2002

Active visual perception relies on the ability to interpret correctly retinal motion signals induced either by moving objects viewed with static eyes or by stationary objects viewed with moving eyes. A motionless environment is not normally perceived as moving during saccadic eye movements. It is commonly believed that this phenomenon involves central oculomotor signals that inhibit intrasaccadic visual motion processing. The keystone of this extraretinal theory relies on experimental reports showing that physically stationary scenes displayed only during saccades, thus producing high retinal velocities, are never perceived as moving but appear as static blurred images. We, however, provide evidence that stimuli optimized for high-speed motion detection elicit clear motion perception against saccade direction, thus making the search for extraretinal suppression superfluous. The data indicate that visual motion is the main cue used by observers to perform the task independently of other perceptual factors covarying with intrasaccadic stimulation. By using stimuli of different durations, we show that the probability of perceiving the stimulus as static, rather than moving, increases when the intrasaccadic stimulation is preceded or followed by a significant extrasaccadic stimulation. We suggest that intrasaccadic motion perception is accomplished by motion-selective magnocellular neurons through temporal integration of rapidly increasing retinal velocities. The functional mechanism that usually prevents this intrasaccadic activity from being perceived seems to rely on temporal masking effects induced by the static retinal images present before and/or after the saccade.
HYPERBOLIC TOPOLOGICAL INVARIANTS AND THE BLACK HOLE GEOMETRY
Authors: BYTSENKO A. A. , ELIZALDE E. , SUKHANOV S. A.
Published: November 2002

We discuss the isometry group structure of three-dimensional black holes and Chern–Simons invariants. Aspects of the holographic principle relevant to black hole geometry are analyzed.
MACH's PHILOSOPHY, HIS CRITICISM OF THE NEWTONIAN SPACE-TIME CONCEPTION AND THE POSSIBILITY OF A DEDUCTIVE COSMOLOGY
Authors: WAHSNER RENATE
Published: November 2002

It is argued that the universe as a whole is not tractable as physical system. Since, as Mach stated, physical notions referring to the universe as a whole have no tangible sense because they imply applications of measurement notions to an object that is not accessible to measurement. Therefore, as well deductive cosmology as extrapolating cosmology contain fundamental difficulties.
VACUUM POLARIZATION BY A MAGNETIC FIELD IN THE COSMIC STRING SPACETIME
Authors: SPINELLY J. , BEZERRA DE MELLO E. R.
Published: November 2002

In this paper we consider a charged massless scalar quantum field operator in the spacetime of an idealized cosmic string which presents a magnetic field confined in a cylindrical tube of finite radius. Three distinct situations are taken into account in this analysis. In three cases the axis of the infinitely long tube of radius R coincides with the cosmic string. Because we study the combined gravitational and electromagnetic Aharanov-Bohm effect, we calculate the vacuum polarization effects outside the tube.
W. GORDON'S INTEGRAL (1929) AND ITS REPRESENTATIONS BY MEANS OF APPELL'S FUNCTIONS F2, F1 AND F3
Authors: TARASOV V. F.
Published: November 2002

Exact analytical representations for W. Gordon's integral by means of Appell's functions are given. It is shown that they correlate between each other. But representation of this integral by means of Appell's function F2 is more attractive.
The Genetics of RNA Silencing
Authors: Tijsterman Marcel , Ketting René F. , Plasterk Ronald H. A.
Published: November 2002

▪ Abstract  Although initially recognized as a handy tool to reduce gene expression, RNA silencing, triggered by double-stranded RNA molecules, is now recognized as a mechanism for cellular protection and cleansing: It defends the genome against molecular parasites such as viruses and transposons, while removing abundant but aberrant nonfunctional messenger RNAs. The underlying mechanisms in distinct gene silencing phenomena in different genetic systems, such as cosuppression in plants and RNAi in animals, are very similar. There are common RNA intermediates, and similar genes are required in RNA silencing pathways in protozoa, plants, fungi, and animals, thus indicating an ancient pathway. This chapter gives an overview of both biochemical and genetic approaches leading to the current understanding of the molecular mechanism of RNA silencing and its probable biological function.
Telechelic cis‐1,4‐oligoisoprenes through the selective oxidolysis of epoxidized monomer units and polyisoprenic monomer units in cis‐1,4‐polyisoprenes
Authors: Gillier‐Ritoit Sandrine , Reyx Danièle , Campistron Irène , Laguerre Albert , Pal Singh Raj
Published: November 2002

Telechelic cis‐1,4‐oligoisoprenes were prepared by the selective cleavage of weak epoxidized units (E) in epoxidized cis‐1,4‐polyisoprenes (EPIs) and by the random cleavage of isoprenic units (I) in cis‐1,4‐polyisoprene (PI). In both cases, cleavage by periodic acid (H5IO6) in tetrahydrofuran led to aldehydic and ketonic chain ends. Through variations in the E/(I + E) molar percentage (E%) in the cleavage of EPI and through variations in the H5IO6/I molar percentage (PA%) in the cleavage of PI, a polydispersity index near 2 and a number‐average molecular weight of 2 – 20 × 103 were obtained. The correlation of the degree of scission with E% and PA%, combined with kinetic, led to the proposal of a two‐step mechanism for the H5IO6 cleavage of double bonds. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 87: 42–46, 2003
Diimide hydrogenation of isoprene–styrene diblock copolymers
Authors: Phinyocheep Pranee , Pasiri Sureemas , Tavichai Orasa
Published: November 2002

Isoprene–styrene diblock copolymers of various molecular weights were prepared by anionic polymerization with n‐BuLi in cyclohexane. Hydrogenation of the unsaturated backbone of the block copolymers was performed with diimide generated in situ by the thermolysis of p‐toluenesulfonylhydrazide (TSH). The reaction was carried out in xylene at 135°C. A molar ratio of TSH to double bonds equal to 4:1 was found to be the optimum ratio, which provided the highest percentage of hydrogenation. The percentage of hydrogenation analyzed by 1H‐NMR, IR spectroscopy, and iodine value (the Wijs method) were compared. Evidence from 1H‐NMR also revealed a change in the ratio of the cis–trans configuration after hydrogenation. The thermal stability of the hydrogenated products was improved as shown by the results from thermogravimetric analysis. From differential scanning calorimetry measurements, the glass‐transition temperatures of the hydrogenated products were found to increase about 10–20°C above those of the original block copolymers. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 87: 76–82, 2003
Cell‐derived microparticles in synovial fluid from inflamed arthritic joints support coagulation exclusively via a factor VII–dependent mechanism
Authors: Berckmans René J. , Nieuwland Rienk , Tak Paul Peter , Böing Anita N. , Romijn Fred P. H. T. M. , Kraan Maarten C. , Breedveld Ferdinand C. , Hack C. Erik , Sturk Augueste
Published: November 2002

Objective

To determine the cellular origin of synovial microparticles, their procoagulant properties, and their relationship to local hypercoagulation.

Methods

Microparticles in synovial fluid and plasma from patients with rheumatoid arthritis (RA; n = 10) and patients with other forms of arthritis (non‐RA; n = 10) and in plasma from healthy subjects (n = 20) were isolated by centrifugation. Microparticles were identified by flow cytometry. The ability of microparticles to support coagulation was determined in normal plasma. Concentrations of prothrombin fragment F1+2 (by enzyme‐linked immunosorbent assay [ELISA]) and thrombin–antithrombin (TAT) complexes (by ELISA) were determined as estimates of the coagulation activation status in vivo.

Results

Plasma from patients and healthy controls contained comparable numbers of microparticles, which originated from platelets and erythrocytes. Synovial microparticles from RA patients and non‐RA patients originated mainly from monocytes and granulocytes; few originated from platelets and erythrocytes. Synovial microparticles bound less annexin V (which binds to negatively charged phospholipids) than did plasma microparticles, exposed tissue factor, and supported thrombin generation via factor VII. F1+2 (median 66 nM) and TAT complex (median 710 μg/liter) concentrations were elevated in synovial fluid compared with plasma from the patients (1.6 nM and 7.0 μg/liter, respectively) as well as the controls (1.0 nM and 2.9 μg/liter, respectively).

Conclusion

Synovial fluid contains high numbers of microparticles derived from leukocytes that are strongly coagulant via the factor VII–dependent pathway. We propose that these microparticles contribute to the local hypercoagulation and fibrin deposition in inflamed joints of patients with RA and other arthritic disorders.
Regulation of fibronectin and metalloproteinase expression by Wnt signaling in rheumatoid arthritis synoviocytes
Authors: Sen Malini , Reifert Jack , Lauterbach Kevin , Wolf Vladimir , Rubin Jeffrey S. , Corr Maripat , Carson Dennis A.
Published: November 2002

Objective

The enhanced release of extracellular matrix proteins by fibroblast‐like synoviocytes (FLS) from rheumatoid arthritis (RA) patients is suggestive of joint remodeling. Because Wnt proteins play a critical role in joint development, we investigated whether up‐regulated Wnt signaling plays a role in the enhanced synthesis of extracellular matrix proteins. The purpose of the present experiments was to determine the role of Wnt‐1–like molecules in the expression of matrix proteins by RA FLS and to ascertain the effects of Wnt antagonists on RA FLS function and survival.

Methods

Transfection with a reporter plasmid (TOPflash) was performed to assess whether Wnt signaling is active in RA FLS. Wnt signaling was up‐regulated in normal FLS by transfection with a Wnt‐1 expression plasmid and was down‐regulated in RA FLS by transfection with dominant‐negative lymphoid enhancer factor 1 (LEF‐1)/T cell factor 4 (TCF‐4) and secreted Frizzled receptor protein 1 (sFRP‐1) expression plasmids. Recombinant sFRP‐1 and anti–Wnt‐1 antibody were also administered to RA FLS to block Wnt signaling.

Results

RA FLS had constitutive activation of the canonical Wnt signaling pathway. Transfection of normal FLS with a Wnt‐1 expression vector enhanced not only fibronectin, but also pro–matrix metalloproteinase 3 (proMMP‐3) expression. In a complementary manner, interference with Wnt signaling using anti–Wnt‐1 antibody, the Wnt antagonist sFRP‐1, or dominant‐negative vectors that inhibited the transcription factors TCF‐4/LEF‐1 blocked the expression of fibronectin by RA FLS and reduced cell survival. Anti–Wnt‐1 antibody and sFRP‐1 also blocked the expression of proMMP‐3.

Conclusion

Our results indicate that the canonical Wnt pathway regulates fibronectin and metalloproteinase expression in RA FLS.
Autoimmune responses to proliferating cell nuclear antigen multiprotein complexes involved in cell proliferation are strongly associated with their structure and biologic function in patients with systemic lupus erythematosus
Authors: Kogure Toshiaki , Takasaki Yoshinari , Takeuchi Ken , Yamada Hirofumi , Nawata Masuyuki , Ikeda Keigo , Matsushita Masakazu , Matsudaira Ran , Kaneda Kazuhiko , Terasawa Katsutoshi , Hashimoto Hiroshi
Published: November 2002

Objective

To analyze the reaction of lupus sera with proliferating cell nuclear antigen (PCNA) multiprotein complexes (PCNA complexes), which are part of the protein machinery involved in cell proliferation.

Methods

PCNA complexes were purified from rabbit thymus extract by affinity chromatography using anti‐PCNA monoclonal antibodies (TOB7, TO17, and TO30); monomeric and trimeric PCNA forms (AK‐PCNA) were purified using anti‐PCNA serum AK. The reactions to these antigens of 10 anti‐PCNA–positive and 40 anti‐PCNA–negative sera selected from 560 lupus patients were tested by immunoblotting, immunoprecipitation, and enzyme‐linked immunosorbent assays (ELISAs).

Results

With one exception (serum OK), anti‐PCNA–positive sera reacted exclusively with only the 34‐kd polypeptide. In contrast, 14 of 40 anti‐PCNA–negative sera reacted with multiple proteins within PCNA complexes. Most anti‐PCNA–positive sera probably recognize as epitopes the binding sites for other proteins on PCNA, which are likely hidden when PCNA is complexed with other proteins. As a consequence, only serum OK reacted with the PCNA complex in a series of ELISAs. Using AK‐PCNA as a competitive inhibitor, it was determined that serum OK reacts with both the 58‐kd polypeptide and the 34‐kd PCNA within complexes. Together with the results of a longitudinal analysis, these results suggest that the immune system of patient OK likely recognized the complexed PCNA protein, after which the autoimmune response spread to other elements of the complexes.

Conclusion

Intermolecular–intrastructural help, leading to the spread of autoimmune response from PCNA to other proteins associated with its biologic function, plays a crucial role in the induction of the autoimmune response seen in lupus patients.
Autoantibodies to lipoprotein lipase and dyslipidemia in systemic lupus erythematosus
Authors: Reichlin Morris , Fesmire James , Quintero‐Del‐Rio Ana I. , Wolfson‐Reichlin Marianne
Published: November 2002

Objective

To demonstrate the binding of bovine lipoprotein lipase (LPL) by IgG from sera obtained from patients with systemic lupus erythematosus (SLE) and other rheumatic diseases, and the relationship of anti‐LPL to triglyceride levels in SLE.

Method

Binding of LPL by IgG from sera obtained from patients with SLE and other rheumatic diseases was measured by an enzyme‐linked immunosorbent assay technique. Lipid profiles for fasting blood samples obtained from SLE patients and control subjects were determined.

Results

Sera obtained from 105 patients with SLE were assessed for reactivity with LPL, and 49 (47%) of the results were positive. Sera obtained from patients with rheumatoid arthritis (RA) (n = 80), Sjögren's syndrome (n = 30), polymyositis and dermatomyositis (n = 30), and progressive systemic sclerosis (n = 31) were also studied, and 10 (13%), 3 (10%), 12 (40%), and 13 (42%), respectively, were positive for reactivity with LPL. It was determined that all affinity‐purified anti–double‐stranded DNA (dsDNA) antibodies and 4 of 5 monoclonal anti‐dsDNA antibodies bound to LPL. The binding of IgG depleted of anti‐dsDNA to LPL indicates a second anti‐LPL activity in SLE. Measurements of fasting lipid levels in SLE patients with anti‐LPL revealed a strong positive correlation of antibody levels and total serum triglycerides, apolipoprotein B, and apolipoprotein E concentrations.

Conclusion

Antibodies to LPL occurred in 47% of SLE patients and in a similar percentage of patients with polymyositis or systemic sclerosis. The prevalence of these antibodies was less in patients with RA or Sjögren's syndrome. It is hypothesized that the elevated triglyceride levels in SLE patients are in part attributable to anti‐LPL, and this lipid abnormality could contribute to the premature atherosclerosis known to be present in patients with SLE.
Interpreting 2hJ(F,N), 1hJ(H,N) and 1J(F,H) in the hydrogen‐bonded FH–collidine complex
Authors: Del Bene Janet E. , Bartlett Rodney J. , Elguero José
Published: November 2002

Ab initio EOM‐CCSD calculations were performed to determine 19F,1H, 19F,15N and 1H,15N spin–spin coupling constants in model complexes FH–NH3 and FH–pyridine as a function of the F—H and F—N distances. The absolute value of 1J(F,H) decreases and that of 1hJ(H,N) increases rapidly along the proton‐transfer coordinate, even in the region of the proton‐shared F—H—N hydrogen bond. In contrast, 2hJ(F,N) remains essentially constant in this region. These results are consistent with the recently reported experimental NMR spectra of FH–collidine which show that 1hJ(H,N) increases and 1J(F,H) decreases, while 2hJ(F,N) remains constant as the temperature of the solution decreases. They suggest that the FH–collidine complex is stabilized by a proton‐shared hydrogen bond over the range of experimental temperatures investigated, being on the traditional side of quasi‐symmetric at high temperatures, and on the ion‐pair side at low temperatures. Copyright © 2002 John Wiley & Sons, Ltd.
NMR diffusion measurements of strong signals: the PGSE‐Q‐switch experiment
Authors: Price William S. , Wälchli Markus
Published: November 2002

NMR diffusion measurements of samples with strong resonances are particularly problematic owing to the effects of radiation damping and become even more difficult at higher static fields and with more sensitive probes. Here, a new PGSE sequence incorporating Q‐switching that totally removes the effects of radiation damping is presented. The sequence affords the possibility of performing diffusion measurements of concentrated samples at normal sample volumes at high field, and thus has particular relevance for gradient calibration, diffusive diffraction and LC–NMR experiments. Further, because the relaxation behaviour of all of the species is unaffected by radiation damping, the incorporation of sophisticated sequence elements is facilitated and data analysis is simplified. The new sequence is demonstrated on a sample containing 90% water and 1% ethanol. Copyright © 2002 John Wiley & Sons, Ltd.
Use of 1H NMR‐determined diffusion coefficients to characterize lipoprotein fractions in human blood plasma
Authors: Liu Maili , Tang Huiru , Nicholson Jeremy K. , Lindon John C.
Published: November 2002

The 1H NMR spectra of human blood plasma show, inter alia, prominent resonances from the methyl and methylene groups of the fatty acyl chains from the triglycerides, phospholipids and cholesteryl esters of lipoproteins. Each band shows some degree of peak resolution due to chemical shift differences between the lipoprotein fractions, namely very low‐density lipoprotein (VLDL), low‐density lipoprotein (LDL) and high‐density lipoprotein (HDL). In order to assign resonances within the NMR bands to individual lipoproteins, previous studies relied upon the measurement of pure fractions obtained by ultracentrifugation. Here a new approach was used where the lipoprotein peaks in the NMR spectrum were deconvolved mathematically and the area of each sub‐peak was monitored using an NMR pulse sequence to yield the diffusion coefficient relating to each sub‐peak and hence to each type of lipoprotein. The validity of the deconvolution results was confirmed by comparison of 1H NMR spectra measured at 600 and 800 MHz. The diffusion coefficient is directly related to the hydrodynamic radius of the particle and hence provides an unambiguous assignment. The derived diffusion coefficients of the lipoprotein fractions therefore provide a direct assignment of the NMR bands and also give a measure of lipoprotein particle size, the results being in agreement with those from conventional measurements. Copyright © 2002 John Wiley & Sons, Ltd.
Translational diffusion measured by PFG‐NMR on full length and fragments of the Alzheimer Aβ(1–40) peptide. Determination of hydrodynamic radii of random coil peptides of varying length
Authors: Danielsson Jens , Jarvet Jüri , Damberg Peter , Gräslund Astrid
Published: November 2002

PFG‐NMR methods were used to measure the translational diffusion coefficients for the Aβ peptide involved in Alzheimer's disease and also for a series of fragments of this peptide. The peptides ranged from a pentamer to the full length Aβ(1–40). They were studied at 25° C and physiological pH in aqueous solution. The measured diffusion coefficients, including those of known monomeric peptides, were fitted without systematic deviations to a scaling law function of the molecular mass. We concluded that under these conditions Aβ(1–40) is in monomeric form. From the diffusion coefficient data, hydrodynamic radii rH were evaluated for the peptides. When combining our results on non‐ or weakly structured peptides with previously reported results on denatured proteins, we found that the hydrodynamic radii for the combined dataset could be well described by the same scaling law relating them to the molecular weight. The same law would even encompass data on single amino acids and di‐ and tripeptides measured by classical methods. From the above‐mentioned experimental data, scaling law parameters were determined. The relation between the measured hydrodynamic radius (rH) and the molecular weight of the polypeptide chain (Mr) for amino acids, peptides and denatured proteins is rH = 0.27Mr0.50 Å. There is a remarkably good fit to this function for the measured hydrodynamic radii in a large range, almost three orders of magnitude, of molecular weights. The numerical value of the exponent, 0.5, is an indication that these polymers behave as Gaussian chains. Copyright © 2002 John Wiley & Sons, Ltd.
Composite concrete‐timber structures
Authors: Ceccotti Ario
Published: November 2002

Composite concrete–timber building and bridge structures are gaining in importance throughout the world. The approach is to pour fresh concrete over the timber. Mechanical linkage between hardened concrete and timber is provided through keyed indentations in the timber or various sorts of mechanical fasteners inserted in the timber before the concrete is poured. The technique is commented on from research and design points of view.
The interactive dynamics of flow and
directional solidification in a Hele-Shaw cell
Part 2. Stability analysis and nonlinear
simulations
Authors: BUDDHAVARAPU SUDHIR S. , MEIBURG ECKART
Published: November 2002

A linear stability analysis as well as nonlinear simulations are performed in order
to analyse the coupling between the directional solidification of a binary alloy and
the flow in its melt. An incompressible, potential flow model is assumed, whose
validity is tested through comparisons with the accompanying experiments of Zhang
& Maxworthy (2002) in a Hele-Shaw cell. The linear stability analysis predicts that
a uniform flow parallel to the interface reduces the growth rates of directional
solidification instabilities. In addition, the dominant wavelength is shifted to larger
values by the flow, and a small propagation velocity in the downstream direction is
observed. These findings are confirmed by the nonlinear simulations as well. While
the overall stabilization is confirmed by the experiments, the predicted values of the
dominant wavenumber and its growth rate are too high by factors of two and four,
respectively. These differences are attributed to the existence of a velocity boundary
layer in the melt, which strongly affects the lateral solute transport.
The VOC's Trade in Indian Textiles with Burma, 1634-80
Authors: Dijk Wil O.
Published: November 2002

The VOC's Burma trade was based on Indian textiles, particularly the cheaper, coarser varieties which would have been surprisingly affordable to the common man or woman. Burmese profits helped fill the coffers of the Company's factories in Coromandel and Bengal. In the end, however, the VOC's establishment in Burma became the victim of a general change in Dutch fortunes.
Transcriptional activity associated with meiotic competence in fully grown mouse GV oocytes
Authors: Liu Honglin , Aoki Fugaku
Published: November 2002

The involvement of cumulus cells and chromatin organisation in transcriptional activity was investigated. In addition, the relationship between transcriptional activity and meiotic competence in fully grown mouse oocytes was surveyed. Transcriptional activity was detected in fully grown oocytes in which chromatin did not surround the nucleolus in the germinal vesicle (NSN-type oocytes), but not in oocytes in which chromatin surrounded the nucleolus (SN-type oocytes). Cumulus cells seemed to downregulate transcriptional activity in NSN-type oocytes, since transcriptional activity was 3 times greater in the denuded NSN-type oocytes free of cumulus cells (DO oocytes) than in NSN-type oocytes enclosed in cumulus cells (COC oocytes). Higher transcriptional
activity corresponded to lower germinal vesicle breakdown (GVB)
competence of fully grown oocytes in culture. Although GVB occurred in nearly
all (99%) the SN-type oocytes, it occurred in 88% of COC/NSN-type oocytes
(cumulus-oocyte complex with SN-type configuration) and in 61% of DO/NSN-type oocytes (denuded oocytes with NSN-type configuration). There was a negative correlation between transcriptional activity and the capacity of a cell to complete the progression to the second metaphase (MII). In GVB oocytes, the percentage of first polar body (PBI) extrusion differed among COC/NSN-type (81%), DO/SN-type (66%), COC/NSN-type (47%) and DO/NSN-type (29%) oocytes. After activation with 10 mM Sr2+, the frequency of parthenogenetic activation was greater in SN-type oocytes (46.9%) than in transcriptionally active NSN-type oocytes (27.5%). These results suggest that transcriptional activity has a detrimental effect on the competence of meiotic maturation and subsequent activation in fully grown GV oocytes. Alternatively, active transcription in the fully grown oocytes suggests that they are still in the process of synthesising substances required for meiotic maturation and are not yet competent for these processes.
Conversation with Steven Holl
Authors: Fisher Thomas
Published: November 2002

Steven Holl, Time Magazine's Architect of the Year, has had his own office in New York since
1976 and has taught at Columbia University since 1981. Winner of over 20 honour awards from the American
Institute of Architects, he has published widely and become one of the most visionary architectural thinkers
and practitioners of our time. Thomas Fisher interviewed him for arq
Necessity and Poetry: David Lea's Bridge Pottery
Authors: Hawkes Dean
Published: November 2002

This small pavilion and related earth-bound woodstore demonstrate
how, on a modest budget, the necessary can rise to the level of the
poetic. An appendix summarises the architect's design approach
Look outwards – or slip lower
Authors: Worthington John
Published: November 2002

Your leader (arq 6/1, p3) raised the
critical issue of the nature of
architectural research and where
the responsibility and leadership
should rest. You rightly point out
that the dilemma for schools of
architecture is how to integrate
design thinking and research, and
whether to see research as arts and
design-based or part of the
tradition of the physical sciences.
Immediate and delayed VEGF‐mediated NO synthesis in endothelial cells: Role of PI3K, PKC and PLC pathways
Authors: Gélinas David S , Bernatchez Pascal N , Rollin Simon , Bazan Nicolas G , Sirois Martin G
Published: November 2002

The mechanism(s) by which vascular endothelial growth factor (VEGF) induces endothelial nitric oxide synthase (eNOS) activation remain(s) unclear up to a certain extent. Therefore, we sought to evaluate the contribution of numerous pathways in VEGF‐induced nitric oxide (NO) synthesis by measuring cGMP production. In addition, as VEGF induces the synthesis of NO and platelet‐activating factor (PAF), we wanted to assess if the induction of PAF and NO is contributing to the synthesis of each other.

Herein, we show that a treatment of endothelial cells with a phospholipase C (PLC) inhibitor (U73122), a calmodulin antagonist (W‐7) or with intracellular calcium chelators (EGTA/AM, BAPTA/AM) prevented VEGF‐mediated eNOS Ser1177‐phosphorylation and NO synthesis measured by cGMP production.

Pretreatment with phosphatidylinositol 3‐kinase (PI3K) (Wortmannin, LY294002) or protein kinase C (PKC) (GF109203X, Ro318220) inhibitors attenuated eNOS Ser1177‐phosphorylation mediated by VEGF, but did not alter immediate (0–10 min) cGMP synthesis induced by VEGF, but abrogated by up to 84% the delayed (10–30 min) cGMP synthesis.

Pretreatment with PAF synthesis inhibitors or with PAF receptor antagonists did not abrogate neither eNOS Ser1177‐phosphorylation nor cGMP synthesis mediated by VEGF.

In conclusion, VEGF induces an immediate cGMP synthesis through the PLC‐Ca2+/CaM pathway, and that the induction of delayed cGMP synthesis implies Akt and PKC activity.

British Journal of Pharmacology (2002) 137, 1021–1030. doi:10.1038/sj.bjp.0704956
Disruption of the checkpoint kinase 1/cell division cycle 25A pathway abrogates ionizing radiation-induced S and G
2
checkpoints
Authors: Zhao Hui , Watkins Janis L. , Piwnica-Worms Helen
Published: November 2002

Checkpoint kinase (Chk)1 is an evolutionarily conserved protein kinase that was first identified in fission yeast as an essential component of the DNA damage checkpoint. In mice, Chk1 provides an essential function in the absence of environmentally imposed genotoxic stress. Here we show that human cells lacking Chk1 exhibit defects in both the ionizing radiation (IR)-induced S and G
2
checkpoints. In addition, loss of Chk1 resulted in the accumulation of a hypophosphorylated form of the Cdc25A protein phosphatase, and Chk1-deficient cells failed to degrade Cdc25A after IR. The IR-induced S and G
2
checkpoints were partially restored in Chk1-deficient cells when Cdc25A accumulation was interfered with. Finally, Cdc25A was phosphorylated by Chk1
in vitro
on similar sites phosphorylated
in vivo
, including serine-123. These findings indicate that Chk1 directly phosphorylates Cdc25A during an unperturbed cell cycle, and that phosphorylation of Cdc25A by Chk1 is required for cells to delay cell cycle progression in response to double-strand DNA breaks.
Orphan G protein-coupled receptors MrgA1 and MrgC11 are distinctively activated by RF-amide-related peptides through the Gα
q/11
pathway
Authors: Han Sang-Kyou , Dong Xinzhong , Hwang Jong-Ik , Zylka Mark J. , Anderson David J. , Simon Melvin I.
Published: November 2002

MrgA1 and MrgC11 belong to a recently identified family of orphan G-protein coupled receptors, called mrgs (
m
as-
r
elated
g
enes). They are only expressed in a specific subset of sensory neurons that are known to detect painful stimuli. However, the precise physiological function of Mrg receptors and their underlying mechanisms of signal transduction are not known. We therefore have screened a series of neuropeptides against human embryonic kidney (HEK) 293 cells that stably express either MrgA1 or MrgC11 to identify ligands and/or agonists. MrgA1- or MrgC11-specific agonists stimulated dose-dependent increases in intracellular free Ca
2+
in a pertussis toxin-insensitive manner, but failed to alter basal or forskolin-stimulated levels of intracellular cAMP. Furthermore, studies using embryonic fibroblasts derived from various Gα protein knockout mice demonstrated that both the MrgA1 and MrgC11 receptors are coupled to the Gα
q/11
signaling pathway. Screening of neuropeptides identified surrogate agonists, most of these peptides included a common C-terminal -RF(Y)G or -RF(Y) amide motif. Structure-function studies suggest that endogenous ligands of Mrg receptors are likely to be RF(Y)G and/or RF(Y) amide-related peptides and that postprocessing of these peptides may serve to determine Mrg receptor-ligand specificity. The differences in ligand specificity also suggest functional diversity amongst the Mrg receptors.
Prebiotic synthesis from CO atmospheres: Implications for the origins of life
Authors: Miyakawa Shin , Yamanashi Hiroto , Kobayashi Kensei , Cleaves H. James , Miller Stanley L.
Published: November 2002

Most models of the primitive atmosphere around the time life originated suggest that the atmosphere was dominated by carbon dioxide, largely based on the notion that the atmosphere was derived via volcanic outgassing, and that those gases were similar to those found in modern volcanic effluent. These models tend to downplay the possibility of a strongly reducing atmosphere, which had been thought to be important for prebiotic synthesis and thus the origin of life. However, there is no definitive geologic evidence for the oxidation state of the early atmosphere and bioorganic compounds are not efficiently synthesized from CO
2
atmospheres. In the present study, it was shown that a CO-CO
2
-N
2
-H
2
O atmosphere can give a variety of bioorganic compounds with yields comparable to those obtained from a strongly reducing atmosphere. Atmospheres containing carbon monoxide might therefore have been conducive to prebiotic synthesis and perhaps the origin of life. CO-dominant atmospheres could have existed if the production rate of CO from impacts of extraterrestrial materials were high or if the upper mantle had been more reduced than today.
Structural features of cytochrome
c
′ folding intermediates revealed by fluorescence energy-transfer kinetics
Authors: Lee Jennifer C. , Engman K. Cecilia , Tezcan F. Akif , Gray Harry B. , Winkler Jay R.
Published: November 2002

We employed fluorescence energy-transfer probes to investigate the polypeptide dynamics accompanying cytochrome
c
′ folding. Analysis of fluorescence energy-transfer kinetics from wild-type Trp-72 or Trp-32 in a crystallographically characterized (1.78 Å) Q1A/F32W/W72F mutant shows that there is structural heterogeneity in denatured cytochrome
c
′. Even at guanidine hydrochloride concentrations well beyond the unfolding transition, a substantial fraction of the polypeptides (≈50%) adopts compact conformations (tryptophan-to-heme distance, ≈25 Å) in both pseudo-wild-type (Q1A) and mutant proteins. A burst phase (≤5 ms) is revealed when stopped flow-triggered refolding is probed by tryptophan intensity: measurements on the Q1A protein show that ≈75% of the Trp-72 fluorescence (83% for Trp-32) is quenched within the mixing deadtime, suggesting that most of the polypeptides have collapsed.
Shape perception reduces activity in human primary visual cortex
Authors: Murray Scott O. , Kersten Daniel , Olshausen Bruno A. , Schrater Paul , Woods David L.
Published: November 2002

Visual perception involves the grouping of individual elements into coherent patterns that reduce the descriptive complexity of a visual scene. The physiological basis of this perceptual simplification remains poorly understood. We used functional MRI to measure activity in a higher object processing area, the lateral occipital complex, and in primary visual cortex in response to visual elements that were either grouped into objects or randomly arranged. We observed significant activity increases in the lateral occipital complex and concurrent reductions of activity in primary visual cortex when elements formed coherent shapes, suggesting that activity in early visual areas is reduced as a result of grouping processes performed in higher areas. These findings are consistent with predictive coding models of vision that postulate that inferences of high-level areas are subtracted from incoming sensory information in lower areas through cortical feedback.
Viable hypomorphic signaling mutant of the Met receptor reveals a role for hepatocyte growth factor in postnatal cerebellar development
Authors: Ieraci Alessandro , Forni Paolo E. , Ponzetto Carola
Published: November 2002

Cerebellar development occurs mainly postnatally and implies cell proliferation and migration. Hepatocyte growth factor (HGF) and Met are involved in mediating these responses in other tissues and are coexpressed in the cerebellum. Here we show that Met is localized in granule cell precursors and that cultures of these cells respond to HGF with proliferation. To study the role of HGF and Met in the cerebellum
in vivo
, we produced a viable hypomorphic Met mutant by knocking in the
met
locus a point mutation to abrogate the receptor Grb2-binding site. A similar mutant was previously described as perinatal lethal. In this “first-generation” knock-in the recombinant locus retained the
Neo
cassette (

Met
grb2/grb2neo+

). In the knock-in presented here
Neo
was
Loxed
and excised by
Cre
recombinase, which led to higher tissue levels of Met
grb2
protein, sufficient to rescue viability. In

Met
grb2/grb2neo−

mice the size of the cerebellum was reduced and foliation defects were evident, especially in the central and posterior half of the
vermis
. Proliferation of granule precursors
in vivo
was 25% lower than in controls. In cultures of mutant granule cells HGF-induced microtubule-associated protein kinase activation was reduced and transient. Behavioral tests indicated a balance impairment in

Met
grb2/grb2neo−

mice. Altogether these data indicate that normal cerebellar development and, possibly, function, require HGF and Met, and that proliferation of granule cells in the cerebellum critically depends on full HGF/Met signaling.