bluuebunny/crossref_metadata_2025 huggingface dataset:
Cannabinoids inhibit gap junctional intercellular communication and activate ERK in a rat liver epithelial cell line
Authors: Upham Brad L. , Rummel Alisa M. , Carbone Joseph M. , Trosko James E. , Ouyang Yanli , Crawford Robert B. , Kaminski Norbert E.
Published: January 2003

Many tumor promoters suppress the immune system; however, the direct effect of immunosuppressants on the tumorigenic pathways of nonimmune cells in solid tissue has not been well documented. Cannabinoids were chosen to explore this question further. Cannabinoids are immune modulators that affect specific intracellular signaling pathways in leukocytes. Since these compounds are nongenotoxic, any tumorigenic effect that might be associated with these compounds would need to occur through an epigenetic mechanism. Therefore, we determined the effect of Δ9‐THC and CBN, 2 plant‐derived cannabinoids, on 2 key epigenetic markers of tumor promotion: inhibition of GJIC, which is essential in removing a cell from growth suppression, and activation of the ERK–MAPK pathway, which is crucial in activating the appropriate genes for mitogenesis. Both Δ9‐THC and CBN reversibly inhibited GJIC at noncytotoxic doses (15 μM) in a normal diploid WB rat liver epithelial oval cell line within 20 min and activated ERK1 and ERK2 within 5 min. Inhibition of MEK with PD98059 prevented the inhibition of GJIC by either cannabinoid, suggesting that inhibition of GJIC was MEK‐dependent. Based on RT‐PCR analysis and employment of an antagonist of CB1 and CB2, the effects on GJIC and MAPK were independent of both cannabinoid receptors. Cannabinoids affected crucial epigenetic pathways associated with cell proliferation in a rodent liver epithelial cell model system. © 2002 Wiley‐Liss, Inc.
Dynamic T1‐weighted monitoring of vascularization in human carcinoma heterotransplants by magnetic resonance imaging
Authors: Kiessling Fabian , Heilmann Melanie , Vosseler Silvia , Lichy Matthias , Krix Martin , Fink Christian , Kiessling Isabel , Steinbauer Heinrich , Schad Lothar , Fusenig Norbert E. , Delorme Stefan
Published: January 2003

Studies on tumor angiogenesis and antiangiogenic therapies are commonly performed with tumor heterotransplants in nude mice. To monitor therapeutic effects, improved noninvasive analyses of functional data are required, in addition to the assessment of tumor volume and histology. Here, we report on sequential monitoring of vascularization of human squamous cell carcinomas growing as heterotransplants in nude mice using MRI. Using a custom‐developed animal coil in a conventional whole‐body 1.5 T MRI scanner, dynamic T1w sequences were recorded after i.v. injection of Gd‐DTPA in tumors grown for 17, 21, 25, 29 and 33 days. Amplitude and the exchange rate constant (kep) were calculated according to a 2‐compartment model, discriminating intravascular and interstitial spaces, and correlated with tumor size and histology. High‐resolution imaging of small heterotransplants from 100 to 1,000 mm3 was achieved, clearly discriminating vital and necrotic areas. Preceding the development of necroses, which were hyperintense in T2w images and confirmed with histology, a local decrease of amplitude and kep values was observed. Significantly higher amplitudes were found in tumor periphery than in central parts, correlating well with the vascular pattern obtained by immunocytochemistry. Tumor size correlated negatively with amplitude, probably as a result of increasing necrotic areas, whereas the reason for the observed increase of kep value with tumor size remains unclear. These data demonstrate that dynamic MRI is an excellent method for noninvasive assessment of tumor vascularization in small animals using a clinical whole‐body scanner with little technical modifications. This technique provides functional data characterizing essential features of tumor biology and is thus appropriate for monitoring antiangiogenic therapies. © 2002 Wiley‐Liss, Inc.
Activation of multiple caspases and modification of cell surface fas (CD95) in proteasome inhibitor‐induced apoptosis of rat natural killer cells
Authors: Lu Min , Kitson Richard P. , Xue Yaming , Goldfarb Ronald H.
Published: January 2003

The proteasome is a multi‐subunit protease complex that is involved in intracellular protein degradation in eukaryotes. Previously, we have reported that selective, synthetic chymotryptic proteasome inhibitors inhibit A‐NK cell‐mediated cytotoxicity by approximately 50%; however, the exact role of the proteasome in NK cell‐mediated cytotoxicity remains unknown. Herein, we report that proteasome inhibitors, MG115 and MG132, decreased the proteasome chymotrypsin‐like activity in the rat natural killer cell line RNK16 by 85% at a concentration of 5 μM. The viability of RNK16 cells was also reduced in the presence of these inhibitors. Both inhibitors induced the apoptosis of RNK16 cells, as shown by DNA fragmentation, caspase‐3 activation and the appearance of sub‐G‐cell populations. An increase in the fraction of apoptotic cells was observed in a dose‐ and time‐dependent manner in our studies. In addition, the activity of caspase‐1, ‐2, ‐6, ‐7, ‐8, and ‐9, was increased following the treatment of RNK16 cells with these inhibitors. Further investigation revealed that the expression of Fas (CD95) protein on the RNK16 cell surface was increased after the treatment by MG115 or MG132, indicating that apoptosis induced by proteasome inhibitors in RNK16 cells might be mediated through the Fas (CD95)‐mediated death pathway as well. Our studies indicate, for the first time, that proteasomal chymotryptic inhibitors can reduce natural killer cell viability and therefore indirectly inhibit cell‐mediated cytotoxicity via the apoptosis‐inducing properties of these agents. © 2002 Wiley‐Liss, Inc.
Myosin heavy chain kinase B participates in the regulation of myosin assembly into the cytoskeleton
Authors: Rico Maribel , Egelhoff Thomas T.
Published: January 2003

Myosin II plays critical roles in events such as cytokinesis, chemotactic migration, and morphological changes during multicellular development. The amoeba Dictyostelium discoideum provides a simple system for the study of this contractile protein. In this system, myosin II filament assembly is regulated by myosin heavy chain (MHC) phosphorylation in the tail region of the molecule. Earlier studies identified an alpha‐kinase, MHC kinase A (MHCK A), which phosphorylates three mapped threonine residues in the myosin tail, driving myosin disassembly. Using molecular and genomic approaches, we have identified a series of related kinases in Dictyostelium. The enzyme MHCK B shares with MHCK A a domain organization that includes a highly novel catalytic domain coupled to a carboxyl‐terminal WD repeat domain. We have engineered, expressed, and purified a FLAG‐tagged version of the novel kinase. In the present study, we report detailed biochemical and cellular studies documenting that MHCK B plays a physiological role in the control of Dictyostelium myosin II assembly and disassembly during the vegetative life of Dictyostelium amoebae. The presented data supports a model of multiple related MHCKs in this system, with different regulatory mechanisms and pathways controlling each enzyme. © 2002 Wiley‐Liss, Inc.
Regulation of the osteoblast‐specific transcription factor, Runx2: Responsiveness to multiple signal transduction pathways
Authors: Franceschi Renny T. , Xiao Guozhi
Published: January 2003

The Cbfa1/Runx2 is an important transcription factor necessary for osteoblast differentiation and bone formation. However, the signaling pathways regulating Runx2 activity are just beginning to be understood. Inconsistencies between Runx2 mRNA or protein levels and its transcriptional activity suggests that posttranslational modification and/or protein‐protein interactions may regulate this factor. Runx2 can be phosphorylated and activated by the mitogen‐activated protein kinase (MAPK) pathway. This pathway can be stimulated by a variety of signals including those initiated by extracellular matrix (ECM), osteogenic growth factors like bone morphogenic proteins (BMPs) and fibroblast growth factor‐2 (FGF‐2), mechanical loading and hormones such as parathyroid hormone (PTH). Protein kinase A (PKA) may also phosphorylate/activate Runx2 under certain conditions. In addition, Runx2 activity is enhanced by protein‐protein interactions as are seen with PTH‐induced Runx2/AP‐1 and BMP‐mediated Runx2/Smads interactions. Mechanisms for interaction with Runx2 are complex including binding of distinct components such as AP‐1 factors and Smads proteins to separate DNA regions in target gene promoters and direct physical interactions between Runx2 and AP‐1/Smad factors. Post‐translational modifications such as phosphorylation may influence interactions between Runx2 and other nuclear factors. These findings suggest that Runx2 plays a central role in coordinating multiple signals involved in osteoblast differentiation. © 2002 Wiley‐Liss, Inc.
Changes of sphingolipid species in the phenotype conversion from myofibroblasts to lipocytes in hepatic stellate cells
Authors: Andrade Claudia M.B. , Trindade Vera M.T. , Cardoso Carla C.A. , Ziulkoski Ana L. , Trugo Luiz C. , Guaragna Regina M. , Borojevic Radovan , Guma Fátima C.R.
Published: January 2003

Sphingolipids play a relevant role in cell–cell interaction, communication, and migration. We studied the sphingolipid content in the murine hepatic stellate cell line GRX, which expresses the myofibroblast phenotype, and can be induced in vitro to display the fat‐storing phenotype. Lipid modifications along this induction were investigated by labeling sphingolipids with [14C]galactose, [14C]serine, or [14C]choline, and determination of fatty acid composition of sphingomyelin. The total ganglioside content and the GM2 synthase activity were lower in myofibroblasts. Both phenotypes presented similar gangliosides of the a‐pathway: GM2, GM1, and GD1a as well as their precursor GM3. Sphingomyelin and all the gangliosides were expressed as doublets; the upper/lower band ratio increased in lipocytes, containing more long‐chain fatty acids in retinol‐induced lipocytes as compared to the insulin/indomethacin induced ones. Time‐course experiments indicated a transfer of metabolic precursors from phosphatidylcholine to sphingomyelin in the two phenotypes. Taken together, these results indicate that myofibroblast and lipocytes can use distinct ceramide pools for sphingolipid synthesis. Differential ganglioside expression and presence of the long‐chain saturated fatty acids suggested that they may participate in formation of distinct membrane microdomains or rafts with specific functions on the two phenotypes of GRX‐cells. © 2002 Wiley‐Liss, Inc.
Nuclear lipids: New functions for old molecules?
Authors: Martelli Alberto M. , Tabellini G. , Borgatti P. , Bortul R. , Capitani S. , Neri L.M.
Published: January 2003

It is becoming increasingly evident that stimulation of nuclear lipid metabolism plays a central role in many signal transduction pathways that ultimately result in various cell responses including proliferation and differentiation. Nuclear lipid metabolism seems to be at least as complex as that existing at the plasma membrane. However, a distinctive feature of nuclear lipid biochemical pathways is their operational independence from their cell periphery counterparts. Although initially it was thought that nuclear lipids would serve as a source for second messengers, recent evidence points to the likelihood that lipids present in the nucleus also fulfil other roles. The aim of this review is to highlight the most intriguing advances made in the field over the last year, such as the production of new probes for the in situ mapping of nuclear phosphoinositides, the identification of two sources for nuclear diacylglycerol production, the emerging details about the peculiar regulation of nuclear phosphoinositide synthesizing enzymes, and the distinct possibility that nuclear lipids are involved in processes such as chromatin organization and pre‐mRNA splicing. © 2003 Wiley‐Liss, Inc.
Immunohistochemical analysis of Bin1/Amphiphysin II in human tissues: Diverse sites of nuclear expression and losses in prostate cancer
Authors: DuHadaway James B. , Lynch Frank J. , Brisbay Shawn , Bueso‐Ramos Carlos , Troncoso Patricia , McDonnell Timothy , Prendergast George C.
Published: January 2003

The Bin1/Amphiphysin II gene encodes at least seven alternately spliced adapter proteins that have been implicated in membrane dynamics and nuclear processes. Nuclear localized Bin1 polypeptides have tumor suppressor and proapoptotic activities, suggesting that Bin1 may suppress cancer in tissues where nuclear expression may occur. One question is the extent to which human tissues express nuclear Bin1 isoforms. A secondary issue has been the need for a specific antibody that can detect all the splice isoforms expressed by the human, mouse, and rat Bin1 genes. Using a novel mouse monoclonal antibody with these characteristics, we performed an immunohistochemical analysis of Bin1 expression in a panel of normal human tissues. We also compared the expression profile of Bin1 in normal or malignant tissues derived from human prostate, where Bin1 is a candidate tumor suppressor gene. In brain, a distinct nuclear staining pattern overlapped with a cytosolic staining pattern present in certain layers of the cerebral cortex and cerebellum. Bone marrow cells displayed mainly nuclear localization whereas peripheral lymphoid cells exhibited mainly cytosolic localization. In several epithelial tissues, nuclear or nucleocytosolic staining patterns were displayed by basal cells in skin, breast, or prostate, whereas cytosolic or plasma membrane‐associated staining patterns were noted in gastrointestinal cells. Interestingly, a striking gradient of expression was observed in gastrointestinal epithelia, particularly in the large intestine, with the strongest staining displayed by cells destined to undergo apoptosis at the villus tip. In prostate, Bin1 staining was frequently absent in cases of primary prostate adenocarcinoma. This study used a novel reagent to document the extent of expression of nuclear Bin1 isoforms, which exhibit cancer suppression and proapoptotic activity in human cells. © 2002 Wiley‐Liss, Inc.
Effect of stream segregation on ozonation for the removal of significant COD fractions from textile wastewater
Authors: Doǧruel Serdar , Germirli‐Babuna Fatoş , Kabdaşlı Işık , Insel Güçlü , Orhon Derin
Published: January 2003

Ozonation was tested on selected streams of cotton finishing textile plant wastewater for optimizing chemical oxygen demand (COD) removal. For this purpose, significant COD fractions in the wastewater were experimentally identified and the effect of ozone on these fractions was investigated. Ozonation experiments were performed with a 1 dm3 sample volume. Ozone treatment of batches of raw wastewater provided, at a rate of 62 mg min−1 and a gas feeding time of 15 min, achieved complete colour removal but only 21% COD reduction. Increasing the feeding time to 30 min slightly increased the COD removal to 32%. At this feeding time, removal of the readily biodegradable COD was 60%, but soluble inert COD reduction remained at 16%, indicating selective preference of ozone for simpler compounds. At low concentrations, ozone was mainly influential on soluble COD compounds. Longer feeding times also affected particulate compounds, resulting in the solubilization of the COD fractions. Pre‐ozonation of the dye‐house wastewater, as a segregated stream, proved much more effective in the breakdown of refractory organic compounds, rendering the overall plant effluent more amenable to biological treatment.

© 2002 Society of Chemical Industry
Performance characteristics of mechanical foam‐breakers fitted to a stirred‐tank reactor
Authors: Takesono Satoshi , Onodera Masayuki , Yoshida Masanori , Yamagiwa Kazuaki , Ohkawa Akira
Published: January 2003

In a stirred‐tank reactor (STR), a comparison of the performance of mechanical foam‐breakers: a six‐blade turbine (F‐B), a six‐blade vaned disk (V‐D), a two‐blade paddle (T‐P), a conical rotor (C‐R), a fluid‐impact dispersion apparatus (FIDA) and a rotating disk mechanical foam‐breaker (MFRD) was carried out using defined foaming media. The foam‐breaking ranges (relative to the gas superficial velocity, Ug) of the T‐P, C‐R and FIDA were inferior to that of the F‐B, V‐D and MFRD. The power consumption, Pkc, for foam‐breaking in the MFRD was the lowest among the F‐B, V‐D and MFRD. Operation of the F‐B and V‐D in the STR caused a considerable amount of liquid droplets from the collapsed foam to be entrained with the exhaust air.

© 2002 Society of Chemical Industry
Degradation of color photographic waste fix solution by anodic oxidation
Authors: Ragauskas Romas , Dikčius Arvydas , Vengris Tomas , Padarauskas Audrius
Published: January 2003

By use of a capillary electrophoretic method for anion analysis the anodic oxidation of thiosulfate, present in color photo bleach‐fix solutions, was investigated. In a specially constructed electrolysis cell with a cation‐exchange membrane separating the electrode chambers and with a carbon flow‐through three‐dimensional anode the two‐stage anodic oxidation of S2O32− anions was realized. In the first stage, S2O32− anions were oxidized to a maximal degree to an intermediate compound – tetrathionate (S4O62−) – then S4O62− anions were oxidized to the sulfate (SO42−), avoiding the decomposition of intermediate compounds and the formation of harmful sulfur compounds.

© 2002 Society of Chemical Industry
Infilling of the Younger Kathmandu–Banepa intermontane lake basin during the Late Quaternary (Lesser Himalaya, Nepal): a sedimentological study
Authors: Dill H. G. , Khadka D. R. , Khanal R. , Dohrmann R. , Melcher F. , Busch K.
Published: January 2003

The Kathmandu and Banepa Basins, Central Nepal, are located in a large syncline of the Lesser Himalayas. The Older Kathmandu Lake evolved during the Pliocene and early Pleistocene; the Younger Kathmandu Lake, which is the focus of this study, is infilled with late Quaternary sediments. Three formations, arranged in stratigraphical order, the Kalimati, Gokarna and Thoka Formations formed during the infilling stage of this lacustrine basin. Structural and textural sedimentological analyses, a chemical survey across the basin and mineralogical investigations of fine‐grained sediments form the basis of this palaeogeographical study. The basin under investigation was covered by a perennial freshwater lake before 30 000 yr BP. The lake was infilled with alluvial and fluvial sediments delivered mainly from the mountains north of the basin. A fairly low gradient was favourable for the formation of diatomaceous earths, carbonaceous mudstones and siltstones, which were laid down in the centre of the lake and in small ponds. Towards the basin edge, lacustrine sediments gave way to deltaic deposits spread across the delta plain. Crevasse splays and anastomosing rivers mainly delivered suspended load for the widespread siltstones and mudstones. The proximal parts of the alluvial–fluvial sedimentary wedge contain debris flows that interfinger with fine‐grained floodplain deposits. Three highstands of the water‐level (>30 000 yr BP, 28 000–19 000 yr BP, 11 000–4000 yr BP (?)) have been recognised in the sedimentary record of the younger Kathmandu Lake in the Late Quaternary. Second‐order water‐level fluctuations are assumed to be triggered by local processes (damming by tectonically induced landslides). First‐order water‐level fluctuations are the result of climatic changes. Copyright © 2003 John Wiley & Sons, Ltd.
Pollen‐ and diatom based environmental history since the Last Glacial Maximum from the Andean core Fúquene‐7, Colombia
Authors: Vélez Maria Isabel , Hooghiemstra Henry , Metcalfe Sarah , Martínez Ignacio , Mommersteeg Herman
Published: January 2003

The late Pleistocene–Holocene ecological and limnological history of Lake Fúquene (2580 m a.s.l.), in the Colombian Andes, is reconstructed on the basis of diatom, pollen and sediment analyses of the upper 7 m of the core Fúquene‐7. Time control is provided by 11 accelerator mass spectrometry (AMS) 14C dates ranging from 19 670 ± 240 to 6040 ± 60 yr BP. In this paper we present the evolution of the lake and its surroundings. Glacial times were cold and dry, lake‐levels were low and the area was surrounded by paramo and subparamo vegetation. Late‐glacial conditions were warm and humid. The El Abra Stadial, a Younger Dryas equivalent, is reflected by a gap in the sedimentary record, a consequence of the cessation of deposition owing to a drop in lake‐level. The early Holocene was warm and humid; at this time the lake reached its maximum extension and was surrounded by Andean forest. The onset of the drier climate prevailing today took place in the middle Holocene, a process that is reflected earlier in the diatom and sediment records than in the pollen records. In the late Holocene human activity reduced the forest and transformed the landscape.

Climate patterns from the Late‐glacial and throughout the Holocene, as represented in our record, are similar to other records from Colombia and northern South America (the Caribbean, Venezuela and Panama) and suggest that the changes in lake‐level were the result of precipitation variations driven by latitudinal shifts of the Intertropical Convergence Zone. Copyright © 2003 John Wiley & Sons, Ltd.
On translations of complete first order theories
Authors: Bagheri Seyed Mohammad
Published: January 2003

In this paper, some basic properties of automorphisms of first order languages and some examples are presented. In particular, an omitting types theorem is proved.
Xanthates as Chain‐Transfer Agents in Controlled Radical Polymerization (MADIX): Structural Effect of the O‐Alkyl Group
Authors: Destarac Mathias , Bzducha Wojciech , Taton Daniel , Gauthier‐Gillaizeau Isabelle , Zard Samir Z.
Published: January 2003

The capability of three chain‐transfer agents, O‐alkyl‐S‐(1‐ethoxycarbonyl)ethyl xanthates (CH3CHCO2C2H5)S(CS)OZ′, to control the free‐radical polymerization of styrene and ethyl acrylate by the MADIX process was examined. The reactivity of the xanthates varied according to the following trend: Z′  CH2CH3 < CH2CF3 < CH[P(O)(OEt)2]CF3. This change in reactivity allowed a lowering of the polydispersity index from 2.0 for Z′  CH2CH3 to 1.15 for Z′  CH[P(O)(OEt)2]CF3 in the case of the polymerization of styrene.

Evolution of Mw/Mn with conversion during the polymerization of ethyl acrylate in the presence of xanthates X1, X2 and X3. Reaction conditions: [EA]0 = 4.6 M, [X]0 = 5.75 × 10−2 M, [AIBN]0 = 1.72 × 10−3 M ; T = 80 °C ; solvent: toluene.

magnified image

Evolution of Mw/Mn with conversion during the polymerization of ethyl acrylate in the presence of xanthates X1, X2 and X3. Reaction conditions: [EA]0 = 4.6 M, [X]0 = 5.75 × 10−2 M, [AIBN]0 = 1.72 × 10−3 M ; T = 80 °C ; solvent: toluene.
Effects of tellington touch in healthy adults awaiting venipuncture
Authors: Cecilia Wendler M.
Published: January 2003

Many natural‐healing modalities administered by professional nurses are provided without adequate scientific scrutiny. Tellington touch (TTouch), a form of gentle physical touch originally developed for the calming of horses, is an emerging nursing intervention. However, the safety and efficacy of human TTouch has not yet been established. The purpose of this study, which used a pretest, posttest repeated‐measures control group design, was to identify patterns of mean blood pressure (MBP), heart rate (HR), state anxiety (SA), and procedural pain (PP) in healthy adults receiving a 5‐min intervention of TTouch (n = 47) just before venipuncture versus a no‐touch control group (n = 46). There were statistically and clinically significant decreases in the TTouch group in MBP and HR. There were no significant differences between groups in SA and PP. Further research is essential to determine the safety and efficacy of this modality for acutely or critically ill patients. © 2003 Wiley Periodicals, Inc. Res Nurs Health 26:40–52, 2003
Methods to document semantic equivalence of a translated scale
Authors: Beck Cheryl Tatano , Bernal Henrietta , Froman Robin D.
Published: January 2003

To ensure the semantic equivalence of the Postpartum Depression Screening Scale (PDSS)–Spanish Version, multiple methods were used, including back‐translation, the committee approach, pretest techniques, and alternate forms equivalence. The back‐translation process involved eight translators who represented the four predominant Hispanic groups in the United States. In the committee approach the Hispanic translators convened together to discuss the results of the back‐translations and to come to group consensus on problematic items. In pretesting the PDSS–Spanish Version was field‐tested with five Hispanic mothers, and it was determined that it accurately captured the connotative meanings of the screening scale. Alternate forms equivalence of the two language versions of the PDSS was assessed with a sample of 30 bilingual Hispanic mothers. Alpha reliability estimates ranged from 0.94 to 0.99. Though lengthy, this systematic procedure was needed to guarantee the production of a fully equivalent linguistic version of the PDSS. © 2003 Wiley Periodicals, Inc. Res Nurs Health 26:64–73, 2003
Pd(0)‐catalyzed polyaddition of bifunctional vinyloxiranes with phenol derivatives: The synthesis of polymers containing an allyl aryl ether moiety in the main chain
Authors: Koizumi Toshio , Imai Takao , Endo Takeshi
Published: January 2003

The palladium(0)‐catalyzed polyaddition of bifunctional vinyloxiranes [1,4‐bis(2‐vinylepoxyethyl)benzene (1a) and 1,4‐bis(1‐methyl‐2‐vinylepoxyethyl)benzene (1b)] with oxygen nucleophiles such as hydroquinone and bisphenol A gave new unsaturated polyethers containing an allyl aryl ether moiety and pendant hydroxy groups. The polyaddition with 1a was largely affected by the phosphine ligands employed and the reaction temperature. The polyaddition with hydroquinone and bisphenol A was conducted at room temperature for 24 h in tetrahydrofuran in the presence of PPh3 and gave the desired polyethers in good yields, the number‐average molecular weights (Mn) of which were 5700 and 7700, respectively. 1,2‐Bis(diphenylphosphino)ethane (dppe) was not effective in the polyaddition with 1a. The polyaddition of 1b with hydroquinone and bisphenol A gave the corresponding polyethers despite the kinds of ligands employed (PPh3 and dppe), contrary to the polyaddition with 1a. The polyaddition of 1b with 4,4′‐biphenol was also carried out in the presence of Pd2(dba)3 · CHCl3/dppe as a catalyst (where dba is dibenzylideneacetone) and afforded the expected polyether with a high Mn value (Mn = 24,900). In addition, vinyloxirane 1b could reacted with racemic 1,1′‐bi‐2‐naphthol to give the corresponding polyether in a good yield. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 476–482, 2003
Possible structural effect of a′,b′‐dihydroxyacetophenone units in the preformed oligoesters upon copolycondensation with isomeric c′,d′‐dihydroxyacetophenones by TsCl/dimethylformamide/pyridine
Authors: Higashi Fukuji , Koshio Masato
Published: January 2003

A two‐stage copolycondensation of a mixture of equal parts of isophthalic acid and terephthalic acid first with a′,b′‐dihydroxyacetophenone (a′,b′‐DHAP) and then with isomeric c′,d′‐DHAP was examined at 60 and 80 °C. A structurally selective reaction was observed. At 80 °C, the preformed oligomers from symmetrically substituted 2′,6′‐DHAP reacted better with similarly substituted 2′,6′‐ or 3′,5′‐DHAP to give the copolymers of significantly higher inherent viscosity values than from the reaction with asymmetrically substituted 2′,4′‐DHAP, whereas at 60 °C they did almost equally well with any c′,d′‐DHAP. Similarly, the reaction of oligomers from 2′,4′‐DHAP with asymmetrically substituted 2′,4′‐DHAP or 2,4‐dihydroxybenzophenone yielded better results than those from the reaction with 2′,6′‐ or 3′,5′‐DHAP at both temperatures. The copolycondensations with comonomers of the structure independent of DHAPs were not affected by the preformed oligomers from DHAPs. The results are discussed in terms of the distributions of resulting oligomers determined by gel permeation chromatography. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 616–623, 2003
Electrospun nanofibers: Internal structure and intrinsic orientation
Authors: Dersch R. , Liu Taiqi , Schaper A. K. , Greiner A. , Wendorff J. H.
Published: January 2003

Electrospinning gives rise to polymer nanofibers. The spinning process is characterized by strong deformations of the polymer material taking place during the spinning process and a very rapid structure formation process happening within milliseconds. We were interested in the influence of the peculiar spinning process on the structures of nanofibers. For this purpose, we analyzed the internal structures of nanofibers spun from polyamide‐6 and polylactide with an average diameter of about 50 nm. The fibers were partially crystalline, with degrees of crystallinity not significantly smaller than those found for less rapidly quenched and much thicker melt‐extruded fibers. The annealing of polyamide fibers at elevated temperatures resulted in a transformation from the disordered γ modification to the more highly ordered α modification, and this again was in close agreement with the response of melt‐extruded fibers. The orientation of the crystals along the fiber axis was strongly inhomogeneous: it was, on average, very weak, yet it could be quite pronounced locally. Small elongations of approximately 10% resulted in well‐developed homogeneous crystal orientations. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 545–553, 2003
Crosslinking polymerization leading to interpenetrating polymer network formation. I. Polyaddition crosslinking reactions of poly(methyl methacrylate‐co‐2‐methacryloyloxyethyl isocyanate)s with ethylene glycol resulting in polyurethane networks
Authors: Kiguchi Tadahiro , Aota Hiroyuki , Matsumoto Akira
Published: January 2003

At the start of our research program concerned with the elucidation of the crosslinking polymerization mechanism leading to interpenetrating polymer network (IPN) formation, in which IPNs consist of both polymethacrylates and polyurethane (PU) networks, this article deals with the polyaddition crosslinking reaction leading to PU network formation. Therefore, 2‐methacryloyloxyethyl isocyanate (MOI) was radically copolymerized with methyl methacrylate (MMA) in the presence of CBr4 as a chain‐transfer agent. The resulting poly(MMA‐co‐MOI)s, having pendant isocyanate (NCO) groups as novel multifunctional polyisocyanates, were used for polyaddition crosslinking reactions with ethylene glycol as a typical diol. The second‐order rate constants depended on both the functionality of poly(MMA‐co‐MOI) and the NCO group concentration. The actual gel points were compared with the theoretical ones calculated according to Macosko's equation; the deviation of the actual gel point from the theoretical value became more remarkable for a greater functionality of poly(MMA‐co‐MOI) and at a lower NCO group concentration or at a lower poly(MMA‐co‐MOI) concentration. These are discussed mechanistically, with consideration given to the significance of intramolecular cyclization and intramolecular crosslinking reactions leading to the shrinkage of the molecular size of the prepolymer, along with the data of the intrinsic viscosities of resulting prepolymers and the swelling ratios of resulting gels. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 606–615, 2003
Ground and excited states of one‐dimensional self‐interacting nonlinear oscillators through time‐dependent quantum mechanics
Authors: Wadehra Amita , Roy Amlan K. , Deb B. M.
Published: January 2003

Energy eigenvalues, probability densities, and 〈x2r〉 values (r = 1 to 6) of one‐dimensional self‐interacting nonlinear oscillators have been obtained by evolving the time‐dependent Schrödinger equation in imaginary time, coupled with the minimization of energy expectation values. For excited states, the orthogonality constraint with lower states is maintained. Probability density plots for the ground and first three excited states are presented. A comparison of energy eigenvalues and probability densities plots is also made between oscillators with and without self‐interaction. © 2002 Wiley Periodicals, Inc. Int J Quantum Chem, 2003
A dynamic model of work quality in a government oversight organization
Authors: Trost Christopher S.
Published: January 2003

Management of a government organization responsible for the oversight of contractor work is a sensitive and challenging task. One such organization is the Supervisor of Shipbuilding (SUPSHIP), Groton, a unit of the U.S. Navy, whose engineering department is responsible for oversight of submarine designs from General Dynamics' Electric Boat Division. Management of the SUPSHIP Engineering Department is further complicated by a high cost of mistakes and a significant lag between the time a mistake is made and when it is discovered in production. Recent defense cutbacks led to a reorganization of the department with significantly fewer personnel and periodic variations in workload have raised questions about the department's ability to maintain a desired level of quality in its design reviews. Quality in this context refers to work done without errors—errors that could affect the final product if they are not caught by supervisors or higher up the chain of command. To understand and explore these issues better, a system dynamics model that integrates the structural elements of the engineering department's workload and workforce was developed. Using the model to analyze expected performance during future peaks and valleys in the workload, as well as expected retirements and new hiring, allowed management to develop policies that keep quality at acceptable levels. Copyright © 2002 John Wiley & Sons, Ltd.
All models are wrong: reflections on becoming a systems scientist
Authors: Sterman John D.
Published: January 2003

Thoughtful leaders increasingly recognize that we are not only failing to solve the persistent problems we face, but are in fact causing them. System dynamics is designed to help avoid such policy resistance and identify high‐leverage policies for sustained improvement. What does it take to be an effective systems thinker, and to teach system dynamics fruitfully? Understanding complex systems requires mastery of concepts such as feedback, stocks and flows, time delays, and nonlinearity. Research shows that these concepts are highly counterintuitive and poorly understood. It also shows how they can be taught and learned. Doing so requires the use of formal models and simulations to test our mental models and develop our intuition about complex systems. Yet, though essential, these concepts and tools are not sufficient. Becoming an effective systems thinker also requires the rigorous and disciplined use of scientific inquiry skills so that we can uncover our hidden assumptions and biases. It requires respect and empathy for others and other viewpoints. Most important, and most difficult to learn, systems thinking requires understanding that all models are wrong and humility about the limitations of our knowledge. Such humility is essential in creating an environment in which we can learn about the complex systems in which we are embedded and work effectively to create the world we truly desire. The paper is based on the talk the author delivered at the 2002 International System Dynamics Conference upon presentation of the Jay W. Forrester Award. Copyright © 2002 John Wiley & Sons, Ltd.
The complete mitochondrial genome sequence of the pathogenic yeast Candida (Torulopsis) glabrata
Authors: Koszul Romain , Malpertuy Alain , Frangeul Lionel , Bouchier Christiane , Wincker Patrick , Thierry Agnès , Duthoy Stéphanie , Ferris Stéphane , Hennequin Christophe , Dujon Bernard
Published: January 2003

We report here the complete sequence of the mitochondrial (mt) genome of the pathogenic yeast Candida glabrata. This 20 kb mt genome is the smallest among sequenced hemiascomycetous yeasts. Despite its compaction, the mt genome contains the genes encoding the apocytochrome b (COB), three subunits of ATP synthetase (ATP6, 8 and 9), three subunits of cytochrome oxidase (COX1, 2 and 3), the ribosomal protein VAR1, 23 tRNAs, small and large ribosomal RNAs and the RNA subunit of RNase P. Three group I introns each with an intronic open reading frame are present in the COX1 gene. This sequence is available under accession number AJ511533.
Bcl‐rambo beta, a special splicing variant with an insertion of an Alu‐like cassette, promotes etoposide‐ and Taxol‐induced cell death
Authors: Yi Peng , Zhang Wei , Zhai Zhiwei , Miao Lin , Wang Yi , Wu Mian
Published: January 2003

The exonization of an Alu‐like element into a coding sequence is unique to primates and this phenomenon distinguishes our genome from other mammals. Here, we report the presence of a special splicing variant of a proapoptotic protein Bcl‐rambo in human lymph node, designated as Bcl‐rambo beta. This variant contains a 98 bp Alu‐like sequence which acts as an exon. There exists an in‐frame stop codon within this inserted Alu‐like cassette, resulting in generation of a premature protein of 104 amino acid residues. Unlike the Bcl‐rambo, Bcl‐rambo beta is lacking of the BH1, BH2 and BH3 motifs and becomes a BH4‐only protein. Bcl‐rambo beta is detected in several adult human tissues such as heart, lymph node and cervix but is absent in human brain tissue. In addition, Bcl‐rambo beta is found not to be associated with mitochondria due to the absence of its C‐terminal membrane anchor region. Nevertheless, this cytosol‐localized protein is capable of promoting etoposide‐ and Taxol‐induced cell death. Although the exact function of the Alu sequence is not fully characterized, the Alu element within the Bcl‐rambo beta appeared to contribute to the proapoptotic capability, since removing of the Alu sequence from Bcl‐rambo beta abrogates its ability to induce cell death. Our data support the speculation that the Alu element insertion during the splicing process may play an important role in the generation of protein diversity in primate cells by a yet uncharacterized mechanism.
Sequence anatomy of mitochondrial anion carriers
Authors: Ježek Petr , Ježek Jan
Published: January 2003

Two hundred and eighty‐four genes of eight eukaryotic genomes for mitochondrial anion carriers were sorted into 43 (+18 single protein) subfamilies. Subfamilies differ by the number, nature, and locations of charges and polar residues in the transmembrane α‐helices. Consequently, these residues and the rarely unique residues of the matrix and cytosolic segments most likely determine the different molecular phenotypes (functions). ‘Common ancestral hydrophilic segments’ were found in matrix and cytosolic segments, with interchangeable polar residues. Thus the hydrophobic microstructures of hydrophilic carrier parts are supposed to predetermine structure/conformation, whereas polar and charged microstructures should predetermine function, namely in the transmembrane spanning α‐helices.
Identification of anArabidopsismitochondrial succinate–fumarate translocator
Authors: Catoni Elisabetta , Schwab Rebecca , Hilpert Melanie , Desimone Marcelo , Schwacke Rainer , Flügge Ulf-Ingo , Schumacher Karin , Frommer Wolf B.
Published: January 2003

Complementation of a yeastacr1mutant carrying a deletion of the succinate/fumarate carrier gene enabled functional identification of a mitochondrial succinate translocator fromArabidopsis thaliana(AtmSFC1). Thus complementation of yeast mutants is applicable also for identification and characterization of organellar transporters. Reverse transcription polymerase chain reaction and promoter‐GUS fusion showed expression of AtmSFC1 in 2 day old dark grown seedlings, which declined in cotyledons during further development, consistent with a role in export of fumarate for gluconeogenesis during lipid mobilization at early germination ofArabidopsisseeds. In mature plants, expression was found in developing and germinating pollen, suggesting a role in ethanolic fermentation.
The transmembranous domain of CD40 determines CD40 partitioning into lipid rafts
Authors: Bock Jürgen , Gulbins Erich
Published: January 2003

Stimulation of CD40 has been previously shown to result in a release of ceramide in small sphingolipid‐enriched rafts in the cell membrane [Grassmé et al., J. Immunol. 168 (2002) 298–307]. Those rafts fused to larger signaling platforms that served to cluster CD40. Here, we defined molecular mechanisms of CD40 clustering in membrane platforms. To this end, we replaced the transmembranous domain of CD40 with that of CD45, a molecule known to be excluded from lipid rafts. Murine T cells were stably transfected with wild‐type CD40 or chimeric CD40/CD45. Flow cytometry confirmed normal binding properties of the mutant to CD40 ligand. Stimulation with CD40 ligand resulted in clustering of wild‐type CD40, while the chimeric CD40/45 receptor failed to cluster. This correlated with a deficiency of the chimeric receptor to activate JNK, p38 MAP kinase and SAPK, known signaling molecules of the intracellular pathway initiated by CD40. Forced crosslinking of the CD40/45 chimeric receptor restored, at least partially, these signaling events. The results suggest that the transmembranous domain of CD40 is central for the recruitment to and clustering of CD40 in membrane platforms.
A tomato xylem sap protein represents a new family of small cysteine‐rich proteins with structural similarity to lipid transfer proteins
Authors: Rep Martijn , Dekker Henk L , Vossen Jack H , de Boer Albert D , Houterman Petra M , de Koster Chris G , Cornelissen Ben J.C
Published: January 2003

The coding sequence of a major xylem sap protein of tomato was identified with the aid of mass spectrometry. The protein, XSP10, represents a novel family of extracellular plant proteins with structural similarity to plant lipid transfer proteins. The XSP10 gene is constitutively expressed in roots and lower stems. The decline of XSP10 protein levels in tomato infected with a fungal vascular pathogen may reflect breakdown or modification by the pathogen.
Myb induced myeloid protein 1 (Mim‐1) is an acetyltransferase
Authors: Allen Stuart C.H , Hebbes Tim R
Published: January 2003

We have screened protein extracts from chicken blood cells for acetyltransferases. An in gel acetyltransferase assay revealed that a 32 kDa protein, which is more prevalent in whole blood when compared with erythrocyte cells, possessed an auto‐acetylation activity. This protein was purified by a series of chromatographic steps, sequenced by Edman degradation and subsequently identified as Myb induced myeloid protein (Mim‐1). Mim‐1 has similarities to the conserved acetyltransferase motifs found in the GNAT superfamily of proteins and also contains three minimal GK acetylation motifs. These data identify Mim‐1 as an acetyltransferase.
Distinct roles of the Src family kinases, SRC‐1 and KIN‐22, that are negatively regulated by CSK‐1 in C. elegans
Authors: Hirose Takashi , Koga Makoto , Ohshima Yasumi , Okada Masato
Published: January 2003

To elucidate the primitive roles of the Src family kinases (SFKs), here we characterized Caenorhabditis elegans orthologues of SFKs (src‐1 and kin‐22) and their regulator kinase Csk (csk‐1). SRC‐1 and KIN‐22 possess the C‐terminal regulatory tyrosines characteristic of SFKs, and their activities are negatively regulated by CSK‐1 in a yeast expression system. The src‐1 and csk‐1 genes are co‐expressed in some head neurons, the anchor cell and the tail region, while kin‐22 and csk‐1 genes are co‐expressed in pharyngeal muscles and tail region. Expression of KIN‐22 induced morphological defects in the pharynx, whereas expression of SRC‐1 did not show any overt phenotype in adult. RNA interference of src‐1, but not that of kin‐22, caused a developmental arrest in early development. These results suggest that SRC‐1 and KIN‐22 play distinct roles under the control of CSK‐1.
Modulation of phosphoinositide 3‐kinase activation by cholesterol level suggests a novel positive role for lipid rafts in lysophosphatidic acid signalling
Authors: Peres Christine , Yart Armelle , Perret Bertrand , Salles Jean-Pierre , Raynal Patrick
Published: January 2003

Methyl‐β‐cyclodextrin (MβCD) was used to explore a role for cholesterol‐enriched plasma membrane microdomains in coupling lysophosphatidic acid (LPA) stimulation to phosphoinositide 3‐kinase (PI3K) activation. Cholesterol depletion strongly inhibited the production of phosphatidylinositol 3,4‐bisphosphate and phosphatidylinositol 3,4,5‐trisphosphate in Vero cells stimulated with LPA. In agreement, the phosphorylation of Akt/protein kinase B, but not of Erk kinases, was suppressed by MβCD. MβCD did not interfere with the overall phospholipid metabolism, and its effects were reversed in cholesterol add‐back experiments. Finally, PI3K was detected in lipid rafts prepared from control but not MβCD‐treated cells, suggesting that these microdomains contribute to LPA signalling by compartmentalising component(s) of the PI3K pathway.
The processing of human mitochondrial leucyl‐tRNA synthetase in the insect cells
Authors: Yao Yong-Neng , Wang Lie , Wu Xiang-Fu , Wang En-Duo
Published: January 2003

A His‐tagged full‐length cDNA of human mitochondrial leucyl‐tRNA synthetase was expressed in a baculovirus system. The N‐terminal sequence of the enzyme isolated from the mitochondria of insect cells was found to be IYSATGKWTKEYTL, indicating that the mitochondrial targeting signal peptide was cleaved between Ser39 and Ile40 after the enzyme precursor was translocated into mitochondria. The enzyme purified from mitochondria catalyzed the leucylation of Escherichia coli tRNA1
Leu(CAG) and Aquifex aeolicus tRNALeu(GAG) with higher catalytic activity in the leucylation of E. coli tRNALeu than that previously expressed in E. coli without the N‐terminal 21 residues.
Protein kinase C‐dependent phosphorylation and mitochondrial translocation of aldose reductase
Authors: Varma Tushar , Liu Si-Qi , West Matthew , Thongboonkerd Visith , Ruvolo Peter P. , May W.Stratford , Bhatnagar Aruni
Published: January 2003

Although aldose reductase (AR) is a critical participant in osmoregulation, and the metabolism of glucose and aldehydes derived from lipid peroxidation, post‐translational mechanisms regulating its activity have not been identified. In this paper, we report that stimulation of protein kinase C (PKC) in several cell types induces phosphorylation of AR and translocation of the phosphorylated protein to the mitochondria. In vitro, recombinant AR was directly phosphorylated by activated PKC, suggesting that AR may be an in vivo PKC substrate. Together, these observations reveal a novel link between PKC activation and the regulation of glucose and aldehyde metabolism.