bluuebunny/crossref_metadata_2025 huggingface dataset:
Acetylation of insulin receptor substrate-1 is permissive for tyrosine phosphorylation
Authors: Kaiser Christina , James Stephen R
Published: November 2004

Background

Insulin receptor substrate (IRS) proteins are key moderators of insulin action. Their specific regulation determines downstream protein-protein interactions and confers specificity on growth factor signalling. Regulatory mechanisms that have been identified include phosphorylation of IRS proteins on tyrosine and serine residues and ubiquitination of lysine residues. This study investigated other potential molecular mechanisms of IRS-1 regulation.

Results

Using the sos recruitment yeast two-hybrid system we found that IRS-1 and histone deacetylase 2 (HDAC2) interact in the cytoplasmic compartment of yeast cells. The interaction mapped to the C-terminus of IRS-1 and was confirmed through co-immunoprecipitation in vitro of recombinant IRS-1 and HDAC2. HDAC2 bound to IRS-1 in mammalian cells treated with phorbol ester or after prolonged treatment with insulin/IGF-1 and also in the livers of ob/ob mice but not PTP1B knockout mice. Thus, the association occurs under conditions of compromised insulin signalling. We found that IRS-1 is an acetylated protein, of which the acetylation is increased by treatment of cells with Trichostatin A (TSA), an inhibitor of HDAC activity. TSA-induced increases in acetylation of IRS-1 were concomitant with increases in tyrosine phosphorylation in response to insulin. These effects were confirmed using RNA interference against HDAC2, indicating that HDAC2 specifically prevents phosphorylation of IRS-1 by the insulin receptor.

Conclusions

Our results show that IRS-1 is an acetylated protein, a post-translational modification that has not been previously described. Acetylation of IRS-1 is permissive for tyrosine phosphorylation and facilitates insulin-stimulated signal transduction. Specific inhibition of HDAC2 may increase insulin sensitivity in otherwise insulin resistant conditions.
Conflict and HIV: A framework for risk assessment to prevent HIV in conflict-affected settings in Africa
Authors: Mock Nancy B , Duale Sambe , Brown Lisanne F , Mathys Ellen , O'Maonaigh Heather C , Abul-Husn Nina KL , Elliott Sterling
Published: November 2004

In sub-Saharan Africa, HIV/AIDS and violent conflict interact to shape population health and development in dramatic ways. HIV/AIDS can create conditions conducive to conflict. Conflict can affect the epidemiology of HIV/AIDS. Conflict is generally understood to accelerate HIV transmission, but this view is simplistic and disregards complex interrelationships between factors that can inhibit and accelerate the spread of HIV in conflict and post conflict settings, respectively. This paper provides a framework for understanding these factors and discusses their implications for policy formulation and program planning in conflict-affected settings.
Systemic chemotherapy induces microsatellite instability in the peripheral blood mononuclear cells of breast cancer patients
Authors: Fonseca Fernando LA , Sant Ana Aleksandra VL , Bendit Israel , Arias Vitor , Costa Luciano J , Pinhal Aparecida A , del Giglio Auro
Published: November 2004

Introduction

Systemic chemotherapy is an important part of treatment for breast cancer. We conducted the present study to evaluate whether systemic chemotherapy could produce microsatellite instability (MSI) in the peripheral blood mononuclear cell fraction of breast cancer patients.

Methods

We studied 119 sequential blood samples from 30 previously untreated breast cancer patients before, during and after chemotherapy. For comparison, we also evaluated 20 women who had no relevant medical history (control group).

Results

In 27 out of 30 patients we observed MSI in at least one sample, and six patients had loss of heterozygosity. We found a significant correlation between the number of MSI events per sample and chemotherapy with alkylating agents (P < 0.0001). We also observed an inverse correlation between the percentage of cells positive for hMSH2 and the number of MSI events per sample (P = 0.00019) and use of alkylating agents (P = 0.019).

Conclusion

We conclude that systemic chemotherapy may induce MSI and loss of heterozygosity in peripheral blood mononuclear cells from breast cancer patients receiving alkylating agents, possibly mediated by a chemotherapy-induced decrease in the expression of hMSH2. These effects may be related to the generation of secondary leukaemia in some patients, and may also intensify the genetic instability of tumours and increase resistance to treatment.
Seasonal, interannual and short‐term variability of planetary waves in Met Office stratospheric assimilated fields
Authors: Fedulina I. N. , Pogoreltsev A. I. , Vaughan G.
Published: November 2004

Met Office stratospheric assimilated data have been used to study the variability of travelling planetary waves in the upper stratosphere during the last decade (1992–2001). To distinguish the various travelling and quasi‐standing waves, a new space‐time filtering method has been developed. The results of this analysis show that longer‐period planetary waves (10<T<20 days) have significant amplitudes mainly during winter in both hemispheres. Westward‐propagating waves are dominant in the northern hemisphere, but in the southern hemisphere eastward‐ and westward‐propagating waves have comparable amplitudes and sometimes eastward‐propagating waves are dominant. It is suggested that the main forcing of longer‐period travelling waves is an internal variability of the quasi‐stationary planetary waves in the tropo/stratosphere, and that the substantial activity of eastward‐propagating waves in the southern hemisphere is associated with seasonal changes of the general circulation of the middle atmosphere. In the shorter‐period part of the wavelet spectra (T<10 days), westward‐propagating waves are dominant and the observed maxima in amplitude spectra can be identified with the first symmetric normal atmospheric modes, the so‐called 5‐ and 4‐day waves. These waves, present in the stratosphere during most of the year, increase in amplitude during seasonal transitions. Analysis of the behaviour of wavelet amplitudes at different pressure levels shows that these normal‐mode waves propagate upward from the lower atmosphere and their amplitudes increase with altitude. There exists also a substantial long‐period modulation of the 5‐day wave amplitude with quasi‐period of about 30 days. Copyright © 2004 Royal Meteorological Society
Aircraft observations of cloud droplet number concentration: Implications for climate studies
Authors: Gultepe I. , Isaac G. A.
Published: November 2004

Droplet number concentration (Nd) is a major parameter affecting cloud physical processes and cloud optical characteristics. In most climate models, Nd is usually assumed to be constant or a function of the droplet and aerosol number concentration (Na). Three types of cloud systems over Canada, namely Arctic clouds, maritime boundary‐layer clouds, and winter storms, were studied to obtain values of Nd as a function of temperature (T). The probability density function of Nd was also calculated to show the variability of this parameter. The results show that Nd reaches a maximum at about 10 °C (200 cm−3) and then decreases gradually to a minimum (∼1–3 cm−3) at about −35°C. A comparison of relationships between Nd and Na indicates that estimates of Nd from Na can have an uncertainty of about 30–50 cm−3, resulting in up to a 42% uncertainty in cloud short‐wave radiative forcing. This study concludes that the typical fixed values of Nd, which are ∼100 cm−3 and ∼200 cm−3 for maritime and continental clouds, respectively, and the present relationships of Nd to Na, could result in a large uncertainty in the heat and moisture budgets of the earth's atmosphere. It is suggested that the use of relationships between Nd and T can improve climate simulations. © Crown copyright, 2004. Royal Meteorological Society
Impact of the GEM model simplified physics on extratropical singular vectors
Authors: Zadra Ayrton , Buehner Mark , Laroche Stéphane , Mahfouf Jean‐françois
Published: November 2004

A simplified physics package, containing parametrizations of vertical diffusion, subgrid‐scale orographic drag, stratiform precipitation and convective precipitation, was built for the four‐dimensional variational data assimilation system that is being developed for the Canadian Global Environmental Multiscale model. To validate this package and measure its impact on the behaviour of unstable disturbances, a series of singular vector experiments was conducted. In a control experiment with vertical diffusion only, a set of 45 extratropical singular vectors was generated for a northern hemisphere winter case, using the total energy norm and an optimization time interval of 48 hours. Subsequently, the remaining components of the simplified physics were activated one by one and their influence was measured by changes in the energy partition, energy growth and spatial distribution of singular vectors. Cross‐propagation tests were also made, where singular vectors from one experiment were evolved with the tangent‐linear model of another. Results show that the orographic drag reduces the growth of singular vectors while the moist physics enhance the growth and shifts the energy of singular vectors toward smaller scales. Integrations of the nonlinear model with full physics indicate that, for amplitudes typical of analysis increments, the evolution of extratropical singular vectors is well described by the linearized model although growth rates are reduced by nonlinearities. © Crown copyright, 2004. Royal Meteorological Society
Bora‐driven potential vorticity banners over the Adriatic
Authors: Grubišíc Vanda
Published: November 2004

A case study is presented of the secondary potential vorticity (PV) banners over the northern Adriatic that occurred in an early stage of a bora on 7 November 1999 during the Mesoscale Alpine Programme (MAP) Special Observation Period. The dynamics and structure of the lee‐side and cross‐mountain flow past the Dinaric Alps were investigated using data collected in a dual‐aircraft (NCAR Electra and NOAA P‐3)MAP Intensive Observing Period 15 mission over the Adriatic and high‐resolution numerical simulations. The observational study employs flight‐level, dropsonde, and Scanning Aerosol Backscatter Lidar data. The observed flow structure is compared with simulations results of the COAMPS model run at a horizontal resolution of 3 km.

The Dinaric Alps, the north‐west/south‐east oriented coastal mountain range of Croatia, has an irregular ridge line with a number of peaks in the range of 1.5–2 km with several prominent mountain passes. The identified jet and wake structure within the east‐north‐easterly bora over the Adriatic was found to be well correlated with the upwind distribution of mountain passes and peaks. The wake flow structure was found also to be in excellent agreement with the climatological profile of the bora strength along the Croatian coast. The attendant secondary PV banners separating individual jets and wakes, diagnosed by computing PV from the flight‐level data, were found to have a characteristic horizontal scale of 10–25 km, and a maximum amplitude of up to ∼6 pvu within the boundary layer. Over the open sea, the thickness of the boundary layer, within which the east‐north‐easterly bora also achieved its maximum strength, was approximately 1 km.

Detailed comparison with the numerical model results shows that, at the horizontal resolution of 3 km, the COAMPS model reproduces well the overall flow structure. The COAMPS‐simulated PV field was found to be in good agreement with the PV derived from observations. The differences in substructure between simulated and experimentally derived PV profiles derive from minor differences between modelled and observed velocity and potential temperature profiles, which are subsequently accentuated by computing differentiated quantities such as vorticity and potential temperature gradients. The high predictability and steadiness of the PV banners, and a good correlation with the geometry of the upwind topography, support the orographic generation mechanism of PV with dissipation in hydraulic jumps and gravity‐wave breaking regions as the likely main source of PV. Copyright © 2004 Royal Meteorological Society
Empirical evaluation of an extended similarity theory for the stably stratified atmospheric surface layer
Authors: Sodemann Harald , Foken Thomas
Published: November 2004

The theory of the atmospheric stable boundary layer (SBL) has recently been extended by a distinction between nocturnal and long‐lived SBLs. The latter SBL type, which includes influences from the free atmosphere on fluxes in the surface layer, requires a modification of the traditional Monin–Obukhov similarity theory. In the present study, the applicability of this extended theory for long‐lived SBLs is evaluated and the required coefficients are estimated using data from Antarctica.

Changes in wind and temperature gradients due to different weather conditions are shown to exert a strong influence on the estimation of the new coefficients CuN and CθN. Using the wind gradient as classification criterion, the momentum flux coefficient CuN is estimated to range between 0.51±0.03 and 2.26±0.08. Using the temperature gradient as classification criterion, the heat flux coefficient CθN is estimated to range between 0.022±0.002 and 0.040±0.001.

At present, the proposed new scaling theory is still in a preliminary stage. Possible future improvements should take into account factors influencing the wind and temperature gradients, such as weather conditions. An artificial background correlation strongly imprints upon the parameter estimation, suggesting that both the methodology for estimating the new coefficients CuN and CθN and the choice of the nondimensional variables for this extended scaling theory may require some revision. Copyright © 2004 Royal Meteorological Society
Interannual variability of stratospheric trace gases: The role of extratropical wave driving
Authors: Ma J. , Waugh D. W. , Douglass A. R. , Kawa S. R. , Newman P. A. , Pawson S. , Stolarski R. , Lin S. J.
Published: November 2004

The interannual variability of methane and ozone from a 35‐year middle atmosphere climate model simulation with no interannual variations in external forcing or chemistry is examined. The internal dynamics in the model produces large tracer interannual variability, particularly in polar regions. During winter and spring the interannual standard deviation in the polar lower‐middle stratosphere is about 30% of the climatological mean for methane and 15% for ozone. Global‐scale, coherent interannual variations in temperature, residual circulation, and tracers are correlated with variability in the extratropical wave forcing. Statistically significant positive correlations between wave driving and polar tracer tendencies, including column ozone, occur from autumn to spring in both hemispheres. These positive correlations imply that interannual variations in polar tracers are dominated by variations in the horizontal eddy transport and not by variations in residual mean descent rates. Copyright © 2004 Royal Meteorological Society
Angiogenic response induced by acellular aortic matrix in vivo
Authors: Conconi Maria Teresa , Nico Beatrice , Mangieri Domenica , Tommasini Mara , di Liddo Rosa , Parnigotto Pier Paolo , Nussdorfer Gastone G. , Ribatti Domenico
Published: November 2004

In this study, we investigated the angiogenic response induced by acellular aortic matrices implanted in vivo onto the chick embryo chorioallantoic membrane (CAM), a useful model for such investigation. Results showed that acellular matrices were able to induce a strong angiogenic response comparable to that of fibroblast growth factor 2 (FGF‐2), a well‐known angiogenic cytokine. The angiogenic response was further increased when exogenous FGF‐2 or transforming growth factor beta 1 (TGF‐β1) were added to the matrices and inhibited by the addition of an anti‐FGF‐2 or anti‐TGF‐β1 antibodies. The response may be considered dependent on a direct angiogenic effect exerted by the matrices and in part also by the presence of FGF‐2 and TGF‐β1 in the acellular matrices. © 2004 Wiley‐Liss, Inc.
Novel photocurable multifunctional acrylate monomers containing perfluorinated aromatic units and their copolymers for photonic applications
Authors: Song Bok Ju , Park Jin Kyu , Kim Hwan Kyu
Published: November 2004

We designed and synthesized novel UV‐curable multifunctional acrylate monomers with perfluorinated aromatic units and their copolymers. The UV‐curable multifunctional acrylate monomers with perfluorinated aromatic units were synthesized as follows. Perfluorinated aromatic methylmethane derivatives were prepared through the reaction of pentaerythritol with hexafluorobenzene and decafluorobiphenyl in the presence of sodium hydride. They were sequentially substituted with 2,2,3,3,4,4,5,5‐octafluoro‐6‐(tetrahydropyran‐2‐yloxy)‐hexan‐1‐ol, and this yielded hydroxy‐functional compounds after tetrahydropyran deprotection. Finally, the reaction of the resultant hydroxy compounds with acryloyl chloride generated the perfluorinated multifunctional acrylate monomers in high yields of greater than 85%. The novel photocrosslinked and perfluorinated copolyacrylates, obtained after the UV and thermal curing of these monomers, satisfied the material requirements for photonic devices. Most of these copolymers were thermally stable over 370 °C, and their glass‐transition temperatures were not detected because of their highly crosslinked nature. The refractive indices of the copolymers ranged from 1.410 to 1.441. The refractive indices of the photocrosslinked and perfluorinated copolyacrylates were easily tuned by the variation of the copolymer composition. Some of these copolymers exhibited a birefringence of less than 0.0003. This was much lower than the birefringence of fluorinated polyacrylate‐based materials. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 6375–6383, 2004
The diet of sperm whales (Physeter macrocephalus) in southern Australian waters
Authors: Evans Karen , Hindell Mark A.
Published: November 2004

Stomach contents were collected from 36 sperm whales (Physeter macrocephalus) involved in two mass stranding events during February 1998 along the west coastline of Tasmania, Australia. Contents were dominated by oceanic cephalopods, with a total of 101 883 cephalopod beaks representing 48 species from 14 families of Teuthids, two species from two families of Octopods, and a single Vampyromorph species identified. Species diversity was higher in these animals than other sperm whales studied in the southern hemisphere, with samples containing an average of (±s.d.) 28.4 ± 11.1 species per sample. Diet samples were dominated by subtropical and muscular cephalopod species. Members of the family Histioteuthidae were the most important numerically, and were also important in terms of estimated reconstituted mass, although members of the Onychoteuthidae were the most dominant species in samples in terms of estimated reconstituted mass. Other families numerically important to species composition included the cranchiid, lepidoteuthid, onychoteuthid, and pholidoteuthid families, while the architeuthid, pholidoteuthid, and ommastrephid families were also important in terms of reconstituted mass. Cephalopod species composition varied with stranding site and with sex, but not with age. However, differences did not represent systemic variation with groups marked by high individual variability. Lower rostral lengths of all cephalopod species ranged from 1.3 to 40.7 mm. Calculated dorsal mantle lengths from all species ranged from 10.7 to 2640.7 mm (mean ± s.d. = 233.7 ± 215.7 mm) and estimated wet weights of cephalopod prey ranged from 2.7 to 110 233.1 g (mean ± s.d. = 828.3 ± 3073.6 g). While there were differences in the size of some cephalopod species between stranding sites and with age, this was marked by high individual variability. Differences in diet composition and prey size between sperm whales reflect individual variability in foraging success and perhaps also foraging groups related to the social structure of this species.
Symptoms and referral of women with epithelial ovarian tumors
Authors: Paulsen T. , Kærn J. , Kjærheim K. , Tropé C. , Tretli S.
Published: November 2004

Objective: To study referral to hospital units and the clinical characteristics of women with epithelial ovarian tumors in a prospective, population‐based study. Methods: Clinical information on all women diagnosed with epithelial invasive (n=486) and borderline ovarian tumors (n=137) in Norway during 2002 was derived from notifications to the Cancer Registry of Norway and medical, surgical and histopathological records. Results: Sixty‐one percent of women with invasive ovarian tumors were initially referred to gynecology units. The 38% of women referred to surgical and medical units were more likely to have symptoms as ‘bowel irregularity’, ‘pain outside the abdominal cavity’, ‘persisting fatigue’ and ‘respiratory difficulties’. These women were older, had lower performance status and had a delay in treatment of 20 and 24 days respectively compared to 11 at gynecology units. Conclusion: Greater awareness of the symptoms of ovarian cancer might lead to earlier diagnosis and treatment and thus possibly improve survival.
ESTminer: a suite of programs for gene and allele identification
Authors: Nelson Rex T. , Grant David , Shoemaker Randy C.
Published: November 2004

Summary: ESTminer is a collection of programs that use expressed sequence tag (EST) data from inbred genomes to identify unique genes within gene families. The algorithm utilizes Cap3 to perform an initial clustering of related EST sequences to produce a consensus sequence of a gene family. These consensus sequences are then used to collect all ESTs in the original EST library that are related using BLAST. A redundancy based criterion is applied to each EST to identify reliable unique gene-sequences. Using a highly inbred genome as a source of ESTs eliminates the necessity of computing covariance on each polymorphism to identify alleles of the same gene, thus making this algorithm more streamlined than other alternatives which must computationally attempt to distinguish genes from alleles.

Availability: The programs were written in PERL and are freely available at http://www.soybase.org/publication_data/Nelson/ESTminer/ESTminer.html

Contact:  nelsonrt@iastate.edu

Supplementary information: Figures and dataset can be obtained from: http://www.soybase.org/publication_data/Nelson/ESTminer/ESTminer.html
In silicogene function prediction using ontology-based pattern identification
Authors: Zhou Yingyao , Young Jason A. , Santrosyan Andrey , Chen Kaisheng , Yan S. Frank , Winzeler Elizabeth A.
Published: November 2004

Motivation: With the emergence of genome-wide expression profiling data sets, the guilt by association (GBA) principle has been a cornerstone for deriving gene functional interpretations in silico. Given the limited success of traditional methods for producing clusters of genes with great amounts of functional similarity, new data-mining algorithms are required to fully exploit the potential of high-throughput genomic approaches.

Results: Ontology-based pattern identification (OPI) is a novel data-mining algorithm that systematically identifies expression patterns that best represent existing knowledge of gene function. Instead of relying on a universal threshold of expression similarity to define functionally related groups of genes, OPI finds the optimal analysis settings that yield gene expression patterns and gene lists that best predict gene function using the principle of GBA. We applied OPI to a publicly available gene expression data set on the life cycle of the malarial parasite Plasmodium falciparum and systematically annotated genes for 320 functional categories based on current Gene Ontology annotations. An ontology-based hierarchical tree of the 320 categories provided a systems-wide biological view of this important malarial parasite.

Availability: A web accessible P. falciparum e-annotation database containing the results of this study can be accessed online at http://carrier.gnf.org/publications/OPI

Contact:  zhou@gnf.org
CGH-Explorer: a program for analysis of array-CGH data
Authors: Lingjærde Ole Christian , Baumbusch Lars O. , Liestøl Knut , Glad Ingrid K. , Børresen-Dale Anne-Lise
Published: November 2004

Summary: CGH-Explorer is a program for visualization and statistical analysis of microarray-based comparative genomic hybridization (array-CGH) data. The program has preprocessing facilities, tools for graphical exploration of individual arrays or groups of arrays, and tools for statistical identification of regions of amplification and deletion.

Availability: The program is available as Java class files that runs on any platform with the Java 2 runtime environment (J2SE JRE) installed, and as a Windows executable. Java source files are also available. See http://www.ifi.uio.no/bioinf/Papers/CGH/

Contact:  ole@ifi.uio.no
The MIPS mammalian protein–protein interaction database
Authors: Pagel Philipp , Kovac Stefan , Oesterheld Matthias , Brauner Barbara , Dunger-Kaltenbach Irmtraud , Frishman Goar , Montrone Corinna , Mark Pekka , Stümpflen Volker , Mewes Hans-Werner , Ruepp Andreas , Frishman Dmitrij
Published: November 2004

Summary: The MIPS mammalian protein–protein interaction database (MPPI) is a new resource of high-quality experimental protein interaction data in mammals. The content is based on published experimental evidence that has been processed by human expert curators. We provide the full dataset for download and a flexible and powerful web interface for users with various requirements.

Availability: The MPPI database is located at http://mips.gsf.de/proj/ppi/

Contact:  d.frishman@wzw.tum.de
Accurate identification of alternatively spliced exons using support vector machine
Authors: Dror Gideon , Sorek Rotem , Shamir Ron
Published: November 2004

Motivation: Alternative splicing is a major component of the regulatory action on mammalian transcriptomes. It is estimated that over half of all human genes have more than one splice variant. Previous studies have shown that alternatively spliced exons possess several features that distinguish them from constitutively spliced ones. Recently, we have demonstrated that such features can be used to distinguish alternative from constitutive exons. In the current study, we used advanced machine learning methods to generate robust classifier of alternative exons.

Results: We extracted several hundred local sequence features of constitutive as well as alternative exons. Using feature selection methods we find seven attributes that are dominant for the task of classification. Several less informative features help to slightly increase the performance of the classifier. The classifier achieves a true positive rate of 50% for a false positive rate of 0.5%. This result enables one to reliably identify alternatively spliced exons in exon databases that are believed to be dominated by constitutive exons.

Availability: Upon request from the authors.

Contact:  gideon@mta.ac.il
AUG codons at the beginning of protein coding sequences are frequent in eukaryotic mRNAs with a suboptimal start codon context
Authors: Kochetov Alex V.
Published: November 2004

Motivation: The translation start site plays an important role in the control of translation efficiency of eukaryotic mRNAs. However, mRNAs with a suboptimal context of start AUG codon are relatively abundant. It is likely that at least some mRNAs with suboptimal start codon context contain the other signals providing additional information for efficient AUG recognition.

Results: Frequency of AUG codons at the beginning of the coding part of eukaryotic mRNAs was analyzed in relation to the context of translation start codon. It was found that the observed downstream AUG content in the mRNAs with optimal start codon context was close to the expected value, whereas it was significantly higher in the mRNAs with a suboptimal context. It is likely that downstream AUG codons can often be utilized as additional start sites to increase translation rate of mRNAs with a suboptimal context of the annotated start codon and many eukaryotic proteins can be characterized by some N-end heterogeneity.

Contact:  ak@bionet.nsc.ru
ISYMOD: a knowledge warehouse for the identification, assembly and analysis of bacterial integrated systems
Authors: Chabalier Julie , Capponi Cécile , Quentin Yves , Fichant Gwennaele
Published: November 2004

Motivation: Complex biological functions emerge from interactions between proteins in stable supra-molecular assemblies and/or through transitory contacts. Most of the time protein partners of the assemblies are composed of one or several domains which exhibit different biochemical functions. Thus the study of cellular process requires the identification of different functional units and their integration in an interaction network; such complexes are referred to as integrated systems. In order to exploit with optimum efficiency the increased release of data, automated bioinformatics strategies are needed to identify, reconstruct and model such systems. For that purpose, we have developed a knowledge warehouse dedicated to the representation and acquisition of bacterial integrated systems involved in the exchange of the bacterial cell with its environment.

Results: ISYMOD is a knowledge warehouse that consistently integrates in the same environment the data and the methods used for their acquisition. This is achieved through the construction of (1) a domain knowledge base (DKB) devoted to the storage of the knowledge about the systems, their functional specificities, their partners and how they are related and (2) a methodological knowledge base (MKB) which depicts the task layout used to identify and reconstruct functional integrated systems. Instantiation of the DKB is obtained by solving the tasks of the MKB, whereas some tasks need instances of the DKB to be solved. AROM, an object-based knowledge representation system, has been used to design the DKB, and its task manager, AROMTasks, for developing the MKB. In this study two integrated systems, ABC transporters and two component systems, both involved in adaptation processes of a bacterial cell to its biotope, have been used to evaluate the feasibility of the approach.

Contact:  julie.chabalier@ibsm.cnrs-mrs.fr
Differences in time-dependent hypoxic phrenic responses among inbred rat strains
Authors: Golder Francis J. , Zabka Andrea G. , Bavis Ryan W. , Baker-Herman Tracy , Fuller David D. , Mitchell Gordon S.
Published: November 2004

Hypoxic ventilatory responses differ between rodent strains, suggesting a genetic contribution to interindividual variability. However, hypoxic ventilatory responses consist of multiple time-dependent mechanisms that can be observed in different respiratory motor outputs. We hypothesized that strain differences would exist in discrete time-dependent mechanisms of the hypoxic response and, furthermore, that there may be differences between hypoglossal and phrenic nerve responses to hypoxia. Hypoglossal and phrenic nerve responses were assessed during and after a 5-min hypoxic episode in anesthetized, vagotomized, and ventilated rats from four inbred strains: Brown Norway (BN), Fischer 344 (FS), Lewis (LW), and Piebald-viral-Glaxo (PVG). During baseline, burst frequency was higher in PVG than LW rats ( P < 0.05), phrenic burst amplitude was higher in PVG vs. other strains ( P < 0.05), and hypoglossal burst amplitude was higher in PVG and BN vs. FS and LW ( P < 0.05). During hypoxia, burst frequency did not change in BN or LW rats, but it increased in PVG and FS rats. The phrenic amplitude response was smallest in PVG vs. other strains ( P < 0.05), and the hypoglossal response was similar among strains. Short-term potentiation posthypoxia was slowest in FS and fastest in LW rats ( P < 0.05). Posthypoxia frequency decline was absent in PVG, but it was observed in all other strains. Augmented breaths were observed during hypoxia in FS rats only. Thus genetic differences exist in the time domains of the hypoxic response, and these are differentially expressed in hypoglossal and phrenic nerves. Furthermore, genetic diversity observed in hypoxic ventilatory responses in unanesthetized rats may arise from multiple neural mechanisms.
Afferent mechanisms underlying stimulation modality-related modulation of acupuncture-related cardiovascular responses
Authors: Zhou Wei , Fu Liang-Wu , Tjen-A-Looi Stephanie C. , Li Peng , Longhurst John C.
Published: November 2004

Despite the use of acupuncture to treat a number of heart diseases, little is known about the mechanisms that underlie its actions. Therefore, we examined the influence of acupuncture on sympathoexcitatory cardiovascular responses to gastric distension in anesthetized Sprague-Dawley rats. Thirty minutes of low-current, low-frequency, (0.3–0.5 mA, 2 Hz) electroacupuncture (EA), at P 5–6, S 36–37, and H 6–7 overlying the median, deep peroneal, and ulnar nerves significantly decreased reflex pressor responses by 40, 39, and 44%, respectively. In contrast, sham acupuncture involving needle insertion without stimulation at P 5–6 or 30 min of EA at LI 6–7 acupoints overlying the superficial radial nerve did not attenuate the reflex. Similarly, EA at P 5–6 using 40- or 100-Hz stimulation frequencies did not inhibit the reflex. Compared with EA at P 5–6, EA at two sets of acupoints, including P 5–6 and S 36–37, did not lead to larger inhibition of the reflex. Two minutes of manual acupuncture (MA; 2 Hz) at P 5–6 every 10 min for 30 min inhibited the reflex cardiovascular pressor response by 33%, a value not significantly different from 2-Hz EA at P 5–6. Single-unit afferent activity was not different between electrical stimulation (ES) and manual stimulation. However, 2-Hz ES activated more somatic afferents than 10- or 20-Hz ES. These data suggest that, although the location of acupoint stimulation and the frequency of stimulation determine the extent of influence of EA, there is little difference between low-frequency EA and MA at P 5–6. Furthermore, simultaneous stimulation using two acupoints that independently exert strong effects did not lead to an additive or a facilitative interaction. The similarity of the responses to EA and MA and the lack of cardiovascular response to high-frequency EA appear to be largely a function of somatic afferent responses.
Uninterrupted Dialogue: Between Two Infinities, the Poem
Authors: Derrida Jacques
Published: November 2004

With the attempt to express my feeling of admiration for Hans-Georg Gadamer an ageless melancholy mingles. This melancholy begins as of the friends' lifetime. A

cogito

of the farewell signs the breathing of their dialogues. One of the two will have been doomed, from the beginning, to carry alone both the dialogue that he must pursue beyond the interruption, and the memory of the first interruption. To carry the world of the other, to carry both the other and his world, the other and the world that have disappeared, in a world without world. That shall be one of the ways to let resound within ourselves the line of poetry by Paul Celan, "

Die Welt ist fort, ich muss dich tragen

."
Gadamer, Aesthetic Modernism, and the Rehabilitation of Allegory: The Relevance of Paul Klee
Authors: Watson Stephen
Published: November 2004

Paul Klee's art found broad impact upon philosophers of varying commitments, including Hans-Georg Gadamer. Moreover, Klee himself was not only one of the most important artists of aesthetic modernism but one of its leading theoreticians, and much in his work, as in Gadamer's, originated in post-Kantian literary theory's explications of symbol and allegory. Indeed at one point in

Truth and Method

, Gadamer associates his project for a general "theory of hermeneutic experience" not only with Goethe's metaphysical account of the symbolic but equally with a "rehabilitation" of allegory. In this paper, I examine this position and Gadamer's own use of it in his analysis of Klee's work, contrasting it with that of Walter Benjamin's account of allegory, equally indebted to Goethe and this archive. Finally, I contrast the resulting interpretations of Klee, discussing the implications that evolve for understanding both Gadamer and Benjamin— but equally for understanding Klee's work and, provisionally, the work of art, thus construed, for philosophy.
On Hölderlin's "Andenken": Heidegger, Gadamer and Henrich—a Decision?
Authors: Freydberg Bernard
Published: November 2004

Often, respectable scholars attack the soundness of Heidegger's "violent" interpretations of Hölderlin (and others). In this case, Dieter Henrich offers a particularly harsh assessment of Heidegger's interpretation of "

Andenken

." Hans-Georg Gadamer, student of Heidegger and teacher of Henrich, attempts to bring harmony where none seems possible. A study of the three interpretations indicates that scholarship alone is sufficient to reach a decision on the strength of the interpretations.
The p53-dependent apoptotic pathway of breast cancer cells (BC-M1) induced by the bis-type bioreductive compound aziridinylnaphthoquinone
Authors: Yang Yu-Ping , Kuo Hsien-Shou , Tsai Hsin-Da , Peng Yi-Chen , Lin Yuh-Ling
Published: November 2004

Introduction

Several aziridinylbenzoquinone drugs have undergone clinical trials as potential antitumor drugs. These bioreductive compounds are designed to kill cells preferentially within the hypoxia tumor microenvironment. The bioreductive compound of bis-type naphthoquinone synthesized in our laboratory, 2-aziridin-1-yl-3-[(2-{2-[(3-aziridin-1-yl-1,4-dioxo-1,4-dihydronaphthalen-2-yl)thio]ethoxy}ethyl)thio]naphthoquinone (AZ-1), had the most potent death effect on the breast cancer cells BC-M1 in our previous screening. In the present study, we determined that the mechanism of the death effect of BC-M1 cells induced by AZ-1 was mediated by the apoptosis pathway.

Methods

We evaluated the cytotoxicity of AZ-1 and the anti-breast cancer drugs tamoxifen and paclitaxel to BC-M1 cells and MCF-7 cells by the MTT assay and measured the apoptosis phenomena by Hoechst 33258 staining for apoptotic bodies. We also quantified the sub-G1 peak area and the ratio of the CH2/CH3 peak area of the cell membrane in BC-M1 cells by flow cytometry and 1H-NMR spectra, respectively.

The apoptosis-related protein expressions, including p53, p21, the RNA-relating protein T-cell restricted intracellular antigen-related protein, cyclin-dependent kinase 2 (cell cycle regulating kinase) and pro-caspase 3, were detected by western blot, and the caspase-3 enzyme activity was also quantified by an assay kit.

Results

AZ-1 induced two of the breast cancer cell lines, with IC50 = 0.51 μM in BC-M1 cells and with IC50= 0.57 μM in MCF-7 cells, and showed less cytotoxicity to normal fibroblast cells (skin fibroblasts) with IC50= 5.6 μM. There was a 10-fold difference between two breast cancer cell lines and normal fibroblasts. Of the two anti-breast cancer drugs, tamoxifen showed IC50= 0.12 μM to BC-M1 cells and paclitaxel had much less sensitivity than AZ-1. The expression of p53 protein increased from 0.5 to 1.0 μM AZ-1 and decreased at 2.0 μM AZ-1. The p21 protein increased from 0.5 μM AZ-1, with the highest at 2 μM AZ-1. Regarding the AZ-1 compound-induced BC-M1 cells mediating the apoptosis pathway, the apoptotic body formation, the sub-G1 peak area, the ratio of CH2/CH3 of phospholipids in the cell membrane and the enzyme activity of caspase-3 were all in direct proportion with the dose-dependent increase of the concentration of AZ-1. The death effect-related proteins, including T-cell restricted intracellular antigen-related protein, cyclin-dependent kinase 2, and pro-caspase-3, all dose-dependently decreased with AZ-1 concentration.

Conclusions

The AZ-1-induced cell death of BC-M1 cells mediating the apoptosis pathway might be associated with p53 protein expression, and AZ-1 could have the chance to be a candidate drug for anti-breast cancer following more experimental evidence, such as animal models.
In silico evaluation of two mass spectrometry-based approaches for the identification of novel human leukocyte cell-surface proteins
Authors: Nicholson I C , Ayhan M , Hoogenraad N J , Zola H
Published: November 2004

The identification and quantitation of cell-surface proteins expressed by leukocytes currently use the wide availability of monoclonal antibodies (mAb) in immunohistochemical and flow cytometric assays. Presently, ∼400 such proteins have been characterized; however, analysis of the completed human genome sequence indicates that it may contain several thousand as-yet unidentified molecules, which may be expressed on the leukocyte cell surface. Recent advances in protein isolation and analysis using mass spectrometry illustrate that it is now feasible to identify the protein composition of a complex sample such as a plasma membrane extract. Such an approach may be useful for the identification of the cell-surface proteins that have not been identified using mAb techniques. Here, we detail the results of an in silico evaluation of the peptides isolated using two methods used to label plasma membrane proteins to determine whether these methods are suitable for the identification of known leukocyte cell-surface proteins by mass spectrometry. The labeling of cell-surface proteins before isolation and characterization is a valuable means of differentiating between plasma membrane and internal membrane proteins The results indicate that although the majority of cell-surface proteins can be identified using either of the approaches, others known to be important diagnostically and/or therapeutically would not be identified using either approach. The implication of this for the use of these techniques in the discovery of new leukocyte cell-surface proteins is discussed.
Flow structure and turbulence characteristics of the daytime atmosphere in a steep and narrow Alpine valley
Authors: Weigel Andreas P. , Rotach Mathias W.
Published: November 2004

Aircraft measurements, radio soundings and sonic data—obtained during the MAP‐Riviera field campaign in autumn 1999 in southern Switzerland—are used to investigate the flow structure, temperature profiles and turbulence characteristics of the atmosphere in a steep and narrow Alpine valley under convective conditions. On all predominantly sunny days of the intensive observation periods, a pronounced valley‐wind system develops. In the southern half of the valley, the daily up‐valley winds have a jet‐like structure and are shifted towards the eastern slope. These up‐valley winds advect potentially colder air, a process which appears to be balanced by vertical warm air advection from above. The profiles of potential temperature show that, with the onset of up‐valley winds, the mixed layer consistently stops growing or—on days with very strong up‐valley winds—even stabilizes almost throughout the entire valley atmosphere. This is probably due to a pronounced secondary circulation in the southern part of the valley, which induces advection of warm air from above. The secondary circulation appears to be a consequence of sharp curvature in the along‐valley topography.

Turbulence variables are calculated from flight legs in the along‐valley direction. Turbulent kinetic energy (TKE) scales surprisingly well (i) if a TKE criterion (TKE >0.5 m2s−2) is employed as a definition of the boundary layer height and (ii) if the ‘surface fluxes’—which exhibit a substantial spatial variability—from the slope sites are used rather than those from directly beneath the profile considered. Significant site‐to‐site differences in incoming solar radiation seem to be the reason for this characteristic behaviour. Profiles of momentum flux—scaled with a surface friction velocity—reveal more scatter than the TKE profiles, but still show a consistent behaviour. A surprisingly strong shear in the cross‐valley direction can be observed and is probably a result of the secondary circulation. Copyright © 2004 Royal Meteorological Society
Assimilating data from a simulated global constellation of stratospheric balloons
Authors: Keil M.
Published: November 2004

In order to evaluate the effect of assimilating data from proposed stratospheric balloon networks, a variation of the standard Observation Systems Simulation Experiment (OSSE), called a Partial (or Poor‐man's) OSSE, was developed. This technique was used to assimilate five different simulated balloon constellations. Increasing the constellation density increased the analysis and forecast accuracy, predominately near the balloon flight level (30 hPa) in the tropics and throughout the depth of the stratosphere at higher latitudes. However, the potential impact may be greater, since the saturation point, where assimilating extra observations produces no additional analysis benefit, was not reached for the range of constellation densities tested. Unrealistic analysis increments were produced during a sudden stratospheric warming period. This weakness arises from the use of climatological background‐error statistics in assimilation schemes. Overall, the results are very encouraging and suggest that proposals to add a permanent constellation of stratospheric balloons to the global observing system are realistic and beneficial to the scientific community. © Crown copyright, 2004. Royal Meteorological Society
Remote ENSO influence on Mediterranean sky conditions during late summer and autumn: Evidence for a slowly evolving atmospheric bridge
Authors: Park Sungsu
Published: November 2004

Several previous studies have reported significant El Niño Southern Oscillation (ENSO) signals in precipitation fields over the Mediterranean region during boreal summer and autumn. However, responsible physical mechanisms are unclear. In this study, we report significant simultaneous ENSO signals in ship‐observed visible‐sky conditions over the north‐eastern Atlantic and western Mediterranean Sea (WM) during late summer and autumn in 1956–95, consistent with previous studies of precipitation. This remote correlation was stronger in 1956–75 than in 1976–95 and 30‐year moving average correlations were stronger throughout the 1956–95 epoch than at any other time over the last 120 years. Previous epochs of relatively weak positive and negative correlation occurred between 1890 and 1920 and between 1920 and 1950, respectively.

Analysis of atmospheric flows during 1956–95 indicates that the strong ENSO–WM correlation in the August–October season arises from a previously unreported quasi‐stationary Rossby wave propagating eastwards from the western equatorial Pacific. This component weakens between 1956–75 and 1976–95, consistent with the reduced correlation of the ENSO–WM sky conditions between the same periods. In order to fully understand the observed long‐term variations of remote ENSO correlation over the WM, further studies are required, including the potential roles of the Pacific Decadal Oscillation, Sahelian rainfall and Atlantic sea surface temperature. Copyright © 2004 Royal Meteorological Society