bluuebunny/crossref_metadata_2025 huggingface dataset:
A Controlled Study of Autonomic Nervous System Function in Adults With Attention-Deficit/Hyperactivity Disorder Treated With Stimulant Medications
Authors: Schubiner Howard , Hassunizadeh Bischan , Kaczynski Richard
Published: November 2006

Objective: Despite the fact that autonomic nervous system (ANS) abnormalities are commonly found in adults and predict increased cardiovascular mortality, no studies have assessed ANS function in adults with attention-deficit/hyperactivity disorder (ADHD) taking stimulants.

Method: This pilot study evaluated ANS function in adults with ADHD in comparison with an age- and gender-matched control group.

Results: The authors found that 4% of the control group had some abnormalities in the ANS in comparison with 24% of the ADHD group.

Conclusion: Because the control group had higher levels of exercise fitness, and the level of abnormalities in the ADHD group was comparable with that of the general population, the significance of these findings is unknown. In addition, we did not determine if ANS abnormalities were present in individuals with ADHD who were not on stimulant medications. Further research is warranted to determine if there is any association between ADHD and stimulant use and ANS abnormalities.
Does ADHD in Adults Affect the Relative Accuracy of Metamemory Judgments?
Authors: Knouse Laura E. , Paradise Matthew J. , Dunlosky John
Published: November 2006

Objective: Prior research suggests that individuals with ADHD overestimate their performance across domains despite performing more poorly in these domains. The authors introduce measures of accuracy from the larger realm of judgment and decision making—namely, relative accuracy and calibration—to the study of self-evaluative judgment accuracy in adults with ADHD.

Method: Twenty-eight adults with ADHD and 28 matched controls participate in a computer-administered paired-associate learning task and predict their future recall using immediate and delayed judgments of learning (JOLs). Retrospective confidence judgments are also collected.

Results: Groups perform equally in terms of judgment magnitude and absolute judgment accuracy as measured by discrepancy scores and calibration curves. Both groups benefit equally from making their JOL at a delay, and the group with ADHD show higher relative accuracy for delayed judgments.

Conclusion: Results suggest that under certain circumstances, adults with ADHD can make accurate judgments about their future memory.
Effects of Coexisting Disorders on Cognition and Behavior in Children With ADHD
Authors: Crawford Susan G. , Kaplan Bonnie J. , Dewey Deborah
Published: November 2006

Objective: To determine whether the presence of coexisting disorders affects memory, visual-motor skills, and daily functioning in children with ADHD.

Method: Eighty-four boys and 18 girls (8 to 16 years old) participate in this study. Twenty children meet criteria for ADHD alone, 42 children for ADHD plus one other disorder, and 40 children for ADHD plus at least two other disorders (reading disability, developmental coordination disorder, oppositional defiant disorder, conduct disorder, anxiety, and depression). Children are assessed on memory and visual-motor skills. Parents complete measures of daily functioning.

Results: No significant group differences emerge for age, socioeconomic status, or IQ. Poorer performance on tests of memory and visual-motor skills, more prevalent behavioral problems, and more impairment in everyday functioning are associated with a higher number of coexisting disorders in children with ADHD.

Conclusion: The presence of coexisting disorders has a significant influence on cognition and behavior of children with ADHD.
Children Should Be Seen and Heard
Authors: Klimkeit Ester , Graham Claire , Lee Paul , Morling Megan , Russo Diana , Tonge Bruce
Published: November 2006

Objective: The belief that children with externalizing disorders have difficulties with self-awareness raises the question of whether children with externalizing disorders are good informants of their own behavior.

Method: This study investigates how children with ADHD rate their behaviors compared to children without ADHD on a new rating scale (the Self-Evaluation Scale for Children).

Results: Preliminary results indicate that this rating scale has acceptable reliability and validity. Furthermore, children with ADHD are found to provide useful information about their feelings and behaviors. Compared to children without ADHD, children with ADHD report more disorganized, disruptive, and impulsive behaviors; poorer self-perception; and poorer social and communication skills. They do not report any less interest in school activities nor more anxiety than the children without ADHD.

Conclusion: These findings suggest that children with ADHD are more self-aware than previously thought, and this information should inform our clinical and research practice.
The Role of Causal Attributions in Survivors’ Emotional Reactions to Downsizing
Authors: Hareli Shlomo , Tzafrir Shay S.
Published: November 2006

Weiner’s (1986) theory of attribution was used for analyzing discrete emotions survivors of downsizing may experience as a function of perceived causes for survival. The study considered emotions not studied in previous research (e.g., pride) and their relation to organizational factors (e.g., organizational citizenship behavior). Moreover, this analysis goes beyond previous research that studied broad affective constructs such as anxiety by also considering positive emotions. Suggested understandings can advance research and facilitate better personal and organizational consequences of downsizing as these are reflected in human resource and human resource development policies and interventions.
Career Development of Foreign-Born Workers: Where is the Career Motivation Research?
Authors: Lopes Tobin P.
Published: November 2006

Immigrants and/or foreign-born workers are entering the American work-force at an increasing rate. Career motivation for these new entrants requires research attention. As this literature review shows, researchers have virtually ignored the expanding immigrant and/or foreign-born worker population. Career motivation differences among international and domestic workers may exist only in the theoretical realm. The relationship between culture and motivation, principally dealing with individualism-collectivism sheds some light on possible differences. Historically, cross-cultural adaptability research has not addressed career motivation. An argument and justification for cross-cultural studies in career motivation is made in this literature review.
Simulation of rolling deformation texture of fcc metals with crystal plasticity finite element model
Authors: Tang J.-G. , Zhang X.-M. , Chen Z.-Y. , Deng Y.-L.
Published: November 2006

A rate dependent crystal plasticity constitutive model with respect to self-hardening and latent hardening in finite element (FE) analysis is developed to simulate rolling texture in the present paper. The influence of grain interaction is modelled by different assignment of orientations to FEs. The simulation results reveal that the grain interaction will lead to mesoscale inhomogeneous deformation and that grains rotate faster in the extended Taylor type crystal plasticity finite element (CPFE) model without consideration of grain interaction than in the full CPFE model with grain interaction. The rotation of grain boundary is slowed down owing to the grain interaction. Assigning more elements to one grain, in which both the boundary and interior of grain are simulated, better simulation results can be obtained.
Influence of annealing on microstructures, mechanical and creep properties of Mg–4Al–2Sr alloy
Authors: Bai J. , Sun Y. S. , Xue F. , Xue S. , Qiang J. , Zhu T. B.
Published: November 2006

Microstructures, mechanical properties and creep resistance of the Mg–4Al–2Sr (AJ42) alloy were investigated both in the as cast condition and after annealing heat treatment at 400°C for 5–200 h. The as cast microstructure of AJ42 alloy consists of dendritic α -Mg and intermetallic compounds, Al4 Sr and a bulky type ternary Mg–Al–Sr phase, distributing at grain boundaries. Annealing the alloy at 400°C results in spheroidisation of eutectic Al4 Sr and breaking up of the continuous grain boundary network existing in the as cast microstructure before annealing gradually. The hardness and tensile properties do not show obvious changes after annealing at 400°C for 200 h. The as cast AJ42 shows a high creep resistance at 175°C/70 MPa in comparison with that of commercial Mg–Al based alloys, however, the creep resistance of the alloy is significantly decreased after annealed at 400°C owing to morphology modification of the grain boundary interphases.
Damping capacity associated with precipitation in Mg2Si/Mg–9Al composite materials
Authors: Liao L. H. , Wang H. W. , Li X. F. , Zhang X. Q. , Ma N. H.
Published: November 2006

Damping capacities of Mg2Si/Mg–9Al after aging treatment at different temperatures and times were investigated. The present paper focuses on the relationship between damping capacities and aging temperature and time. Results show that strain independent damping capacities increase and strain dependent damping values decrease for long time aging. Particular emphasis is placed on the characteristics of grain boundary damping peaks at high temperature. Damping peaks produced by the relaxation of grain boundaries have lower temperature with smaller activation energy when aging time is prolonged to 12 h, which can be explained by the growth up and coarsening of precipitates around grain boundaries.
Effect of bonding temperature on interface microstructure and properties of titanium–304 stainless steel diffusion bonded joints with Ni interlayer
Authors: Kundu S. , Chatterjee S.
Published: November 2006

The diffusion bonding was carried out between commercially pure titanium and 304 stainless steel (SS) using nickel as an intermediate material in the temperature range of 800–950°C for 1·8 ks under a 3 MPa uniaxial load in vacuum. The microstructures of the transition joints were revealed in optical and scanning electron microscopy (SEM). TiNi3, TiNi and Ti2 Ni are formed at the nickel/titanium interface whereas, SS–Ni diffusion zones is free from intermetallic phases for all bonding temperatures. At 950°C, Ni/Ti interface exhibits the presence of α- β Ti discrete islands in the matrix of Ti2Ni intermetallic. The bond strength was evaluated and maximum tensile strength of ∼281 MPa along with 7·2% ductility and shear strength of ∼202 MPa were obtained for the diffusion couple processed at 900°C owing to the better coalescence of the mating surfaces. With increasing joining temperature to 950°C, the bond strength drops owing to an increase in the width of the nickel–titanium based reaction products. At lower joining temperatures, bond strengths are also lower owing to incomplete coalescence of the mating surfaces. The activation energy and growth constant were calculated in the temperature range of 800–950°C for the reaction layers and it was found that, the values were maximum for Ti2Ni. Observation of fracture surfaces in SEM using energy dispersion spectroscopy (EDS) demonstrates that, failure takes place mainly through nickel/titanium interface.
Low temperature aluminisation of alloy steels by pack cementation process
Authors: Xiang Z. D. , Datta P. K.
Published: November 2006

The pack aluminisation process is normally applied at temperatures >973 K at which the mechanical properties of alloy steels would degrade. Thus, the present study was undertaken to apply this process to aluminising the alloy steels at temperatures <973 K in order to increase their high temperature oxidation resistance while maintaining their microstructure and hence mechanical strength and creep resistance. A type of commercial alloy steel P92 (9Cr–1Mo) was used for the present study. Pack powder mixtures consisting of Al, AlCl3 (anhydrous) or NH4Cl and Al2O3 were used to carry out the process. The aluminising temperature was varied from 773 to 973 K, pack Al content from 1 to 30 wt-% and aluminising time from 1 to 16 h to investigate their effects on the coating growth kinetics in the AlCl3 activated packs. It was observed that all the coatings formed in the AlCl3 activated packs were of a single layer structure with Fe2Al5 as the main coating phase. It was established that the interrelationship between the thickness h (in μm) of this coating layer and aluminising temperature T (in K), time t (in h) and pack Al content W (in wt-%) can be described by h=83005·9 W1/2 t1/2 e−73330/( RT). In the NH4Cl activated packs, it was found that coating formation and dissolution took place simultaneously at 923 K and stable growth of a coating layer was only possible when the pack Al content was sufficiently high. However, the coatings formed in these packs had highly uneven regions.
A phase 2 study of the farnesyltransferase inhibitor tipifarnib in poor-risk and elderly patients with previously untreated acute myelogenous leukemia
Authors: Lancet Jeffrey E. , Gojo Ivana , Gotlib Jason , Feldman Eric J. , Greer Jacqueline , Liesveld Jane L. , Bruzek Laura M. , Morris Lawrence , Park Youn , Adjei Alex A. , Kaufmann Scott H. , Garrett-Mayer Elizabeth , Greenberg Peter L. , Wright John J. , Karp Judith E.
Published: November 2006

Outcomes for older adults with acute myelogenous leukemia (AML) are poor due to both disease and host-related factors. In this phase 2 study, we tested the oral farnesyltransferase inhibitor tipifarnib in 158 older adults with previously untreated, poor-risk AML. The median age was 74 years, and a majority of patients had antecedent myelodysplastic syndrome. Complete remission (CR) was achieved in 22 patients (14%); partial remission or hematologic improvement occurred in 15 patients, for an overall response rate of 23%. The median duration of CR was 7.3 months and the median survival of complete responders was 18 months. Adverse karyotype, age 75 years or older, and poor performance status correlated negatively with survival. Early death in the absence of progressive disease was rare, and drug-related nonhematologic serious adverse events were observed in 74 patients (47%). Inhibition of farnesylation of the surrogate protein HDJ-2 occurred in the large majority of marrow samples tested. Baseline levels of phosphorylated mitogen-activated protein kinase and AKT did not correlate with clinical response. Tipifarnib is active and well tolerated in older adults with poor-risk AML and may impart a survival advantage in those patients who experience a clinical response.
Facilitating matched pairing and expression of TCR chains introduced into human T cells
Authors: Kuball Jürgen , Dossett Michelle L. , Wolfl Matthias , Ho William Y. , Voss Ralf-Holger , Fowler Carla , Greenberg Philip D.
Published: November 2006

Adoptive transfer of T lymphocytes is a promising treatment for a variety of malignancies but often not feasible due to difficulties generating T cells that are reactive with the targeted antigen from patients. To facilitate rapid generation of cells for therapy, T cells can be programmed with genes encoding the α and β chains of an antigen-specific T-cell receptor (TCR). However, such exogenous α and β chains can potentially assemble as pairs not only with each other but also with endogenous TCR α and β chains, thereby generating αβTCR pairs of unknown specificity as well as reducing the number of exogenous matched αβTCR pairs at the cell surface. We demonstrate that introducing cysteines into the constant region of the α and β chains can promote preferential pairing with each other, increase total surface expression of the introduced TCR chains, and reduce mismatching with endogenous TCR chains. This approach should improve both the efficacy and safety of ongoing efforts to use TCR transfer as a strategy to generate tumor-reactive T cells.
A GMCSF and IL-15 fusokine leads to paradoxical immunosuppression in vivo via asymmetrical JAK/STAT signaling through the IL-15 receptor complex
Authors: Rafei Moutih , Wu Jian Hui , Annabi Borhane , Lejeune Laurence , François Moïra , Galipeau Jacques
Published: November 2006

We hypothesized that a granulocyte macrophage colony-stimulating factor (GMCSF) and interleukin 15 (IL-15) fusokine (GIFT15) would possess greater immune-stimulatory properties than their combined use. Unexpectedly, tumor cells engineered to secrete GIFT15 protein led to suppression of natural killer (NK) and NKT-cell recruitment in vivo, suggesting an unanticipated immune-suppressive effect. We found GIFT15 to have pleiotropic effects on an array of immune-competent cells. Among these, macrophages treated with GIFT15 secrete de novo the tissue inhibitor of metalloproteinase-2 (TIMP-2); activated matrix metalloproteinase-2 (MMP-2); transforming growth factor-β (TGF-β); as well as vascular endothelial growth factor (VEGF). We show that the GIFT15 fusokine has increased affinity for the α chain component of the IL-15R, leading to aberrant signaling through the β chain manifested by the hyperphosphorylation of STAT3 both in macrophages and splenocytes. Suppression of common γ chain–mediated STAT5 phosphorylation and blockade of the IL-15–dependent IFN-γ response in mouse splenocytes were also observed. We tested GIFT15 as an immunosuppressor and demonstrated that it allowed engraftment of allogeneic B16F0 and human xenograft U87GM glioma cells in immunocompetent mice. Thus, GIFT15 defines a new class of fusokine that mediates proangiogenic and immunosuppressive effects via aberrant signaling by the IL-15R in lymphomyeloid cells.
Thrombospondin-1 limits ischemic tissue survival by inhibiting nitric oxide–mediated vascular smooth muscle relaxation
Authors: Isenberg Jeff S. , Hyodo Fuminori , Matsumoto Ken-Ichiro , Romeo Martin J. , Abu-Asab Mones , Tsokos Maria , Kuppusamy Periannan , Wink David A. , Krishna Murali C. , Roberts David D.
Published: November 2006

The nitric oxide (NO)/cGMP pathway, by relaxing vascular smooth muscle cells, is a major physiologic regulator of tissue perfusion. We now identify thrombospondin-1 as a potent antagonist of NO for regulating F-actin assembly and myosin light chain phosphorylation in vascular smooth muscle cells. Thrombospondin-1 prevents NO-mediated relaxation of precontracted vascular smooth muscle cells in a collagen matrix. Functional magnetic resonance imaging demonstrated that an NO-mediated increase in skeletal muscle perfusion was enhanced in thrombospondin-1–null relative to wild-type mice, implicating endogenous thrombospondin-1 as a physiologic antagonist of NO-mediated vasodilation. Using a random myocutaneous flap model for ischemic injury, tissue survival was significantly enhanced in thrombospondin-1–null mice. Improved flap survival correlated with increased recovery of oxygen levels in the ischemic tissue of thrombospondin-1–null mice as measured by electron paramagnetic resonance oximetry. These findings demonstrate an important antag-onistic relation between NO/cGMP signaling and thrombospondin-1 in vascular smooth muscle cells to regulate vascular tone and tissue perfusion.
Novel metaheuristic for parameter estimation in nonlinear dynamic biological systems
Authors: Rodriguez-Fernandez Maria , Egea Jose A , Banga Julio R
Published: November 2006

Background

We consider the problem of parameter estimation (model calibration) in nonlinear dynamic models of biological systems. Due to the frequent ill-conditioning and multi-modality of many of these problems, traditional local methods usually fail (unless initialized with very good guesses of the parameter vector). In order to surmount these difficulties, global optimization (GO) methods have been suggested as robust alternatives. Currently, deterministic GO methods can not solve problems of realistic size within this class in reasonable computation times. In contrast, certain types of stochastic GO methods have shown promising results, although the computational cost remains large. Rodriguez-Fernandez and coworkers have presented hybrid stochastic-deterministic GO methods which could reduce computation time by one order of magnitude while guaranteeing robustness. Our goal here was to further reduce the computational effort without loosing robustness.

Results

We have developed a new procedure based on the scatter search methodology for nonlinear optimization of dynamic models of arbitrary (or even unknown) structure (i.e. black-box models). In this contribution, we describe and apply this novel metaheuristic, inspired by recent developments in the field of operations research, to a set of complex identification problems and we make a critical comparison with respect to the previous (above mentioned) successful methods.

Conclusion

Robust and efficient methods for parameter estimation are of key importance in systems biology and related areas. The new metaheuristic presented in this paper aims to ensure the proper solution of these problems by adopting a global optimization approach, while keeping the computational effort under reasonable values. This new metaheuristic was applied to a set of three challenging parameter estimation problems of nonlinear dynamic biological systems, outperforming very significantly all the methods previously used for these benchmark problems.
Machine learning techniques in disease forecasting: a case study on rice blast prediction
Authors: Kaundal Rakesh , Kapoor Amar S , Raghava Gajendra PS
Published: November 2006

Background

Diverse modeling approaches viz. neural networks and multiple regression have been followed to date for disease prediction in plant populations. However, due to their inability to predict value of unknown data points and longer training times, there is need for exploiting new prediction softwares for better understanding of plant-pathogen-environment relationships. Further, there is no online tool available which can help the plant researchers or farmers in timely application of control measures. This paper introduces a new prediction approach based on support vector machines for developing weather-based prediction models of plant diseases.

Results

Six significant weather variables were selected as predictor variables. Two series of models (cross-location and cross-year) were developed and validated using a five-fold cross validation procedure. For cross-year models, the conventional multiple regression (REG) approach achieved an average correlation coefficient (r) of 0.50, which increased to 0.60 and percent mean absolute error (%MAE) decreased from 65.42 to 52.24 when back-propagation neural network (BPNN) was used. With generalized regression neural network (GRNN), the r increased to 0.70 and %MAE also improved to 46.30, which further increased to r = 0.77 and %MAE = 36.66 when support vector machine (SVM) based method was used. Similarly, cross-location validation achieved r = 0.48, 0.56 and 0.66 using REG, BPNN and GRNN respectively, with their corresponding %MAE as 77.54, 66.11 and 58.26. The SVM-based method outperformed all the three approaches by further increasing r to 0.74 with improvement in %MAE to 44.12. Overall, this SVM-based prediction approach will open new vistas in the area of forecasting plant diseases of various crops.

Conclusion

Our case study demonstrated that SVM is better than existing machine learning techniques and conventional REG approaches in forecasting plant diseases. In this direction, we have also developed a SVM-based web server for rice blast prediction, a first of its kind worldwide, which can help the plant science community and farmers in their decision making process. The server is freely available at http://www.imtech.res.in/raghava/rbpred/.
Effects of brain polarization on reaction times and pinch force in chronic stroke
Authors: Hummel Friedhelm C , Voller Bernhard , Celnik Pablo , Floel Agnes , Giraux Pascal , Gerloff Christian , Cohen Leonardo G
Published: November 2006

Background

Previous studies showed that anodal transcranial DC stimulation (tDCS) applied to the primary motor cortex of the affected hemisphere (M1affected hemisphere) after subcortical stroke transiently improves performance of complex tasks that mimic activities of daily living (ADL). It is not known if relatively simpler motor tasks are similarly affected. Here we tested the effects of tDCS on pinch force (PF) and simple reaction time (RT) tasks in patients with chronic stroke in a double-blind cross-over Sham-controlled experimental design.

Results

Anodal tDCS shortened reaction times and improved pinch force in the paretic hand relative to Sham stimulation, an effect present in patients with higher impairment.

Conclusion

tDCS of M1affected hemisphere can modulate performance of motor tasks simpler than those previously studied, a finding that could potentially benefit patients with relatively higher impairment levels.
GP-initiated preconception counselling in a randomised controlled trial does not induce anxiety
Authors: de Jong-Potjer LC , Elsinga J , le Cessie S , van der Pal-de Bruin KM , Neven A Knuistingh , Buitendijk SE , Assendelft WJJ
Published: November 2006

Background

Preconception counselling (PCC) can reduce adverse pregnancy outcome by addressing risk factors prior to pregnancy. This study explores whether anxiety is induced in women either by the offer of PCC or by participation with GP-initiated PCC.

Methods

Randomised trial of usual care versus GP-initiated PCC for women aged 18–40, in 54 GP practices in the Netherlands. Women completed the six-item Spielberger State Trait Anxiety Inventory (STAI) before PCC (STAI-1) and after (STAI-2). After pregnancy women completed a STAI focusing on the first trimester of pregnancy (STAI-3).

Results

The mean STAI-1-score (n = 466) was 36.4 (95% CI 35.4 – 37.3). Following PCC there was an average decrease of 3.6 points in anxiety-levels (95% CI, 2.4 – 4.8). Mean scores of the STAI-3 were 38.5 (95% CI 37.7 – 39.3) in the control group (n = 1090) and 38.7 (95% CI 37.9 – 39.5) in the intervention group (n = 1186).

Conclusion

PCC from one's own GP reduced anxiety after participation, without leading to an increase in anxiety among the intervention group during pregnancy. We therefore conclude that GPs can offer PCC to the general population without fear of causing anxiety.

Trial Registration: ISRCTN53942912
Differential cooperation of oncogenes with p53 and Bax to induce apoptosis in rhabdomyosarcoma
Authors: Taylor Alan C , Schuster Katja , McKenzie Pamela P , Harris Linda C
Published: November 2006

Background

Deregulated expression of oncogenes such as MYC and PAX3-FKHR often occurs in rhabdomyosarcomas. MYC can enhance cell proliferation and apoptosis under specific conditions, whereas PAX3-FKHR has only been described as anti-apoptotic.

Results

In order to evaluate how MYC and PAX3-FKHR oncogenes influenced p53-mediated apoptosis, rhabdomyosarcoma cells were developed to independently express MYC and PAX3-FKHR cDNAs. Exogenous wild-type p53 expression in MYC transfected cells resulted in apoptosis, whereas there was only a slight effect in those transfected with PAX3-FKHR. Both oncoproteins induced BAX, but BAX induction alone without expression of wild-type p53 was insufficient to induce apoptosis. Data generated from genetically modified MEFs suggested that expression of all three proteins; MYC, BAX and p53, was required for maximal cell death to occur.

Conclusion

We conclude that cooperation between p53 and oncoproteins to induce apoptosis is dependent upon the specific oncoprotein expressed and that oncogene-mediated induction of BAX is necessary but insufficient to enhance p53-mediated apoptosis. These data demonstrate a novel relationship between MYC and p53-dependent apoptosis, independent of the ability of MYC to induce p53 that may be important in transformed cells other than rhabdomyosarcoma.
Myb proteins inhibit fibroblast transformation by v-Rel
Authors: Fu Shu-ling , Ganter Brigitte , Lipsick Joseph S
Published: November 2006

Genes that cause cancer have been divided into two general classes – oncogenes that act in a dominant fashion to transform normal cells into a malignant state, and tumor suppressor genes that act in a dominant fashion to prevent such transformation. In this report, we demonstrate that both the v-myb retroviral oncogene, which causes leukemic transformation of hematopoietic cells, and the c-myb proto-oncogene can also function as inhibitors of fibroblast transformation by the v-rel oncogene. These results imply that the myb genes can function either as oncogenes or as tumor suppressors in different cellular contexts.
Stromal Derived Factor-1 (SDF-1/CXCL12) and CXCR4 in renal cell carcinoma metastasis
Authors: Pan Judong , Mestas Javier , Burdick Marie D , Phillips Roderick J , Thomas George V , Reckamp Karen , Belperio John A , Strieter Robert M
Published: November 2006

Renal cell carcinoma (RCC) is characterized by organ-specific metastases. The chemokine stromal derived factor-1 (SDF-1/CXCL12) and its receptor CXCR4 have been suggested to regulate organ-specific metastasis in various other cancers. On this basis, we hypothesized that the biological axis of CXCL12 via interaction with its receptor, CXCR4, is a major mechanism for RCC metastasis. We demonstrated that CXCR4 was significantly expressed on circulating cytokeratin+ RCC cells from patients with known metastatic RCC. We detected up-regulation of CXCR4 mRNA and protein levels on a human RCC cell line by either knockdown of the von Hippel-Lindau (VHL) tumor suppressor protein, or incubating the cells under hypoxic conditions. The enhanced CXCR4 expression was mediated through the interaction of the Hypoxia Inducible Factor-1α (HIF-1α) with the promoter region of the CXCR4 gene. Furthermore, the expression of CXCR4 on human RCC directly correlated with their metastatic ability in vivo in both heterotopic and orthotopic SCID mouse models of human RCC. Neutralization of CXCL12 in SCID mice abrogated metastasis of RCC to target organs expressing high levels of CXCL12; without altering tumor cell proliferation, apoptosis, or tumor-associated angiogenesis. Therefore, our data suggest that the CXCL12/CXCR4 biological axis plays an important role in regulating the organ-specific metastasis of RCC.
Heparan sulfate proteoglycan-dependent neutrophil chemotaxis toward PR-39 cathelicidin
Authors: Djanani Angela , Mosheimer Birgit , Kaneider Nicole C , Ross Christopher R , Ricevuti Giovanni , Patsch Josef R , Wiedermann Christian J
Published: November 2006

Cathelicidins are mammalian proteins containing a C-terminal cationic antimicrobial domain. Porcine PR-39 cathelicidin affects leukocyte biology. Mechanisms of action may involve alteration of heparan sulfate proteoglycan-dependent functions in inflammatory cells. It was tested whether PR-39 affects human neutrophil migration and if such effects involve heparan sulphate proteoglycans. Neutrophils were from forearm venous blood of healthy donors. Migration was tested in modified Boyden chamber assays. Involvement of heparan sulfate proteoglycans was tested by their chemical modification and by the use of specific antibodies. PR-39 induced migration in neutrophils in a concentration dependent manner. Modification of heparan sulfate proteoglycans with sodium chlorate inhibited migration whereas chemotaxis toward the chemoattractant formyl-Met-Leu-Phe was not affected. Removal of heparan sulfates or chondroitin sulfates from the surface of neutrophils by heparinase or chondroitinase inhibited migration toward PR-39. In conclusion, antimicrobial PR-39 stimulates human neutrophil chemotaxis in a heparan sulfate proteoglycan-dependent manner. Involvment of syndecans is likely as both heparinase and chondroitinase were abrogating. Data suggest active participation of heparan sulfate proteoglycans of neutrophils in cathelicidin peptide-mediated regulation of the antimicrobial host defense.
The effects of incomplete protein interaction data on structural and evolutionary inferences
Authors: de Silva Eric , Thorne Thomas , Ingram Piers , Agrafioti Ino , Swire Jonathan , Wiuf Carsten , Stumpf Michael PH
Published: November 2006

Background

Present protein interaction network data sets include only interactions among subsets of the proteins in an organism. Previously this has been ignored, but in principle any global network analysis that only looks at partial data may be biased. Here we demonstrate the need to consider network sampling properties explicitly and from the outset in any analysis.

Results

Here we study how properties of the yeast protein interaction network are affected by random and non-random sampling schemes using a range of different network statistics. Effects are shown to be independent of the inherent noise in protein interaction data. The effects of the incomplete nature of network data become very noticeable, especially for so-called network motifs. We also consider the effect of incomplete network data on functional and evolutionary inferences.

Conclusion

Crucially, when only small, partial network data sets are considered, bias is virtually inevitable. Given the scope of effects considered here, previous analyses may have to be carefully reassessed: ignoring the fact that present network data are incomplete will severely affect our ability to understand biological systems.
Causes of death and determinants of outcome in critically ill patients
Authors: Mayr Viktoria D , Dünser Martin W , Greil Veronika , Jochberger Stefan , Luckner Günter , Ulmer Hanno , Friesenecker Barbara E , Takala Jukka , Hasibeder Walter R
Published: November 2006

Introduction

Whereas most studies focus on laboratory and clinical research, little is known about the causes of death and risk factors for death in critically ill patients.

Methods

Three thousand seven hundred patients admitted to an adult intensive care unit (ICU) were prospectively evaluated. Study endpoints were to evaluate causes of death and risk factors for death in the ICU, in the hospital after discharge from ICU, and within one year after ICU admission. Causes of death in the ICU were defined according to standard ICU practice, whereas deaths in the hospital and at one year were defined and grouped according to the ICD-10 (International Statistical Classification of Diseases and Related Health Problems) score. Stepwise logistic regression analyses were separately calculated to identify independent risk factors for death during the given time periods.

Results

Acute, refractory multiple organ dysfunction syndrome was the most frequent cause of death in the ICU (47%), and central nervous system failure (relative risk [RR] 16.07, 95% confidence interval [CI] 8.3 to 31.4, p < 0.001) and cardiovascular failure (RR 11.83, 95% CI 5.2 to 27.1, p < 0.001) were the two most important risk factors for death in the ICU. Malignant tumour disease and exacerbation of chronic cardiovascular disease were the most frequent causes of death in the hospital (31.3% and 19.4%, respectively) and at one year (33.2% and 16.1%, respectively).

Conclusion

In this primarily surgical critically ill patient population, acute or chronic multiple organ dysfunction syndrome prevailed over single-organ failure or unexpected cardiac arrest as a cause of death in the ICU. Malignant tumour disease and chronic cardiovascular disease were the most important causes of death after ICU discharge.
Understanding Surge Capacity: Essential Elements
Authors: Barbisch Donna F. , Koenig Kristi L.
Published: November 2006

As economic forces have reduced immediately available resources, the need to surge to meet patient care needs that exceed expectations has become an increasing challenge to the health care community. The potential patient care needs projected by pandemic influenza and bioterrorism catapulted medical surge to a critical capability in the list of national priorities, making it front‐page news. Proposals to improve surge capacity are abundant; however, surge capacity is poorly defined and there is little evidence‐based comprehensive planning. There are no validated measures of effectiveness to assess the efficacy of interventions. Before implementing programs and processes to manage surge capacity, it is imperative to validate assumptions and define the underlying components of surge. The functional components of health care and what is needed to rapidly increase capacity must be identified by all involved. Appropriate resources must be put into place to support planning factors. Using well‐grounded scientific principles, the health care community can develop comprehensive programs to prioritize activities and link the necessary resources. Building seamless surge capacity will minimize loss and optimize outcomes regardless of the degree to which patient care needs exceed capability.
Surge Capacity for Health Care Systems: Early Detection, Methodologies, and Process
Authors: Estacio Peter L.
Published: November 2006

Excessive demand on hospital services from large‐scale emergencies is something that every emergency department health care provider and hospital administrator knows could happen at any time. Nowhere in this country have we recently faced a disaster of the magnitude of concern we now face involving agents of mass destruction or social disruption, especially those in the area of infectious diseases and radiological materials. The war on terrorism is not a conventional war, and terrorists may use any means of convenience to carry out their objectives in an unpredictable time line. Have we adequately prepared for the potentially excessive surge in demand for medical services that a large‐scale event could bring to our medical care system? Are our emergency departments ready for such events? Surveillance systems, such as BioWatch, BioSense, the National Biosurveillance Integration System, and the countermeasure program BioShield, offer hope that we will be able to meet these new challenges.
Differentiating Large‐scale Surge versus Daily Surge
Authors: Jenkins J. Lee , O'Connor Robert E. , Cone David C.
Published: November 2006

This breakout session at the Academic Emergency Medicine 2006 Consensus Conference examined how baseline overcrowding impedes the ability of emergency departments to respond to sudden, unexpected surges in demand for patient care. Differences between daily and catastrophic surge were discussed, and the need to invoke a hospital‐wide response to surge was explored.
Annotated Bibliography on the Teaching of Psychology: 2005
Authors: Johnson David E. , Schroder Simone I.
Published: November 2006

This bibliography is a continuation of those previously published in Teaching of Psychology (e.g., Berry & Daniel, 1984; Fulkerson & Wise, 1987; Johnson & Schroder, 1997; Wise & Fulkerson, 1996). We maintained similar search methods and criteria for inclusion that were used in previous bibliographies. We also continued the cumulative numbering of the items.

To help the reader locate relevant articles, we arranged items into a small number of subject categories. Generally, if fewer than 3 items fell into a specific subject category, we relegated them to a category labeled miscellaneous.
Teaching Advanced Psychopathology: A Method That Promotes Basic Undergraduate Clinical and Research Experience
Authors: Balsis Steve , Eaton Nicholas R. , Zona Denise Martin , Oltmanns Thomas F.
Published: November 2006

Students in advanced psychopathology courses can learn key concepts by administering semistructured interviews designed to identify specific mental disorders. Such an active learning approach potentially can help students gain fundamental knowledge about psychopathology and begin to develop clinical and research skills. To explore the value of this technique as a tool for teaching about personality disorders, 7 students participated in an applied 2-semester course that focused on diagnostic interviewing. As part of the course, students learned to identify specific forms of personality pathology reliably in participants they interviewed (average K =.95, SD = .09), developed valuable clinical and research skills, and examined important conceptual issues.
Transgelin Functions as a Suppressor via Inhibition of ARA54-Enhanced Androgen Receptor Transactivation and Prostate Cancer Cell Growth
Authors: Yang Zhiming , Chang Yu-Jia , Miyamoto Hiroshi , Ni Jing , Niu Yuanjie , Chen Zhaodian , Chen Yuh-Ling , Yao Jorge L. , di Sant’Agnese P. Anthony , Chang Chawnshang
Published: November 2006

The androgen receptor (AR) requires coregulators for its optimal function. However, whether AR coregulators further need interacting protein(s) for their proper function remains unclear. Here we describe transgelin as the first ARA54-associated negative modulator for AR. Transgelin suppressed ARA54-enhanced AR function in ARA54-positive, but not in ARA54-negative, cells. Transgelin suppressed AR transactivation via interruption of ARA54 homodimerization and AR-ARA54 heterodimerization, resulting in the cytoplasmic retention of AR and ARA54. Stable transfection of transgelin in LNCaP cells suppressed AR-mediated cell growth and prostate-specific antigen expression, whereas this suppressive effect was abolished by the addition of ARA54-small interfering RNA. Results from tissue surveys showing decreased expression of transgelin in prostate cancer specimens further strengthened the suppressor role of transgelin. Our findings reveal the novel mechanisms of how transgelin functions as a suppressor to inhibit prostate cancer cell growth. They also demonstrate that AR coregulators, like ARA54, might have dual in vivo roles functioning as both a direct coactivator and as an indirect mediator in AR function. The finding that a protein can modulate AR function without direct interaction with AR might provide a new therapeutic approach, with fewer side effects, to battle prostate cancer by targeting AR indirectly.
An Adaptive Large Neighborhood Search Heuristic for the Pickup and Delivery Problem with Time Windows
Authors: Ropke Stefan , Pisinger David
Published: November 2006

The pickup and delivery problem with time windows is the problem of serving a number of transportation requests using a limited amount of vehicles. Each request involves moving a number of goods from a pickup location to a delivery location. Our task is to construct routes that visit all locations such that corresponding pickups and deliveries are placed on the same route, and such that a pickup is performed before the corresponding delivery. The routes must also satisfy time window and capacity constraints.

This paper presents a heuristic for the problem based on an extension of the large neighborhood search heuristic previously suggested for solving the vehicle routing problem with time windows. The proposed heuristic is composed of a number of competing subheuristics that are used with a frequency corresponding to their historic performance. This general framework is denoted adaptive large neighborhood search.

The heuristic is tested on more than 350 benchmark instances with up to 500 requests. It is able to improve the best known solutions from the literature for more than 50% of the problems.

The computational experiments indicate that it is advantageous to use several competing subheuristics instead of just one. We believe that the proposed heuristic is very robust and is able to adapt to various instance characteristics.
Robust Airline Fleet Assignment: Imposing Station Purity Using Station Decomposition
Authors: Smith Barry C. , Johnson Ellis L.
Published: November 2006

Fleet assignment models (FAM) are used by many airlines to assign aircraft to flights in a schedule to maximize profit. Major airlines report that the use of FAM increases annual profits by more than $100 million. The results of FAM affect subsequent planning, marketing, and operational processes within the airline. Anticipating these processes and developing solutions favorable to them can further increase the benefits of FAM. We develop fleet assignment solutions that increase planning flexibility and reduce cost by imposing station purity, limiting the number of fleet types allowed to serve each airport in the schedule. We demonstrate that imposing station purity on the FAM can limit aircraft dispersion in the network and make solutions more robust relative to crew planning, maintenance planning, and operations. Because station purity can significantly degrade computational efficiency, we develop a solution approach, station decomposition, which takes advantage of airline network structure. Station decomposition uses a column generation approach to solving the fleet assignment problem; we further improve the performance of station decomposition by developing a primal-dual method that increases solution quality and model efficiency. Station decomposition solutions can be highly fractional; we develop a “fix-and-price” heuristic to efficiently find integer solutions to the fleet assignment problem. We estimate that the annual net benefit of station purity because of reduced maintenance and crew scheduling costs is greater than $100 million for a major U.S. domestic airline.
The Effect of Reference Point on Stochastic Network Equilibrium
Authors: Avineri Erel
Published: November 2006

Following studies of human decision making under risk and uncertainty, an extensive evidence of loss aversion and asymmetric risk-taking behavior around a reference point was found. Prospect theory proposes an alternative framework to the traditional risk-taking modeling in travel behavior, which might be too simplistic. This paper examines the possibility of applying prospect theory for modeling stochastic network equilibrium, and presents an investigation of the effect of reference point value on such equilibrium. Conceptual and methodological issues that could be addressed by further research in transportation research are suggested.
Solving a Dynamic and Stochastic Vehicle Routing Problem with a Sample Scenario Hedging Heuristic
Authors: Hvattum Lars M. , Løkketangen Arne , Laporte Gilbert
Published: November 2006

The statement of the standard vehicle routing problem cannot always capture all aspects of real-world applications. As a result, extensions or modifications to the model are warranted. Here we consider the case when customers can call in orders during the daily operations; i.e., both customer locations and demands may be unknown in advance. This is modeled as a combined dynamic and stochastic programming problem, and a heuristic solution method is developed where sample scenarios are generated, solved heuristically, and combined iteratively to form a solution to the overall problem.
MALDI-TOF Mass Spectrometry for Multiplex Genotyping of CYP2B6 Single-Nucleotide Polymorphisms
Authors: Blievernicht Julia K , Schaeffeler Elke , Klein Kathrin , Eichelbaum Michel , Schwab Matthias , Zanger Ulrich M
Published: November 2006

Background: CYP2B6 is a highly variable and polymorphic cytochrome P450 (CYP) enzyme involved in the biotransformation of an increasing number of drugs, including cyclophosphamide, bupropion, and the nonnucleosidic reverse transcriptase inhibitor efavirenz. Several nonsynonymous and promoter single-nucleotide polymorphisms (SNPs) in the CYP2B6 gene are associated with altered hepatic expression and function, which affect drug plasma concentrations.

Methods: We used multiplex PCR to amplify relevant gene fragments while avoiding amplification of the CYP2B7P1 pseudogene. Polymorphic sites were analyzed by allele-specific primer extension followed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Method evaluation was performed on a panel of 287 genomic DNA samples previously genotyped by other methods.

Results: Five multiplex assays were developed, comprising the following 15 SNPs: −82T→C (*22); 86G→C (R29T, *17); 136A→G (M46V, *11); 296G→A (G99E, *12); 415A→G (K139E, *8, *13); 419G→A (R140Q, *14); 516G→T (Q172H, *6, *7, *9, *13, *19, *20), 547G→A (V183I); 769G→A (D257N); 785A→G (K262R, *4, *6, *7, *13, *16, *19, *20); 983T→C (I328T, *16, *18); 1006C→T (R336C, *19); 1172T→A (I391N, *15); 1282C→A (P428T, *21); 1459C→T (R487C, *5, *7). In 9 DNA samples showing discrepant genotypes, correctness of the MALDI-TOF MS result was confirmed by direct sequencing.

Conclusions: This genotyping method enabled sensitive, specific, accurate, and comprehensive determination of 15 relevant SNPs of CYP2B6. The assay design allows analysis of SNP subsets, incorporation of additional SNPs, and performance of high-throughput genotyping.