bluuebunny/crossref_metadata_2025 huggingface dataset:
IGF-I differentially regulates IGF-binding protein expression in primary mammary fibroblasts and epithelial cells
Authors: Fleming J M , Leibowitz B J , Kerr D E , Cohick W S
Published: July 2005

Elucidating how mitogens facilitate epithelial/stromal interactions is critical given that mitogens regulate mammary gland development and function. IGF-I is a potent mammary cell mitogen that is locally produced in the mammary gland. Since IGF-binding proteins (IGFBPs) regulate IGF-I bioavailability, we characterized the cell-type-specific production of IGFBP in primary bovine mammary epithelial (BME) and fibroblast (BMF) cells. Cells were treated with IGF-I and mRNA levels were analyzed via quantitative real-time (qRT)-PCR and Northern blot analysis. Media conditioned by cells treated with IGF-I for 48 h were analyzed via ligand blotting with 125I-labeled IGF-I and -II and immunoblotting with specific IGFBP antibodies. A reciprocal regulation of IGFBP-3 and -5 by IGF-I was observed between the two cell types. IGF-I induced large dose-dependent increases in IGFBP-3 mRNA and protein levels in BME cells, while IGFBP-5 protein was barely detectable and mRNA levels were detectable only by qRT-PCR. In BMFs, IGF-I induced large increases in IGFBP-5 mRNA and protein while IGFBP-3 mRNA was only slightly increased by IGF-I treatment and the protein was difficult to detect. IGFBP-6 mRNA was detected by Northern blot analysis in both cell types but was not regulated by IGF-I. In BME cells, IGFBP-6 protein levels were readily detectable under basal conditions and were increased by IGF-I. Interestingly, IGFBP-6 protein could not be detected in media conditioned by BMFs. IGFBP-4 mRNA was readily seen by Northern blot analysis in BMFs, however qRT-PCR was required to detect IGFBP-4 mRNA in BME cells. IGF-I increased IGFBP-4 mRNA levels by 2-fold in both cell types. IGFBP-4 protein was only detectable in media conditioned by BME cells when stimulated by IGF-I. In contrast, IGFBP-4 was present in media conditioned by untreated BMFs but was not consistently increased by IGF-I treatment. This was explained by the finding that IGF-I stimulated proteolysis of IGFBP-4, as evidenced by the appearance of two immuno-responsive fragments of 18 and 14 kDa. This proteolysis was specific to IGFBP-4, and was not observed in BME cells. We confirmed the protease to be pregnancy-associated plasma protein A (PAPP-A) by immunoblotting with an antibody against human PAPP-A/proMBP (pro form of eosinophil major basic protein) complex. In vitro immuno-neutralization experiments showed that blocking PAPP-A prevented the ability of IGF-I to stimulate IGFBP-4 proteolysis. IGFBP-2 mRNA and protein levels were observed under basal conditions in both cell types, with no significant regulation by IGF-I. The analysis of cell-type-specific regulation of the IGF system in both primary mammary epithelial cells and stromal cells will assist in the characterization of the mechanisms behind the role of the IGF system in normal mammary physiology and ultimately breast cancer.
Approximative kinetic formats used in metabolic network modeling
Authors: Heijnen Joseph J.
Published: July 2005

An overview is presented of the different approximative enzyme kinetic formats that have been proposed for use in metabolic modeling studies. It is considered that the following four general properties are relevant for approximative kinetics: the rate must be proportional to enzyme level; at high metabolite concentrations, there is downward concave behavior of rate versus concentration; the number of kinetic parameters should be as small as possible; analytical solutions of steady‐state network balances are desirable. Six different approximative kinetic formats are evaluated (linear, logarithmic‐linear, power law GMA, power law S‐systems, thermokinetic, linear‐logarithmic) and it is concluded that only the recently proposed linear‐logarithmic approach combines all desired properties and therefore seems a most appropriate approximate kinetic format. © 2005 Wiley Periodicals, Inc.
Rheology, Sedimentation, and Filtration of TiO2 Suspensions
Authors: Gesenhues U.
Published: July 2005

It is shown that with aqueous suspensions of colloidal oxide and hydroxide particles simple rheometric and sedimentation experiments allow the determination of the optimum pH for filtration and washing. This approach is more practical than zeta potential measurements, as explained by a theoretical review and illustrated by experiments with industrial TiO2 white pigments of varying surface chemistry. Besides, the solids content of the filter cake and its dependence on pH is correctly predicted from the rheology of the suspension, thus giving an idea of the mechanism of filter cake formation. This follows from a comparison to the results of filtration experiments. There, the influences of filter vacuum as well as of pH and solids content of the pigment feed suspension on filtration capacity and washing efficiency have been studied. The experiments also illustrate an inexpensive method of how to find the optimum set of parameters for an economical drum filter operation in the plant.
Simulation of Pipeline Slurry Flow under Conditions of Granular Phase Ablation
Authors: Eskin D. , Leonenko Y. , Vinogradov O.
Published: July 2005

A model of granular flow in the regime of a moving bed under conditions of granular phase ablation is developed. The model is based on the well‐known two‐layer representation of stratified slurry flow, which assumes a dynamic equilibrium between the bottom (granular) layer and the upper layer of solids‐liquid suspension. The mass transfer rate from the bottom layer to the upper one is defined on the basis of digestion model for a single spherical lump. The model developed allows estimation of the lengths required for the total digestion of lumps in a moving bed and the axial pressure gradient distribution for different flow regimes.
The Barton Reaction: Can a More Tenable Pathway Be Hypothesized for the Formation of Nitrosoalkyl Derivatives?
Authors: Grossi Loris
Published: July 2005

Herein, we report that in the formation of nitrosoalkyl derivatives during the photolysis of alkyl nitrites, the formation of the intermediate alkyl alkoxy nitroxide, due to the trapping of alkyl radicals by the starting nitrite, is the key step of the entire process. In fact, these nitroxides, detectable by EPR spectroscopy, decay to the final nitroso derivatives under thermodynamic control. In light of this, the Barton reaction mechanism has been reviewed. The nitrosoalkyl derivatives, or the hydroxamic acids when steroids are involved, have now to be considered as the ending products of the entire process and not, unless a very high concentration of NO is present in the medium, the result of a direct reaction of NO with the alkyl radical, as is commonly accepted.
A potential role for β‐ and γ‐crystallins in the vascular remodeling of the eye
Authors: Zhang Cheng , Gehlbach Peter , Gongora Celine , Cano Marisol , Fariss Robert , Hose Stacey , Nath Avindra , Green William R. , Goldberg Morton F. , Zigler J. Samuel , Sinha Debasish
Published: July 2005

We demonstrate that expression of β‐ and γ‐crystallins is associated with intraocular vessels during normal vascular development of the eye and also in the Nuc1 rat, a mutant in which the hyaloid vascular system fails to regress normally. Real‐Time RT PCR, Western blot and metabolic labeling studies indicate an increased expression of β‐ and γ‐crystallins in Nuc1 retina. The increased expression of crystallins was localized to the astrocytes surrounding the intraocular vessels. A similar pattern of crystallin expression was also observed in the retinal vessels during normal development. Cultured human astrocytes exposed to 3‐nitropropionic acid, an established model of neuronal hypoxia, increased VEGF expression, as expected, but also increased expression of crystallins. Our data suggest that crystallins may function together with VEGF during vascular remodeling. Interestingly, in human PFV (persistent fetal vasculature) disease, where the hyaloid vasculature abnormally persists after birth, we show that astrocytes express both VEGF and crystallins. Developmental Dynamics 234:36–47, 2005. © 2005 Wiley‐Liss, Inc.
Heterogeneous expression of GAGE, NY‐ESO‐1, MAGE‐A and SSX proteins in esophageal cancer: Implications for immunotherapy
Authors: Akcakanat Argun , Kanda Tatsuo , Tanabe Tadashi , Komukai Shintarou , Yajima Kazuhito , Nakagawa Satoru , Ohashi Manabu , Hatakeyama Katsuyoshi
Published: July 2005

Cancer/testis antigens (CTAs) elicit immune response in cancer patients and are therefore targets of immunotherapy. Current information on CTA expression is primarily based on mRNA assays and little is known about their expression at the protein level. The objectives of our study are to analyze GAGE, NY‐ESO‐1, MAGE‐A and SSX protein expression in esophageal cancer and to correlate their expression patterns with clinicopathologic parameters and survival. We examined CTA protein expression in 213 patients with esophageal cancer by immunohistochemistry. Antigen‐positive tumors were evaluated once and antigen‐negative tumors were evaluated 3 times by examining different parts of the cancer specimen. GAGE, NY‐ESO‐1 and MAGE‐A were heterogeneously expressed in 42 (20%), 44 (21%) and 111 (52%) tumors, respectively, whereas SSX expression was not detected. Of the 126 (59%) patients expressing CTAs, 70 (33%) expressed 1, 41 (19%) expressed 2 and 15 (7%) expressed 3 antigens. The expression of MAGE‐A was correlated with those of GAGE (p=0.001) and NY‐ESO‐1 (p=0.002), and the expression of GAGE was correlated with that of NY‐ESO‐1 (p=0.002). One hundred fifty‐six (79%) sections were positively stained in the first evaluation, whereas 37 (19%) and 4 (2%) positive sections were identified in the second and third evaluations, respectively. Particularly, MAGE and GAGE expression showed overlaps. GAGE, NY‐ESO‐1 and MAGE‐A protein expression was not correlated with the disease progression, TNM factors or survival. The detection of immunonegative cells in every specimen suggests addition of other drugs such as 5‐aza‐2′‐deoxycytidine to increase the therapeutic effect of CTA‐specific cancer vaccines. © 2005 Wiley‐Liss, Inc.
Efficacy of the MMP inhibitor MMI270 against lung metastasis following removal of orthotopically transplanted human colon cancer in rat
Authors: Ogata Yutaka , Matono Keiko , Nakajima Motowo , Sasatomi Teruo , Mizobe Tomoaki , Nagase Hideaki , Shirouzu Kazuo
Published: July 2005

We have investigated the antitumor effects of synthetic MMP inhibitor MMI270 against postoperative lung metastasis from colon cancer in nude rat. The KM12SM human colon cancer cells were injected into the cecal wall, and at 5 weeks after the injection, the cecum was removed including the tumor. Then, 30 mg/kg of MMI270 was administered perorally twice per day for 2 or 4 weeks, either immediately after removal or after week 2 after the removal. At week 7 after the removal, lung metastasis was significantly inhibited by the early administration of MMI270 immediately after the tumor removal but not by the late administration. The survival rates were significantly higher in the rats treated by early administration of MMI270 compared to the survival rate in untreated rats. Moreover, no lung metastasis was detected in some rats with 24‐weeks' survival treated by early administration. Lower microvessel density, lower PCNA Index and higher Apoptotic Index in the lung metastases of the rats treated with MMI270 were found compared to those in untreated rats. A beneficial effect of by early administration of MMI270 against postoperative lung metastases may be expected through inhibiting neovascularization of metastases in nude rat. © 2005 Wiley‐Liss, Inc.
Enhanced cytotoxicity induced by gefitinib and specific inhibitors of the Ras or phosphatidyl inositol‐3 kinase pathways in non‐small cell lung cancer cells
Authors: Janmaat Maarten L. , Rodriguez José A. , Gallegos‐Ruiz Mariëlle , Kruyt Frank A.E. , Giaccone Giuseppe
Published: July 2005

In this study, we have characterized a panel of NSCLC cell lines with differential sensitivity to gefitinib for activating mutations in egfr, pik3ca, and k‐ras, and basal protein expression levels of PTEN. The egfr mutant NSCLC cell line H1650 as well as the egfr wild type cell lines H292 and A431 were highly sensitive to gefitinib treatment, indicating that other factors determine gefitinib‐sensitivity in egfr wild type cells. Activating k‐ras mutations were specifically detected in gefitinib‐resistant cells, suggesting that the occurrence of k‐ras mutations is correlated with resistance to EGFR antagonists. No pik3ca mutations were detected within the panel of cell lines, and PTEN protein expression levels did not correlate with gefitinib sensitivity. Gefitinib effectively blocked Akt and Erk phosphorylation in two gefitinib‐sensitive NSCLC cell lines, further supporting our previous findings that persistent activity of the PI3K/Akt and/or Ras/Erk pathways is associated with gefitinib‐resistance of NSCLC cell lines. Gefitinib‐resistant NSCLC cell lines, showing EGFR‐independent activity of the PI3K/Akt or Ras/Erk pathways, were treated with gefitinib in combination with specific inhibitors of mTOR, P13K, Ras, and MEK. Additive cytotoxicity was observed in A549 cells co‐treated with gefitinib and the MEK inhibitor U0126 or the farnesyl transferase inhibitor SCH66336 and in H460 cells treated with gefitinib and the PI3K inhibitor LY294002, but not in H460 cells treated with gefitinib and rapamycin. These data suggest that combination treatment of NSCLC cells with gefitinib and specific inhibitors of the PI3K/Akt and Ras/Erk pathways may provide a successful strategy. © 2005 Wiley‐Liss, Inc.
EGFR and erbB2 mutation status in Japanese lung cancer patients
Authors: Sasaki Hidefumi , Shimizu Shigeki , Endo Katsuhiko , Takada Minoru , Kawahara Masaaki , Tanaka Hisaichi , Matsumura Akihide , Iuchi Keiji , Haneda Hiroshi , Suzuki Eriko , Kobayashi Yoshihiro , Yano Motoki , Fujii Yoshitaka
Published: July 2005

Much evidence has accumulated that the epidermal growth factor receptor (EGFR) and its family members are strongly implicated in the development and progression of lung cancers. Somatic mutations of the EGFR gene were found in about 25–40% of Japanese lung cancer patients. More recently, erbB2 mutations are found in about 4% of European‐derived lung cancer patients. We have investigated EGFR and erbB2 mutation status in 95 surgically treated nonsmall cell lung cancer (NSCLC) cases from Nagoya City University Hospital. Seventy‐five adenocarcinoma cases were included. The presence or absence of EGFR and ernB2 mutations of kinase domains were analyzed by reverse transcription polymerase chain reaction (RT‐PCR) amplifications and direct sequences. We have also investigated erbB2 mutation status in 27 surgically treated NSCLC cases followed by treatment with gefitinib from Kinki‐chuo Chest Medical Center. EGFR mutations (CTG→CGG; L858R) were found from 14 of 95 lung cancer patients. We also detected the deletion 1a‐type mutations from 9 patients and deletion 4‐type mutations from 6 patients in exon 19. In exon 20, 4 mutations including 2 novel mutations were found. Total EGFR mutations were present in 35 patients (36.8%). These mutation statuses were significantly correlated with gender (women 73.3% vs. men 20%, p < 0.0001), smoking status (never smoker 69.4% vs. smoker 16.9%, p < 0.0001), pathologic subtypes (adenocarcinoma 45.1% vs. nonadenocarcinoma 12.5%, p = 0.0089) and differentiation status of the lung cancers (well 51% vs. moderately or poorly 18.4%, p = 0.0021). On the other hand, erbB2 mutation was only found from 1 of 95 patients, at exon 20. This patient was female and a never smoker with adenocarcinoma. This 12 nucleotide insertion mutation (2324–2325 ins ATACGTGATGGC) was located in the exon 20 at kinase domain (775–776 ins YVMA). There was no erbB2 mutation in 27 gefitinib‐treated NSCLC patients. In total, we have found only 1 erbB2 mutation from 122 (0.8%) Japanese NSCLC patients. There was a significantly higher erbB2 positive (2+/3+) ratio in EGFR mutant patients (13/25, 52.0%) compared to EGFR wild‐type patients (10/62, 16.1%; p = 0.0247). The NSCLC specimen with erbB2 mutation showed 1+ immunoreactivity. The EGFR mutation status might correlate with the clinicopathologic features related to good response to gefitinib, such as gender, smoking history and pathologic subtypes of lung cancers. However, erbB2 mutation is rare from Japanese lung cancer and is of limited value for molecular target therapy. © 2005 Wiley‐Liss, Inc.
Betulinic acid, a natural cytotoxic agent, fails to trigger apoptosis in human Burkitt's lymphoma‐derived B‐cell lines
Authors: Karpova Maria B. , Sanmun Duangmanee , Henter Jan‐Inge , Smirnov Aleksandr F. , Fadeel Bengt
Published: July 2005

Betulinic acid (BA), a pentacyclic triterpene of natural origin, effectively induces apoptosis in neuroectodermal tumors and was recently shown to be a potent trigger of cell death in human leukemia‐derived cell lines. To explore the potential of BA in the treatment of hematologic malignancies, we tested a panel of 10 Burkitt's lymphoma (BL)‐derived B‐cell lines for sensitivity to BA. The human Jurkat T leukemia cell line was included as a positive control. Our studies show that BA exerts cytotoxic effects in some of the BL cell lines tested, including DG75, a chemoresistant BL cell line. However, cell death was caspase‐independent, as evidenced by a lack of protection by zVAD‐fmk, a pancaspase inhibitor, and displayed signs of necrosis. Furthermore, BA‐induced caspase activation was seen to a minor extent in only 1 of the 10 BL cell lines tested (Ramos, a p53‐deficient cell line), but was readily detected in Jurkat cells. Together, these studies indicate that resistance to BA‐induced apoptosis is a common feature of BL‐derived cell lines. © 2005 Wiley‐Liss, Inc.
Molecular mechanisms of HLA class I antigen abnormalities following viral infection and transformation
Authors: Seliger Barbara , Ritz Ulrike , Soldano Ferrone
Published: July 2005

In humans as in other animal species, CD8+cytotoxic T lymphocytes (CTLs) play an important if not the major role in controlling virus‐infected and malignant cell growth. The interactions between CD8+T cells and target cells are mediated by human leukocyte antigen (HLA) class I antigens loaded with viral and tumor antigen‐derived peptides along with costimulatory receptor/ligand stimuli. Thus, to escape from CD8+T‐cell recognition and destruction, viruses and tumor cells have developed strategies to inhibit the expression and/or function of HLA class I antigens. In contrast, cells with downregulated MHC class I surface expression can be recognized by NK cells, although NK cell‐mediated lysis could be abrogated by the expression of inhibiting NK cell receptors. This review discusses the molecular mechanisms utilized by viruses to inhibit the formation, transport and/or expression of HLA class I antigen/peptide complexes on the cell surface. The knowledge about viral interference with MHC class I antigen presentation is not only crucial to understand the pathogenesis of viral diseases, but contributes also to the design of novel strategies to counteract the escape mechanisms utilized by viruses. These investigations may eventually lead to the development of effective immunotherapies to control viral infections and virus‐associated malignant diseases. © 2005 Wiley‐Liss, Inc.
Bioadhesive Properties of a Polyaminoacidic Hydrogel: Evaluation by ATR FT‐IR Spectroscopy
Authors: Saiano Filippo , Pitarresi Giovanna , Mandracchia Delia , Giammona Gaetano
Published: July 2005

Summary: The bioadhesive properties of a novel chemical hydrogel based on a polymer of protein‐like structure, have been investigated by using ATR FT‐IR spectroscopy. In particular, the copolymer PHG obtained by partial derivatization of PHEA with GMA was chemically crosslinked by UV irradiation at 313 nm. Crosslinked PHG was treated with water to obtain a swelled sample, named PHG‐UV gel, that was brought into contact with a phosphate buffer/citric acid solution at pH 7.0 in the absence or in the presence of mucin at various concentrations (0.01, 0.1 and 1 wt.‐%). Preliminary dynamic swelling studies have evidenced the occurrence of an interaction between the PHG‐UV gel and the glycoprotein. This result was confirmed by ATR FT‐IR measurements. A diffusion model using a solution of Ficks' second law was employed to determine the diffusion coefficient of water into PHG‐UV gel as a consequence of adsorption and/or interdiffusion which occur at the PHG‐UV gel/mucin solution interface. Experimental results suggest a potential use of PHG‐UV gel to prepare bioadhesive devices.

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Targeting NAD(P)H:quinone oxidoreductase (NQO1) in pancreatic cancer
Authors: Lewis Anne M. , Ough Matthew , Hinkhouse Marilyn M. , Tsao Ming‐Sound , Oberley Larry W. , Cullen Joseph J.
Published: July 2005

NAD(P)H:quinone oxidoreductase (NQO1) functions as an important part of cellular antioxidant defense by detoxifying quinones, thus preventing the formation of reactive oxygen species (ROS). The aim of our study was to determine if NQO1 is elevated in pancreatic cancer specimens and pancreatic cancer cell lines and if so, would compounds previously demonstrated to redox cycle with NQO1 be effective in killing pancreatic cancer cells. Immunohistochemistry of resected pancreatic specimens demonstrated an increased immunoreactivity for NQO1 in pancreatic cancer and pancreatic intraepithelial neoplasia (PanIN) specimens versus normal human pancreas. Immunocytochemistry and Western immunoblots demonstrated increased immunoreactivity in pancreatic cancer cells when compared to a near normal immortalized human pancreatic ductal epithelial cell line and a colonic epithelial cell line. Streptonigrin, a compound known to cause redox cycling in the presence of NQO1, decreased clonogenic survival and decreased anchorage‐independent growth in soft agar. Streptonigrin had little effect on cell lines with absent or reduced levels of NQO1. The effects of streptonigrin were reversed in pancreatic cancer cells pretreated with dicumarol, a known inhibitor of NQO1. NQO1 may be a therapeutic target in pancreatic cancer where survival is measured in months. © 2005 Wiley‐Liss, Inc.
Evidence for motor axon depolarization in Fabry disease
Authors: Tan Stella V. , Lee Philip J. , Walters Richard J. L. , Mehta Atul , Bostock Hugh
Published: July 2005

To investigate the pathophysiology of neuropathy in Fabry disease, multiple nerve excitability properties of median motor axons in 20 patients with this disorder but without hyperkalemia were compared with 35 age‐matched normal controls. In the patients, depolarizing threshold electrotonus was reduced (P < 0.0001) and superexcitability was reduced (P < 0.001), but late subexcitability was normal. These findings indicate that the axons were mildly depolarized, probably due to ischemia, and are consistent with the hypothesis that poor nerve perfusion in Fabry disease contributes to axonal damage. Muscle Nerve, 2005
Production of Highly Charged Heavy Ions by Means of a Hybrid Source in DC Mode and in Afterglow Mode
Authors: Gammino Santo , Ciavola Giovanni , Torrisi Lorenzo , Celona Luigi , Andò Lucio , Manciagli Sebastiano , Consoli Fabrizio , Galatà Alessio , Picciotto Antonio , Mezzasalma Angela M. , Krása Josef , Láska Leos , Pfeifer Mirek , Rohlena Karel , Wolowski Jerzy , Woryna Eugeniusz , Parys Piotr , Shirkov Grigori D. , Hitz Denis
Published: July 2005

Summary: An ECLISSE experiment has been carried out by coupling a laser ion source (based on a Nd:YAG laser (0.9 J/9 ns, laser power densities < 1011 W · cm−2) to the SERSE superconducting electron cyclotron resonance ion source. Continuous wave beams of highly charged ions from metal samples without the use of ovens or sputtering techniques were obtained under a variety of experimental conditions. The maximum charge states obtained from the ECRIS were 38+ for Ta and 41+ for Au. The peak current was obtained for 25+ and 29+, respectively, and it was in the order of some tens of µA. In this work the analysis of some preliminary results obtained in afterglow mode will also be presented. We employed microwave pulses (length 4 ms) and laser pulses (length 9 ns) with the same frequency (30 Hz) and variable relative phase. For appropriate phase values, a current enhancement of about one order of magnitude was observed.

The extraction electrode featuring the traces of deposited tantalum and gold.

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The extraction electrode featuring the traces of deposited tantalum and gold.
Folding and activity of cAMP‐dependent protein kinase mutants
Authors: Langer Thomas , Sreeramulu Sridhar , Vogtherr Martin , Elshorst Bettina , Betz Marco , Schieborr Ulrich , Saxena Krishna , Schwalbe Harald
Published: July 2005

The catalytic subunit of cAMP‐dependent protein kinase (PKA) can easily be expressed in Escherichia coli and is catalytically active. Four phosphorylation sites are known in PKA (S10, S139, T197 and S338), and the isolated recombinant protein is a mixture of different phosphorylated forms. Obtaining uniformly phosphorylated protein requires separation of the protein preparation leading to significant loss in protein yield. It is found that the mutant S10A/S139D/S338D has similar properties as the wild‐type protein, whereas additional replacement of T197 with either E or D reduces protein expression yield as well as folding propensity of the protein. Due to its high sequence homology to Akt/PKB, which cannot easily be expressed in E. coli, PKA has been used as a surrogate kinase for drug design. Several mutations within the ATP binding site have been described to make PKA even more similar to Akt/PKB. Two proteins with Akt/PKB‐like mutations in the ATP binding site were made (PKAB6 and PKAB8), and in addition S10, S139 and S338 phosphorylation sites have been removed. These proteins can be expressed in high yields but have reduced activity compared to the wild‐type. Proper folding of all proteins was analyzed by 2D 1H, 15N‐TROSY NMR experiments.
Thioredoxin overexpression in HT‐1080 cells induced cellular senescence and sensitization to gamma radiation
Authors: Byun Hee Sun , Cho Eun Wie , Kim Jin Sik , Moon Myung Sook , Yum Jung Joo , Kim Kug Chan , Kim In Gyu
Published: July 2005

An increment of thioredoxin‐1 (TRX) is observed in many human primary cancers and appears to contribute to an increase of cell growth and a resistance to chemotherapy. On the contrary, when TRX was overexpressed in the HT‐1080 fibrosarcoma cells, the cell growth was retarded and chromosomal polyploidy and cellular senescence were induced. TRX‐overexpression made HT‐1080 cells resistant to an oxidative stress caused by H2O2 or paraquat. But these cells were significantly sensitive to ionizing radiation, showing an abrogation of the G2 checkpoint. Their DNA contents were twice of the controls and they expressed typical senescence markers. Their expression levels of p53 and cyclin‐dependent kinase inhibitors (CDKI) were about 2–3‐fold higher than the control. Nevertheless, cyclin D1 and D3, which are negatively regulated by CDKIs, were also increased. Overall, in HT‐1080 cells the TRX‐overexpression created a state of cellular senescence caused by a simultaneous stimulation of the mitogen‐activated pathways and an inhibition of the cyclin‐dependent kinases, which is known as a hypermitogenic arrest.
Functional replacement of Drosophila Btk29A with human Btk in male genital development and survival
Authors: Hamada Noriko , Bäckesjö Carl-Magnus , Smith C.I. Edvard , Yamamoto Daisuke
Published: July 2005

Drosophila type 2 Btk29A reveals the highest homology to Btk among mammalian Tec kinases. In Btk29A

ficP
mutant males, the apodeme holding the penis split into two pieces. Human Btk rescued this phenotype in 39% of Btk29A

ficP
males, while the Drosophila transgenes did so in 90–100% of mutants. The Btk29A

ficP
mutation reduced adult longevity to 11% that of wild‐type. This effect was counteracted by Drosophila type 2, yielding 76% of the wild‐type lifespan. Human Btk extended the lifespan of Btk29A

ficP
mutants only to 20% that of wild‐type. Thus human Btk can partially replace Drosophila Btk29A
+ in male genital development and survival.
The co‐chaperone p23 is degraded by caspases and the proteasome during apoptosis
Authors: Mollerup Jens , Berchtold Martin W.
Published: July 2005

The heat shock protein 90 co‐chaperone p23 has recently been shown to be up‐regulated in cancer cells and down‐regulated in atheroschlerotic plaques. We found that p23 is degraded during apoptosis induced by several stimuli, including Fas and TNFα‐receptor activation as well as staurosporine treatment. Caspase inhibition protected p23 from degradation in several cell lines. In addition, recombinant caspase‐3 and 8 cleaved p23 at Asp 142 generating a degradation product of 18 kDa as seen in apoptotic cells. Truncated p23 is further degraded in a proteasome dependent process during apoptosis. Furthermore, we found that the anti‐aggregating activity of truncated p23 was reduced compared to full length p23 indicating that caspase mediated p23 degradation contributes to protein destabilisation in apoptosis.
Comparative study of the presence of Trypanosoma cruzi kDNA, inflammation and denervation in chagasic patients with and without megaesophagus
Authors: da SILVEIRA A. B. M. , ARANTES R. M. E. , VAGO A. R. , LEMOS E. M. , ADAD S. J. , CORREA-OLIVEIRA R. , D'AVILA REIS D.
Published: July 2005

Neuronal lesions have been considered the hallmark of chagasic megaesophagus, but the role of Trypanosoma cruzi and the participation of the inflammatory cells in this process are still debated. In the present study we counted neurons in the oesophagus from patients with and without megaesophagus and further examined these samples for the presence of parasite kDNA and cells with cytolytic potential (Natural Killer cells, cytotoxic lymphocytes and macrophages). The presence of parasite kDNA was demonstrated in 100% of cases with megaesophagus and in 60% of patients without megaesophagus. When analysed for the number of neurons, the patients without megaesophagus could be classified into 2 groups, as having normal or a decreased number of neurons. The former group did not show any inflammatory process, but interestingly, all patients without megaesophagus presenting decreased number of neurons also presented both parasite kDNA and inflammatory process in the organ. We further observed that the numbers of cytotoxic cells in the myenteric plexus region inversely correlate with the number of neurons. These data together strongly suggest that chronic lesions in chagasic megaesophagus might be a consequence of immune-mediated mechanisms, that last until the chronic phase of infection, and are dependent on the persistence of parasite in the host's tissue.
Trashing Identity Politics: Does It Really Get Us Back to Class?
Authors: Lichtenstein Nelson
Published: July 2005

Verity Burgmann creates an unnecessary and ahistorical distinction between the politics of class and that of the various identities through which the contemporary working class defines itself. Indeed, her vision of a self-conscious proletariat seems too male and too musty. Racial and gender identities have achieved a privileged status, compared to that of class, but this has less to do with the outlook of the left-wing academy than with the late twentieth-century transformation of law, politics, and social policy, both in the US and other multicultural nations.
Sweated Labor Then and Now
Authors: Tabb William K.
Published: July 2005

From the first usage in nineteenth-century America of the term “sweatshop,” the definition of this emotive term has “reflected social anxiety about global flows and exchange of people, goods, culture, and capital,” Bender and Greenwald write in their useful edited volume, Sweatshops USA. And if the term sweatshop today connotes a race to the bottom in which a market structure of intense competition reflects the absence, or lack of the enforcement of, effective protective legislation across the relevant market, then there is little basically new in the organization of garment production and the unrelenting pressures on its workers. Essential characteristics of sweated labor in the industry result from structural characteristics which have remained and are only ameliorated by strong unions, public concern for the conditions of labor, and enforced social regulation. While it has often seemed to be an outlier in its exploitative norms, the idea that garment work is totally unique in the flexibility it demands, the excesses and abuses inherent in the contracting system with its pressures to respond to unpredictable and rapidly changing fashion, its production of a labor-intensive product not easily mechanized, and its ability to seek out and control a vulnerable labor force is a misjudgment. It is rather an industry which represents an extreme but not a different form of the way labor markets operate. It is not a vanishing past but a worrisome globalized future of just-in-time production and multisourced internationalized commodity chain organization of production which should be worrying.
“Is It Labor or Is It Working Class?”: The Midwest Labor and Working-Class History Colloquium
Authors: Cantwell Christopher D. , Helgeson Jeffrey
Published: July 2005

On 17–18 April 2004, the Midwest Labor and Working-Class History Colloquium (MLWCH) met at the University of Illinois at Chicago. Formed in 1994, MLWCH is a consortium of graduate students and faculty connected to the Midwest either through research interest or institutional affiliation. MLWCH exists to foster scholarly exchange amongst the field's future and current practitioners, provide an informal setting for students to present and receive feedback on their research, and nurture the collegial relationships that are essential to the study of history. This year's colloquium brought together eighteen graduate students and featured three events: an open forum on the question “Is it Labor or Working-Class History?” two roundtable discussions on participants' research, and a faculty-led roundtable on professional development.
Nitrogen cycle of the Baltic Sea from an isotopic perspective
Authors: Voss M. , Emeis K.‐C. , Hille S. , Neumann T. , Dippner J. W.
Published: July 2005

Stable nitrogen isotope ratios (15N/14N; δ15N) were determined in sediments, suspended matter, and water at selected sites in the Baltic Sea area in order to set up a source budget and trace the fate of anthropogenic N sources. Sediments of the shallow near‐coastal area of the southern and eastern Baltic Sea have an average δ15N of 7.3 ± 2.1‰, interpreted as a characteristic trace of residual anthropogenic nitrogen delivered by rivers and diffuse runoff. In contrast, δ15N values in sediments deposited in the basins of the central Baltic Sea are depleted (average δ15N of 3.5 ± 0.6‰), indicating a significant contribution by diazotrophic cyanobacteria. Statistical analysis of long‐term nutrient data (1969–2001) indicates no increase in nitrate concentrations in the central Baltic Proper, where only phosphate concentrations have increased. The physical circulation pattern and the enthalpy, as derived from a circulation model, show a closed circulation cell in the Baltic Proper with limited transport of riverine material into the basins and elevated temperatures in the Baltic Proper. Together, the isotope and nutrient data suggest that eutrophication by riverine nitrogen is pronounced in the coastal rim of the Baltic Sea, and that coastal sediments appear to be very efficient in removing riverborne nitrogen by denitrification. A nitrogen isotope mass balance model suggests that N loss by sediment denitrification and N input by N fixation can be as high as 855 ktons N yr−1.
Modeling the deep eddy field in the southwestern Mediterranean: The life cycle of Sardinian eddies
Authors: Testor P. , Béranger K. , Mortier L.
Published: July 2005

During the MATER experiment, an eddy characterized by marked Levantine Intermediate Water (LIW) in its core at intermediate depth, and called Sardinian Eddy (SE), has been observed in the Algerian Basin located in the western Mediterranean Sea. Here, results from a numerical simulation allow to investigate thoroughly such structures. The formation of SEs and their life cycle in the model are detailed and compared to in‐situ observations. The formation of SEs is associated with the detachment from the continental slope of Sardinia of the large‐scale cyclonic gyre found in the Algerian Basin. Once formed, SEs leave the slope westwards. They are strongly barotropic and about 3 to 4 SEs are created each year. At a later stage, SEs develop a baroclinic component as revealed by an emerging surface signature about 1 month after their formation. Coalescence processes and merging of these eddies are documented between Minorca and Sardinia where these eddies accumulate.
Model of bifurcated current sheets in the Earth's magnetotail: Equilibrium and stability
Authors: Camporeale Enrico , Lapenta Giovanni
Published: July 2005

Recent observations of CLUSTER have reconfirmed the recurring presence of bifurcated current sheets. The present paper revisits the model of Schindler and Birn (2002) to describe analytically bifurcated current sheets. Our contributions are in order. First, we describe a number of analytical velocity distribution functions that lead to bifurcated current sheets. Second, we derive necessary and sufficient conditions that determine when current sheets can be produced within the mathematical model of Schindler and Birn (2002). Third, we present a class of bifurcated current sheets, and we describe their properties. Fourth, we study the stability of bifurcated current sheets to the tearing instability finding that bifurcated current sheets tend to be more stable. Finally, we investigate the stability of bifurcated current sheets to the lower hybrid drift instability (LHDI) and kinking instability proving their presence. The work reported here is intended to extend and investigate the properties of instabilities from the typical but academic case of the Harris current sheet to current sheet equilibria that are more realisticly representative of the real magnetotail.
Vertical stratification and air‐sea CO2 fluxes in the Patagonian shelf
Authors: Bianchi Alejandro A. , Bianucci Laura , Piola Alberto R. , Pino Diana Ruiz , Schloss Irene , Poisson Alain , Balestrini Carlos F.
Published: July 2005

The thermohaline structure across the tidal fronts of the continental shelf off Patagonia is analyzed using historical and recent summer hydrographic sections. The near‐summer tidal front location is determined on the basis of the magnitude of vertical stratification of the water column as measured by the Simpson parameter. Sea surface and air CO2 partial pressures based on data from eleven transects collected in summer and fall from 2000 to 2004 are used to estimate CO2 fluxes over the shelf. The near‐shore waters are a source of CO2 to the atmosphere while the midshelf region is a CO2 sink. The transition between source and sink regions closely follows the location of tidal fronts, suggesting a link between vertical stratification of the water column and the regional CO2 balance. The highest surface values of Chl a are associated with the strongest CO2 sinks. The colocation of lowest CO2 partial pressure (pCO2) and highest Chl a suggests that phytoplankton blooms on the stratified side of the fronts draw the ocean's CO2 to very low levels. The mean shelf sea‐air difference in pCO2 (ΔpCO2) is −24 μatm and rises to −29 μatm if the shelf break front is included. Peaks in ΔpCO2 of −110 μatm, among the highest observed in the global ocean, are observed. The estimated summer mean CO2 flux over the shelf is −4.4 mmol m−2 d−1 and rises to −5.7 mmol m−2 d−1 when the shelf break area is taken into account. Thus, during the warm season the shelf off Patagonia is a significant atmospheric CO2 sink.
Are sawtooth oscillations of energetic plasma particle fluxes caused by periodic substorms or driven by solar wind pressure enhancements?
Authors: Huang Chao‐Song , Reeves Geoff D. , Le Guan , Yumoto Kiyo
Published: July 2005

Energetic electron and proton fluxes measured by geosynchronous satellites often show sawtooth‐like variations during magnetic storms. We examine whether the sawtooth oscillations and relevant magnetospheric‐ionospheric disturbances are caused by periodic substorms or driven by a series of enhancements in the solar wind pressure. We show that there are significant differences between periodic substorms and solar wind‐induced variations. The energetic fluxes at geosynchronous orbit may increase by orders of magnitude after each onset of periodic substorms and by 10–50% in response to a large solar wind pressure impulse. The sudden increases of the energetic fluxes during periodic substorms show significant time delays of 30–50 min at different longitudes/local times, indicating that the fluxes are injected on the nightside and then drift to the dayside. In contrast, the small flux increases caused by solar wind pressure enhancements occur almost simultaneously at all local times. The periodic substorms always have a strong spectrum peak at 2–3 hours, no matter whether the solar wind pressure and/or IMF have similar spectrum peaks. The nightside magnetospheric magnetic elevation angle shows a large (30–60°) increase at each onset of periodic substorms through dipolarization and a small (<10°) decrease in response to a solar wind pressure impulse. Each cycle of periodic substorms can cause a deviation of 40–60 nT in the midlatitude geomagnetic field; the midlatitude geomagnetic deviations caused by solar wind pressure enhancements are proportional to the square root of the pressure change. The increase of the polar cap index caused by substorms is ∼4 times that caused by solar wind pressure enhancements. We conclude that the sawtooth‐like flux oscillations represent flux injections during periodic substorms and that the period of substorms is determined by the magnetosphere.
Introduction to special section on Mitigation of Radio Frequency Interference in Radio Astronomy
Authors: Ellingson Steven W.
Published: July 2005

The papers contained in this special section are extended versions of some of the papers presented at the Workshop on the Mitigation of Radio Frequency Interference in Radio Astronomy (RFI2004), held in Penticton, British Columbia, Canada, in July 2004.
Area of Left Ventricular Regional Conduction Delay and Preserved Myocardium Predict Responses to Cardiac Resynchronization Therapy
Authors: TSE HUNG‐FAT , LEE KATHY LF , WAN SIU‐HONG , YU YINGHONG , HOERSCH WALTER , PASTORE JOSEPH , ZHU QINGSHENG , KENKNIGHT BRUCE , SPINELLI JULIO , LAU CHU‐PAK
Published: July 2005

Background: A significant proportion of patients with dilated cardiomyopathy and left bundle branch block (LBBB) do not respond to cardiac resynchronization therapy (CRT). The purpose of this study was to investigate whether the electromechanical properties of the myocardium would predict acute hemodynamic improvement during left ventricular (LV) pacing.

Methods and Results: We studied 10 patients with idiopathic dilated cardiomyopathy and LBBB (ejection fraction (EF): 27%± 7%; QRS duration: 166 ± 16 msec) using three‐dimensional electromechanical endocardial mapping technique to assess endocardial activation time (Endo‐AT), unipolar voltage, and local linear shortening during sinus rhythm. LV stimulation was performed in VDD mode at five different sites and three atrioventricular delays within the coronary sinus. LV + dP/dtmax changes from baseline were measured during LV stimulation at each site (%ΔdP/dtmax). There was no significant relationship between maximum %ΔdP/dtmax during LV stimulation at the best coronary sinus site and LV EF, baseline LV + dP/dtmax, total LV Endo‐AT, baseline QRS duration nor changes in QRS duration during LV pacing. However, the maximum %ΔdP/dtmax was significantly positively correlated with percentage area of late Endo‐AT (r = 0.97, P < 0.001) and preserved LV myocardium (r = 0.81, P = 0.005), respectively. Patients with >20% of LV area with late Endo‐AT and >30% of preserved LV myocardium had five times better acute hemodynamic response with LV stimulation. Multivariate analysis showed that only percentage area of late Endo‐AT was independently correlated with %ΔdP/dtmax (P < 0.05).

Conclusion: The presence of a larger amount of LV area with late Endo‐AT and preserved LV myocardium measured by electromechanical mapping could identify patients who have better acute improvement in systolic performance during LV stimulation.
Enhancing Electrical Cardioversion and Preventing Immediate Reinitiation of Hemodynamically Deleterious Atrial Fibrillation with Class III Drug Pretreatment
Authors: HAYASHI MEISO , TANAKA KEIJI , KATO TAKAO , MORITA NORISHIGE , SATO NAOKI , YASUTAKE MASAHIRO , KOBAYASHI YOSHINORI , TAKANO TERUO
Published: July 2005

Introduction: In severely ill patients, the development of atrial fibrillation (AF) may provoke lethal hemodynamic instability requiring immediate electrical defibrillation, which often is unsuccessful. Using the novel potassium channel blocking agent nifekalant, we prospectively assessed the hypothesis that class III antiarrhythmic drugs facilitate electrical cardioversion and suppress the immediate recurrence of hemodynamically deleterious AF.

Methods and Results: Among 1896 adults admitted to the intensive care unit for cardiovascular diseases, hemodynamically destabilizing new‐onset AF (systolic blood pressure <90 mm Hg) resistant to conventional electrical cardioversion occurred in 27 patients, and of these, 24 patients (70 ± 12 years) were enrolled. Twenty‐one patients had congestive heart failure and 11 patients had been mechanically ventilated. After three failed transthoracic cardioversions due to failure of conversion to SR (11 patients) or immediate reinitiation (13 patients), nifekalant (0.25 ± 0.04 mg/kg) was administered intravenously, and electrical defibrillation was reattempted. In 18 patients (75%), sinus rhythm was restored and maintained after nifekalant infusion (6 patients) or subsequent transthoracic cardioversion (12 patients). Nifekalant administration significantly decreased the heart rate and increased systolic blood pressure during AF (P < 0.001), and successful cardioversion rapidly further ameliorated these parameters (P < 0.001). Logistic regression analysis showed that atrial defibrillation failure (relative risk [RR] 19.34, P = 0.05) and age of >75 years (RR 15.25, P = 0.03) were independent predictors of in‐hospital death.

Conclusion: Nifekalant renders electrical defibrillation and the prevention of the early recurrence of hemodynamically unstable AF more successful without deteriorating hemodynamics, and successful defibrillation is associated with a more favorable patient outcome. Pretreatment with other class III drugs, e.g., ibutilide or dofetilide, would also be efficacious in patients with failed urgent electrical cardioversion.
Atrioventricular Node Ablation and Permanent Ventricular Pacemaker Implantation Without Fluoroscopy: Use of an Electroanatomic Navigation System
Authors: RUIZ‐GRANELL RICARDO , MORELL‐CABEDO SALVADOR , FERRERO‐DE‐LOMA ANGEL , GARCÍA‐CIVERA ROBERTO
Published: July 2005

Fluoroscopic guidance is the standard tool used for transvenous pacemaker implantations and for electrophysiological and ablation procedures. It implies X‐ray exposure, occasionally with high dose of radiation for the patient and operator. We describe the case of a 47‐year‐old man with uncontrollable permanent atrial fibrillation to whom ablation of the AV conduction and a permanent ventricular pacemaker implantation were successfully performed under the guidance of an electroanatomic navigation EnSite NavX® system and with no use of fluoroscopy. This case illustrates the stand‐alone use of one of the new non‐fluoroscopic navigation systems for a complete procedure such as AV ablation and pacemaker implantation.