bluuebunny/crossref_metadata_2025 huggingface dataset:
Tumor suppressor Smad4 mediates downregulation of the anti‐adhesive invasion‐promoting matricellular protein SPARC: Landscaping activity of Smad4 as revealed by a “secretome” analysis
Authors: Volmer Martin W. , Radacz Yvonne , Hahn Stephan A. , Klein‐Scory Susanne , Stühler Kai , Zapatka Marc , Schmiegel Wolff , Meyer Helmut E. , Schwarte‐Waldhoff Irmgard
Published: March 2004

We have demonstrated previously that restoration of Smad4 expression in Smad4‐deficient SW480 human colon carcinoma cells was adequate to suppress tumorigenicity and invasive potential, whereas cell growth in vitro was not affected. Here we show that Smad4‐positive and Smad4‐negative SW480 cells deposit extracellular matrices in tissue culture which are functionally different with respect to their adhesiveness. We present a “differential secretomics analysis” as the most direct approach to identify the underlying alterations. The protein composition of conditioned media produced by Smad4‐positive and Smad4‐negative SW480 cells was compared by two‐dimensional (2‐D) gel electrophoresis. A major group of protein spots was detected in media derived from Smad4‐negative cells, only, which were identified as “secreted protein, acidic and rich in cysteins” (SPARC) by mass spectrometry. SPARC expression in SW480 cells was suppressed by Smad4 at the level of transcription. SPARC is a glycoprotein of the extracellular matrix, characterized as an anti‐adhesive and invasion‐promoting protein. Differential secretomics appeared as a powerful method to identify a novel Smad4 target gene, which may be one of the players involved in reduced adhesiveness of extracellular matrices and thus consistent with Smad4's emerging role as an invasion suppressor.
Microheterogeneity of the major grass group 6 allergen Phl p 6: Analysis by mass spectrometry
Authors: Blume Cornelia , Lindner Buko , Becker Wolf‐Meinhard , Petersen Arnd
Published: March 2004

The precise structural characterization of allergens is a basic requirement to improve diagnostics and to find therapeutic strategies against allergic disorders. Natural grass pollen allergens exhibit a wide variety of isoforms and it is still unknown whether this microheterogeneity is essential for the allergic reaction or has a functional effect on sensitization. Well‐defined recombinant allergens are considered to replace natural allergens for clinical trials. For the major timothy grass pollen allergen Phl p 6 (∼12 kDa) and a recombinant rPhl p 6 we determined the structural microheterogeneity by two‐dimensional electrophoresis (2‐DE), high‐resolution electrospray ionization‐Fourier transform‐mass spectrometry (ESI‐FT‐MS) of the intact molecules, and by tryptic peptide mass fingerprinting using matrix‐assisted laser desorption/ionization‐time of flight‐mass spectrometry (MALDI‐TOF‐MS). Natural Phl p 6 is a mixture of mainly two isoforms that differ by two amino acids leading to a mass difference of 5 Da. For each of this two isoforms six variants were identified with modifications at the C‐ and/or N‐terminus. The recombinant Phl p 6 comprises the same structure as one of the main isoforms indicating that it represents a major part of the natural Phl p 6.
Proteome analysis of intraclonal diversity of two Pseudomonas aeruginosa TB clone isolates
Authors: Arevalo‐Ferro Catalina , Buschmann Julia , Reil Gerold , Görg Angelika , Wiehlmann Lutz , Tümmler Burkhard , Eberl Leo , Riedel Kathrin
Published: March 2004

Two strains, Pseudomonas aeruginosa TB10839 and TB121838, which belong to the TB clonal lineage, have been isolated from sputa of cystic fibrosis patients. Despite the fact that the strains are closely related, their pathogenic potential differs dramatically: while strain TB10839 is capable of proliferating in polymorphonuclear granulocytes, strain TB121838 is not. Comparative two‐dimensional polyacrylamide gel electrophoresis coupled to matrix‐assisted laser desorption/ionization‐time of flight (MALDI‐TOF)‐mass spectrometry was employed to map the extracellular, intracellular, and surface sub‐proteomes of TB10839 and TB121838 and to identify differentially expressed proteins. About 4% of all detected protein spots were differentially expressed between both strains including absent or present spots and spots with a more than 2‐fold changed intensity. This percentage reflects a relatively high degree of intraclonal variability. Many of the protein spots in TB10839 that were missing or expressed at lower levels in TB121838 were identified as quorum‐sensing regulated virulence factors. It might be speculated that the increased expression of these proteins contributes to pathogenic competence of TB10839.
Double chip protein arrays using recombinant single‐chain Fv antibody fragments
Authors: Gilbert Ilka , Schiffmann Susanne , Rubenwolf Susanne , Jensen Kristian , Mai Thao , Albrecht Christian , Lankenau Andreas , Beste Gerald , Blank Kerstin , Gaub Hermann E. , Clausen‐Schaumann Hauke
Published: March 2004

Protein arrays permit the parallel analysis of many different markers in a small sample volume. However, the problem of cross‐reactivity limits the degree of multiplexing in parallel sandwich immunoassays (using monoclonal antibodies (mAbs)), meaning antibodies must be prescreened in order to reduce false positives. In contrast, we use a second chip surface for the local application of detection antibodies, thereby efficiently eliminating antibody cross‐reactions. Here, we illustrate the potential advantages of using single‐chain Fv fragments rather than mAbs as capture and detection molecules with this double chip technology.
A combination of different mass spectroscopic techniques for the analysis of dynamic changes of histone modifications
Authors: Bonaldi Tiziana , Imhof Axel , Regula Jörg T.
Published: March 2004

The N‐terminal tails of the histones are subject to many enzyme‐mediated post‐translational modifications, such as lysine acetylation, lysine and arginine methylation, serine phosphorylation, poly‐ADP ribosylation and the attachment of the small peptide ubiquitin. These modifications, singly or in combination, are thought to generate an epigenetic code that specifies different patterns of gene activity. We present a detailed study on the mapping of histone post‐translational modifications using a combination of matrix‐assisted laser desorption/ionization‐time of flight and electrospray ionization tandem mass spectrometry analysis of peptides generated by protease cleavage of individual histones isolated from different developmental stages. Due to their high content in basic amino acid residues and in order to be able to quantitatively compare two different samples we developed a chemical derivatization protocol. This strategy enabled us to determine the primary sequence of the peptides and to unambiguously assign specific modifications. This method is generally applicable to histone samples from various sources and can be used to study changes of modification patterns during early embryonic development or tissue differentiation and regeneration.
Heterogeneous nuclear ribonucleoprotein A2/B1 identified as an autoantigen in autoimmune hepatitis by proteome analysis
Authors: Huguet Stèphanie , Labas Valèrie , Duclos‐Vallee Jean‐Charles , Bruneel Arnaud , Vinh Joëlle , Samuel Didier , Johanet Catherine , Ballot Eric
Published: March 2004

Our aim was to characterize antinuclear antibody (ANA) targets in type 1 autoimmune hepatitis (AIH1) using a proteomic tool. ANA‐positive sera from 29 patients with AIH1 and 14 negative controls were analyzed by sodium dodecyl sulfate‐polyacrylamide gel electrophoresis (SDS‐PAGE) and immunoblotting. The principal antigens identified were a 30 kDa triplet band which was recognized by 79% of patient sera and 14% of control sera, and a 36 kDa antigen which was recognized by 52% and 14% of sera, respectively. The latter antigen was studied in more detail using two‐dimensional electrophoresis (2‐DE) and mass spectrometry (MS). Its identification corresponded to heterogeneous nuclear ribonucleoprotein A2/B1. This paper presents the first description of this protein as an antigen in AIH1.
Towards a standardized human proteome database: Quantitative proteome profiling of living cells
Authors: Traxler Elisabeth , Bayer Editha , Stöckl Johannes , Mohr Thomas , Lenz Christof , Gerner Christopher
Published: March 2004

Comparative proteome profiling, performed by two‐dimensional polyacrylamide gel electrophoresis or multidimensional protein identification technology, usually relies on the relative comparison of samples of interest with respect to a reference. Currently, no standardized quantitative protein expression database of human cells, facilitating data comparisons between different laboratories, exists. Recently, we have published two‐dimensional polyacrylamide gel electrophoresis‐based techniques to assess absolute protein data comprising protein amounts, synthesis rates and biological half‐lives (Mol. Cell. Proteomics 2002, 1, 528–537). Determination of protein amounts by fluorography of two‐dimensional gels was followed by the exact quantification of the amount of incorporated 35S radiolabel. Here we demonstrate an application of this highly standardized method to quiescent human T cells, phythaemagglutinin‐stimulated T cells and Jurkat cells, a human T lymphoblast cell line. While the protein composition of quiescent T cells differed significantly compared to that of Jurkat cells, it was only slightly different compared to the activated T cells. Synthesis profile analyses demonstrated that activated T cells clearly differed from the quiescent cells, performing apparently almost like lymphoblast cells. The great sensitivity of this approach was further demonstrated with human umbilical vein endothelial cells treated for six hours with vascular endothelial growth factor. While no significant alteration of protein amounts was detected at all upon activation, the synthesis rate of several proteins was found to be more than doubled.
Proteome analysis of Madrid E strain of Rickettsia prowazekii
Authors: Chao Chien‐Chung , Chelius Dirk , Zhang Terry , Daggle Lindsey , Ching Wei‐Mei
Published: March 2004

Rickettsia prowazekii, an obligate intracellular Gram‐negative bacterium, is the etiologic agent of epidemic typhus. The threat of typhus as a biological weapon lies in its stability in the dried louse feces and in its infection by inhalation of an aerosol. Consequently, it is listed as a select agent and warrants more research to understand its pathogenesis. Although the genomic DNA sequence of strain Madrid E has been completed, the actual expression of the individual protein has not been investigated. In order to provide a global view of the expressed protein profile, the whole cell lysate of purified rickettsia (Madrid E strain) was reduced, alkylated, and digested with trypsin. The total digest was characterized by a two‐dimensional liquid chromatography mass spectrometry system and analyzed with a modified version of the ProteomeX workstation. A total of 252 proteins out of 834 predicted protein‐coding genes were identified, 238 proteins were identified by the detection of at least two unique peptides. Only 14 proteins were identified by the detection of one unique peptide in all three separate analyses. Among the 238 proteins identified by multiple unique peptides, 230 proteins were found in at least two of three separate analyses. The reproducible and convenient methodology and the information described here have provided a foundation for future proteome study of various R. prowazekii strains with different virulence.
An antisense oligonucleotide to cIAP‐1 sensitizes prostate cancer cells to fas and TNFα mediated apoptosis
Authors: McEleny Kevin , Coffey Ronan , Morrissey Colm , Williamson Kate , Zangemeister‐Wittke Uwe , Fitzpatrick John M. , Watson R. William G.
Published: March 2004

BACKGROUND

The inhibitors of apoptosis (IAP) proteins are a family of structurally homologous caspase inhibitors. We synthesized an antisense oligonucleotide (AO) to target a region within the BIR domain of cIAP‐1 and examined its ability to facilitate apoptosis in prostate cancer cells.

METHODS

We transfected the IAP AO into PC3 and DU145 cells and determined alterations in IAP expression using Western blotting. Apoptosis and viability were assessed using propidium iodide (PI) DNA incorporation with flow cytometry. Pacitaxel, caffeic acid phenethyl ester (CAPE), Fas antibody, and TNFα were used as ‘second hit’ agents in association with the AO.

RESULTS

Western blotting showed a down‐regulation in cIAP‐1 expression and higher levels of spontaneous apoptosis in both cell types with no alteration in overall cell viability. AO sensitized PC3 cells, to Fas antibody and TNFα‐mediated apoptosis, but not to apoptosis mediated by paclitaxel or CAPE.

CONCLUSIONS

cIAP‐1 down‐regulation increased spontaneous apoptosis in prostate cancer cells and sensitized PC3 cells to receptor‐mediated apoptosis.
Vitamin D receptor gene polymorphisms and prostate cancer risk
Authors: Cheteri Mahesh B. Keitheri , Stanford Janet L. , Friedrichsen Danielle M. , Peters Mette A. , Iwasaki Lori , Langlois Mariela C. , Feng Ziding , Ostrander Elaine A.
Published: March 2004

BACKGROUND

Vitamin D is a steroid hormone that is thought to play a role in the etiology and progression of prostate cancer. Hormone activity requires binding to the vitamin D receptor (VDR), which contains several genetic polymorphisms that have been associated with risk of prostate cancer. To further evaluate this relationship, we conducted a population‐based case‐control study of the VDR BsmI, FokI, and Poly‐A polymorphisms, and prostate cancer.

METHODS

Germline DNA samples and survey data from incident prostate cancer cases (n = 559) and controls (n = 523) of similar age (40–64 years) without a history of the disease who resided in King County, Washington were analyzed.

RESULTS

The frequency of the BsmI, FokI, and Poly‐A genotypes were similar in cases and controls, and no overall association between any variants and prostate cancer risk were noted. Stratification by clinical features of disease revealed that among men with localized stage disease, the BsmI bb genotype was associated with a modest increase in risk (OR, 1.49; 95% CI, 1.02–2.17; P = 0.04) compared to the BB genotype.

CONCLUSIONS

These results suggest that polymorphisms in the VDR gene are not strong predictors of prostate cancer risk among Caucasian men in the U.S. © 2004 Wiley‐Liss, Inc.
Met160Val polymorphism in the TRMPSS2 gene and risk of prostate cancer in a population‐based case‐control study
Authors: Lubieniecka Joanna M. , Cheteri Mahesh Keitheri , Stanford Janet L. , Ostrander Elaine A.
Published: March 2004

BACKGROUND

Serine proteases play an important role in prostate cancer (PCa) invasion through the degradation of extracellular matrix proteins and interaction with growth modulating factors. The transmembrane serine protease 2 (TMPRSS2) gene encodes a type II transmembrane protein which, due to its cell surface localization, could be a potentially useful predictive marker for PCa.

METHODS

We screened a population of 24 unrelated individuals for sequence variants in the TMPRSS2 gene, and found a Met160Val change in 33%. We then tested 559 cases and 523 controls from a population‐based case‐control study of middle‐aged men from Washington State.

RESULTS

Men with the GG genotype and a first‐degree family history of PCa had a significantly higher risk for PCa relative to men without a family history (OR = 2.05; 95% CI = 1.3–3.2). However, the interaction between genotype and family history of PCa was not significant (P = 0.52).

CONCLUSIONS

Larger, more detailed studies are needed to fully investigate the role of serine proteases in PCa. © 2004 Wiley‐Liss, Inc.
In vivo real‐time imaging of TGF‐β‐induced transcriptional activation of the RANK ligand gene promoter in intraosseous prostate cancer
Authors: Zhang Jian , Lu Yi , Dai Jinlu , Yao Zhi , Kitazawa Riko , Kitazawa Sohei , Zhao Xinping , Hall Daniel E. , Pienta Kenneth J. , Keller Evan T.
Published: March 2004

BACKGROUND

Current animal models of prostate cancer (CaP) bone metastasis do not allow measurement of either tumor growth in bone over time or activation of gene promoters in intraosseous tumors. To develop these methods, we used bioluminescent imaging (BLI) to determine if expression of receptor activator of NF‐κB ligand (RANKL), a pro‐osteoclastogenic factor that promotes CaP bone metastases, is modulated by the bone matrix protein transforming growth factor‐β (TGF‐β) in vivo.

METHODS

C4‐2B human CaP cells were treated with TGF‐β in vitro and RANKL mRNA and protein production were measured by polymerase chain reaction (PCR) and ELISA, respectively. Then C4‐2B cells stably transfected with the RANKL promoter driving luciferase (lux) were injected intra‐tibially into severe combined immundeficient (SCID) mice. Tumors were subjected to BLI every 2 weeks for 6 weeks and serum prostate specific antigen (PSA) was measured using ELISA. Vehicle (V), 1,25 dihydroxyvitamin D (VitD), or TGF‐β was administered to mice with established tumors and BLI to measure RANKL promoter activity was performed. Tumors were then subjected to immunohistochemistry for lux and assayed for RANKL mRNA levels.

RESULTS

TGF‐β induced RANKL protein and mRNA expression and activated the RANKL promoter activity in a dose‐dependent manner in vitro. BLI demonstrated an increase in intraosseous tumor size over time, which correlated with serum PSA levels. Administration of TGF‐β and VitD to mice with established intraosseous tumors increased lux activity compared to V. Intratibial tumor RANKL mRNA expression paralleled the increased promoter activity. Immunohistochemistry confirmed the presence of lux in the intraosseous tumors.

CONCLUSIONS

These results demonstrate the ability to measure intraosseous tumor growth over time and gene promoter activation in an established intraosseous tumor in vivo and also demonstrate that TGF‐β induces activates the RANKL promoter. These results provide a novel method to explore the biology of CaP bone metastases. © 2004 Wiley‐Liss, Inc.
An inherently safer process of cyclohexane oxidation using pure oxygen—An example of how better process safety leads to better productivity
Authors: Chen Jenq‐Renn
Published: March 2004

This paper discusses how detailed studies on flammability at elevated pressures and temperatures can be applied to liquid‐phase oxidation of cyclohexane using air/oxygen and lead to an inherently safer process with better productivity. Flammability tests of cyclohexane/oxygen vapor and vapor bubbles under actual oxidation conditions were performed. The flammability of the vapor and vapor bubbles was found to be moderated by the addition of water into the cyclohexane liquid. The added water forms minimum boiling azeotrope with cyclohexane and its vapor renders the cyclohexane vapor and vapor bubble inflammable. Oxidations of the cyclohexane/water azeotrope utilizing pure oxygen were carried out and found to outperform the traditional air oxidation process by a factor of 2. This paper summarizes our work during the past few years toward a safer and better process development for the liquid‐phase oxidation of cyclohexane. © 2004 American Institute of Chemical Engineers Process Saf Prog 23: 72–81, 2004
Effective thermal conductivity: application to photothermal experiments for the case of bulk light absorption
Authors: Gurevich Yuriy , Logvinov Georgiy , Lashkevich Igor
Published: March 2004

We suggest a new theoretical approach to obtain effective thermal parameters of two‐layer structures in photothermal experiments, and calculate the effective thermal conductivity in the quasistatic approximation. Unlike previous works devoted to this problem, it is supposed that a non‐equilibrium temperature originates due to the bulk modulated light absorption. It is shown that in this case the effective thermal parameters have to be obtained together with the effective optical parameters. As a result, the effective thermal parameters in the general case are dependent on the optical parameters of the layers. The role of the thermal properties of the interface between the layers is discussed. It is concluded that the effective parameters are not single‐valued. They depend on the manner of measurements and the point of these measurements. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Theory of related to shear strain u6 physical properties of ferroelectrics and antiferroelectrics of the KH2PO4 family
Authors: Levitskii R. R. , Lisnii B. M.
Published: March 2004

We propose an extension of the proton tunneling model in order to study related to the shear strain u6 dielectric, piezoelectric, and elastic properties of ferro‐ and antiferroelectrics of the KH2PO4 family. This strain is introduced into the proton Hamiltonian via the linear contributions into the configurational energies of protons surrounding an oxygen tetrahedron. In the four‐particle cluster approximation for the short‐range interactions and the mean field approximation for the long‐range interaction we explore the phase transition and piezoelectric effect in the KH2PO4 ferroelectrics. In the paraelectric phase the dielectric, piezoelectric, and elastic characteristics of the NH4H2PO4 antiferroelectrics are calculated. At the proper choice of the theory parameters a good agreement between theoretical and experimental results is obtained. Taking into account of the piezoelectric coupling with the shear strain u6 allows one to calculate the static dielectric permittivities of free and clamped crystals as well as to obtain a good description of ferroelectric spontaneous shear strain u6. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Stability of single‐wall carbon nanotube tori
Authors: Yang Linfeng , Chen Jiangwei , Dong Jinming
Published: March 2004

We obtained the formation threshold energy expression of SWNT torus by treating single‐walled carbon nanotube (SWNT) as a continuum elastic shell, the obtained formation threshold energy is the function of the radius of formed SWNT torus. The radius of SWNT torus is found to be the most probable radius (energy preferred), which corresponds to the minimum formation threshold energy. Taking into account the rebonding energy of the dangling bond of two ends, the formation energy of the SWNT torus is negative, indicating the formed SWNT torus is stable both physically and chemically. This model can well explain the average radius of 270 nm and the narrow radius distribution of the SWNT tori in experiments. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Effective depths for surface excitation derived by reflection electron energy‐loss spectroscopy analysis
Authors: Zhang Zengming , Iyasu Takeshi , Shimizu Ryuichi , Goto Keisuke , Koshikawa Takanori , Tamura Keiji
Published: March 2004

A method of estimation is proposed for determining the effective depth of surface excitation. For this, the effective differential inverse inelastic mean free path (DIIMFP) is presumed to be represented as a linear combination of theoretical DIIMFPs for surface and bulk excitation, which are derived by the use of optical dielectric constants. The effective DIIMFP in the approach is derived by a reflected electron energy‐loss spectroscopy analysis based on the extended Landau approach. The present analysis for 1 kV electrons has led to a simple estimation of the effective depth for surface excitations (∼14.5 Å for Al and ∼21 Å for Ag), agreeing well with an estimation given by υ/ωs, where υ and ωs are the velocity of the primary electrons and the average surface plasmon frequency, respectively. Copyright © 2004 John Wiley & Sons, Ltd.
Chemical environment of copper at the surface of a CuAl2 model alloy: XPS, MEIS and TEM analyses
Authors: Liu Yanwen , Bailey Paul , Noakes Timothy C. Q. , Thompson George E. , Skeldon Peter , Alexander Morgan R.
Published: March 2004

Air‐formed oxide on a CuAl2 model alloy is shown to be free of copper species, with copper enriching in the alloy. With thickening of the oxide by anodizing, copper enriches further to a critical concentration at which its oxidation proceeds with incorporation of Cu(II) species into the film. Such species migrate more rapidly through the film than aluminium species. Incorporation of copper species is associated with generation of oxygen gas within the film and subsequent film rupture is due to release of the gas. Reduction of Cu(II) to Cu(I) species during XPS analysis is characterized and the accelerating role of charge neutralizing is highlighted. Copyright © 2004 John Wiley & Sons, Ltd.
Positive and negative regulators of Ras in T cells
Authors: Patrussi Laura , Baldari Cosima T.
Published: March 2004

The Ras/MAP kinase pathway plays a central role in T cell development and activation. Here we briefly review the current knowledge on the modulators of Ras activity in T lymphocytes.
Effectiveness of multimedia‐based instruction that emphasizes molecular representations on students' understanding of chemical change
Authors: Ardac Dilek , Akaygun Sevil
Published: March 2004

The present study makes use of the capabilities of computerized environments to enable simultaneous display of molecular representations that correspond to observations at the macroscopic level. This study questions the immediate and long‐term effects of using a multimedia instructional unit that integrates the macroscopic, symbolic, and molecular representations of chemical phenomena. Forty‐nine eighth graders received either multimedia‐based instruction that emphasized molecular representations (n = 16), or regular instruction (n = 33). Students who received multimedia‐based instruction that emphasized the molecular state of chemicals outperformed students from the regular instruction group in terms of the resulting test scores and the ease with which they could represent matter at the molecular level. However, results relating to the long‐term effects suggest that the effectiveness of a multimedia‐based environment can be improved if instruction includes additional prompting that requires students to attend to the correspondence between different representations of the same phenomena. © 2004 Wiley Periodicals, Inc. J Res Sci Teach 41: 317–337, 2004
In search of pedagogical content knowledge in science: Developing ways of articulating and documenting professional practice
Authors: Loughran John , Mulhall Pamela , Berry Amanda
Published: March 2004

This study examines the development of ways of documenting and portraying science teachers' pedagogical content knowledge (PCK). As a result of a longitudinal study into science teachers' pedagogical content knowledge, a method is developed for capturing and portraying PCK that comprises two important elements. The first is linked to the particular science content, termed Content Representation (CoRe), and the second is linked to teaching practice, termed Professional and Pedagogical experience Repertoire (PaP‐eR). Through this approach new understandings of PCK emerge that are of interest in terms of both academic (knowledge building about PCK) and teaching perspectives. This study includes a full CoRe and one PaP‐eR and fully demonstrates how these two elements interact to begin to portray science teachers' pedagogical content knowledge. © 2004 Wiley Periodicals, Inc. J Res Sci Teach 41: 370–391, 2004
Out‐of‐school‐hours learning in the United Kingdom
Authors: Fordham Ian
Published: March 2004

In the United Kingdom, out‐of‐school‐hours learning (OSHL) is incorporated into education policy. This is the story of how demonstration projects, political lobbying, and funding combined with training, youth work, and schools to make such innovation mainstream “across the pond.”
Sodium and potassium transport in the halophilic yeast Debaryomyces hansenii
Authors: González‐Hernández J. C. , Cárdenas‐Monroy C. A. , Peña A.
Published: March 2004

Debaryomyces hansenii, a halophile yeast found in shallow sea waters and salty food products grows optimally in 0.6 M of either NaCl or KCl, accumulating high concentrations of Na+ or K+. After growth in NaCl or KCl, a rapid efflux of either accumulated cation was observed if the cells were incubated in the presence of KCl or NaCl, respectively, accompanied by a slower accumulation of the cation present in the incubation medium. However, a similar, rapid efflux was observed if cells were incubated in buffer, in the absence of external cations. This yeast shows a cation uptake activity of both 86Rb+ and 22Na+ with saturation kinetics, and much higher affinity for 86Rb+ than for 22Na+. The pH dependence of the kinetics constants was similar for both cations, and although Km values were higher at pH 8.0, there was also an increase in the Vmax values. The accumulation of 22Na+ was found to be increased in cells grown in the presence of 0.6 M NaCl. 86Rb+ was also accumulated more in these cells, but to a slightly greater extent. The inhibition kinetics of the uptake of 22Na+ by K+, and that of 86Rb+ by Na+ was found to be non‐competitive. It can be concluded that Na+ in D. hansenii is not excluded but instead, its metabolic systems must be resistant to high salt concentrations. Copyright © 2004 John Wiley & Sons, Ltd.
The Development of Antibiotic Resistant Organisms with the Use of Ototopical Medications
Authors: Weber Peter C. , Roland Peter S. , Hannley Maureen , Friedman Rick , Manolidis Spiros , Matz Greg , Owens Fred , Rybak Leonard , Stewart Michael G.
Published: March 2004

OBJECTIVE

There is growing concern over the use of systemic antibiotics and the development of bacterial resistance. The question remains as to whether ototopical medications may also promote antibiotic‐resistant organisms, either on a local level (in the ear) or in other areas of the aerodigestive tract. We performed an evidence‐based review to answer the following clinical question, “Do antibiotic ototopical medications induce antibiotic resistant organisms?”

STUDY DESIGN

We performed a MEDLINE search of the published literature from 1966 to the present. We used appropriate search terms such as “ototopical antibiotics,” “ototopical drops,” “antibiotic resistance,” “topical antibiotics and otitis externa,” “otitis externa and treatment,” “otitis externa and antibiotic drops,” “otitis externa and ototopical drops,” “otitis media,” “otitis media and treatment,” “otitis media and antibiotic drops,” “chronic suppurative otitis media,” “chronic suppurative otitis media and treatment,” “chronic suppurative otitis media and antibiotic drops,” “ otitis externa and resistant organisms,” “otitis media and resistant organisms,” “chronic suppurative otitis media and resistant organisms,” “ophthalmic antibiotic drops,” “draining ear,” “P.E. tube otorrhea,” “pressure equalizing tube otorrhea,” “pressure equalizing tube otorrhea and treatment,” and “pressure equalizing tube otorrhea and ototopical therapy” to identify pertinent articles. These articles were reviewed and graded according to the evidence quality.

RESULTS

After an initial screening of over 2,500 articles, 38 articles were analyzed further; of these, 11 were determined to warrant extensive review. Eight articles evaluated chronic suppurative otitis media; 2, otitis externa; and 1, post‐tympanostomy tube otorrhea, whereas 3 others studied systemic absorption. Of the 8 chronic suppurative otitis media studies, there were thought to be 5 grade 2B studies, 1 grade 1B study, and 1 grade 2C study. These studies did not demonstrate a propensity for the development of resistant organisms. No study answered the question as to whether resistance to systemic antibiotics might occur in otitis externa.

CONCLUSIONS

Overall grade B evidence seems to indicate that no significant antibiotic resistance develops from the use of ototopical antibiotic treatment.
Keeping fingers crossed: heterochromatin spreading through interdigitation of nucleosome arrays
Authors: Grigoryev Sergei A
Published: March 2004

Interphase eukaryotic nuclei contain diffuse euchromatin and condensed heterochromatin. Current textbook models suggest that chromatin condensation occurs via accordion‐type compaction of nucleosome zigzag chains. Recent studies have revealed several structural aspects that distinguish the highly compact state of condensed heterochromatin. These include an extensive lateral self‐association of chromatin fibers, prominent nucleosome linker ‘stems’, and special protein factors that promote chromatin self‐association. Here I review the molecular and structural determinants of chromatin compaction and discuss how heterochromatin spreading may be mediated by lateral self‐association of zigzag nucleosome arrays.
G protein‐activated K+ channels: a reporter for rapid activation of G proteins by lysophosphatidic acid in Xenopus oocytes
Authors: Itzhaki Van-Ham Irit , Peleg Sagit , Dascal Nathan , Shapira Hagit , Oron Yoram
Published: March 2004

Threshold concentrations of lysophosphatidic acid (LPA) or acetylcholine (ACh) induce pertussis toxin (PTX)‐sensitive rapid desensitization of responses to LPA in Xenopus oocytes. To demonstrate that threshold [LPA] rapidly activates Gi/o proteins, we used the G protein‐activated K+ channel (GIRK) as a reporter. Low [LPA] induced I
K + in <3 s of the agonist addition with little or no activation of chloride current. Depletion of Gαo/Gαo1 each decreased the LPA‐induced I
K + by approximately 40–50%, while PTX completely abolished it. This is the first direct evidence showing the activation of GIRK by LPA, and the involvement of G proteins of the Go family in rapid desensitization of LPA responses.
Beyond Drama: Writing for Postdramatic Theatre
Authors: SUGIERA MAŁGORZATA
Published: March 2004

The article begins with a short description of the current situation in Polish theatre where the traditional understanding of a dramatic text has made the reception of formally innovative European playwriting difficult. On the basis of recent German plays by Rainald Goetz, Dea Loher and Roland Schimmelpfennig, which have been translated into Polish and published but have not yet received significant productions, the article tries to answer two important questions. Firstly, how the postdramatic texts written for avant-garde, feminist and postcolonial theatre during last three decades have influenced plays written for and put on the mainstream stages in the 1990s. Secondly, in what ways the new texts, which in many respects go far beyond the borders of traditional drama, have changed the existing definitions of theatrical mimesis and theories of drama
Theatre of Potentiality. Communicability and the Political in Contemporary Performance Practice
Authors: MÜLLER-SCHÖLL NIKOLAS
Published: March 2004

Much contemporary experimental theatre and many performance practitioners in Germany and Austria share an interest in what one might call the material conditions or the medium of their performances. The article discusses different examples where the sharing of space, language and time in performance and thereby the ‘communicability’ (W. Benjamin) of communication is explored. Directors and writers discussed include H.J. Kapp, W. Golonka, L. Chetouane, R. Pollesch, C. Bosse, J. Szeiler. It is argued that in these cases theatre is done in a political way, because it allows the experience of alterity and opens up a space of potentiality.
Statistical comparison of Regional Atmospheric Modelling System forecasts with observations
Authors: Buckley Robert L. , Weber Allen H. , Weber Jilene H.
Published: March 2004

A statistical comparison of observations and forecasts using the Regional Atmospheric Modelling System (RAMS) for operations at the Savannah River Site (SRS) in South Carolina is discussed. Simulated and observed values of wind direction and wind speed, collected twice daily for a two‐year period from April 1998 to March 2000, are compared in a variety of ways for five different locations in the southeastern United States. Simulated and observed turbulence intensities are also compared for a one‐year period beginning in February 1999 for the SRS. Statistical measures used for comparison are the mean absolute error, mean relative error and standard deviation. Directional errors tend to increase with forecast time while speeds tend to be underestimated over the entire forecast range, especially those exceeding 8 m s−1. Seasonally, winds are predicted with greater accuracy during the winter and spring months, when speeds in the southeastern United States are higher and direction is less variable. Vertical turbulence intensity at SRS is slightly underestimated, while horizontal turbulence intensity is slightly overestimated. In general, the statistical measures show that the model produces results with reasonable skill for the wind speed, direction and turbulence. Copyright © 2004 Royal Meteorological Society.
Peer Suicide Prevention in a Prison
Authors: Hall Barry , Gabor Peter
Published: March 2004

Summary: Suicide rates among inmate populations in prisons are considerably higher than in the general population. Suicide prevention is a common need among penal institutions around the world. Traditional approaches involving only correctional staff in suicide prevention efforts have proven to have their limitations. The involvement of inmates in peer prevention efforts seems to be a reasonable alternative approach. This study examines such a program, called SAMS in the Pen, operated jointly between the prison and the Samaritans of Southern Alberta. This service, the first of its kind in Canada, involved inmate volunteers, known as SAMS, who were trained in listening skills, suicide prevention, and risk assessment. Data was collected for the research from volunteers, correctional staff, general inmate population, and professional staff. However, given the low absolute number in the one institution where the study was carried out, statistical analyses were not practical. As with any new service, the SAMS in the Pen experienced some developmental problems but was perceived to be a worthwhile service to both inmates and staff of the prison.
An Active Postvention Program
Authors: Campbell Frank R. , Cataldie Louis , McIntosh John , Millet Kari
Published: March 2004

Summary: The Active Postvention Model (APM) described in this article demonstrates how survivors of suicide can be an installation of hope for the newly bereaved and an effective referral resource for support in the grief process. The benefit of active postvention compared to passive postvention results in a dramatic reduction in the elapsed time between death and seeking help for the survivors who receive the active postvention. Other benefits of the APM are discussed as well.
A Multiagent Model of Negotiation Processes between Multiple Actors in Urban Developments: A Framework for and Results of Numerical Experiments
Authors: Arentze Theo , Timmermans Harry
Published: March 2004

We propose a multiagent model in which developers and suppliers negotiate and generate proposals for developing a site, given multiple candidate locations in an urban area. In the model, the developer takes the initiative and coordinates the negotiation process with the aim of obtaining commitments from suppliers to open an outlet at a location. In this process, suppliers indicate their preferences and make yes – no decisions to participate in a proposal. We formulate and investigate two alternative negotiation protocols and various possible decision strategies for the developer and supplier agents. The model is applied to a hypothetical study area to investigate long-term dynamics as a function of the choice of protocol and strategies. We show that the model is capable of reproducing the typical hierarchical structure of real retail systems. Furthermore, it appears that the choice of protocol and strategy has an impact on the degree of spatial clustering of outlets as well as on the performance of each individual supplier. The choice of strategy is particularly critical for relatively weak suppliers. We conclude that the multiagent model is useful for planners, developers, and suppliers to explore the impacts their choices have on outcomes, and we identify promising avenues of future research.
Assessment of Visual Qualities, Impacts, and Behaviours, in the Landscape, by Using Measures of Visibility
Authors: Bishop Ian D
Published: March 2004

The application of information technology to landscape analysis dates back to the early work in computer-based mapping. Indeed, much of the early development of what became geographic information systems (GIS) and three-dimensional landscape simulation was undertaken by landscape architects. Mapping of viewsheds quickly became a key element of the landscape-planning process. The process was applied to determination of both view characteristics and potential visual impacts. The algorithms for viewshed analysis were incorporated into GIS products at an early stage in their evolution, but have evolved very little since despite the identification of significant potential enhancements. Extension of the simple binary mapping of GIS has therefore depended on specific developments by individual researchers. These GIS extensions have generated models of visual quality and visual impact using mapped variables. More recently it has become apparent that the essentially two-dimensional approach to view analysis afforded by GIS is inadequate in situations with strong three-dimensional elements. The upsurge in agent-based modeling has demanded a new standard in computer-based visual interpretation of landscape. Both the historic role of GIS-based visual modeling and the potential of 3D-based visual modeling are reviewed.
How to Improve the Social Utility Value of Geographic Information Systems for French Local Governments? A Delphi Study
Authors: Roche Stéphane , Sureau Karine , Caron Claude
Published: March 2004

Today, geographic information technologies (GITs) stand out as the unavoidable answers to the French local governments' new stakes. Yet, an important discrepancy has been noticed between the utility levels (in the qualitative sense) and the theoretical intrinsic potential of these technologies. The social utility value of GIT seems quite low compared with the quantitative level at which they are diffused. The authors focus on the ‘determination of value’, by considering the obstacles to the development of a spatial data infrastructure in the French context. From the results of a Delphi study, the authors bring to the fore the fact that the institutional and organisational barriers 0ack of a clear policy in matters of access and dissemination; cost of public data; absence of fully operational norms and standards; failure to raise the awareness of the potential users as a whole; etc) more than technical difficulties, are the prime causes of this phenomenon. Through this analysis, the authors emphasise the need to organise a French national spatial data infrastructure, strongly linked with most of the local initiatives developed by the local governments.
The Rank-Size Rule and Fractal Hierarchies of Cities: Mathematical Models and Empirical Analyses
Authors: Chen Yanguang , Zhou Yixing
Published: March 2004

This paper contributes to the demonstration that the self-similar city hierarchies with cascade structure can be modeled with a pair of scaling laws reflecting the recursive process of urban systems. First we transform the Beckmann's model on city hierarchies and generalize Davis's 2 n -rule to an rn-rule on the size – number relationship of cities ( r > 1), and then reduce both Beckmann's and Davis's models to a pair of scaling laws taking the form of exponentials. Then we derive an exact three-parameter Zipf-type model from the scaling laws to revise the commonly used two-parameter Zipf model. By doing so, we reveal the fractal essence of central place hierarchies and link the rank-size rule to central place model logically. The new mathematical frameworks are applied to the class counts of the 1950–70 world city hierarchy presented by Davis in 1978, and several alternative approaches are illustrated to estimate the fractal dimension.
Landscape Visibility Computation: Necessary, but Not Sufficient
Authors: Ervin Stephen , Steinitz Carl
Published: March 2004

In this essay we review the major developments in the history and techniques of landscape visibility analysis, providing a number of examples and identifying a few critical challenges to the community of those who would seek to evaluate visibility—and related characteristics such as visual quality or preference—in landscapes. We argue that visibility per se is a necessary prerequisite, but insufficient in itself, as a basis for the common planning, design, and public policy questions in the context of which many visibility analyses are instigated.
Adaptation from invisible flicker
Authors: Shady Sherif , MacLeod Donald I. A. , Fisher Heidi S.
Published: March 2004

Human ability to resolve temporal variation, or flicker, in the luminance (brightness) or chromaticity (color) of an image declines with increasing frequency and is limited, within the central visual field, to a critical flicker frequency of ≈50 and 25 Hz, respectively. Much remains unknown about the neural filtering that underlies this frequency-dependent attenuation of flicker sensitivity, most notably the number of filtering stages involved and their neural loci. Here we use the process of flicker adaptation, by which an observer's flicker sensitivity is attenuated after prolonged exposure to flickering lights, as a functional landmark. We show that flicker adaptation is more sensitive to high temporal frequencies than is conscious perception and that prolonged exposure to invisible flicker of either luminance or chromaticity, at frequencies above the respective critical flicker frequency, can compromise our visual sensitivity. This suggests that multiple filtering stages, distributed across retinal and cortical loci that straddle the locus for flicker adaptation, are involved in the neural filtering of high temporal frequencies by the human visual system.
Mitochondrial DNA ligase in
Crithidia fasciculata
Authors: Sinha Krishna Murari , Hines Jane C. , Downey Nicholas , Ray Dan S.
Published: March 2004

Kinetoplast DNA (kDNA), the form of mitochondrial DNA in trypanosomatids, consists of thousands of interlocked circular DNAs organized into a compact disk structure. A type II DNA topoisomerase, a DNA polymerase β, and a structure-specific endonuclease have been localized to antipodal sites flanking the kDNA disk along with nascent DNA minicircles. We have cloned a gene (
LIG k
) encoding a mitochondrial DNA ligase in the trypanosomatid
Crithidia fasciculata
, and we show that an epitope-tagged form of the ligase colocalizes with the other replication proteins at the antipodal sites and also at the two faces of the kDNA disk. DNA LIG k becomes adenylated in reactions with ATP, and the adenylate moiety is removed by incubation with pyrophosphate or nicked DNA. The ligase interacts physically with the β polymerase and is proposed to be involved in the repair of gaps in the newly synthesized minicircles. In yeast and mammals, a single gene encodes both nuclear and mitochondrial forms of DNA ligase. The LIG K protein sequence has low similarity to mitochondrial DNA ligases in other eukaryotes and is distinct from the
C. fasciculata
nuclear DNA ligase (LIG I).