bluuebunny/crossref_metadata_2025 huggingface dataset:
Three-dimensional photonic crystals for optical wavelengths assembled by micromanipulation
Authors: Aoki Kanna , Miyazaki Hideki T. , Hirayama Hideki , Inoshita Kyoji , Baba Toshihiko , Shinya Norio , Aoyagi Yoshinobu
Published: October 2002

We have established a profitable fabrication technique for three-dimensional (3D) photonic crystals for optical wavelengths. In our method, two-dimensional photonic plates, which serve as unit parts for 3D structures, are prepared by the semiconductor nanofabrication technique. Then, these plates are assembled into 3D structures by micromanipulation. Accurate lamination of the plates is assured by linking fiducial holes of neighboring plates with matching microspheres. With this technique, we have succeeded in fabricating 3D photonic crystals with one to four layers of woodpile structures. From scanning electron microscope observation of the crystals, the periodic error was determined to be within 50 nm. The optical properties of the crystals indicate existence of the photonic band gap at the expected wavelength of 3–4 μm.
Solar-blind AlGaN-based Schottky photodiodes with low noise and high detectivity
Authors: Biyikli Necmi , Aytur Orhan , Kimukin Ibrahim , Tut Turgut , Ozbay Ekmel
Published: October 2002

We report on the design, fabrication, and characterization of solar-blind Schottky photodiodes with low noise and high detectivity. The devices were fabricated on n−/n+ AlGaN/GaN heterostructures using a microwave compatible fabrication process. True solar-blind operation with a cutoff wavelength of ∼274 nm was achieved with AlxGa1−xN (x=0.38) absorption layer. The solar-blind detectors exhibited <1.8 nA/cm2 dark current density in the 0–25 V reverse bias regime, and a maximum quantum efficiency of 42% around 267 nm. The photovoltaic detectivity of the devices were in excess of 2.6×1012 cm Hz1/2/W, and the detector noise was 1/f limited with a noise power density less than 3×10−29 A2/Hz at 10 kHz.
PARTITIONING COLORED POINT SETS INTO MONOCHROMATIC PARTS
Authors: DUMITRESCU ADRIAN , PACH JÁNOS
Published: October 2002

We show that any two-colored set of n points in general position in the plane can be partitioned into at most [Formula: see text] monochromatic subsets, whose convex hulls are pairwise disjoint. This bound cannot be improved in general. We present an O(n log n) time algorithm for constructing a partition into fewer parts, if the coloring is unbalanced, i.e., the sizes of the two color classes differ by more than one. The analogous question for k-colored point sets (k > 2) and its higher dimensional variant are also considered.
The early pattern of joint involvement predicts disease progression in children with oligoarticular (pauciarticular) juvenile rheumatoid arthritis
Authors: Al‐Matar Mohammad J. , Petty Ross E. , Tucker Lori B. , Malleson Peter N. , Schroeder Maria‐Louise , Cabral David A.
Published: October 2002

Objective

To evaluate features during the first 6 months of disease that may be associated with a poor outcome as measured principally by extension to a polyarticular disease course in patients with oligoarticular‐onset juvenile rheumatoid arthritis (oligo‐JRA).

Methods

This study was a retrospective review of patients who fulfilled the American College of Rheumatology criteria for oligo‐JRA, were followed up for at least 5 years, and did not have juvenile psoriatic arthritis, spondylarthropathy‐like disease, or rheumatoid factor positivity. Data from the first 6 months of disease were collected. Continuous variables were dichotomized and then screened by univariate analysis for association with poor outcome at the last followup visit, as measured by extension of involvement (>4 accumulated involved joints) and by “clinically meaningful” extension (≥10 accumulated joints). Variables significantly associated with this latter outcome, with the addition of disease duration as a confounding independent variable, were included in a multiple logistic regression analysis. The same variables were then examined in separate multiple logistic regression models to look at other measures of outcome, including use of disease‐modifying antirheumatic drugs (DMARDs) at any time, erosive disease on radiographs, any remission of disease ever occurring, physician's global assessment of disease activity at the last visit, and disability as measured by the Childhood Health Assessment Questionnaire (C‐HAQ)/HAQ.

Results

Of the 205 patients (160 of whom were female) studied for a median of 10.8 years (range 5–26.6 years), 39.5% developed extension to >4 joints and 17.6% developed arthritis in ≥10 joints. Using the logistic regression model, symmetric disease was predictive of all measures of poor outcome: extension to ≥10 joints (odds ratio [OR] 19.2), the need to use DMARDs (OR 11.5), radiographic demonstration of erosive disease (OR 4.73), inflammatory activity at last followup visit (OR 3.23), no remission of disease (OR 4.73), and disability as measured by a C‐HAQ score >0.12 (OR 2.95). Ankle and/or wrist disease was predictive of extension (OR 6.61) and erosions (OR 3.59). Wrist disease alone was predictive of the need to use DMARDs (OR 5.87) and of inflammatory disease activity at the last followup visit (OR 4.01). An elevated erythrocyte sedimentation rate (ESR) was predictive of extension (OR 3.76), the need to use DMARDs (OR 6.47), and no remission of disease (OR 2.30). Disease duration was a confounding variable for extension (OR 1.18) and erosive disease (OR 1.19).

Conclusion

The early presence of ankle and/or wrist disease, symmetric joint involvement, and an elevated ESR in a child with oligo‐JRA indicates the likelihood of disease progression.
Lack of isoprenoid products raises ex vivo interleukin‐1β secretion in hyperimmunoglobulinemia D and periodic fever syndrome
Authors: Frenkel Joost , Rijkers Ger T. , Mandey Saskia H. L. , Buurman Sandra W. M. , Houten Sander M. , Wanders Ronald J. A. , Waterham Hans R. , Kuis Wietse
Published: October 2002

Objective

To investigate whether the increased interleukin‐1β (IL‐1β) secretion in hyperimmunoglobulinemia D and periodic fever syndrome is due to the accumulation of mevalonate kinase (MK), the substrate of the deficient enzyme, or the lack of its products, the isoprenoid compounds.

Methods

The effects of lovastatin and farnesol (FOH), geranylgeraniol (GGOH), and mevalonate on peripheral blood mononuclear cells (PBMCs) from 8 patients with MK deficiency and from 13 controls were studied. Lovastatin inhibits isoprenoid biosynthesis by reducing the production of mevalonate. FOH and GGOH restore isoprenoid biosynthesis downstream from MK. Culture supernatants were collected for cytokine analysis 48 hours after stimulation with monoclonal antibodies against CD2 + CD28.

Results

Lovastatin induced a 15‐fold rise in IL‐1β secretion by normal anti–CD2 + CD28–stimulated cells (P < 0.001). This effect could be countered by mevalonate and, to a lesser extent, by FOH and GGOH. In the absence of lovastatin, mevalonate did not change IL‐1β secretion. Stimulated MK‐deficient cells secreted 9‐fold more IL‐1β than control PBMCs (P < 0.005), rising 2.4‐fold in the presence of lovastatin. The effect of lovastatin on IL‐1β secretion was reduced by mevalonate, FOH, and GGOH. Isoprenoid biosynthesis in PBMCs from patients was impaired due to the endogenous MK deficiency. Bypassing this defect with FOH, in the absence of lovastatin, led to a 62% reduction (P < 0.02) in IL‐1β secretion by these cells.

Conclusion

In this model, shortage of isoprenoid end products contributes to increased IL‐1β secretion by MK‐deficient PBMCs, whereas excess mevalonate does not.
Association of global brain damage and clinical functioning in neuropsychiatric systemic lupus erythematosus
Authors: Bosma G. P. Th. , Middelkoop H. A. M. , Rood M. J. , Bollen E. L. E. M. , Huizinga T. W. J. , Van Buchem M. A.
Published: October 2002

Objective

To investigate the relationship between quantitative estimates of global brain damage based on magnetization transfer imaging (MTI) and cerebral functioning, as measured by neurologic, psychiatric, and cognitive assessments, as well as disease duration in patients with a history of neuropsychiatric systemic lupus erythematosus (NPSLE).

Methods

In a clinically heterogeneous group of 24 female patients (age range 19–65 years, mean age 35 years) with a history of NPSLE, the correlation values of several volumetric MTI measures and an estimate of cerebral atrophy, neurologic functioning (Kurtzke's Expanded Disability Status Scale [EDSS]), psychiatric functioning (the Hospital Anxiety and Depression Scale [HADS]), and cognitive functioning (cognitive impairment score [CIS] derived from the revised Wechsler Adult Intelligence Scale), as well as several measures of disease duration were assessed using Pearson's correlation coefficient.

Results

Quantitative volumetric estimates of global brain damage based on MTI and a measure of global brain atrophy correlated significantly with the EDSS, HADS, and CIS scores. No significant correlation was found between the quantitative estimates of global brain damage and the measures of disease duration.

Conclusion

The results of this study demonstrate that volumetric MTI parameters and cerebral atrophy reflect functionally relevant brain damage in patients with NPSLE. Furthermore, the absence of a linear relationship between disease duration and results of volumetric MTI measures and atrophy suggests a complicated pattern of accumulating brain damage in patients with NPSLE.
Human intervertebral disc aggrecan inhibits nerve growth in vitro
Authors: Johnson William E. B. , Caterson Bruce , Eisenstein Stephen M. , Hynds Dianna L. , Snow Diane M. , Roberts Sally
Published: October 2002

Objective

To assess the effects of human intervertebral disc aggrecan on nerve growth and guidance, using in vitro techniques.

Methods

Aggrecan extracted from human lumbar intervertebral discs was incorporated into tissue culture substrata for the culture of the human neuronal cell line, SH‐SY5Y, or explants of chick dorsal root ganglia. The effects on nerve growth of different concentrations of aggrecan extracted from the anulus fibrosus and nucleus pulposus, and of these aggrecan preparations following enzymic deglycosylation, were compared.

Results

Disc aggrecan inhibited the growth of neurites from SH‐SY5Y cells and induced growth cone turning of chick sensory neurites in a concentration‐dependent manner. Aggrecan isolated from the anulus fibrosus was more inhibitory than that isolated from the nucleus pulposus, but enzymic pretreatments to reduce the glycosylation of both types of disc aggrecan partially abrogated their inhibitory effects.

Conclusion

Nerve growth into degenerate intervertebral discs has been linked with the development of low back pain, but little is known about factors affecting disc innervation. The finding that disc aggrecan inhibits nerve growth in vitro, and that this inhibitory activity depends on aggrecan glycosylation, has important implications for our understanding of mechanisms that may regulate disc innervation in health and disease.
Cachexia in rheumatoid arthritis is not explained by decreased growth hormone secretion
Authors: Rall Laura C. , Walsmith Joseph M. , Snydman Laura , Reichlin Seymour , Veldhuis Johannes D. , Kehayias Joseph J. , Abad Leslie W. , Lundgren Nancy T. , Roubenoff Ronenn
Published: October 2002

Objective

Patients with rheumatoid arthritis (RA) lose body cell mass (BCM) by unknown mechanisms. Since the loss of BCM in normal aging individuals parallels the characteristic age‐related decline in growth hormone (GH) secretion, this study was carried out to determine whether further decreased GH secretion plays a role in the pathogenesis of this loss of BCM in RA patients, termed “rheumatoid cachexia.”

Methods

GH secretory kinetics were determined by deconvolution analysis in 16 patients with RA and 17 healthy controls matched for age (mean ± SD 45.4 ± 13.2 years and 47.1 ± 14.6 years, respectively), sex, race, and body mass index. Blood samples were obtained every 20 minutes for 24 hours. Body composition was ascertained using total‐body potassium (TBK) as a measure of BCM and dual x‐ray absorptiometry to determine fat mass.

Results

BCM was reduced in patients with RA compared with healthy controls (mean ± SD gm TBK 79.5 ± 9.5 versus 94.9 ± 11.9; P < 0.0005), but there was no difference in fat mass. GH kinetic parameters in patients with RA did not differ from those in controls.

Conclusion

These findings suggest that GH kinetics are unaltered in RA patients compared with healthy subjects; thus, GH deficiency does not account for rheumatoid cachexia.
Evaporation heat transfer of steady thin film in micro capillary tubes of micron scale
Authors: Qu Wei , Ma Tongze
Published: October 2002

This paper reports that the heat transfer mechanism of phase change in a capillary tube belongs to liquid film conduction and surface evaporation. The surface evaporation is influenced by vapor temperature, vapor‐liquid interfacial temperature, and vapor‐liquid pressure difference. In the vapor‐liquid flow mechanism, flow is effected by both the gradient of disjoining pressure, and the gradient of capillary pressure. The mechanism of vapor‐liquid interaction consists of the shear stress caused by momentum transfer owing to evaporation, and frictional shear stress due to the velocity difference between vapor and liquid. In the model presented for a capillary tube, the heat transfer, vapor‐liquid flow, and their interaction are more comprehensively considered. The thin film profile and heat transfer characteristics have close relations with a capillary radius and heat transfer power. The results of calculation indicate that the length of the evaporating interfacial region decreases to some extent with decreasing capillary radius and increasing heat transfer power. © 2002 Wiley Periodicals, Inc. Heat Trans Asian Res, 31(7): 513–523, 2002; Published online in Wiley InterScience (www.interscience.wiley.com).DOI 10.1002/htj.10050
Hyaluronidase reduces human breast cancer xenografts in SCID mice
Authors: Shuster Svetlana , Frost Gregory I. , Csoka Antonei B. , Formby Bent , Stern Robert
Published: October 2002

A hyaluronan‐rich environment often correlate with tumor progression. and may be one mechanism for the invasive behavior of malignancies. Eradication of hyaluronan by hyaluronidase administration could reduce tumor aggressiveness and would provide, therefore, a new anti‐cancer strategy. Hyaluronan interaction with its CD44 receptor and the resulting signal transduction events may be among the mechanisms for hyaluronan‐associated cancer progression. We have shown previously that hyaluronidase treatment of breast cancer cells in vitro not only eradicates hyaluronan but also modifies expression of CD44 variant exons of tumor cells. We now determine if such effects occur in vivo and if it is accompanied by tumor regression. SCID mice bearing xenografts of human breast carcinomas were given intravenous hyaluronidase. Tumor volumes decreased 50% in 4 days. Tumor sections showed decreased hyaluronan. Intensity of staining for CD44s was not affected, whereas staining for specific CD44 variant exon isoforms was greatly reduced in residual tumors. Necrosis was not evident. Hyaluronidase, used previously as an adjunct in cancer treatment, presumably to enhance penetration of chemotherapeutic drugs, may itself have intrinsic anti‐cancer activity. Removing peritumor hyaluronan appears to cause an irreversible change in tumor metabolism. Continuous hyaluronan binding to CD44 variant exon isoforms may also be required to stabilize inherently unstable isoforms that participate perhaps in tumor progression. Further investigation is required to confirm a cause and effect relationship between loss of hyaluronan, changes in CD44 variant exon expression and tumor reduction. If confirmed, hyaluronidase may provide a new class of anti‐cancer therapeutics and one without toxic side effects. © 2002 Wiley‐Liss, Inc.
After hMSH2 and hMLH1—what next? Analysis of three‐generational, population‐based, early‐onset colorectal cancer families
Authors: Jenkins Mark A. , Baglietto Laura , Dite Gillian S. , Jolley Damien J. , Southey Melissa C. , Whitty Jonathan , Mead Leeanne J. , St. John D. James B. , Macrae Finlay A. , Bishop D. Timothy , Venter Deon J. , Giles Graham G. , Hopper John L.
Published: October 2002

The aim of our study was to examine the role of genetic factors on early‐onset colorectal cancer after excluding the impact of germline mutations in the two major mismatch repair genes. A total of 131 incident probands, under 45 years at diagnosis of a first primary colorectal cancer selected from the Victorian Cancer Registry, and their first‐and second‐degree relatives, were interviewed. Germline DNA from all 12 probands with a family history meeting the modified Amsterdam Criteria for Hereditary Non‐Polyposis Colorectal Cancer (HNPCC) and a random sample of 31 of the remaining probands was screened for mutations in hMSH2 and hMLH1 via manual sequencing. Germline mutations were identified in 6 of the 131 probands (5%), all from the “HNPCC” families. Of the remaining 125 probands, 51 (41%) reported at least one first‐or second‐degree relative with colorectal cancer with an excess of colorectal cancer in first‐degree relatives (SMR = 2.7, 95% CI = 1.7–4.1, p < 0.001). The lifetime risk to age 70 for first‐degree relatives was 8.0% (5.0–12.8%), compared to the Victorian population risk of 3.2% (p = 0.01). The best fitting major gene model was a recessively‐inherited risk of 98% to age 70 (95% CI = 24–100%) carried by 0.17% of the population and would explain 15% of all colorectal cancer in cases with a diagnosis before age 45. Early‐onset colorectal cancer is strongly familial even after excluding families found to be segregating a mutation in either of the 2 major mismatch repair genes. There is evidence for a role of yet to be identified genes associated with a high recessively‐inherited risk of colorectal cancer. © 2002 Wiley‐Liss, Inc.
Tumor‐targeting properties of antibody–vascular endothelial growth factor fusion proteins
Authors: Halin Cornelia , Niesner Uwe , Villani Maria Elena , Zardi Luciano , Neri Dario
Published: October 2002

A major problem of antibody‐based targeting of solid tumors is the poor penetration of antibodies into tumor tissue. Vasoactive immunoconjugates have been proposed as a means of increasing antibody uptake in tumors. In principle, VEGF (also known as vascular permeability factor) could selectively alter vascular permeability, leading to improved tumor targeting. A possible role for VEGF in the targeting of tumor neovasculature has been postulated, based on the overexpression of VEGF receptors in tumor endothelial cells. However, quantitative biodistribution studies on this topic are not available. In this report, we describe the cloning, expression, characterization and biodistribution in tumor‐bearing mice of antibodies fused to either VEGF120 or VEGF164 The MAb fragments chosen for analysis were scFv(L19), specific for the ED‐B domain of fibronectin, a marker of angiogenesis, and scFv(HyHEL‐10), a negative control antibody of irrelevant specificity in mice. Neither unconjugated VEGF nor scFv(HyHEL‐10)–VEGF fusion proteins showed accumulation in the tumor (tumor:blood ratios approx. 1 at 4 hr and 24 hr postinjection). By contrast, scFv(L19)–VEGF120 but not scFv(L19)–VEGF164 showed significant accumulation in tumors (tumor:blood ratio = 9.3 at 24 hr) but was not superior to unconjugated scFv(L19). Preinjection of unlabeled scFv(L19)–VEGF120 prior to administration of radiolabeled fusion protein led to increased accumulation of radiolabeled scFv(L19)–VEGF120 in the tumor but only at very high concentrations (20 μg/mouse). © 2002 Wiley‐Liss, Inc.
Mutation analysis of EP300 in colon, breast and ovarian carcinomas
Authors: Bryan Emma J. , Jokubaitis Venta J. , Chamberlain Narelle L. , Baxter Simon W. , Dawson Elisabeth , Choong David Y.H. , Campbell Ian G.
Published: October 2002

The putative tumour suppressor gene EP300 is located on chromosome 22q13 which is a region showing frequent loss of heterozygosity (LOH) in colon, breast and ovarian cancers. We analysed 203 human breast, colon and ovarian primary tumours and cell lines for somatic mutations in EP300. LOH across the EP300 locus was detected in 38% of colon, 36% of breast, and 49% of ovarian primary tumours but no somatic mutations in EP300 were identified in any primary tumour. Analysis of 17 colon, 11 breast, and 11 ovarian cancer cell lines identified truncating mutations in 4 colon cancer cell lines (HCT116, HT29, LIM2405 and LIM2412). We confirmed the presence of a previously reported frameshift mutation in HCT116 at codon 1699 and identified a second frameshift mutation at codon 1468. Bi‐allelic inactivation of EP300 was also detected in LIM2405 that harbours an insC mutation at codon 927 as well an insA mutation at codon 1468. An insA mutation at codon 1468 was identified in HT29 and a CGA>TGA mutation at codon 86 was identified in LIM2412. Both these lines were heterozygous across the EP300 locus and western blot analysis confirmed the presence of an apparently wild‐type protein. Our study has established that genetic inactivation of EP300 is rare in primary colorectal, breast and ovarian cancers. In contrast, mutations are common among colorectal cancer cell lines with 4/17 harbouring homozygous or heterozygous mutations. The rarity of EP300 mutations among these tumour types that show a high frequency of LOH across 22q13 may indicate that another gene is the target of the loss. It is possible that bi‐allelic inactivation of EP300 is not necessary and that haploinsufficiency is sufficient to promote tumorigenesis. Alternatively, silencing of EP300 may be achieved by epigenetic mechanisms such as promoter methylation. © 2002 Wiley‐Liss, Inc.
BRCA2 mutations in a population‐based series of patients with ocular melanoma
Authors: Scott Rodney J. , Vajdic Claire M. , Armstrong Bruce K. , Ainsworth Christopher J. , Meldrum Cliff J. , Aitken Joanne F. , Kricker Anne
Published: October 2002

We studied the BRCA2 gene for germline mutations in 71 of 99 patients (72%) with ocular melanoma who were diagnosed consecutively in Australia in 1997 and 1998. Patients considered for our study fulfilled one of the following critiera: (i) were 50 years of age or less at diagnosis; (ii) had bilateral disease (2 patients); (iii) reported a family history of ocular melanoma (4 patients). Mutation detection was performed using the protein truncation test and denaturing high‐performance liquid chromatography with primers designed to include intron‐exon boundaries. Six DNA changes were found of which 2 were exonic, in exons 14 (A>C in nucleotide 7244 leading to His>Arg) and 27 (base pair substitution in nucleotide 9976 leading to a stop codon). One exonic change has been reported previously. None of the intronic mutations were deemed to affect splicing efficiency. Neither exonic mutation was in a person with bilateral ocular melanoma or a family history of cutaneous melanoma. We estimated the prevalence of possible loss of function changes in BRCA2 in patients with ocular melanoma at 3% (95% CI 0–10%). This figure was similar to previous estimates of 2.8% and 2% in nonrepresentative samples of patients with ocular melanoma and 2.1% in a representative sample of young women with breast cancer. © 2002 Wiley‐Liss, Inc.
Targets of transcriptional regulation by two distinct type I receptors for transforming growth factor‐β in human umbilical vein endothelial cells
Authors: Ota Tatsuru , Fujii Makiko , Sugizaki Takashi , Ishii Masami , Miyazawa Keiji , Aburatani Hiroyuki , Miyazono Kohei
Published: October 2002

Transforming growth factor‐β (TGF‐β) plays a crucial role in vascular development and homeostasis by regulating many transcriptional targets. Activin receptor‐like kinase 5 (ALK‐5) is a TGF‐β type I receptor expressed in various TGF‐β‐responsive cells. In contrast, ALK‐1 functions as a TGF‐β type I receptor in endothelial cells, and is responsible for human hereditary hemorrhagic telangiectasia (HHT) type II. ALK‐5 and ALK‐1 mediate TGF‐β signals through distinct Smad proteins, i.e., Smad2/Smad3 and Smad1/Smad5, respectively. To identify target genes of ALK‐1 and ALK‐5 in endothelial cells, we conducted oligonucleotide microarray analysis. Human umbilical vein endothelial cells (HUVEC) were infected with recombinant adenoviruses carrying a constitutively active form of ALK‐1 or ALK‐5. ALK‐5 inhibited the proliferation, network formation, and tube formation of HUVEC and induced their apoptosis, whereas ALK‐1 did not exhibit significant effects on HUVEC in vitro. mRNAs were extracted from HUVEC and used for hybridization of oligonucleotide arrays representing approximately 7,000 human genes. Northern blot and quantitative real‐time polymerase chain reaction (PCR) analyses were also performed for some of these genes, confirming the validity of this microarray analysis. We found that ALK‐1 specifically upregulated Smad6, Smad7, Id1, Id2, endoglin, STAT1, and interleukin 1 receptor‐like 1. ALK‐5, in contrast, upregulated PlGF, SM22α, connexin 37, βIG‐H3, and LTBP1. ALK‐1 downregulated Smad1, CXCR4, Ephrin‐A1, and plakoglobin, whereas ALK‐5 downregulated claudin 5 and integrin β5. These results revealed some new targets of TGF‐β in endothelial cells, and differences in transcriptional regulation patterns between ALK‐1 and ALK‐5. J. Cell. Physiol. 193: 299–318, 2002. © 2002 Wiley‐Liss, Inc.
K vitamins, PTP antagonism, and cell growth arrest
Authors: Carr Brian I. , Wang Ziqiu , Kar Siddhartha
Published: October 2002

The main function of K vitamins is to act as co‐factors for γ‐glutamyl carboxylase. However, they have also recently been shown to inhibit cell growth. We have chemically synthesized a series of K vitamin analogs with various side chains at the 2 or 3 position of the core naphthoquinone structure. The analogs with short thio‐ethanol side chains are found to be more potent growth inhibitors in vitro of various tumor cell lines. Cpd 5 or [2‐(2‐mercaptoethanol)‐3‐methyl‐1,4‐naphthoquinone] is one of the most potent. The anti‐proliferation activity of these compounds is antagonized by exogenous thiols but not by non‐thiol antioxidants. This suggests that the growth inhibition is mediated by sulfhydryl arylation of cellular glutathione and cysteine‐containing proteins and not by oxidative stress. The protein tyrosine phosphatases (PTP) are an important group of proteins that contain cysteine at their catalytic site. PTPs regulate mitogenic signal transduction and cell cycle progression. PTP inhibition by Cpd 5 results in prolonged tyrosine phosphorylation and activation of several kinases and transcription factors including EGFR, ERK1/2, and Elk1. Cpd 5 could activate ERK1/2 either by signaling from an activated EGFR, which is upstream in the signaling cascade, or by direct inhibition of ERK1/2 phosphatase(s). Prolonged ERK1/2 phosphorylation strongly correlates with Cpd 5‐mediated growth inhibition. Cpd 5 can also bind to and inhibit the Cdc25 family of dual specific phosphatases. As a result, several Cdc25 substrates (Cdk1, Cdk2, Cdk4) involved in cell cycle progression are tyrosine phosphorylated and thereby inhibited by its action. Cpd 5 could also inhibit both normal liver regeneration and hepatoma growth in vivo. DNA synthesis during rat liver regeneration following partial hepatectomy, transplantable rat hepatoma cell growth, and glutathione‐S‐transferase‐pi expressing hepatocytes after administration of the chemical carcinogen diethylnitrosamine, are all inhibited by Cpd 5 administration. The growth inhibitory effect during liver regeneration and transplantable tumor growth is also correlated with ERK1/2 phosphorylation induced by Cpd 5. Thus, Cpd 5‐mediated inhibition of PTPs, such as Cdc25 leads to cell growth arrest due to altered activity of key cellular kinases involved in signal transduction and cell cycle progression. This prototype K vitamin analog represents a novel class of growth inhibitor based upon its action as a selective PTP antagonist. It is clearly associated with prolonged ERK1/2 phosphorylation, which is in contrast with the transient ERK1/2 phosphorylation induced by growth stimulatory mitogens. © 2002 Wiley‐Liss, Inc.
Role for cellular Src kinase in myoblast proliferation
Authors: Rosoff William J. , Swope Sheridan L.
Published: October 2002

In this study, a role for cellular Src in muscle cell proliferation and differentiation was investigated. Pharmacological inhibition of Src‐class kinases repressed proliferation and promoted differentiation of the C2C12 muscle cell line, even when the cells were cultured under growth‐inducing conditions of high serum. Pharmacological inhibition of Src‐class kinases also affected cellular components that regulate proliferation and differentiation in muscle; cyclin D1 levels were reduced while, myogenin was increased. Suppression of cyclin D1 and enhancement of myogenin levels also occurred upon expression of a dominant negative Src, corroborating a role for Src kinases in regulating proliferation and differentiation. Inhibition of Src‐family kinases also blocked fibroblast growth factor (FGF) induced proliferation but, notably, did not reverse the effect of FGF to inhibit differentiation. Evidence for the Src‐class kinase Src in myoblast mitogenesis was obtained by determining the pattern of protein expression and activity for this kinase. Under all conditions examined, Src's expression and enzymatic activity were high in cultures of myoblasts and down‐regulated during differentiation. Importantly, Src's activity was rapidly stimulated by mitogen‐containing serum and attenuated when myoblasts were switched to low serum‐containing differentiation medium. These data indicate that Src is important for maintaining muscle cell proliferation. J. Cell. Physiol. 193: 328–339, 2002. © 2002 Wiley‐Liss, Inc.
Combined action of anticonvective and thermocapillary mechanisms of instability
Authors: Nepomnyashchy A. A. , Simanovskii I. B.
Published: October 2002

The combined action of the anticonvective and thermocapillary mechanisms of instabilities in two-layer systems has been considered. The systems are subject to an external heating from above and interfacial heat release. Two analytically solvable cases, the case of a model system with the infinitely large heat diffusivity of the bottom fluid and the infinitely small heat expansion coefficient of the top fluid, and the case of long-wave instability in the system between heat insulated horizontal boundaries, have been studied. The convective flows in the real system silicon oil-10 cs-ethylene glycol have been studied by means of the linear stability theory and nonlinear simulations.
Stability of a vortex sheet roll-up
Authors: Abid Malek , Verga Alberto
Published: October 2002

The stability of vortex sheet roll-up is studied using a Lagrangian vortex method. We consider an initially unstable (Kelvin–Helmholtz) vortex sheet. During its nonlinear evolution, a perturbation is added to test it for a secondary instability. The growth of the perturbation depends on its phase and on the local strain rate. In the linear stage of this secondary instability, the dispersion relation is calculated. It is found that the growth rate and the cutoff wave number are fixed by the regularization parameter of the Birkhoff–Rott equation.
Resonance-leaking to specific background states: A loss mechanism in molecular multiphoton transitions
Authors: Jakubetz W. , Lan B.-L.
Published: October 2002

We report a remarkably robust phenomenon in the HCN/HNC molecule where the population of a target state induced by a resonant multiphoton (MP) π-pulse along a strongly-coupled subset of states can leak to a background state only weakly coupled to this subset. This resonance leaking of population, which may be complete, is due to the overlap of the resonant MP transition to the target state with a resonant MP transition to the background state that includes the target state as an intermediate. We also demonstrate how the population leak can be fully controlled using fields of greater complexity compared to a single π-pulse, such as two overlapping, phase-adjusted Gaussian pulses. The robustness of resonance leaking in the HCN/HNC molecule suggests that the phenomenon have a significant probability of occurrence in other molecular systems as well. The implications of our findings for the viability of reduced basis set treatments in providing converged ab initio fields and the predictability of these fields in laser-controlled molecular processes are discussed.
Relative diffusion of a pair of fluid particles in the inertial subrange of turbulence
Authors: Ishihara Takashi , Kaneda Yukio
Published: October 2002

Turbulent diffusion of a pair of fluid particles in 3-dimensional homogeneous and isotropic turbulence was studied using a high-resolution direct numerical simulation (DNS) with 10243 grid points. The DNS showed that the mean square of the distance δx between the two fluid particles grows with time t as 〈|δx|2〉∼Cεt3 in the inertial subrange, which is in agreement with Richardson (1926) and Obukhov (1941), where C≈0.7 and ε is the mean dissipation rate per unit mass. A simple Lagrangian closure approximation for 〈|δx|2〉 is shown to be in good agreement with the DNS.
Self-sustained oscillations in the wake of a sphere
Authors: Schouveiler L. , Provansal M.
Published: October 2002

The periodic wake of a sphere maintained in a uniform flow is experimentally characterized. Visualizations of the vortical structures periodically shed in this regime are presented and measurements of amplitude and frequency of the streamwise velocity fluctuations are performed. The experiments show that the resulting self-sustained oscillations of the wake flow appear via a supercritical Hopf bifurcation. Then, the relevance of a Landau-type equation to describe the temporal dynamics of the shedding modes near the instability threshold is discussed. For this purpose transient experiments of growth of the shedding modes are performed under supercritical conditions. From the evolutions during these transients of the instantaneous growth rate and frequency, the parameters of the Landau model are estimated. Dependence on the Reynolds number of these parameters is also deduced from the measurements.
Temporal instabilities of a mixing layer with uniform and nonuniform particle loadings
Authors: Narayanan Chidambaram , Lakehal Djamel
Published: October 2002

Temporal stability analysis of particle-laden mixing layers with uniform and nonuniform particle loadings is presented. New analytical results have been derived in the limit of small and large Stokes numbers using small-parameter expansions. A dichotomy in the behavior of the fluid–particle system, based on whether the particle diameter or density is increased to achieve large Stokes numbers, is clarified. Good agreement between the limiting analytical expressions and numerical results is obtained. Additional unstable modes are observed for nonuniform particle loadings for large Stokes numbers and high mass loadings conditions. The effect of the steepness of the nonuniformity is presented for the first time. The primary effect of nonuniformity, is an increase in the range of unstable wave numbers for small to intermediate Stokes numbers, and a change in the nature of the dominant Kelvin–Helmholtz instability from stationary to dispersive. The value of the most unstable wave number is shown to remain unaffected by the nonuniformity.
Stability and temporal evolution of a swirling jet with centrifugally unstable azimuthal velocity
Authors: Sun De-Jun , Hu Guo-Hui , Gao Zhi , Yin Xie-Yuan
Published: October 2002

A temporal linear instability analysis by the normal mode method and a direct numerical simulation (DNS) are performed to investigate the stability and temporal evolution of a swirling jet with centrifugally unstable Taylor vortex-like azimuthal velocity. A marked instability character is that the Kelvin–Helmholtz modes are dominant at lower axial wave numbers and the modes of centrifugal instability are dominant at higher axial wave numbers. The results of DNS show that the early linear stage of evolution of swirling jet agrees well with that predicted by linear stability theory. In the nonlinear stage, the centrifugally unstable velocity profile has important influences on the evolution dynamics. For the basic flow with small vortex core (ρ=1), the negative axial vorticity suppresses the eruption of vorticity from the core and the formation of secondary vortex ring pairs with opposite vorticity. For the basic flow with larger vortex core (ρ=4.5), the negative axial vorticity is away from the core region. Centrifugally unstable swirl is favorable for the formation of secondary ring pairs and their outward radial movement at computing parameters, and is thus beneficial for mixing enhancement.
Orbitally dependent kinetic exchange in a heterobimetallic pair: Ferromagnetic spin alignment and magnetic anisotropy in the cyano-bridged Cr(III)Fe(II) dimer
Authors: Palii A. V. , Tsukerblat B. S. , Verdaguer M.
Published: October 2002

The problem of the kinetic exchange interaction in the cyanide-bridged heterobinuclear dimers involving orbitally degenerate transition metal ions is considered. The developed approach is based on the concept of the effective Hamiltonian of the orbitally dependent kinetic exchange. We deduce this many-electron Hamiltonian on the microscopic background so that all relevant biorbital transfer processes are taken into account as well as the properties of the many-electron states. The bioctahedral cyanide-bridged Cr(III)Fe(II) dimer is considered in detail as an example distinctly exhibiting new quantitative and qualitative features of the orbitally dependent exchange and as a structural unit of three-dimensional ferromagnetic crystals {Fe(II)3[Cr(III)(CN)6]2}⋅13H2O. The proposed mechanism of the kinetic exchange involves the electron transfer from the double occupied t2 orbitals of Fe(II) [ground state T52(t24e2)] to the half occupied t2 orbitals of Cr(III) [ground state A42(t23)] resulting in the charge transfer state T31(t24)Cr(II)−6A1(t23e2)Fe(III) and the transfer between the half-occupied t2 orbitals of the metal ions resulting in the charge transfer state T31(t24)Cr(II)−4T2(t23e2)Fe(III). The effective Hamiltonian of the orbitally dependent exchange for the Cr(III)Fe(II) pair deduced within this theoretical framework describes competitive ferro- and antiferromagnetic contributions arising from these two charge transfer states. This Hamiltonian leads to a complex energy pattern, consisting of two interpenetrating Heisenberg-like schemes, one exhibiting ferromagnetic and another one antiferromagnetic splitting. The condition for the ferromagnetic spin alignment in the ground state is deduced. The orbitally dependent terms of the Hamiltonian are shown to give rise to a strong magnetic anisotropy of the system, this result as well as the condition for the spin alignment in the ground term are shown to be out of the scope of the Goodenough–Kanamori rules. Along with the full spin S the energy levels are labeled by the orbital quantum numbers providing thus the direct information about the magnetic anisotropy of the system. Under a reasonable estimation of the excitation energies based on the optical absorption data we conclude that the kinetic exchange in the cyanide-bridged Cr(III)Fe(II) pair leads to the ferromagnetic spin alignment exhibiting at the same time strong axial magnetic anisotropy with C4 easy axis of magnetization.
Covalency in the uranyl ion: A polarized x-ray spectroscopic study
Authors: Denning R. G. , Green J. C. , Hutchings T. E. , Dallera C. , Tagliaferri A. , Giarda K. , Brookes N. B. , Braicovich L.
Published: October 2002

Polarized oxygen Kα x-ray absorption and emission spectra, near 530 eV, of a single crystal of Cs2UO2Cl4 are reported. With the aid of density functional theory calculations and the absorption data, the relative energies of the empty molecular orbitals having primarily uranium 5f and 6d character are assigned. The emission spectra give access to the energy of excitations to these orbitals from the various filled valence-shell orbitals. These energies support the conclusion from the optical spectra that valence excitations from the σu occupied valence orbitals occur at substantially lower energies than those from the σg, πg, and πu orbitals. This latter group of molecular orbitals have much larger oxygen-2p character. The participation of the pseudocore 6p shell in the covalent bonding is established directly by the presence of a charge-transfer transition in emission. With the aid of previous work on the polarized uranium L1- and L3-edge absorption spectra, the order of the empty metal-centered antibonding valence orbitals is established as 5fπ<5fσ∼6dδ∼6dσ<6dπ. The greater antibonding character of 6dπ compared with 6dσ can be explained by the relatively small overlap of the latter orbital with oxygen 2p. However, the relative energies of 5fπ and 5fσ cannot be due to differences in overlap and are attributed instead to a strong hybridization between 5fσ and 6pσ. This superposition is confirmed by the linear dichroism in the U L1-edge absorption spectrum.
Mass and momentum transport from a sphere in steady and oscillatory flows
Authors: Blackburn H. M.
Published: October 2002

Heat or mass transfer from spherical particles in oscillatory flow has important applications in combustion and spray drying. This work provides a parametric investigation of drag forces experienced by, and transport of a passive scalar from, an isolated rigid fixed sphere in steady and oscillatory axisymmetric flows. At Schmidt (Prandtl) number of 1, oscillatory flows with Reynolds numbers in the range 1–100 and oscillation amplitudes in the range 0.05–5 sphere diameters are investigated using numerical simulation. Scalar concentration is uniform on the surface of the sphere and zero in the far field. Coefficients of peak drag for steady and oscillatory flows are presented and compared to values obtained from Basset’s analytical solution for Stokes flow, and the relative contributions of the added mass, Stokes drag, and Basset history terms are examined. At the higher Reynolds numbers and amplitudes, it is found that the time-average mass transfer rate can be more than double that for diffusion in quiescent fluid, or in Stokes flow. Time-average Sherwood (Nusselt) numbers for oscillatory flows asymptote to the Stokes limit at low oscillation amplitude, regardless of Reynolds number. An unexpected result is that at intermediate Reynolds numbers and oscillation amplitudes, it is possible to depress the time-average mass-transfer coefficient slightly below that for Stokes flow. Within the Reynolds number range considered, Sherwood–Nusselt numbers in steady flow are found to be always higher than for an oscillatory flow of the same root-mean-square (rms) velocity.
Fully relativistic calculation of nuclear magnetic shieldings and indirect nuclear spin-spin couplings in group-15 and -16 hydrides
Authors: Gomez Sergio S. , Romero Rodolfo H. , Aucar Gustavo A.
Published: October 2002

Fully relativistic calculations of the isotropic and anisotropic parts of both indirect nuclear spin–spin couplings J1(X-H) and J2(H-H) and nuclear magnetic shieldings σ(X) and σ(H) for the group-15 and -16 hydrides are presented. Relativistic calculations were performed with Dirac–Fock wave functions and the random phase approximation method. Results are compared to its nonrelativistic counterpart. Paramagnetic and diamagnetic contributions to the nuclear magnetic shielding constants are also reported. We found very large relativistic corrections to both properties in the sixth-row hydrides (BiH3 and PoH2). Our calculations of the relativistic corrections to the isotropic part of σ at the heavy nucleus X show that it is roughly proportional to Z3.2 in both series of molecules. Paramagnetic term σp is more sensitive to the effects of relativity than the diamagnetic one σd, even though both have a behavior proportional to third power of the nuclear charge Z.
Ostwald ripening with size-dependent rates: Similarity and power-law solutions
Authors: Madras Giridhar , McCoy Benjamin J.
Published: October 2002

The dynamics of Ostwald ripening is treated by cluster distribution kinetics represented by a population balance equation that also describes growth or dissolution. Unlike simple crystal growth driven by supersaturation, the smaller, more soluble clusters in the distribution dissolve during ripening near equilibrium and vanish when they reach the critical nucleus size. Larger clusters accordingly grow as the supersaturation decreases. The long-time asymptotic result of the numerical solution of the scaled population balance equation is power-law decrease of cluster number and growth of average cluster mass, Cavg(θ). The cluster distribution approximates an exponential self-similar solution, and eventually narrows until but one large cluster remains, satisfying the mass balance. A previous theory is here extended to include mass-dependent rate coefficients for growth and dissolution that satisfy microscopic reversibility. The asymptotic power-law growth, Cavg∼θ1/(4/3-λ), is determined by the power λ on the mass for rate coefficients. The power is λ=1/3 for diffusion-controlled and λ=2/3 for surface-controlled processes. Experimentally observed ripening behavior is realized by an apt choice of λ for a given time range.
Receptivity and aeroacoustic resonance in channels with blowing walls
Authors: Griffond J.
Published: October 2002

In this article, the creation of instability waves by acoustic waves in the two-dimensional Taylor flow developing in channels with blowing walls is studied. The receptivity of the flow to a localized defect of injection velocity is investigated by assuming normal mode form of the instabilities thanks to a theory of Hill [J. Fluid Mech. 292, 183 (1995)] based on adjoint methods. The results show good agreement with direct numerical simulations. A mechanism of aeroacoustic resonance is numerically put in light which involves the receptivity process together with the creation of acoustic waves by instability waves passing through a surface at constant pressure. Theoretical predictions of the temporal growth or damping rate of both acoustic and instability waves give satisfactory results. Discussion about experimental results available from the so-called VECLA facility is finally provided.
Nanopatterning of Si/SiGe electrical devices by atomic force microscopy oxidation
Authors: Bo Xiang-Zheng , Rokhinson Leonid P. , Yin Haizhou , Tsui D. C. , Sturm J. C.
Published: October 2002

Two nanopatterning methods for silicon/silicon-germanium (Si/SiGe) heterostructures are demonstrated: (1) direct atomic force microscopy (AFM) oxidation on SiGe layers and (2) AFM oxidation on silicon followed by selective wet etching of SiGe. When directly oxidizing SiGe alloys, minimum linewidths of 20 nm were achieved by adjusting the bias voltage of the AFM tip. By AFM oxidation and selective wet etching, a 10-nm-thick conducting SiGe layer was patterned to form features under ∼50 nm. Fabricated SiGe quantum dots with side gates exhibited Coulomb blockade oscillation.
Photonic pseudo-gap-based modification of photoluminescence from CdS nanocrystal satellites around polymer microspheres in a photonic crystal
Authors: Lin Y. , Zhang J. , Sargent E. H. , Kumacheva E.
Published: October 2002

We report the combination of microsphere self-organization to form a photonic crystal, providing spectrally and angularly dependent electromagnetic structural resonances; with nanocrystal growth in situ on microsphere surfaces, providing optical functionalization with spectral control achieved through the quantum size effect. We demonstrate this material system using CdS nanocrystals coating the surfaces of poly(methyl methacrylate)–poly(methacrylic acid) (PMMA–PMAA) micrometer spheres. The in situ synthesis of the CdS nanocrystals on the surface of the PMMA/PMAA microspheres preserves the propensity of the hybrid microspheres to form ordered colloid arrays. Luminescence from surface states ensures that light is emitted at energies significantly below the absorption edge of the emitting species. Transmission and photoluminescence measurements reveal the interaction of the photonic stop band with photoluminescence from the nanocrystals.