bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel aminopropiophenones as potential antidepressants
Authors: Foley Kevin F. , Cozzi Nicholas V.
Published: November 2003

The atypical antidepressant drug bupropion and the psychostimulant drug methcathinone are both members of a chemical class known as aminopropiophenones. Differences in the psychoactive effects of these two drugs result from small variations in their chemical structures, but the relationship between chemical structure and psychoactivity has not been characterized. To investigate how structural modifications to aminopropiophenones affect antidepressant or stimulant activity, we synthesized several analogs of bupropion and methcathinone and tested the new compounds for antidepressant‐like or psychostimulant effects. The synthesized compounds are 2‐(methylamino)‐1‐(3‐bromophenyl)propan‐1‐one (3‐BMAP), 2‐(methylamino)‐1‐(4‐bromophenyl)propan‐1‐one (4‐BMAP), 2‐(iso‐propylamino)‐1‐phenylpropan‐1‐one (i‐PAP), and ‐(tert‐butylamino)‐1‐phenylpropan‐1‐one (t‐BAP). Bupropion, methcathinone, desipramine, and the newly‐synthesized aminopropiophenones were administered to rats for behavioral testing. We used the Porsolt swim test to assess antidepressant‐like activity and a locomotor activity assay to test for psychostimulant effects. All of the compounds displayed antidepressant‐like effects in the Porsolt swim test. Some compounds, including bupropion, increased locomotor activity at moderate‐to‐high doses. A halogenated analog of methcathinone, 4‐BMAP, increased swim time but did not stimulate locomotor activity, even at the highest dose tested. The data indicate that phenyl ring substitution or branched alkylamines can shift the psychopharmacological profile of aminopropiophenones from stimulant activity to antidepressant‐like activity. Several of the new drugs may be effective antidepressants in humans with fewer stimulant‐like side effects compared to bupropion. Drug Dev. Res. 60:252–260, 2003. © 2003 Wiley‐Liss, Inc.
Biological study of naphthalene derivatives with antiinflammatory activities
Authors: Huang Mei‐Han , Wu Sheng‐Nan , Wang Jih‐Pyang , Lin Chen‐Hsing , Lu Shih‐I , Liao Li‐Fang , Shen Ai‐Yu
Published: November 2003

In this study, 18 synthetic naphthalene derivatives were tested for their inhibitory effects on the activation of neutrophils stimulated with N‐formyl‐methionyl‐leucyl‐phenylalanine (fMLP) or phorbol myristic acetate (PMA). Some of these compounds showed significant antiinflammatory activities. In general, esterification of 1‐naphthalene to compound 14 (2‐hydroxymethyl‐1‐naphthol diacetate; TAC) enhanced the antioxidant activity. Compound 15, N,N‐bis(2‐hydroxy‐1‐naphthylmethyl) amine, has moderate inhibitory activity on neutrophils stimulated with fMLP as compared to Mannich bases of naphthylene derivatives. Either substitution at 1 or 2 position, except TAC, disfavored the inhibitory effects evoked by PMA stimulation. The influence of these compounds on the release of granule enzyme lysozyme‐induced by fMLP was measured. TAC had the highest potency on the inhibition of lysozyme release from rat neutrophil degranulation. The effects of TAC on ionic currents in a mouse neuroblastoma and rat glioma hybrid cell line, NG105‐18, were also investigated with the aid of the whole‐cell patch‐clamp technique. TAC caused an inhibitory effect on voltage‐dependent L‐type Ca2+ current (ICa,L) with an IC50 value of 0.8 µM. The inhibitory effect of TAC on ICa,L may not be caused by its inhibition of superoxide formation. Such an effect may, also in part, affect neuronal function. Drug. Dev. Res. 60:261–269, 2003. © 2003 Wiley‐Liss, Inc.
N‐n‐alkylnicotinium and N‐n‐alkylpyridinium analogs inhibit the dopamine transporter: Selectivity as nicotinic receptor antagonists
Authors: Zhu J. , Crooks P. A. , Ayers J. T. , Sumithran S. P. , Dwoskin L. P.
Published: November 2003

N‐n‐Alkylnicotinium and N‐n‐alkylpyridinium analogs act as antagonists at nicotinic acetylcholine receptors (nAChRs) mediating nicotine‐evoked [3H]dopamine (DA) overflow from superfused rat striatal slices in the presence of a DA transporter (DAT) inhibitor. However, the potential interaction of these nAChR antagonists with DAT has not been evaluated. In the present study, analog inhibition of [3H]DA uptake into striatal synaptosomes and inhibition of [3H]GBR 12935 binding to striatal membranes was determined. N‐n‐Alkylnicotinium analogs with n‐alkyl chains of C6–12 and N‐n‐alkylpyridinium analogs with n‐alkyl chains of C7–20 inhibited [3H]DA uptake with a wide affinity range. With the exception of the C20 N‐n‐alkylpyridinium, a linear relationship between chain length and inhibition of [3H]DA uptake was found in both analog series. Similarly, these analogs inhibited [3H]GBR 12935 binding (Ki=5.7–250 μM), and a linear relationship with chain length was observed, with the exception of the C8 N‐n‐alkylnicotinium analog. Kinetic analyses of inhibition of [3H]DA uptake and [3H]GBR 12935 binding using representative C12 analogs from each series revealed decreases in maximal [3H]DA transport velocity and maximal [3H]GBR 12935 binding without alterations in affinity, indicating noncompetitive interactions with DAT. In comparison, classical nAChR antagonists (mecamylamine, dihydro‐β‐erythroidine and methyllycaconitine) did not inhibit [3H]DA uptake or [3H]GBR 12935 binding. Moreover, inhibition of DAT function occurred at analog concentrations 10–120‐fold higher than those inhibiting nAChR function. Taken together with the inability of these analogs to inhibit field‐stimulation‐evoked [3H]DA overflow, the results indicate that these analogs act selectively as antagonists at nAChRs mediating nicotine‐evoked [3H]DA overflow. Drug Dev. Res. 60:270–284, 2003. © 2003 Wiley‐Liss, Inc.
Flow resistance in gravel‐bed channels with large‐scale roughness
Authors: Ferro Vito
Published: November 2003

A previously published mixing length (ML) model for evaluating the Darcy–Weisbach friction factor for a large‐scale roughness condition (depth to sediment height ratio ranging from 1 to 4) is brieﬂy reviewed and modiﬁed (MML). Then the MML model and a modiﬁed drag (MD) model are experimentally tested using laboratory measurements carried out for gravel‐bed channels and large‐scale roughness condition. This analysis showed that the MML gives accurate estimates of the Darcy–Weisbach coefﬁcient and for Froude number values greater than 0·5 the MML model coincides with the ML one. Testing of the MD model shows limited accuracy in estimating ﬂow resistance.

Finally, the MML and MD models are compared with the performance of a quasi‐theoretical (QT) model deduced applying the P‐theorem of the dimensional analysis and the incomplete self‐similarity condition for the depth/sediment ratio and the Froude number. Using the experimental gravel‐bed data to calibrate the QT model, a constant value of the exponent of the Froude number is determined while two relationships are proposed for estimating the scale factor and the exponent of the depth/sediment ratio. This indirect estimate procedure of the coefﬁcients (b0, b1 and b2) of the QT model can produce a negligible overestimation or underestimation of the friction factor. Copyright © 2003 John Wiley & Sons, Ltd.
Post‐fire thin debris flows: sediment transport and numerical modelling
Authors: Gabet Emmanuel J.
Published: November 2003

The creation of a hydrophobic layer in the soil during ﬁres in semi‐arid environments inhibits the inﬁltration of rainfall. This leads to increased rates of runoff and associated sediment transport. When the hydrophobic layer is deposited beneath the soil surface, a perched water table develops which may cause thin (1–2 cm) hillslope failures that are distinguishable from features caused by rilling and sheetﬂow. Evidence for these failures was observed after a ﬁre near Santa Barbara, California. The amount of sediment eroded from some hillslopes was substantial, with 290 kg of sediment per metre width of hillslope delivered to the valley ﬂoor. The mechanics of these failures are examined with a numerical model that incorporates a stability analysis with subsurface ﬂow routing along a typical hillslope proﬁle. The model correctly predicts the location of the failures as well as the rainfall amount necessary to trigger them. Copyright © 2003 John Wiley & Sons, Ltd.
Fluvial thermal erosion investigations along a rapidly eroding river bank: application to the Lena River (central Siberia)
Authors: Costard F. , Dupeyrat L. , Gautier E. , Carey‐Gailhardis E.
Published: November 2003

In Central Yakutia, frozen river banks are affected by a combination of thermal and mechanical erosion. Exceptional bank retreat of up to 40 m per year is observed. This results from ground thawing produced by heat transfer from the ﬂow of water through the frozen ground, followed by mechanical transport of the thawed sediments. A one‐dimensional model is proposed to estimate the thermal erosion efﬁciency. A test of this model is a comparison of results obtained from experiments carried out in a cold room. A hydraulic channel allows measurements of the thaw front propagation, as well as the thermal erosion rate, in simulated ground ice that is subjected to warm water ﬂow. Various laboratory simulations demonstrate the validity of the mathematical model for the range of laboratory conditions. A hierarchy of parameters (Reynolds number, water and ground ice temperatures) is proposed to explain the present efﬁciency of thermal erosion along the Siberian rivers. From the characteristics of the Lena River (geometry, temperature and discharge) during the ﬂood season, the erosion of banks with different ice content predicted by the model is in agreement with ﬁeld observations. Copyright © 2003 John Wiley & Sons, Ltd.
High density of immobilized galactose ligand enhances hepatocyte attachment and function
Authors: Yin Chao , Ying Lei , Zhang Peng‐Chi , Zhuo Ren‐Xi , Kang En‐Tang , Leong Kam W. , Mao Hai‐Quan
Published: November 2003

Galactosylated surface is an attractive substrate for hepatocyte culture because of the specific interaction between the galactose ligand and the asialoglycoprotein receptor on hepatocytes. In this study, we described a scheme to achieve high density of immobilized galactose ligands on polyethylene terephthalate (PET) surface by first surface‐grafting polyacrylic acid on plasma‐pretreated PET film under UV irradiation, followed by conjugation of a galactose derivative (1‐O‐(6′‐aminohexyl)‐D‐galactopyranoside) to the grafted polyacrylic acid chains. A high galactose density of 513 nmol/cm2 on the PET surface was used in this study to investigate the behavior of cultured hepatocyte. This engineered substrate showed high affinity to fluorescein isothiocyanate‐lectin binding. Primary rat hepatocytes, when seeded at a density of 2 × 105 cells/cm2, attached to the galactosylated PET substrate at a similar efficiency compared with collagen‐coated substrate. The hepatocytes spontaneously formed aggregates 1 day after cell seeding and showed better maintenance of albumin secretion and urea synthesis functions than those cultured on collagen‐coated surface. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 67A: 1093–1104, 2003
Corrosion behavior of nitinol wires in body fluid environments
Authors: Carroll W. M. , Kelly M. J.
Published: November 2003

In this study, breakdown potentials were measured for unpolished and mechanically polished nitinol wires in simulated body fluids. These wires are similar to those used in the manufacture of stents. Considerable scatter was observed in the results indicating a variable surface state. After appropriate heat treatments, the measured breakdown values were lower but more reproducible for the mechanically polished samples. Significantly higher breakdown potentials were observed for cross‐section wire samples. Some wires were tested in human blood and the breakdown values were higher than in Ringer and 0.9% NaCl solutions. Energy dispersive X‐ray analysis of the surface layers indicated that oxide thickening occurred after heat treatments. Dynamic secondary ion mass spectroscopy also revealed thickened surface oxides on the wires. The oxide was predominantly made up of TiO2 with a very thin layer of NiO at the outer surface. Galvanic corrosion tests were performed on nitinol wires coupled with gold, elgiloy/phynox, and stainless steel. Nitinol was found to be anodic in all cases yet the currents measured were small. In tests in which nitinol–gold couples were immersed in 0.9% NaCl for periods up to 12 months, only very small amounts of nickel (in the part per billion range) were released into solution and scanning electron microscopy examination revealed no corrosion. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 67A: 1123–1130, 2003
Remineralization of demineralized albumin‐calcium phosphate coatings
Authors: Liu Y. , Hunziker E. B. , Layrolle P. , Van Blitterswijk C. , Calvert P. D. , de Groot K.
Published: November 2003

Calcium phosphate and bovine serum albumin were coprecipitated (under physiological conditions of temperature and pH) upon the surfaces of titanium‐alloy samples, which thereby became coated with a dense, proteinaceous mineral layer 30–50 μm in thickness. Dissolution of the inorganic phase by treatment with acidic saline yielded a self‐supporting protein scaffold, 7–10 μm in thickness. Energy‐dispersive X‐ray analysis and Fourier‐transform infrared spectroscopy confirmed the absence of inorganic components from the demineralized albumin scaffolds. When titanium‐alloy samples bearing these demineralized protein scaffolds were immersed in a supersaturated solution of calcium phosphate (again at physiological temperature and pH), they remineralized. These redux albumin‐calcium phosphate layers corresponded in thickness to the original coatings. When titanium‐alloy discs bearing the demineralized protein scaffolds were implanted ectopically (subcutaneously) in mice, they, too, remineralized. No uniform mineral layer was deposited upon the surfaces of naked titanium‐alloy implants. To the best of our knowledge, this is the first demonstration of remineralization within the interstices of a noncollagenous protein scaffold, either in vitro or in vivo. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 67A: 1155–1162, 2003
Antibacterial properties of nitric oxide–releasing sol‐gels
Authors: Nablo Brian J. , Schoenfisch Mark H.
Published: November 2003

The antibacterial characteristics of nitric oxide (NO)‐releasing sol‐gel coatings are described. The NO release from these surfaces is steady over short periods (≈1 h) and measurable over several days. The ability of NO to prevent bacterial adhesion is evaluated by exposing controls and NO‐releasing sol‐gels to ≈108 colony‐forming units (cfu)/mL saline suspensions of Pseudomonas aeruginosa. Pseudomonas aeruginosa adhesion to sol‐gel controls varies depending on the sol‐gel formulation. Sol‐gel surfaces capable of NO release decrease bacterial adhesion by 30% to 95% relative to controls. The contact angle measurements of control and NO‐releasing surfaces are similar, supporting NO's action as an antibacterial agent against bacterial adhesion. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 67A: 1276–1283, 2003
Change in electrophoretic mobility of PC12 cells after culturing on PVA membranes modified with different diamines
Authors: Young Tai‐Horng , Hung Chih‐Huang
Published: November 2003

The cell–biomaterial interaction is of extreme importance in regulating the numerous functions necessary for cell adhesion, growth, and differentiation. In the current study, electrophoresis was used to investigate the interactions between cells and biomaterials by measuring the change in electrophoretic mobility of pheochromocytoma (PC12) cells after they were cultured on the poly (vinyl alcohol) membranes modified with different diamines. Variations in cellular activity and electrophoretic mobility of cultured cells were compared. It was found that the intracellular metabolism and the cell surface charge properties were altered after cells contacting biomaterials and the variation of the latter occurred earlier than that of the former. Although the precise mechanism by which the variation of electrophoretic mobility of cultured PC12 cells was unknown, the biomaterials could influence the cell mobility within a short incubation time. It was hypothesized that changes in extracellular matrix components of cell surface may be in part responsible. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 67A: 1238–1244, 2003
Bone regeneration by grafting of an autogenous cultured bone/ceramic construct
Authors: Yoshikawa Takafumi , Iida Jin , Ueda Yurito , Koizumi Munehisa , Takakura Yoshinori , Nonomura Akitaka
Published: November 2003

The in vivo osteogenic potential of autogenous cultured bone/ceramic constructs in large animals or humans is unknown, and thus we performed a preliminary study of this issue prior to clinical application. All autogenous cultured–bone/ceramic constructs at 3 weeks after implantation in dogs showed obvious histological bone formation within the ceramic pores. In many pores, the HE staining of decalcified specimens revealed thick lamellar bone formation on the pore surface of ceramic. On the surface of bone tissue, numerous active cuboidal osteoblasts were evident. Biochemically, high alkaline phosphatase activity was detected in all dogs. Histological examination of the constructs at 8 weeks postimplantation showed lamellar bone formation with vascular system invasion into the pores, and regenerated hematopoietic bone marrow was often detected in association with the new bone in grafting of human cultured bone/ceramic constructs. Trilineage hematopoietic cells (i.e., granulocytic, erythroblastic, and megakaryocytic cells) were identified in the ceramic pores. Biochemically, high alkaline phosphatase activity and significant human osteocalcin content was detected in the constructs. Based on these findings, in the near future, this technique (grafting of patient‐derived cultured bone/HA constructs) will be able to be applied to various bone reconstruction surgical treatments. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 67A: 1437–1441, 2003
Effect of calcium salt content in the poly(ε‐caprolactone)/silica nanocomposite on the nucleation and growth behavior of apatite layer
Authors: Rhee Sang‐Hoon
Published: November 2003

The effect of calcium salt content in the poly(ε‐caprolactone) (PCL)/silica nanocomposite on the nucleation and growth behavior of apatite layer in simulated body fluid (SBF) was investigated. The specimens were prepared with low (L) and high (H) concentrations of calcium nitrate tetrahydrate through a sol‐gel method. After soaking in the SBF at 36.5°C for 1 week, a densely packed apatite layer that had a smooth surface and a Ca/P ratio similar to bone was formed on specimens containing a low concentration of calcium salt while a loosely packed apatite layer with a rugged surface and a higher Ca/P ratio than that of bone occurred on specimens containing a high concentration of calcium salt. The results are explained in terms of the degree of supersaturation of apatite in the SBF, as determined by the concentrations of constituent ions of apatite and pH. The practical implication of the results is that a dense and bone‐like apatite layer on the PCL/silica nanocomposite in vitro, and perhaps in vivo, can be achieved by adopting an appropriate calcium salt content. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 67A: 1131–1138, 2003
Engineering porous polyurethane scaffolds by photografting polymerization of methacrylic acid for improved endothelial cell compatibility
Authors: Zhu Yabin , Gao Changyou , Guan Jianjun , Shen Jiacong
Published: November 2003

Using a preadsorbing‐monomer method, polyurethane (PU) porous scaffolds were modified by grafting polymerization of methacrylic acid (MAA) initiated under UV light. Fourier transform infrared–attenuated total reflection spectroscopy and X‐ray photoelectron spectroscopy characterizations confirmed the occurrence of the grafting polymerization of poly(methacrylic acid) (PMAA) on PU scaffolds and the measurement of water adsorption also demonstrated enhanced hydrophilicity. The PMAA grafting degree correlated to the amount of MAA adsorbed, the pore average diameter, and the porosity. It was verified that the higher porosity the scaffold has, the larger porous area (or the larger contact area with MAA) it has, and therefore the higher amount of MAA adsorbed and higher grafting degree obtained. The results of human endothelial cells cultured in vitro showed that the PU scaffolds modified with the hydrophilic PMAA had more improved cell compatibility than the control matrix. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 67A: 1367–1373, 2003
Human cytomegalovirus proteins PP65 and IEP72 are targeted to distinct compartments in nuclei and nuclear matrices of infected human embryo fibroblasts
Authors: Arcangeletti M.C. , De Conto F. , Ferraglia F. , Pinardi F. , Gatti R. , Orlandini G. , Calderaro A. , Motta F. , Medici M.C. , Martinelli M. , Valcavi P. , Razin S.V. , Chezzi C. , Dettori G.
Published: November 2003

The cellular distribution of the human cytomegalovirus (HCMV)‐specific UL83 phosphoprotein (pp65) and UL123 immediate‐early protein (IEp72) in lytically infected human embryo fibroblasts was studied by means of indirect immunofluorescence and confocal microscopy. Both proteins were found to have a nuclear localization, but they were concentrated in different compartments within the nuclei. The pp65 was located predominantly in the nucleoli; this was already evident with the parental viral protein, which was targeted to the above nuclear compartment very soon after infection. The nucleolar localization of pp65 was also observed at later stages of the HCMV infectious cycle. After chromatin extraction (in the so‐called in situ nuclear matrices), a significant portion of the pp65 remained associated with nucleoli within the first hour after infection, then gradually redistributed in a perinucleolar area, as well as throughout the nucleus, with a granular pattern. A quite different distribution was observed for IEp72 at very early stages after infection of human embryo fibroblasts with HCMV; indeed, this viral protein was found in bright foci, clearly observable in both non‐extracted nuclei and in nuclear matrices. At later stages of infection, IEp72 became almost homogeneously distributed within the whole nucleus, while the foci increased in size and were more evenly spread; in several infected cells some of them lay within nucleoli. This peculiar nuclear distribution of IEp72 was preserved in nuclear matrices as well. The entire set of data is discussed in terms of the necessity of integration for HCMV‐specific products into the pre‐existing nuclear architecture, with the possibility of subsequent adaptation of nuclear compartments to fit the needs of the HCMV replicative cycle. © 2003 Wiley‐Liss, Inc.
Role of PTEN and Akt in the regulation of growth and apoptosis in human osteoblastic cells
Authors: Nielsen‐Preiss Sheila M. , Silva Selina R. , Gillette Jennifer M.
Published: November 2003

Cancer cells are characterized by either an increased ability to proliferate or a diminished capacity to undergo programmed cell death. PTEN is instrumental in regulating the balance between growth and death in several cell types and has been described as a tumor suppressor. The chromosome arm on which PTEN is located is deleted in a subset of human osteosarcoma tumors. Therefore, we predicted that the loss of PTEN expression was contributing to increased Akt activation and the subsequent growth and survival of osteosarcoma tumor cells. Immunoblot analyses of several human osteosarcoma cell lines and normal osteoblasts revealed relatively abundant levels of PTEN. Furthermore, stimulation of cell growth or induction of apoptosis in osteosarcoma cells failed to affect PTEN expression or activity. Therefore, routine regulation of osteosarcoma cell growth and survival appears to be independent of changes in PTEN. Subsequently, the activation of a downstream target of PTEN activity, the survival factor Akt, was analyzed. Inappropriate activation of Akt could bypass the negative regulation by PTEN. Analyses of Akt expression in several osteosarcoma cell lines and normal osteoblasts revealed uniformly low basal levels of phosphorylated Akt. The levels of phosphorylated Akt did not increase following growth stimulation. In addition, osteosarcoma cell growth was unaffected by inhibitors of phosphatidylinositol‐3 kinase, an upstream activator of the Akt signaling pathway. These data further suggest that the Akt pathway is not the predominant signaling cascade required for osteoblastic growth. However, inhibition of PTEN activity resulted in increased levels of Akt phosphorylation and enhanced cell proliferation. These data suggest that while abundant levels of PTEN normally maintain Akt in an inactive form in osteoblastic cells, the Akt signaling pathway is intact and functional. © 2003 Wiley‐Liss, Inc.
Increases in cytosolic calcium, but not fluid flow, affect aggrecan mRNA levels in articular chondrocytes
Authors: Alford A.I. , Yellowley C.E. , Jacobs C.R. , Donahue H.J.
Published: November 2003

Fluctuations in intracellular free calcium concentration ([Ca2+]i) is thought to be one mechanism by which cells transduce mechanical signals into biological responses. Primary cultures of bovine articular chondrocytes (BAC) respond to oscillating fluid flow with a transient rise in [Ca2+]i. However, specific down‐stream effects of [Ca2+]i on gene expression and phenotype in BAC remain to be defined. The present work was designed to determine whether [Ca2+]i mobilization regulates aggrecan mRNA levels. [Ca2+]i was transiently elevated by exposing BAC to the [Ca2+]‐specific ionophore, ionomycin. The results show that ionomycin increases [Ca2+]i in a dose‐dependent fashion. Semi‐quantitative real time (RT)‐PCR was used to study the effects of increased [Ca2+]i on steady state levels of aggrecan mRNA. Four hours after a brief exposure to 1.5 μM ionomycin, BAC displayed a nearly four‐fold decrease in aggrecan mRNA levels compared to control cells. This effect of ionomycin on aggrecan mRNA was no longer evident 6 or 10 h later. Despite previous observations that oscillating fluid flow elicits increased [Ca2+]i in BAC, it did not affect aggrecan mRNA levels. Taken together, these data suggest that ionomycin‐induced [Ca2+]i fluctuations regulate aggrecan mRNA levels, but that flow induced [Ca2+]i fluctuations do not. © 2003 Wiley‐Liss, Inc.
Induction of stromelysin‐1 (MMP‐3) by fibroblast growth factor‐2 (FGF‐2) in FGF‐2−/− microvascular endothelial cells requires prolonged activation of extracellular signal‐regulated kinases‐1 and ‐2 (ERK‐1/2)
Authors: Pintucci Giuseppe , Yu Pey‐Jen , Sharony Ram , Baumann F. Gregory , Saponara Fiorella , Frasca Antonio , Galloway Aubrey C. , Moscatelli David , Mignatti Paolo
Published: November 2003

Basic fibroblast growth factor (FGF‐2) and matrix metalloproteinases (MMPs) play key roles in vascular remodeling. Because FGF‐2 controls a number of proteolytic activities in various cell types, we tested its effect on vascular endothelial cell expression of MMP‐3 (stromelysin‐1), a broad‐spectrum proteinase implicated in coronary atherosclerosis. Endothelial cells (EC) from FGF‐2−/− mice are highly responsive to exogenous FGF‐2 and were therefore used for this study. The results showed that treatment of microvascular EC with human recombinant FGF‐2 results in strong induction of MMP‐3 mRNA and protein expression. Upregulation of MMP‐3 mRNA by FGF‐2 requires de novo protein synthesis and activation of the ERK‐1/2 pathway. FGF‐2 concentrations (5–10 ng/ml) that induce rapid and prolonged (24 h) activation of ERK‐1/2 upregulate MMP‐3 expression. In contrast, lower concentrations (1–2 ng/ml) that induce robust but transient (<8 h) ERK‐1/2 activation are ineffective. Inhibition of ERK‐1/2 activation at different times (−0.5 h to +8 h) of EC treatment with effective FGF‐2 concentrations blocks MMP‐3 upregulation. Thus, FGF‐2 induces EC expression of MMP‐3 with a threshold dose effect that requires sustained activation of the ERK‐1/2 pathway. Because FGF‐2 controls other EC functions with a linear dose effect, these features indicate a unique role of MMP‐3 in vascular remodeling. © 2003 Wiley‐Liss, Inc.
IGF‐I and MAP kinase involvement in the stimulatory effects of LNCaP prostate cancer cell conditioned media on cell proliferation and protein synthesis in MC3T3‐E1 osteoblastic cells
Authors: Bhattacharyya Rumi S. , Stern Paula H.
Published: November 2003

Bone metastases from prostate cancer cause abnormal new bone formation, however, the factors involved and the pathways leading to the response are incompletely defined. We investigated the mechanisms of osteoblast stimulatory effects of LNCaP prostate carcinoma cell conditioned media (CM). MC3T3‐E1 osteoblastic cells were cultured with CM from confluent LNCaP cells. LNCaP CM stimulated MAP kinase, cell proliferation (3H‐thymidine incorporation), and protein synthesis (14C‐proline incorporation) in the MC3T3‐E1 cells. The increases in cell proliferation and protein synthesis were prevented by inhibition of the MAP kinase pathway. IGF‐I mimicked the effects of the CM on the MC3T3‐E1 cells and inhibition of IGF‐I action decreased the LNCaP CM stimulation of 3H‐thymidine and 14C‐proline incorporation and MAP kinase activity. The findings indicate that IGF‐I is an important factor for the stimulatory effects of LNCaP cell CM on cell proliferation and protein synthesis in osteoblastic cells, and that MAP kinase is a component of the signaling pathway for these effects. © 2003 Wiley‐Liss, Inc.
Coplanar waveguide structures loaded with split‐ring resonators
Authors: Falcone F. , Martín F. , Bonache J. , Marqués R. , Sorolla M.
Published: November 2003

Coplanar waveguide (CPW) transmission lines periodically coupled to split‐ring resonators (SRRs) are analyzed, designed, and characterized. Due to inductive coupling between the lines and SRRs, signal propagation is inhibited in the vicinity of the resonant frequency of the rings. The result is a stop‐band behavior that can be of interest for the elimination of frequency parasitics in CPW‐based devices. Two different approaches are envisaged: a uniplanar structure, where CPW and rings share the same metal level; and a bimetal structure with SRRs etched on the back side of the substrate. It has been found that the latter exhibits almost negligible insertion losses in the pass band, and sharp cutoff and a high level of rejection in the stop band, with few unit cells. Since ring dimensions are small compared to the signal wavelength at resonance, the proposed SRR‐CPWs are very promising for the design of miniaturized microwave circuits. © 2004 Wiley Periodicals, Inc. Microwave Opt Technol Lett 40: 3–6, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.11269
Numerical analysis of a fiber connected to an inhomogeneous embedded waveguide with rectangular cross‐section
Authors: Momoda M. , Miyamoto T. , Yasumoto K.
Published: November 2003

The Fourier series expansion method is applied to realize an accurate full‐vectorial analysis of the problem of a step‐index optical fiber connected to an inhomogeneous embedded optical waveguide with rectangular cross section, using periodic boundary conditions in both transverse directions. Using this method, the Maxwell's equations in the waveguide system are reduced to a simple eigenvalue problem of a linear system for the Fourier coefficients. Then the behavior of the transmitted and reflected powers of the guided and radiation modes is clarified for each gap distance and transverse shift between the two waveguides, and compared with the cases of the homogeneous embedded waveguide and different transverse refractive index variations. © 2004 Wiley Periodicals, Inc. Microwave Opt Technol Lett 40: 14–18, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.11272
Performance improvements in XGM‐based wavelength converters with converted signal feedback
Authors: Sun Junqiang
Published: November 2003

A large‐signal theoretical model is presented for wavelength conversion using cross‐gain modulation (XGM) in semiconductor optical amplifiers with converted signal feedback. Theoretical results on the performance of the converter, in terms of extinction ratio, frequency chirping, and conversion speed, are discussed and analyzed. The converter performance can be enhanced and restrictions of the low‐facet reflectivity can be relaxed due to the enhancement of the carrier–photon interaction. © 2004 Wiley Periodicals, Inc. Microwave Opt Technol Lett 40: 18–22, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.11274
Modelling of microstrip antennas on a finite ground plane using the 2D physical optics model
Authors: Volski Vladimir , Vandenbosch Guy A. E.
Published: November 2003

A method for the computation of radiation patterns of microstrip antennas on a finite ground plane is presented. The method is based on the geometrical theory of diffraction and the 2D physical optics model. The diffraction of space waves and surface waves is taken into consideration. © 2004 Wiley Periodicals, Inc. Microwave Opt Technol Lett 40: 26–29, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.11276
Fast semivectorial non‐linear finite‐difference beam‐propagation method
Authors: de‐Oliva‐Rubio J. , Molina‐Fernández I.
Published: November 2003

In this paper a new semivectorial finite‐difference beam‐propagation method (FD‐BPM) technique for the analysis of nonlinear optical devices is presented. The proposed technique relies on the application of the Runge–Kutta method to perform each propagation step; it is easier to use than the Crank–Nicholson‐based FDBPM method and exhibits better numerical performance. © 2004 Wiley Periodicals, Inc. Microwave Opt Technol Lett 40: 73–77, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.11288
Investigation of alternatives to methyl bromide for management of Meloidogyne javanica on greenhouse grown tomato
Authors: Tzortzakakis Emmanuel A , Petsas Serafim E
Published: November 2003

The root galling index and the densities of eggs in roots and juveniles in soil of the root‐knot nematode Meloidogyne javanica (Treub) Chitwood on tomato, and the effect of these on crop yield were assessed in greenhouse experiments applying various treatments at two different sites in Crete, Greece. Tomato crops were grown for four cycles by rotating nematode‐resistant (first and third spring crops) with susceptible (second and fourth autumn crops) cultivars and receiving the following treatments: (a) untreated control; (b) methyl bromide application before the first and third crops; (c) application of the fungus Pochonia chlamydosporia (Goddard) Zare, Gams & Evans before planting the first, third and fourth crops with a supplementary application three weeks after the beginning of the fourth crop; (d) application of oxamyl in both sites and fenamiphos in site 1 only at the second and fourth crops; (e) combination of treatments (c) and (d). The fungus density in soil was monitored three weeks after application and at the end of each crop, when roots were lifted. Pochonia chlamydosporia had a variable establishment and did not control the nematode. Its pathogenicity on eggs was not demonstrated, as in all cases galls were big, with all egg masses inside and protected from infection. The methyl bromide treatment significantly reduced root galling and egg production compared to other treatments in all crop cycles and the yield of the fourth crop was significantly greater. Nematicides reduced nematode densities compared with untreated controls and the fungus treatment, but they were less effective than methyl bromide and resulted in increased yield in one site only. Copyright © 2003 Society of Chemical Industry
Multiple mechanisms account for variation in base‐line sensitivity to azole fungicides in field isolates of Mycosphaerella graminicola
Authors: Stergiopoulos Ioannis , van Nistelrooy Johannes GM , Kema Gert HJ , De Waard Maarten A
Published: November 2003

Molecular mechanisms that account for variation in base‐line sensitivity to azole fungicides were examined in a collection of twenty field isolates, collected in France and Germany, of the wheat pathogen Mycosphaerella graminicola (Fuckel) Schroeter. The isolates tested represent the wide base‐line sensitivity to the azole fungicide tebuconazole described previously. The isolates were cross‐sensitive to other azoles tested, such as cyproconazole and ketoconazole, but not to unrelated chemicals like cycloheximide, kresoxim‐methyl or rhodamine 6G. Progenies from a genetic cross between an isolate with an intermediate and a high sensitivity to azoles displayed a continuous range of phenotypes with respect to cyproconazole sensitivity, indicating that variation in azole sensitivity in this haploid organism is polygenic. The basal level of expression of the ATP‐binding cassette transporter genes MgAtr1‐MgAtr5 from M graminicola significantly varied amongst the isolates tested, but no clear increase in the transcript level of a particular MgAtr gene was found in the less sensitive isolates. Cyproconazole strongly induced expression of MgAtr4, but no correlation between expression levels of this gene and azole sensitivity was observed. One isolate with intermediate sensitivity to azoles over‐expressed CYP51, encoding cytochrome P450 sterol 14α‐demethylase from M graminicola. Isolates with a low or high sensitivity to azoles were tested for accumulation of cyproconazole, but no clear correlation between reduced accumulation of the fungicide in mycelium and sensitivity to azoles was observed. Therefore, differences in accumulation cannot account exclusively for the variation in base‐line sensitivity of the isolates to azoles. The results indicate that multiple mechanisms account for differences in base‐line sensitivity to azoles in field isolates of M graminicola. Copyright © 2003 Society of Chemical Industry
An on‐line performance visualization technology
Authors: Bakić Aleksandar M. , Mutka Matt W. , Rover Diane T.
Published: November 2003

A new software technology for on‐line performance analysis and the visualization of complex parallel and distributed systems is presented. Often heterogeneous, these systems need capabilities for the flexible integration and configuration of performance analysis and visualization. Our technology is based on an object‐oriented framework for the rapid prototyping and development of distributable visual objects. The visual objects consist of two levels, a platform/device‐specific low level and an analysis‐ and visualization‐specific high level. We have developed a very high‐level markup language called VOML and a compiler for the component‐based development of high‐level visual objects. The VOML is based on a software architecture for on‐line event processing and performance visualization called EPIRA. The technology lends itself to constructing high‐level visual objects from globally distributed component definitions. Details of the technology and tools used, as well as how an example visual object can be rapidly prototyped from several reusable components, are presented. Copyright © 2003 John Wiley & Sons, Ltd.
Implementation of visual languages using pattern‐based specifications
Authors: Schmidt Carsten , Kastens Uwe
Published: November 2003

The implementation of visual languages requires a wide range of conceptual and technical knowledge from issues of user interface design and graphical implementation to aspects of analysis and transformation for languages in general. We present a powerful toolset that incorporates such knowledge. Our toolset generates editors from high‐level specifications. A language is specified by identifying certain patterns in the language structure and selecting a visual representation from a set of precoined solutions. Visual programs are represented by attributed abstract trees. Therefore, further phases of processing visual programs can be generated by state‐of‐the‐art tools for language implementation. We demonstrate that even challenging visual languages can be implemented with reasonably little effort and with rather limited technical knowledge. The approach is suitable for a large variety of visual language styles. Copyright © 2003 John Wiley & Sons, Ltd.
A method for Doppler acoustic measurement of black smoker flow fields
Authors: Jackson Darrell R. , Jones Christopher D. , Rona Peter A. , Bemis Karen G.
Published: November 2003

A method is developed for using multibeam sonar to map the flow velocity field of black smoker plumes. The method is used to obtain two‐dimensional cross‐sectional maps of vertical velocity, but is capable of mapping velocity in three dimensions. This is in contrast to conventional current meters, which measure only at several points and acoustic Doppler current profilers, whose diverging beams cannot readily map the interior of a plume. Geometric corrections are used to estimate the vertical component of velocity, compensating for ambient current. The method is demonstrated using data from the main plume at the Grotto vent complex in the Main Endeavour Field, Juan de Fuca Ridge, and the errors due to noise, signal fluctuations, and fluctuations in plume structure are estimated.
Observations of non‐conjugate theta aurora
Authors: Østgaard N. , Mende S. B. , Frey H. U. , Frank L. A. , Sigwarth J. B.
Published: November 2003

Based on simultaneous imaging data from IMAGE FUV and Polar VIS Earth camera and DMSP particle measurements we report two events where a theta aurora was observed in one hemisphere but not in the other. IMF control and hemispherical conductivity differences are suggested as possible explanations for the occurrence of non‐conjugate theta aurora.
Magma generation by slab steepening and breakoff beneath a subduction‐accretion complex: An alternative model for collision‐related volcanism in Eastern Anatolia, Turkey
Authors: Keskin Mehmet
Published: November 2003

Eastern Anatolia is regarded as one of the best examples of continental collision, represented by a 2 km high plateau. It displays shallow and diffuse seismicity, indicating that the crust is still being actively deformed. Perhaps the most striking aspect of Eastern Anatolia is the volume and compositional variability of collision‐related volcanic products erupted during the Neogene and Quaternary time. A number of models have been proposed for the genesis of this volcanism in the region. However, recent geophysical studies have revealed that a mantle lithosphere is almost completely absent beneath a greater portion of the region, which makes us question the validity of the previous models. In this paper, we propose a new model for magma genesis: slab steepening and breakoff beneath a large subduction‐accretion complex. This model holds that a northward subducting oceanic lithosphere beneath the Eastern Anatolia Accretionary Prism gets steepened and eventually detached from the continental lithosphere of the Bitlis‐Poturge Massif, following the continent‐accretionary complex collision. This brings the asthenospheric mantle in contact with the accretionary complex at shallow depths (e.g., around 50 km), resulting in rapid regional uplift and extensive melting which leads to collisional volcanism.
An overview of ACE‐Asia: Strategies for quantifying the relationships between Asian aerosols and their climatic impacts
Authors: Huebert Barry J. , Bates Timothy , Russell Philip B. , Shi Guangyu , Kim Young Joon , Kawamura Kimitaka , Carmichael Greg , Nakajima Teruyuki
Published: November 2003

The International Global Atmospheric Chemistry Program (IGAC) has conducted a series of Aerosol Characterization Experiments (ACE) that integrate in situ measurements, satellite observations, and models to reduce the uncertainty in calculations of the climate forcing due to aerosol particles. ACE‐Asia, the fourth in this series of experiments, consisted of two focused components: (1) An intensive field study that sought to quantify the spatial and vertical distribution of aerosol concentrations and properties, the processes controlling their formation, evolution, and fate, and the column‐integrated radiative effect of the aerosol (late March through May 2001). (2) A longer‐term network of ground stations that used in situ and column‐integrated measurements to quantify the chemical, physical, and optical properties of aerosols in the ACE‐Asia study area and to assess their spatial and temporal (seasonal and interannual) variability (2000–2003). The approach of the ACE‐Asia science team was to make simultaneous measurements of aerosol chemical, physical, and optical properties and their radiative impacts in a variety of air masses, often coordinated with satellite overpasses. Three aircraft, two research ships, a network of lidars, and many surface sites gathered data on Asian aerosols. Chemical transport models (CTMs) were integrated into the program from the start, being used in a forecast mode during the intensive observation period to identify promising areas for airborne and ship observations and then later as tools for integrating observations. The testing and improvement of a wide range of aerosol models (including microphysical, radiative transfer, CTM, and global climate models) was one important way in which we assessed our understanding of the properties and controlling processes of Asian aerosols. We describe here the scientific goals and objectives of the ACE‐Asia experiment, its observational strategies, the types of observations made by the mobile platforms and stationary sites, the models that will integrate our understanding of the climatic effect of aerosol particles, and the types of data that have been generated. Eight scientific questions focus the discussion. The intensive observations took place during a season of unusually heavy dust, so we have a large suite of observations of dust and its interaction with air pollutants. Further information about ACE‐Asia can be found on the project Web site at http://saga.pmel.noaa.gov/aceasia/.
Vices of Inattention
Authors: Jenni Kathie
Published: November 2003

abstract  Why do we routinely betray moral commitments that, in some sense, we authentically embrace? One explanation involves inattention: failure to attend to morally important aspects of our lives. Inattention ranges from an unmotivated lack of focus, or “simple” inattention, to more purposeful and wilful self‐deception. Self‐deception has received exhaustive and insightful treatment by philosophers and psychologists; what remains unexamined is the less complex, but more pervasive phenomenon of simple inattention. Since inattention is at least equally important in accounting for our routine moral failures, this gap is an important one to fill.

In this essay I examine moral dimensions of inattention: what makes it problematic, what vices it reflects, what duties we have to overcome it, and how we might try to do that. I argue that inattention obscures responsibilities to prevent harm, erodes autonomy, manifests a lack of virtue, and undermines integrity. For these reasons, we have obligations of attentiveness. I propose that we should attend (at least) to apparent violations of our moral values in which we are personally implicated, which we have power to affect, and to which we have been directed by clues that something is amiss. I end with practical suggestions for enhancing our attentiveness.
The Bush Presidency and the American Electorate
Authors: Jacobson Gary C.
Published: November 2003

George W. Bush's leadership in response to the terrorist attacks of September 11, 2001 raised his standing with the American people dramatically. The rally in approval was sufficiently durable that, with the help of the shift in national priorities from domestic to defense issues and a pro‐Republican reapportionment, the president's party was able to pick up seats in both houses in the 2002 elections. But aside from altering attitudes toward the president himself, September 11 and its aftermath (including successful wars in Afghanistan and Iraq) have yet to show any lasting effect on partisan attitudes, the partisan balance, or the degree of polarization in the electorate.