bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cell++—simulating biochemical pathways
Authors: Sanford Chris , Yip Matthew L.K. , White Carl , Parkinson John 
Published: October 2006

Abstract
Motivation: With the generation of a wealth of information, detailing cellular components, their functions and interactions, there is a growing need for the development of new computational tools capable of interpreting these data within spatial and dynamic contexts. Here, we introduce Cell++, a novel stochastic simulation environment with the capacity to study a wide variety of biochemical processes within a spatial context.
Results: Focusing on three case studies, we highlight the potential impact of spatial organization in the evolution and engineering of signaling and metabolic pathways. In addition to altering signaling and metabolic efficiency, simulations also demonstrated features consistent with the phenomenon of metabolic channeling.
Availability: Cell++ is licensed under the GNU general public license (GPL) and has been successfully implemented under Linux and IRIX operating systems. Source code together with a simple tutorial is available at .
Contact: jparkin@sickkids.ca
Supplementary information: Supplementary data for this paper are available at Bioinformatics online.
Supporting the SBML layout extension
Authors: Deckard Anastasia , Bergmann Frank T. , Sauro Herbert M. 
Published: October 2006

Abstract
Motivation: Researchers studying large or complex biochemical networks would benefit from the ability to automatically create lucid visualizations and store them in a portable and widely accepted format.
Summary: Two modules, SBMLSupportLayout and SBWAutoLayout, support reading, creating, manipulating and writing layout information for biochemical models. SBMLSupportLayout can read, update, add and render model layout information. SBWAutoLayout can automatically layout models, graphically manipulate model layout and generate layout information for models without layout information.
Availability: SBMLSupportLayout and SBWAutoLayout are distributed with the Systems Biology Workbench (SBW), which can be downloaded from . Additionally, their visualization and layout capabilities are available online at . Both modules run on Win32, Linux and the Mac OS X version is forthcoming.
Contact: fbergman@kgi.edu
Parameter estimation using Simulated Annealing for S-system models of biochemical networks
Authors: Gonzalez Orland R. , Küper Christoph , Jung Kirsten , Naval Prospero C. , Mendoza Eduardo 
Published: October 2006

AbstractMotivation: High-throughput technologies now allow the acquisition of biological data, such as comprehensive biochemical time-courses at unprecedented rates. These temporal profiles carry topological and kinetic information regarding the biochemical network from which they were drawn. Retrieving this information will require systematic application of both experimental and computational methods.Results: S-systems are non-linear mathematical approximative models based on the power-law formalism. They provide a general framework for the simulation of integrated biological systems exhibiting complex dynamics, such as genetic circuits, signal transduction and metabolic networks. We describe how the heuristic optimization technique simulated annealing (SA) can be effectively used for estimating the parameters of S-systems from time-course biochemical data. We demonstrate our methods using three artificial networks designed to simulate different network topologies and behavior. We then end with an application to a real biochemical network by creating a working model for the cadBA system in Escherichia coli.Availability: The source code written in C++ is available at . All the necessary programs including the required compiler are described in a document archived with the source code.Contact: gonzalez@bio.ifi.lmu.deSupplementary information: Supplementary material is available at Bioinformatics online.
PHARMACOGENETICS, RACE AND GLOBAL INJUSTICE1
Authors: HOLM SØREN 
Published: October 2006

ABSTRACTThis paper discusses the link between pharmacogenetics and race, and the global justice issues that the introduction of pharmacogenetics in pharmaceutical research and clinical practice will raise. First, it briefly outlines the likely impact of pharmacogenetics on pharmaceutical research and clinical practice within the next five to ten years and then explores the link between pharmacogenetic traits and ‘race’. It is shown that any link between apparent race and pharmacogenetics is problematic and that race cannot be used as a proxy for pharmacogenetic knowledge. The final section considers the implications of the development of pharmacogenetics for health care systems in low‐ and middle‐income countries.
Right Ventricular Outflow Tract Pacing: Radiographic and Electrocardiographic Correlates of Lead Position
Authors: McGAVIGAN ANDREW D. , ROBERTS‐THOMSON KURT C. , HILLOCK RICHARD J. , STEVENSON IRENE H. , MOND HARRY G. 
Published: October 2006

Objective:
To characterize the pacing site in an unselected series of patients undergoing right ventricular outflow tract (RVOT) lead placement and investigate the role of the electrocardiogram (ECG) in predicting implantation.
Background:
Right ventricular apical pacing is associated with long‐term adverse effects on left ventricular function, fuelling interest in alternative pacing sites, especially the RVOT. Previous studies have been conflicting, possibly due to poor definition of pacing site within the RVOT.
Methods:
In 150 patients undergoing pacemaker implantation, implanters were asked to place the lead in the RVOT. Radiographs were performed in the antero‐posterior (AP) and 40° right and left anterior‐oblique projections post procedure. Fifty‐six had left lateral radiographs. Lead position was categorized using AP/RAO (right anterior oblique) to confirm RVOT placement and left anterior oblique to distinguish free wall from septum. A 12‐lead ECG was performed during ventricular pacing.
Results:
Leads were below the RVOT in 18. Of the remaining 132, the majority (94%) were in the inferior/low RVOT. Eighty‐one out of 132 were septal and 51 free wall. Septal sites were associated with shorter QRS duration (134 ms vs 143 ms, P < 0.02). Free wall sites displayed more frequent notching of the inferior leads (P < 0.01). A negative deflection in lead I provided a positive predictive value of 90% for septal sites. In those with lateral radiographs, a posteriorly projected lead was 100% specific for septal placement.
Conclusions:
This study demonstrates the heterogeneity of lead placement within the RVOT. Septal and free wall sites display characteristic ECG patterns which may be used to aid placement. The left lateral radiograph is useful in confirming a true septal location.
Ventricular Repolarization and Heart Rate Responses During Cardiovascular Autonomic Function Testing in LQT1 Subtype of Long QT Syndrome
Authors: HAAPALAHTI PETRI , VIITASALO MATTI , PERHONEN MERJA , MÄKIJÄRVI MARKKU , VÄÄNÄNEN HEIKKI , OIKARINEN LASSE , HEKKALA ANNA‐MARI , SALORINNE YRJÖ , SWAN HEIKKI , TOIVONEN LAURI 
Published: October 2006

Background: In the most prevalent LQT1 form of inherited long QT syndrome symptoms often occur during abrupt physical or emotional stress. Sympathetic stimulation aggravates repolarization abnormalities in experimental LQT1 models. We hypothesized that autonomic function tests might reveal the abnormal repolarization in asymptomatic LQT1 patients.
Methods: We measured heart rates (HRs) and QT intervals in nine asymptomatic carriers of a C‐terminal KCNQ1 mutation and 8 unaffected healthy subjects using an approach of global QT values derived from 28 simultaneous electrocardiographic leads on beat‐to‐beat base during Valsalva maneuver, mental stress, sustained handgrip, and light supine exercise.
Results: LQT1 patients exhibited impaired shortening of both QTpeak and QTend intervals during autonomic interventions but exaggerated lengthening of the intervals—a QT overshoot—during the recovery phases. The number of tests with a QT overshoot was 2.4 ± 1.7 in LQT1 patients and 0.8 ± 0.7 in unaffected subjects (P = 0.02). Valsalva strain prolonged T wave peak to T wave end interval (TPE) in LQT1 but not in unaffected patients. LQT1 patients showed diminished HR acceleration in response to adrenergic challenge whereas HR responses to vagal stimuli were similar in both groups.
Conclusions: Standard cardiovascular autonomic provocations induce a QT interval overshoot during recovery in asymptomatic KCNQ1 mutation carriers. Valsalva maneuver causes an exaggerated fluctuation of QT and TPE intervals partly explaining the occurrence of cardiac events during abrupt bursts of autonomic activity in LQT1 patients.
Sickle cell disease due to compound heterozygosity for Hb S and a novel 7.7‐kb β‐globin gene deletion
Authors: Andersson B. Anders R. , Wering Mikaela E. L. , Luo Hong‐Yuan , Basran Raveen K. , Steinberg Martin H. , Smith Hedy P. , Chui David H. K. 
Published: October 2006

AbstractA young woman originally from Cape Verde islands presented with mild sickle cell disease. Her blood counts and hemoglobin analysis results initially suggested that she might be either homozygous for the sickle cell hemoglobin (Hb S) with concomitant α‐thalassemia, or compound heterozygous for Hb S and β0‐thalassemia, deletional δβ‐thalassemia or hereditary persistence of fetal hemoglobin (HPFH). We utilized a novel polymerase chain reaction (PCR)‐based screening technique and found a hitherto unrecognized 7.7‐kb deletion, starting from the HBB IVSII to 3′ downstream of the β‐globin gene. This diagnostic approach can be applied to decipher other similar deletional mutations. This is the second known deletion that removes the 3′‐end but preserves the integrity of the 5′‐end of the β‐globin gene. Furthermore, the identification of the deletion allows proper genetic counseling for affected families.
A Mesoscale Data Analysis and Downscaling Method over Complex Terrain
Authors: Steinacker Reinhold , Ratheiser Matthias , Bica Benedikt , Chimani Barbara , Dorninger Manfred , Gepp Wolfgang , Lotteraner Christoph , Schneider Stefan , Tschannett Simon 
Published: October 2006

Abstract
A mesoscale data analysis method for meteorological station reports is presented. Irregularly distributed measured values are combined with measurement-independent a priori information about the modification of analysis fields due to topographic forcing. As a physical constraint to a thin-plate spline interpolation, the so-called “fingerprint method” recognizes patterns of topographic impact in the data and allows for the transfer of information to data-sparse areas. The results of the method are small-scale interpolation fields on a regular grid including topographically induced patterns that are not resolved by the station network. Presently, the fingerprint method is designed for the analysis of scalar meteorological variables like reduced pressure or air temperature. The principles for the fingerprint technique are based on idealized influence fields. They are calculated for thermal and dynamic surface forcing. For the former, the effects of reduced air volumes in valleys, the elevated heat sources, and the stability of the valley atmosphere are taken into account. The increase of temperature under ideal conditions in comparison to flat terrain is determined on a 1-km grid using height and surface geometry information. For the latter, a perturbation of an originally constant cross-Alpine temperature gradient is calculated by a topographical weighting. As a result, the gradient is steep where the mountain range is high and steep. If, during the interpolation process, some signal of the idealized patterns is found in the station data, it is used to downscale the analysis. It is shown by a cross validation of a case study that the interpolation of a mean sea level pressure field over the Alpine region is improved objectively by the method. Thermally induced mesoscale patterns are visible in the interpolated pressure field.
Evaluation of the Soil Model of the Hydro–Thermodynamic Soil–Vegetation Scheme by Observations and a Theoretically Advanced Numerical Scheme
Authors: Narapusetty Balachandrudu , Mölders Nicole 
Published: October 2006

Abstract
The soil module of the Hydro–Thermodynamic Soil–Vegetation Scheme is evaluated by soil temperature observations and independent theoretical numerical results. To gain the latter, a Galerkin weak finite-element (GWFE) scheme is implemented for solving the heat and water balance equations that are originally solved by a Crank–Nicholson finite-difference (CNFD) scheme. The GWFE scheme captures discontinuities well and has a high phase fidelity. When/where frozen ground thaws and under moderate advection-dominated regimes, peak temperatures simulated with the CNFD scheme are up to seven days off compared with observations and the results of the GWFE scheme. If freeze–thaw cycles repeat for more than a month, CNFD predictions will oscillate ±1 K around the observations but will converge to the observations and results of the GWFE scheme afterward. Under diffusion-dominated regimes, CNFD runs perform well with similar quality to the GWFE predictions. Comparisons of the results of both numerical schemes substantiate that the long spinup time of CNFD simulations results from the numerical scheme and not from the initialization procedure and that the diffusive nature of the CNFD scheme and not parameterized physical processes causes phase shifts. GWFE requires 1.6–2.8 more CPU time than CNFD in this study. Unless CPU time is an issue, the GWFE scheme is recommended because of its high phase fidelity and short spinup.
Mechanisms for the Generation of Mesoscale Vorticity Features in Tropical Cyclone Rainbands
Authors: Franklin Charmaine N. , Holland Greg J. , May Peter T. 
Published: October 2006

AbstractA high-resolution tropical cyclone model with explicit cloud microphysics has been used to investigate the dynamics and energetics of tropical cyclone rainbands. Analysis of the vorticity interactions that occur within the simulated rainbands demonstrates that couplets of cyclonic–anticyclonic mesovortices can be produced in outer bands. The primary source of this vorticity is the upward tilting of system-generated horizontal vorticity by diabatic heating gradients. The vertical heating gradient in the stratiform cloud also creates a potential vorticity (PV) dipole that accelerates the tangential flow and develops a midlevel jet. The strength of the jet is enhanced by the vortex pair that is oriented radially across the rainband. The Fourier decomposition of the absolute vorticity field shows two counterpropagating vortex Rossby waves associated with the rainband. The wave located on the inner side of the band transports energy toward the vortex center. The outer wave is made up of high wavenumbers and uses the vorticity gradients generated by the rainband. The results support the hypothesis that the heating profile in the stratiform regions of rainbands generates cyclonic PV across the freezing level, which develops a midlevel jet. This mechanism creates a vorticity gradient that enables the propagation of vortex Rossby waves that could allow the rainbands to interact with the mean flow and potentially influence the evolution of the storm by contributing to the symmetric component of vorticity and the development of secondary eyewalls.
Fourier-Ray Modeling of Transient Trapped Lee Waves
Authors: Broutman Dave , Ma Jun , Eckermann Stephen D. , Lindeman John 
Published: October 2006

Abstract
The Fourier-ray method involves ray tracing in a Fourier-transform domain. The ray solutions are then Fourier synthesized to produce a spatial solution. Here previous steady-state developments of the Fourier-ray method are extended to include a transient source of mountain waves. The method is illustrated with an initial value problem in which the background flow is started abruptly from rest and then maintained at steady velocity. The resulting wave transience is modeled in a simple way. All rays that radiate from the mountain, including the initial rays, are assigned the full amplitude of the longtime steady-state solution. Time dependence comes in through the changing position of the initial rays. This is sufficient to account for wave transience in a test case, as demonstrated by comparison with simulations from a mesoscale numerical model.
Precursors to Convection over Peninsular India during March–May in AMSU-B Data
Authors: Puranik Dileep M. , Karekar R. N. 
Published: October 2006

Abstract
In the present work the locations of precursors to summer thunderstorms over peninsular India are sought in images from the Advanced Microwave Sounding Unit-B (AMSU-B). At these locations, moisture maxima and brightness temperature (BT) minima may be expected. Prior literature suggests that the 150-GHz channel is useful in detecting the BT minima due to moisture in the lowest 1 km, the 183.3 ± 7- GHz channel is useful for detecting middle-level moist layers and clouds, and the other 183.3-GHz channels are useful for upper-air features such as high-level dry air incursion or upper-air troughs. Cloudy or moist pixels and low-emissivity ground pixels have similar BTs. The extraction of the locations of BT minima is therefore difficult. The scale 1 or 2 à trous wavelet transform (WT) allows unambiguous location of the BT minima due to clouds or moist regions from AMSU-B images.
On 3–4 April 2001 there was a middle-level moisture incursion over the peninsula and on 17–18 April 2001 there was an upper-level dry air incursion. The wavelet components of AMSU-B data were extracted during these two events. From the Meteosat-5 infrared images it was verified that convection occurred within 2 h of the AMSU-B pass in the low-BT regions separated by the à trous WT. On the other hand, peninsular discontinuities on 3–4 April 2001 and 7 April 2002 and other days in 2002 showed that useful precursors could not be extracted from the 150-GHz signal. The BTs for the 150-GHz channel in dry air are affected significantly by ground altitude and by changes in surface emissivity. Failure and success in precursor detection are both attributed to the variability in the BTs.
Synoptic and Mesoscale Analysis of a High-Latitude Derecho–Severe Thunderstorm Outbreak in Finland on 5 July 2002
Authors: Punkka Ari-Juhani , Teittinen Jenni , Johns Robert H. 
Published: October 2006

Abstract
On 5 July 2002, a rapidly propagating bow echo formed over eastern Finland causing severe wind damage in an exceptionally large area. The Ministry of the Interior’s Emergency Response Centers received nearly 400 thunderstorm-related wind damage reports. The 5 July 2002 case is the highest-latitude derecho that has ever been documented. The bow echo developed ahead of a northeastward-moving 500-hPa trough inside of the warm sector of a secondary low and moved north-northwestward on the eastern (warm) side of the quasi-stationary front. The leading edge of the bow echo was oriented perpendicular to the low-level southerly wind shear and the convective system propagated along the 850-hPa equivalent potential temperature ridge with a speed that was close to the maximum wind throughout the troposphere. It is particularly noteworthy that the synoptic pattern was oriented about 90° counterclockwise when compared with the typical synoptic pattern associated with warm season derechos in the United States. This kind of synoptic situation associated along with the derecho mesoscale convective system’s (MCS’s) motion toward the north-northwest has not been mentioned in literature before. The MCS started as a cluster of thunderstorms and became a bow echo a few hours later. The leading edge of the bow echo had a strong reflectivity gradient and the region of stratiform precipitation was behind the strongest echoes. At the most intense stage, a rear-inflow notch was visible both in radar and satellite pictures. It was in good accordance with the location of an area of the most severe damage. Moreover, the storm-relative winds derived from the proximity sounding in the wake of the system showed the existence of rear-to-front flow above 850 hPa. The downdraft air appeared to originate from 4 km ASL, where the relative humidity was less than 50%. This probably led to enhanced evaporative cooling and the intense cold pool, which propagated faster than the mean wind. In the mesoscale, the 5 July 2002 derecho had many similarities to other derecho MCSs that have been described in the literature.
Constitutive activation of Stat5 promotes its cytoplasmic localization and association with PI3-kinase in myeloid leukemias
Authors: Harir Noria , Pecquet Christian , Kerenyi Marc , Sonneck Karoline , Kovacic Boris , Nyga Remy , Brevet Marie , Dhennin Isabelle , Gouilleux-Gruart Valerie , Beug Hartmut , Valent Peter , Lassoued Kaiss , Moriggl Richard , Gouilleux Fabrice 
Published: October 2006

AbstractPersistent activation of Stat5 is frequently found in hematologic neoplasms. Studies conducted with constitutively active Stat5 mutants (Stat51*6 and cS5F) have shown that deregulated Stat5 activity promotes leukemogenesis. To investigate the oncogenic properties of these mutants, we used cS5F-expressing bone marrow cells which induce a multilineage leukemia when transplanted into recipient mice. Here, we show by immunocytochemistry that cS5F is localized mainly in the cytoplasmic compartment of leukemic cells, suggesting that the transforming nature of cS5F may be associated with a cytoplasmic function. In support of this hypothesis, we found that cS5F forms a complex with the p85 subunit of the phosphatidylinositol 3-kinase (PI3-K) and the scaffolding adapter Gab2 in leukemic bone marrow cells, resulting in the activation of Akt/PKB, a crucial downstream target of PI3-K. By using transducible TAT-Gab2 or TAT-Akt recombinant proteins, we were able to demonstrate that activation of the PI3-kinase/Akt pathway by cS5F molecules through Gab2 is essential for induction of cell growth. We also found that persistently phosphorylated Stat5 in primary cells from patients with myeloid leukemias has a cytoplasmic localization. These data suggest that oncogenic Stat5 proteins exert dual transforming capabilities not only as transcriptional activators but also as cytoplasmic signaling effectors.
Receptor activator of nuclear factor (NF)–κB ligand (RANKL) increases vascular permeability: impaired permeability and angiogenesis in eNOS-deficient mice
Authors: Min Jeong-Ki , Cho Young-Lai , Choi Jae-Hoon , Kim Yonghak , Kim Jeong Hun , Yu Young Suk , Rho Jaerang , Mochizuki Naoki , Kim Young-Myeong , Oh Goo Taeg , Kwon Young-Guen 
Published: October 2006

AbstractReceptor activator of nuclear factor (NF)–κB ligand (RANKL) is emerging as an important regulator of vascular pathophysiology. Here, we demonstrate a novel role of RANKL as a vascular permeability factor and a critical role of endothelial nitric oxide synthase (eNOS) in RANKL-induced endothelial function. RANKL increased the vascular permeability and leukocyte infiltration in vivo and caused the breakdown of the blood-retinal barrier in wild-type mice but not in eNOS-deficient mice. In vitro, it increased endothelial permeability and reduced VE-cadherin–facilitated endothelial cell-cell junctions in a NO-dependent manner. RANKL also led to the activation of Akt and eNOS and to NO production in endothelial cells (ECs). These effects were suppressed by the inhibition of TRAF6, phosphoinositide 3′-kinase (PI3K), Akt, or NOS by genetic or pharmacologic means. Inhibition of the TRAF6-mediated NO pathway reduced EC migration and capillary-like tube formation in response to RANKL. Moreover, the effects of RANKL on ECs sprouting from the aorta, and neovessel formation in both the mouse Matrigel plug assay and corneal micropocket assay, were impaired in eNOS-deficient mice. These results demonstrate that RANKL promotes vascular permeability and angiogenesis by stimulating eNOS by a TRAF6-PI3K-Akt–dependent mechanism. These properties may be relevant to the pathogenesis of angiogenesis-dependent and inflammatory vascular diseases.