bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modeling of cell signaling pathways in macrophages by semantic networks
Authors: Hsing Michael , Bellenson Joel L , Shankey Conor , Cherkasov Artem 
Published: November 2004

Abstract
Background
Substantial amounts of data on cell signaling, metabolic, gene regulatory and other biological pathways have been accumulated in literature and electronic databases. Conventionally, this information is stored in the form of pathway diagrams and can be characterized as highly "compartmental" (i.e. individual pathways are not connected into more general networks). Current approaches for representing pathways are limited in their capacity to model molecular interactions in their spatial and temporal context. Moreover, the critical knowledge of cause-effect relationships among signaling events is not reflected by most conventional approaches for manipulating pathways.

Results
We have applied a semantic network (SN) approach to develop and implement a model for cell signaling pathways. The semantic model has mapped biological concepts to a set of semantic agents and relationships, and characterized cell signaling events and their participants in the hierarchical and spatial context. In particular, the available information on the behaviors and interactions of the PI3K enzyme family has been integrated into the SN environment and a cell signaling network in human macrophages has been constructed. A SN-application has been developed to manipulate the locations and the states of molecules and to observe their actions under different biological scenarios. The approach allowed qualitative simulation of cell signaling events involving PI3Ks and identified pathways of molecular interactions that led to known cellular responses as well as other potential responses during bacterial invasions in macrophages.

Conclusions
We concluded from our results that the semantic network is an effective method to model cell signaling pathways. The semantic model allows proper representation and integration of information on biological structures and their interactions at different levels. The reconstruction of the cell signaling network in the macrophage allowed detailed investigation of connections among various essential molecules and reflected the cause-effect relationships among signaling events. The simulation demonstrated the dynamics of the semantic network, where a change of states on a molecule can alter its function and potentially cause a chain-reaction effect in the system.
Enhanced Dupuytren's disease fibroblast populated collagen lattice contraction is independent of endogenous active TGF-β2
Authors: Tse Raymond , Howard Jeffrey , Wu Yan , Gan Bing Siang 
Published: November 2004

Abstract
Background
Dupuytren's disease (DD) is a debilitating fibro-proliferative disorder of the hand characterized by the appearance of fibrotic lesions (nodules and cords) leading to flexion contractures of the fingers and loss of hand function. Although the molecular mechanism of DD is unknown, it has been suggested that transforming growth factor-β2 (TGF-β2) may play an important role in the underlying patho-physiology of the disease. The purpose of this study was to further explore this hypothesis by examining the effects of TGF-β2 on primary cell cultures derived from patient-matched disease and normal palmar fascia tissue using a three-dimensional collagen contraction assay.

Methods
Fibroblast-populated collagen lattice (FPCL) contraction assays using primary cell cultures derived from diseased and control fascia of the same DD patients were studied in response to exogenous TGF-β2 and neutralizing anti-TGF-β2 antibodies.

Results
Contraction of the FPCLs occurred significantly faster and to a greater extent in disease cells compared to control cells. The addition of TGF-β2 enhanced the rate and degree of collagen contraction in a dose-dependent fashion for both control and diseased cells. Neutralizing anti-TGF-β2 antibodies abolished exogenous TGF-β2 stimulated collagen contraction, but did not inhibit the enhanced basal collagen contraction activity of disease FPCL cultures.

Conclusions
Although exogenous TGF-β2 stimulated both disease and control FPCL contraction, neutralizing anti-TGF-β2 antibodies did not affect the elevated basal collagen contraction activity of disease FPCLs, suggesting that the differences in the collagen contraction activity of control and disease FPCL cultures are not due to differences in the levels of endogenous TGF-β2 activity.
Omega-3 fatty acids and major depression: A primer for the mental health professional
Authors: Logan Alan C 
Published: November 2004

AbstractOmega-3 fatty acids play a critical role in the development and function of the central nervous system. Emerging research is establishing an association between omega-3 fatty acids (alpha-linolenic, eicosapentaenoic, docosahexaenoic) and major depressive disorder. Evidence from epidemiological, laboratory and clinical studies suggest that dietary lipids and other associated nutritional factors may influence vulnerability and outcome in depressive disorders. Research in this area is growing at a rapid pace. The goal of this report is to integrate various branches of research in order to update mental health professionals.
Methodology for evaluating Insite: Canada's first medically supervised safer injection facility for injection drug users
Authors: Wood Evan , Kerr Thomas , Lloyd-Smith Elisa , Buchner Chris , Marsh David C , Montaner Julio SG , Tyndall Mark W 
Published: November 2004

AbstractMany Canadian cities are experiencing ongoing infectious disease and overdose epidemics among injection drug users (IDUs). In particular, Human Immunodeficiency Virus (HIV) and hepatitis C Virus (HCV) have become endemic in many settings and bacterial and viral infections, such as endocarditis and cellulitis, have become extremely common among this population. In an effort to reduce these public health concerns and the public order problems associated with public injection drug use, in September 2003, Vancouver, Canada opened a pilot medically supervised safer injecting facility (SIF), where IDUs can inject pre-obtained illicit drugs under the supervision of medical staff. The SIF was granted a legal exemption to operate on the condition that its impacts be rigorously evaluated. In order to ensure that the evaluation is appropriately open to scrutiny among the public health community, the present article was prepared to outline the methodology for evaluating the SIF and report on some preliminary observations. The evaluation is primarily structured around a prospective cohort of SIF users, that will examine risk behavior, blood-borne infection transmission, overdose, and health service use. These analyses will be augmented with process data from within the SIF, as well as survey's of local residents and qualitative interviews with users, staff, and key stakeholders, and standardised evaluations of public order changes. Preliminary observations suggest that the site has been successful in attracting IDUs into its programs and in turn helped to reduce public drug use. However, each of the indicators described above is the subject of a rigorous scientific evaluation that is attempting to quantify the overall impacts of the site and identify both benefits and potentially harmful consequences and it will take several years before the SIF's impacts can be appropriately examined.
Assessment of possible impact of a health promotion program in Korea from health risk trends in a longitudinally observed cohort
Authors: Park J , Jee SH , Edington DW 
Published: November 2004

Abstract
Background
Longitudinally observed cohort data can be utilized to assess the potential for health promotion and healthcare planning by comparing the estimated risk factor trends of non-intervened with that of intervened. The paper seeks (1) to estimate a natural transition (patterns of movement between states) of health risk state from a Korean cohort data using a Markov model, (2) to derive an effective and necessary health promotion strategy for the population, and (3) to project a possible impact of an intervention program on health status.

Methods
The observed transition of health risk states in a Korean employee cohort was utilized to estimate the natural flow of aggregated health risk states from eight health risk measures using Markov chain models. In addition, a reinforced transition was simulated, given that a health promotion program was implemented for the cohort, to project a possible impact on improvement of health status. An intervened risk transition was obtained based on age, gender, and baseline risk state, adjusted to match with the Korean cohort, from a simulated random sample of a US employee population, where a health intervention was in place.

Results
The estimated natural flow (non-intervened), following Markov chain order 2, showed a decrease in low risk state by 3.1 percentage points in the Korean population while the simulated reinforced transition (intervened) projected an increase in low risk state by 7.5 percentage points. Estimated transitions of risk states demonstrated the necessity of not only the risk reduction but also low risk maintenance.

Conclusions
The frame work of Markov chain efficiently estimated the trend, and captured the tendency in the natural flow. Given only a minimally intense health promotion program, potential risk reduction and low risk maintenance was projected.
Rate of first recorded diagnosis of autism and other pervasive developmental disorders in United Kingdom general practice, 1988 to 2001
Authors: Smeeth Liam , Cook Claire , Fombonne Professor Eric , Heavey Lisa , Rodrigues Laura C , Smith Peter G , Hall Andrew J 
Published: November 2004

Abstract
Background
There has been concern that the incidence of autism and other pervasive developmental disorders (PDDs) is increasing. Previous studies have been smaller, restricted to autism (excluding other pervasive developmental disorders such as Asperger's syndrome), included boys only, or have not been based on a national sample. We investigated time trends in the rates of diagnosis of pervasive developmental disorders.

Methods
We analysed the rates of first diagnosis of pervasive developmental disorders among people registered with a practice contributing to the United Kingdom General Practice Research Database during the period 1988 to 2001. We included 1410 cases from over 14 million person-years of observation. The main outcome measures were rates of diagnosis of pervasive developmental disorders by year of diagnosis, year of birth, gender and geographical region.

Results
The rate increased progressively from 0.40/10,000 person-years (95% CI 0.30 to 0.54) in 1991 to 2.98/10,000 (95% CI 2.56 to 3.47) in 2001. A similar change occurred in the age standardised incidence ratios, from 35 (95% CI: 26–47) in 1991 to 365 (95% CI: 314–425) in 2001. The temporal increase was not limited to children born during specific years nor to children diagnosed in a specific time period. The rate of diagnosis of PDDs other than autism rose from zero for the period 1988–1992 to 1.06/10,000 person-years in 2001. The rate of diagnosis of autism also increased but to a lesser extent. There was marked geographical variation in rates, with standardised incidence ratios varying from 66 for Wales to 141 for the South East of England.

Conclusions
Better ascertainment of diagnosis is likely to have contributed to the observed temporal increase in rates of diagnosis of PDD, but we cannot exclude a real increase.
Is immunotherapy an effective treatment for Alzheimer's disease?
Authors: Licastro Federico , Caruso Calogero 
Published: November 2004

AbstractImmunotherapy in patients with Alzheimer's disease (AD) is rapidly becoming a hot topic of modern geriatric and clinical gerontology. Current views see immunization with Aβ peptide, the amyloidogenic protein found in senile plaque of AD patient's brains, or the infusion of preformed antibody specific for human Aβ, as possible therapeutic approaches to improve the cognitive status in the disease. Animal models of the disease have provided positive results from both approaches. Thus, an initial clinical trial using immunization with human Aβ in AD patients was started, but then shortly halted because of an unusually high incidence (6%) of meningoencephalitis. A long and currently ongoing debate in the scientific community about the pro or contra of vaccination or passive immunization with Aβ in AD is thereafter started. Here, the authors would like to stress few points of concern regarding these approaches in clinical practice.
Development of analytical methods for fuselage design: Validation by means of finite element analyses
Authors: Boni L , Fanteria D 
Published: November 2004

The paper presents the results of a set of finite element analyses (FEAs) carried out to support the development of an integrated design procedure that, based on semi-empirical and analytical methods, is capable of defining generic fuselage sections of a transport aircraft. The procedure, which is implemented in a structural optimization code, defines a structure that, compliant with durability and damage tolerance requirements, is characterized by a post-critical behaviour of the stiffened panels and by a design of the frames that takes the frame flexibility and the presence of the floor beams into account. FEAs, carried out on a reference configuration defined by the optimization code, are used to acquire a deeper knowledge of the advantages and disadvantages of the analytical approach in the design of complex structures subjected to realistic load cases. In particular, the influence of the actual frame flexibility on the distribution of the skin shear flow induced by the frame is evaluated; moreover, the effects on the stress distribution in skin and frames, caused by the presence of the stringers, and of the stiffness concentration introduced by the floor beam are addressed. Finite element method results demonstrate the effectiveness of the analytical model of the flexible frame in evaluating the shear flow that a single loaded frame transfers to the skin and highlight the effects of the presence of adjacent loaded frames. By means of geometrically non-linear FEAs, the effects of the stringers on the stress distribution of a pressurized cylinder are evaluated, as well as the magnitude and extension of the perturbation introduced by the floor beams.
Methods of structural analysis and computer program JANA2000
Authors: Petříček Václav , Dušek Michal 
Published: November 2004

Abstract
State of the art is presented in the field of structure analysis of aperiodic crystals. Based on the superspace theory that recovers translation periodicity of aperiodic crystals in a (3 + d)-dimensional space, generalized crystallographic methods have been developed that work analogous to standard tools in the classical crystallography. After introducing the basic types of modulations their combination and possible discontinuity is discussed as well as the basic concepts of composite structures. The ways of solution of modulated structures are described with special emphasis to the heavy atom method as an instructive example. The potential of the refinement methods is perspicuous in the example of hexagonal perovskite structure with discontinuous modulation functions and modulated anharmonic ADP. Finally we describe the basic features of the computing system Jana2000 that is the most used program in the field.
Genetics of Species Differences in the Wild Annual Sunflowers, Helianthus annuus and H. petiolaris
Authors: Lexer Christian , Rosenthal David M , Raymond Olivier , Donovan Lisa A , Rieseberg Loren H 
Published: November 2004

Abstract
Much of our knowledge of speciation genetics stems from quantitative trait locus (QTL) studies. However, interpretations of the size and distribution of QTL underlying species differences are complicated by differences in the way QTL magnitudes are estimated. Also, many studies fail to exploit information about QTL directions or to compare inter- and intraspecific QTL variation. Here, we comprehensively analyze an extensive QTL data set for an interspecific backcross between two wild annual sunflowers, Helianthus annuus and H. petiolaris, interpret different estimates of QTL magnitudes, identify trait groups that have diverged through selection, and compare inter- and intraspecific QTL magnitudes. Our results indicate that even minor QTL (in terms of backcross variance) may be surprisingly large compared to levels of standing variation in the parental species or phenotypic differences between them. Morphological traits, particularly flower morphology, were more strongly or consistently selected than life history or physiological traits. Also, intraspecific QTL were generally smaller than interspecific ones, consistent with the prediction that larger QTL are more likely to spread to fixation across a subdivided population. Our results inform the genetics of species differences in Helianthus and suggest an approach for the simultaneous mapping of inter- and intraspecific QTL.
Protein Kinase A Regulates Constitutive Expression of Small Heat-Shock Genes in an Msn2/4p-Independent and Hsf1p-Dependent Manner in Saccharomyces cerevisiae
Authors: Ferguson Scott B , Anderson Erik S , Harshaw Robyn B , Thate Tim , Craig Nancy L , Nelson Hillary C M 
Published: November 2004

Abstract
Hsf1p, the heat-shock transcription factor from Saccharomyces cerevisiae, has a low level of constitutive transcriptional activity and is kept in this state through negative regulation. In an effort to understand this negative regulation, we developed a novel genetic selection that detects altered expression from the HSP26 promoter. Using this reporter strain, we identified mutations and dosage compensators in the Ras/cAMP signaling pathway that decrease cAMP levels and increase expression from the HSP26 promoter. In yeast, low cAMP levels reduce the catalytic activity of the cAMP-dependent kinase PKA. Previous studies had proposed that the stress response transcription factors Msn2p/4p, but not Hsf1p, are repressed by PKA. However, we found that reduction or elimination of PKA activity strongly derepresses transcription of the small heat-shock genes HSP26 and HSP12, even in the absence of MSN2/4. In a strain deleted for MSN2/4 and the PKA catalytic subunits, expression of HSP12 and HSP26 depends on HSF1 expression. Our findings indicate that Hsf1p functions downstream of PKA and suggest that PKA might be involved in negative regulation of Hsf1p activity. These results represent a major change in our understanding of how PKA signaling influences the heat-shock response and heat-shock protein expression.
Prospective study of routine contrast radiology after total gastrectomy (Br J Surg 2004; 91: 1015-1019)
Authors: Saunders R N , French J , Ubhi S 
Published: November 2004

Abstract
The Editors welcome topical correspondence from readers relating to articles published in the Journal. Responses can be sent electronically via the BJS website (www.bjs.co.uk) or by post. All letters will be reviewed and, if approved, appear on the website. A selection of these will be edited and published in the Journal. Letters must be no more than 250 words in length. Letters submitted by post should be typed on A4-sized paper in double spacing and should be accompanied by a diskx.
Nanoscale lead and noble gas inclusions in aluminum: Structures and properties
Authors: Johnson Erik , Andersen Hans Henrik , Dahmen Ulrich 
Published: November 2004

AbstractTransmission electron microscopy has been used for structural and physical characterization of nanoscale inclusions of lead and noble gases in aluminum. When the inclusion sizes approach nanoscale dimensions, many of their properties are seen to deviate from similar properties in bulk and in most cases the deviations will increase as the inclusion sizes decrease. Binary alloys of lead and noble gases with aluminum are characterized by extremely low mutual solubilities and inclusions will, therefore, exist as practically pure components embedded in the aluminum matrix. Furthermore, the thermal vacancy mobility in aluminum at and above room temperature is sufficiently high to accommodate volume strains associated with the inclusions thus leading to virtually strain free crystals. The inclusions grow in parallel cube alignment with the aluminum matrix and have a cuboctahedral shape, which reflects directly the anisotropy of the interfacial energies. Inclusions in grain boundaries can have single crystalline or bicrystalline morphology that can be explained from a generalized Wulff analysis such as the ξ‐vector construction. The inclusions have been found to display a variety of nanoscale features such as high Laplace pressure, size‐dependent superheating during melting, deviations from the Wulff shape displaying magic size effects, a shape dependence of edge energy, and so on. All these effects have been observed and monitored by TEM using conventional imaging conditions and high‐resolution conditions in combination with in‐situ analysis at elevated temperatures. Microsc. Res. Tech. 64:356–372, 2004. © 2004 Wiley‐Liss, Inc.
Developmental changes in the embryo, pronymph, and first molt of the scorpion Centruroides vittatus (Scorpiones: Buthidae)
Authors: Farley Roger D. 
Published: November 2004

AbstractFor the first time the scanning electron microscope was used to compare developmental changes in scorpion embryos and the first and second stadia. In the buthid species of this study, Centruroides vittatus, and all other scorpions, the newborn climb up on their mother's back and remain there without feeding for several days. At this location, they undergo their first molt and in a few days they disperse, fully capable of foraging in the terrestrial environment. The results here support earlier suggestions that the first stadium (pronymph) is a continuation and extension of embryological development. The first molt results in a nymph with exoskeletal features much like those in the adult. In the first molt the metasoma becomes relatively longer, and the sting (aculeus) becomes sharp and functional. The metasomal segments are modified for dorsal flexion and sting use. The embryos and the pronymphs have spiracles that open into an invagination near the posterior margin of flap‐like abdominal plates in segments 4–7 of the ventral mesosoma. The second instars have spiracles that lead to book lungs farther anterior in sternites. Tubular legs with cylindrical segments in embryos and pronymphs become more sculptured and oval in the transverse plane. Each leg in the pronymph has a blunt, cup‐shaped tip while distal claws (ungues, dactyl) are present in the second instar and subsequent stages. There are some sharp bristles and primordial sensilla in the pronymphs, but the second stadium has adult‐like surface features: rows of knobs or granulations (carinae), serrations on the inner surfaces of cheliceral and pedipalpal claws, filtering hairs at the mouthparts, peg sensilla on the pectines, and mechano‐ and chemoreceptor sensilla on the body and appendages. Scorpion embryos and pronymphs have some structures like fossil scorpions thought to have been aquatic. There is a gradual development of features that appear to be terrestrial adaptations. Evidence is provided for the formation of the sternum from third and fourth leg coxal primordia and possibly from the first abdominal segment. This study is the first to provide evidence for a forward shift of the gonopore along with other structures in the anterior abdomen. © 2004 Wiley‐Liss, Inc.