bluuebunny/crossref_metadata_2025 huggingface dataset:
Triad Instability of Planetary Rossby Waves
Authors: Zhang Yu , Pedlosky Joseph
Published: September 2007

The triad instability of the large-scale, first-mode, baroclinic Rossby waves is studied in the context of the planetary scale when the Coriolis parameter is to its lowest order varying with latitude. Accordingly, rather than remain constant as in quasigeostrophic theory, the deformation radius also changes with latitude, yielding new and interesting features to the propagation and triad instability processes. On the planetary scale, baroclinic waves vary their meridional wavenumbers along group velocity rays while they conserve both frequencies and zonal wavenumbers. The amplitudes of both barotropic and baroclinic waves would change with latitude along a ray path in the same way that the Coriolis parameter does if effects of the nonlinear interaction are ignored. The triad interaction for a specific triad is localized within a small latitudinal band where the resonance conditions are satisfied and quasigeostrophic theory is applicable locally. Using the growth rate from that theory as a measure, at each latitude along the ray path of the basic wave, a barotropic wave and a secondary baroclinic wave are picked up to form the most unstable triad and the distribution of this maximum growth rate is examined. It is found to increase southward under the assumption that triad interactions do not cause a noticeable decrease in the quantity of the basic wave’s amplitude divided by the Coriolis parameter. Different barotropic waves that maximize the growth rate at different latitudes have almost the same meridional length scale, on the order of the deformation radius. With many rays starting from different latitudes on the eastern boundary and with wavenumbers on each of them satisfying the no-normal-flow condition, the resulting two-dimensional distribution of the growth rate is a complicated function of the relative relations of zonal wavenumbers or frequencies on different rays and the orientation of the eastern boundary. In general, the growth rate is largest on rays originating to the north.
The Role of Bottom Vortex Stretching on the Path of the North Atlantic Western Boundary Current and on the Northern Recirculation Gyre
Authors: Zhang Rong , Vallis Geoffrey K.
Published: September 2007

The mechanisms affecting the path of the depth-integrated North Atlantic western boundary current and the formation of the northern recirculation gyre are investigated using a hierarchy of models, namely, a robust diagnostic model, a prognostic model using a global 1° ocean general circulation model coupled to a two-dimensional atmospheric energy balance model with a hydrological cycle, a simple numerical barotropic model, and an analytic model. The results herein suggest that the path of this boundary current and the formation of the northern recirculation gyre are sensitive to both the magnitude of lateral viscosity and the strength of the deep western boundary current (DWBC). In particular, it is shown that bottom vortex stretching induced by a downslope DWBC near the south of the Grand Banks leads to the formation of a cyclonic northern recirculation gyre and keeps the path of the depth-integrated western boundary current downstream of Cape Hatteras separated from the North American coast. Both south of the Grand Banks and at the crossover region of the DWBC and Gulf Stream, the downslope DWBC induces strong bottom downwelling over the steep continental slope, and the magnitude of the bottom downwelling is locally stronger than surface Ekman pumping velocity, providing strong positive vorticity through bottom vortex-stretching effects. The bottom vortex-stretching effect is also present in an extensive area in the North Atlantic, and the contribution to the North Atlantic subpolar and subtropical gyres is on the same order as the local surface wind stress curl. Analytic solutions show that the bottom vortex stretching is important near the western boundary only when the continental slope is wider than the Munk frictional layer scale.
Regimes of Thermocline Scaling: The Interaction of Wind Stress and Surface Buoyancy
Authors: Cessi Paola
Published: September 2007

The role of the relative geometry of mechanical forcing (wind stress) and buoyancy forcing (prescribed surface temperature) in the maintenance of the main thermocline is explored. In particular, the role of the wind stress curl in enhancing or suppressing the generation of baroclinic eddies is studied in simplified domains. The dependence of key quantities, such as the depth of the thermocline and the maximum heat transport, on the external parameters such as diapycnal mixing and dissipation rate is examined. Qualitatively different regimes are found depending on the relative phase of the wind stress and surface buoyancy distribution. The most efficient arrangement for eddy generation has Ekman pumping (suction) in conjunction with high (low) surface buoyancy. This corresponds to the situation found in the midlatitudes, where the surface Ekman flow carries heat toward the warmer region (i.e., upgradient of the surface temperature). In this case, strong eddy fluxes are generated in order to counteract the upgradient heat transport by the Ekman cell. The result is a thermocline whose depth is independent of the diapycnal diffusivity. However, the competition between these opposing heat fluxes leads to a weak net heat transport, proportional to the diffusivity responsible for the diabatic forcing. This arrangement of wind stress provides a large source of available potential energy on which eddies can grow, so the mechanical energy balance for the eddies is consistent with a substantial eddy heat flux. When the same surface temperature distribution is paired with the opposite wind stress curl, the mean flow produces a sink, rather than a source, of available potential energy and eddies are suppressed. With this arrangement, typical of low latitudes and the subpolar regions, the Ekman overturning cell carries heat downgradient of the surface temperature. Thus, the net heat transport is almost entirely due to the Ekman flow and is independent of the diapycnal diffusivity. At the same time the thermocline is a thin, diffusive boundary layer. Quantitative scalings for the thermocline depth and the poleward heat transport in these two limiting cases are contrasted and successfully compared with eddy-resolving computations.
Gravity Current Dynamics and Entrainment—A Process Study Based on Observations in the Arkona Basin
Authors: Arneborg Lars , Fiekas Volker , Umlauf Lars , Burchard Hans
Published: September 2007

A 19-h time series of dissipation, stratification, and horizontal velocities has been obtained for a dense gravity current flowing into the Arkona Basin in the western Baltic Sea. The observations are compared with one-dimensional, quasi-steady theory, in which the gravity component in the flow direction is balanced by bottom friction, while that in the cross-flow direction is balanced by the Coriolis force. The observations deviate from the theory in that the bottom shear stress is more than 2 times as large as that required to balance the gravity. Several reasons for this discrepancy are discussed. A 1D turbulence model is also compared with the observations. Profiles of velocity, stratification, and dissipation rates generally show similar variations with depth as the observations, although the observed dissipation rates are somewhat larger than the modeled and the modeled transverse velocities are much larger than the observed. Subsequently, the model is used to investigate the variation of the entrainment parameter for a large range of Ekman and Froude numbers. Within the modeled parameter space, the entrainment parameter can be collapsed onto a curve that is an increasing function of both the Froude and the Ekman numbers. There is one puzzling result of the observations that differs from the model results and earlier observations: the observed entrainment rate increases dramatically during the observation period, where the Froude number decreases slightly. Some reasons for this increase are discussed.
Thermodynamic Analysis of Ocean Circulation
Authors: Nycander J. , Nilsson J. , Döös K. , Broström G.
Published: September 2007

Calculating a streamfunction as function of depth and density is proposed as a new way of analyzing the thermodynamic character of the overturning circulation in the global ocean. The sign of an overturning cell in this streamfunction directly shows whether it is driven mechanically by large-scale wind stress or thermally by heat conduction and small-scale mixing. It is also shown that the integral of this streamfunction gives the thermodynamic work performed by the fluid. The analysis is also valid for the Boussinesq equations, although formally there is no thermodynamic work in an incompressible fluid. The proposed method is applied both to an idealized coarse-resolution three-dimensional numerical ocean model, and to the realistic high-resolution Ocean Circulation and Climate Advanced Model (OCCAM). It is shown that the overturning circulation in OCCAM between the 200- and 1000-m depth is dominated by a thermally indirect cell of 24 Sverdrups (1 Sv ≡ 106 m3 s−1), forced by Ekman pumping. In the densest and deepest waters there is a thermally direct cell of 18 Sv, which requires a forcing by around 100 GW of parameterized small-scale mixing.
Unpackaging Cross-Cultural Differences in Initiation Between Israeli Subgroups
Authors: Kurman Jenny , Dan Orrie
Published: September 2007

This study was designed to gain a better understanding of cross-cultural differences in initiation behavior within the relatively Westernized Israeli society. It has been suggested that traditional subgroups in Israel exhibit lower initiation behavior than the majority group and that control orientations mediate this difference based on their high relevance to initiation and their previously established difference in modern versus traditional cultures. A sample of 178 students comprised of members of the majority group and of two traditional subgroups (Israeli Arabs and Israelis of Ethiopian origin) was investigated. The modern and traditional groups were compared on two measures of initiation: a behavioral measure that required minimal initiation and a self-reported measure of initiation behavior. Models showed that the expected cross-cultural differences in initiation were unpackaged by tradition and control orientations, with tradition, secondary control, and relinquished control serving as meaningful mediators. Primary control was a less proximal predictor.
Embracing American Culture
Authors: Mok Aurelia , Morris Michael W. , Benet-Martínez Verónica , Karakitapoğlu-Aygün Zahide
Published: September 2007

This study examines the relationship between bicultural individuals' identity structure and their friendship network. A key dimension of identity structure for first-generation immigrants is the degree to which the secondary, host-culture identity is integrated into the primary, ethnic identity. Among first-generation Chinese Americans, regression analyses controlling for cultural identification strengths show that more integrated identity structures are associated with larger and more richly interconnected circles of non-Chinese friends.
Toward a Useful Theory of Mentoring
Authors: Bozeman Barry , Feeney Mary K.
Published: September 2007

In this review and critique of mentoring theory and research, the authors identify persistent problems in the development of mentoring theory. Their conceptual analysis highlights these problems with a “thought experiment” illustrating the inability of mentoring theory and research to resolve certain fundamental issues, the resolution of which is a prerequisite for the advancement of explanatory theory. They conclude with ideas about demarcating “mentoring” from the sometimes confounding concepts “training” or “socialization.” Absent an ability to distinguish mentoring from related activities, progress in explanatory theory will remain impeded.
Distortions of Progress
Authors: Sementelli Arthur
Published: September 2007

Evolution and evolutionary theories in the social sciences in general, and applied fields in particular, are often grounded in the discredited (in biology) Lamarckian conceptualization. Lamarckian ideas of progress, with their associated teleology and totalizing influences, tend not to be useful for public administration. This article proposes that public administration instead consider an alternative image of evolution that enables the practical use of evolutionary theories, enabling them to better understand the nature of wicked problems in both theory and practice.
From “Pure” to “Hybrid” Professionalism
Authors: Noordegraaf Mirko
Published: September 2007

Public sectors struggle with professionalism. Classic professions are weakened, welfare state occupations professionalize, and public managers try to become professionals. This raises questions. What is professionalism? What is professional control in ambiguous occupational domains? What happens when different types of occupational control get mixed up? The first question is answered by portraying classic professionalism as “controlled content.” The second question is answered by tracing a transition from “pure” to “hybrid” professionalism in domains such as health care and social work. The third question is answered by portraying present-day professionalism as “content of control” instead of controlled content.
Popular Support for Grassroots Self-Government in Urban China
Authors: Jie Chen  , Chunlong Lu  , Yiyin Yang
Published: September 2007

Since the post-Mao reforms began, the Chinese central government has made efforts to revitalize the grassroots self-government system in urban areas in order to cope with the resulting sociopolitical changes. In 2000 the government stepped up its efforts by changing the old Residential Committee ( jumin weiyuanhui, or RC) to the new Community Residents' Committee ( shequ jumin weiyuanhui, or CRC) and by giving the latter more autonomy. Survey data that the authors collected in the urban areas of Beijing in 2004 indicate that most of their respondents supported the new CRCs and the current self-government system as a whole. Moreover, the authors found that urban residents' subjective orientations—such as their assessment of existing CRCs' performance, belief in democratic principles, sense of political efficacy, and life satisfaction—significantly influenced their support for the system; the type of housing complex was a sociopolitical contextual factor that also helped shape their support. These findings have important political implications for the future viability of the urban self-government system.
Roads Less Taken
Authors: Dykstra Pearl A. , Hagestad Gunhild O.
Published: September 2007

This article provides the rationale for doing research on childlessness and parenthood in late life. Childless older adults have been rendered invisible in the social scientific literature. A central goal of this issue is to make them visible and to expose unstated assumptions about normal adult life. Parenthood emerges as a key organizer of the life course and a major factor in social integration. Because the childless tend to be conceptualized as “the other,” focusing on them teaches lessons about the dangers of dichotomous thinking, that is, overlooking diversity and assuming deficiency. Studying older adults without children reveals the necessity of considering life pathways over time and of putting lives in a historical context.
Characteristics of Older Childless Persons and Parents
Authors: Koropeckyj-Cox Tanya , Call Vaughn R. A.
Published: September 2007

The prevalence and implications of childlessness in old age are compared across nine major surveys in seven countries: Australia, Finland, Germany, Japan, the Netherlands, the United Kingdom, and the United States. Specifically, the researchers examine indicators of the well-being and resources of childless men and women, compare them to their within-country peers with children, and explore the similarities and differences among childless older adults in different countries. The results show strikingly similar patterns across countries (with the exception of Japan). Childless elders are more likely than parents to live alone or in an institution. Childless never-married women have consistently higher education levels than other groups of women. Among men, marriage rather than parenthood is consistently linked with higher socio-economic status. The results suggest important structural processes that differentially shape the resources and well-being of men and women, childless and parents, over the life course and in old age.
Three-Dimensional Vibration Analyses of Functionally Graded Plates under Various Boundary Conditions
Authors: Uymaz Bahar , Aydogdu Metin
Published: September 2007

Three-dimensional vibration solutions are presented for rectangular functionally graded plates with different boundary conditions, based on the small strain linear elasticity theory. The material properties are assumed to vary as a power form of the thickness coordinate. The Ritz method with Chebyshev displacement functions is used to solve the vibration problem of functionally graded plates. The convergence and comparison studies demonstrate the accuracy and correctness of the present method. The effects of aspect and thickness ratios, and gradient index, on the free vibration frequencies are investigated. Some results are given in the form of tables and figures, which can serve as the benchmark for further research.
Working Memory in an Editing Task
Authors: Hayes John R. , Ann Chenoweth N.
Published: September 2007

A number of studies have found that writers produce text in bursts of language. That is, when creating a text, writers produce a few words, pause, produce a few more words, pause, and so on. Chenoweth and Hayes (2003) hypothesized that language bursts occur when writers translate ideas in to new language. This study tested this hypothesis against the following two alternative hypotheses: (a) Language bursts are caused by proposing new ideas rather than by translating ideas in to written language and (b) language bursts depend on the form of the input to the writing process rather than on the translation process. The study employed an editing task in which participants were required to translate a written language input. The alternative hypotheses led to contradictory predictions about writers' performance in this task. The study also explored the impact of working memory restrictions on task performance.
More Than Just Error Correction
Authors: Myhill Debra , Jones Susan
Published: September 2007

Drawing on the second phase of a 2-year study of students' linguistic and compositional processes, this article describes students' reflections on their online revision processes, those revisions made during the process of translating thoughts into written text. The data collected were from classroom observation and post hoc interviews with 34 students, who were observed during a writing task in the English classrooms and interviewed subsequently to elicit their reflections and understandings of their own revising processes. The analysis indicates that students tend to conceptualize revision as a macro-strategy and as a task that is predominantly undertaken as a posttextual production reviewing activity. It also indicates that students engage in multiple revising activities during writing, including many revisions that are not concerned with simple matters of surface accuracy, and many students are able to talk about these perceptively and with insight.
Professional Editing Strategies Used by Six Editors
Authors: Bisaillon Jocelyne
Published: September 2007

Identifying the approach used by those revision experts par excellence—that is, professional editors—should enable researchers to better grasp the revision process. To further explore this hypothesis, the author conducted research among professional editors, six of whom she filmed as they engaged in their practice. An analysis of their work approach strategies showed their detection strategies to consist in anticipating errors and in comparing the author's text with the editor's knowledge, which appears in a range of states: certitude, uncertainty, and ignorance. Furthermore, the participating editors used problem-solving strategies to automatically solve more than half of the problems encountered in the text. Otherwise, they used immediate or postponed strategies. This description of professional editors in action opens a number of avenues for the further research and development of in-class instruction of self-revision and professional editing.
Management of platinum-based chemotherapy-induced acute nausea and vomiting: is there a superior serotonin receptor antagonist?
Authors: Hamadani Mehdi , Chaudhary Lubna , Awan Farrukh T. , Khan Jawad K. , Kojouri Kiarash , Ozer Howard , Tfayli Arafat
Published: September 2007

Objective. The last decade has witnessed the great impact of 5-hydroxytryptamine-3 receptor (5-HT3) antagonists in revolutionizing the management of platinum-based chemotherapy–induced acute nausea and vomiting (CINV). However, despite the availability of a variety of 5-HT3 antagonists, little data is published to support superiority of one drug over another, leaving the choice of serotonin receptor antagonist largely empirical. The National Comprehensive Cancer Network and American Society of Clinical Oncology guidelines for management of chemotherapy-associated nausea and vomiting clearly endorse the use of serotonin receptor antagonist; however, no single agent is preferred over the rest.

Methods. Data for patients (n¼159) receiving platinum-based chemotherapy regimens were retrospectively collected. Patients getting 5-HT3 antagonists without steroids or those with known history of brain metastasis, gastroparesis, and intestinal obstruction were not eligible for the study. Patient characteristics including age, gender, primary diagnosis, history of heavy alcohol intake, chemotherapy regimen administered, number of cycles, and Eastern Cooperative Oncology Group performance status at the start of therapy were noted. Primary outcome was the complete control of platinum-induced acute nausea and vomiting. Secondary outcome measures included control of >grade 1 nausea or vomiting, comparison of two doses of dexamethasone, and antiemetic efficacy among various platinum drugs. National Cancer Institute Common Toxicity Criteria version 2.0 was used to assess toxicity.

Results. A total of 126 patients received 369 cycles of platinum-based therapy. Dolasetron (n¼157), granisetron (n¼81), and ondansetron (n¼131) achieved complete control of vomiting in 89.8, 95.5, and 92.3% (p¼0.67) of cycles, respectively. Respectively, complete nausea control was observed in 68.1, 75.3 and, 69.4% (p¼0.50). Dexamethasone 20 mg was not superior to 10 mg in complete control of nausea and vomiting (p¼0.15 and p¼0.63, respectively). However, complete nausea control was significantly better in the subgroup of patients getting cisplatin-compared with carboplatin-based regimens (78.8% vs. 67.7%, p50.05).

Conclusion. No significant difference exists in the antiemetic efficacy of the three 5-HT3 antagonists studied in controlling CINV when administered in combination with dexamethasone. Choice of antiemetic regimen should therefore be based on drug cost.
Dose-banding of carboplatin: rationale and proposed banding scheme
Authors: Kaestner Sabine , Sewell Graham
Published: September 2007

Background. In dose-banding (DB) prescribed doses of cancer chemotherapy are fitted to doseranges or ‘bands’ and standard doses for each band are provided using a selection of pre-filled infusions or syringes, either singly or in combination. DB is used for several drugs where dose is based on body surface area. No DB-scheme has been reported for carboplatin, which, in clinical practice, is routinely dosed according to renal function.

Study objective. To assess the rationale for DB of carboplatin with regards to factors that influence dosing accuracy, develop a DB scheme, and discuss its potential use and limitations.

Methods. Prospective evaluations of carboplatin area under the plasma concentration – time curve (AUC) following application of the Calvert-formula were identified by a literature search. A relevant carboplatin dose range for construction of a DB-scheme with Calvert-formula based doses was obtained from published glomerular filtration rate distributions for patients receiving carboplatin.

Results. A DB-scheme was developed for individually calculated carboplatin doses of 358–1232 mg, with 35 mg increments between each standard dose and a maximum deviation of 4.7% from prescribed dose. The proposed DB-scheme covers the GFR-ranges 47–221 mL/min and 26–151 mL/min for patients receiving doses based on the target AUCs of 5 and 7 mg/mL/min, respectively.

Conclusion. There is a strong scientific rationale to support DB of carboplatin. The proposed banding scheme could introduce benefits to patients and healthcare staff but, as with other DB schemes, should be validated with prospective clinical and pharmacokinetic studies to confirm safety and efficacy.
A sequential temperature cycling study for the investigation of carboplatin infusion stability to facilitate `dose-banding'
Authors: Kaestner Sabine , Sewell Graham
Published: September 2007

Study objective. To determine the physical and chemical stability of carboplatin infusion for dosebanding, with cycling between refrigerated storage and room temperature in-use conditions.

Design. A sequential study design was selected to closely simulate the temperatures and conditions experienced by drug infusions in pharmaceutical storage and in clinical use. Carboplatin infusions, 0.70 and 2.15 mg/mL, were stored refrigerated for up to 84 days, followed by incubation at 258C for 24 h. The infusions were also returned to refrigerated storage for 3 and 7 days, to replicate a situation in which returned, unused infusions are kept for re-issuing. On pre-determined time-points, infusion chemical and physical stability were determined by HLPC, sub-visual particulatecounts, pH-measurement, and weighing of infusions.

Results. Light protected carboplatin infusions at both study concentrations were chemically and physically stable following refrigerated storage for 84 days, followed by a further 24 h under ‘in-use’ conditions at 258C. Additionally, the infusions were stable following return to refrigerated storage again for at least 7 days.

Conclusion. This study has demonstrated extended stability of carboplatin infusions which enables batch-scale preparation of standard infusions for dose- J Oncol Pharm Practice (2007) 13: 119–126.
The Coming Son of Man Revisited
Authors: Kazen Thomas
Published: September 2007

The interpretation of the synoptic Son of Man is still a formidable swamp with no consensus emerging. Unfortunately, one of the most interesting suggestions, the collective interpretation of Manson, Moule and Gaston, has been somehow left by the wayside. It has certain advantages, however, in respecting both the basic `generic' sense of an underlying Semitic expression and the Danielic kingdom imagery, without denying this expression for the historical Jesus. The present article focuses on the coming Son of Man sayings and demonstrates the plausibility of applying a collective interpretation to them. The result is an eschatology, focusing not on an individual redeemer figure, but on the manifestation of the Kingdom in community practice. Some suggestions are offered for how such an eschatology, based on a collective interpretation of the coming Son of Man, could `mutate' so quickly into the idea of a second coming of Christ.
Effect of single nucleotide polymorphisms on expression of the gene encoding thrombin-activatable fibrinolysis inhibitor: a functional analysis
Authors: Boffa Michael B. , Maret Deborah , Hamill Jeffrey D. , Bastajian Nazareth , Crainich Paul , Jenny Nancy S. , Tang Zhonghua , Macy Elizabeth M. , Tracy Russell P. , Franco Rendrik F. , Nesheim Michael E. , Koschinsky Marlys L.
Published: September 2007

Thrombin-activable fibrinolysis inhibitor (TAFI) is a plasma zymogen that acts as a molecular link between coagulation and fibrinolysis. Numerous single nucleotide polymorphisms (SNPs) have been identified in CPB2, the gene encoding TAFI, and are located in the 5′-flanking region, in the coding sequences, and in the 3′-untranslated region (UTR) of the CPB2 mRNA transcript. Associations between CPB2 SNPs and variation in plasma TAFI antigen concentrations have been described, but the identity of SNPs that are causally linked to this variation is not known. In the current study, we investigated the effect of the SNPs in the 5′-flanking region on CPB2 promoter activity and SNPs in the 3′-UTR on CPB2 mRNA stability. Whereas the 5′-flanking region SNPs (with 2 exceptions) did not have a significant effect on promoter activity, either alone or in haplotypic combinations seen in the human population, all of the 3′-UTR SNPs substantially affected mRNA stability. We speculate that these SNPs, in part, contribute to variation in plasma TAFI concentrations via modulation of CPB2 gene expression through an effect on mRNA stability.
Aberrant V(D)J recombination is not required for rapid development of H2ax/p53-deficient thymic lymphomas with clonal translocations
Authors: Bassing Craig H. , Ranganath Sheila , Murphy Mike , Savic Velibor , Gleason Meagan , Alt Frederick W.
Published: September 2007

Histone H2AX is required to maintain genomic stability in cells and to suppress malignant transformation of lymphocytes in mice. H2ax−/−p53−/− mice succumb predominantly to immature αβ T-cell lymphomas with translocations, deletions, and genomic amplifications that do not involve T-cell receptor (TCR). In addition, H2ax−/−p53−/− mice also develop at lower frequencies B and T lymphomas with antigen receptor locus translocations. V(D)J recombination is initiated through the programmed induction of DNA double-strand breaks (DSBs) by the RAG1/RAG2 endonuclease. Because promiscuous RAG1/RAG2 cutting outside of antigen receptor loci can promote genomic instability, H2ax−/−p53−/− T-lineage lymphomas might arise, at least in part, through erroneous V(D)J recombination. Here, we show that H2ax−/−p53−/−Rag2−/− mice exhibit a similar genetic predisposition as do H2ax−/−p53−/− mice to thymic lymphoma with translocations, deletions, and amplifications. We also found that H2ax−/−p53−/−Rag2−/− mice often develop thymic lymphomas with loss or deletion of the p53+ locus. Our data show that aberrant V(D)J recombination is not required for rapid onset of H2ax/p53-deficient thymic lymphomas with genomic instability and that H2ax deficiency predisposes p53−/−Rag2−/− thymocytes to transformation associated with p53 inactivation. Thus, H2AX is essential for suppressing the transformation of developing thymocytes arising from the aberrant repair of spontaneous DSBs.
Support Vector Machine-based method for predicting subcellular localization of mycobacterial proteins using evolutionary information and motifs
Authors: Rashid Mamoon , Saha Sudipto , Raghava Gajendra PS
Published: September 2007

Background

In past number of methods have been developed for predicting subcellular location of eukaryotic, prokaryotic (Gram-negative and Gram-positive bacteria) and human proteins but no method has been developed for mycobacterial proteins which may represent repertoire of potent immunogens of this dreaded pathogen. In this study, attempt has been made to develop method for predicting subcellular location of mycobacterial proteins.

Results

The models were trained and tested on 852 mycobacterial proteins and evaluated using five-fold cross-validation technique. First SVM (Support Vector Machine) model was developed using amino acid composition and overall accuracy of 82.51% was achieved with average accuracy (mean of class-wise accuracy) of 68.47%. In order to utilize evolutionary information, a SVM model was developed using PSSM (Position-Specific Scoring Matrix) profiles obtained from PSI-BLAST (Position-Specific Iterated BLAST) and overall accuracy achieved was of 86.62% with average accuracy of 73.71%. In addition, HMM (Hidden Markov Model), MEME/MAST (Multiple Em for Motif Elicitation/Motif Alignment and Search Tool) and hybrid model that combined two or more models were also developed. We achieved maximum overall accuracy of 86.8% with average accuracy of 89.00% using combination of PSSM based SVM model and MEME/MAST. Performance of our method was compared with that of the existing methods developed for predicting subcellular locations of Gram-positive bacterial proteins.

Conclusion

A highly accurate method has been developed for predicting subcellular location of mycobacterial proteins. This method also predicts very important class of proteins that is membrane-attached proteins. This method will be useful in annotating newly sequenced or hypothetical mycobacterial proteins. Based on above study, a freely accessible web server TBpred http://www.imtech.res.in/raghava/tbpred/ has been developed.
The extracellular Leucine-Rich Repeat superfamily; a comparative survey and analysis of evolutionary relationships and expression patterns
Authors: Dolan Jackie , Walshe Karen , Alsbury Samantha , Hokamp Karsten , O'Keeffe Sean , Okafuji Tatsuya , Miller Suzanne FC , Tear Guy , Mitchell Kevin J
Published: September 2007

Background

Leucine-rich repeats (LRRs) are highly versatile and evolvable protein-ligand interaction motifs found in a large number of proteins with diverse functions, including innate immunity and nervous system development. Here we catalogue all of the extracellular LRR (eLRR) proteins in worms, flies, mice and humans. We use convergent evidence from several transmembrane-prediction and motif-detection programs, including a customised algorithm, LRRscan, to identify eLRR proteins, and a hierarchical clustering method based on TribeMCL to establish their evolutionary relationships.

Results

This yields a total of 369 proteins (29 in worm, 66 in fly, 135 in mouse and 139 in human), many of them of unknown function. We group eLRR proteins into several classes: those with only LRRs, those that cluster with Toll-like receptors (Tlrs), those with immunoglobulin or fibronectin-type 3 (FN3) domains and those with some other domain. These groups show differential patterns of expansion and diversification across species. Our analyses reveal several clusters of novel genes, including two Elfn genes, encoding transmembrane proteins with eL RRs and an FN 3 domain, and six genes encoding transmembrane proteins with eLR Rs on ly (the Elron cluster). Many of these are expressed in discrete patterns in the developing mouse brain, notably in the thalamus and cortex. We have also identified a number of novel fly eLRR proteins with discrete expression in the embryonic nervous system.

Conclusion

This study provides the necessary foundation for a systematic analysis of the functions of this class of genes, which are likely to include prominently innate immunity, inflammation and neural development, especially the specification of neuronal connectivity.
Molecular characterization and temporal expression profiling of presenilins in the developing porcine brain
Authors: Madsen Lone B , Thomsen Bo , Larsen Knud , Bendixen Christian , Holm Ida E , Fredholm Merete , Jørgensen Arne L , Nielsen Anders L
Published: September 2007

Background

The transmembrane presenilin (PSEN) proteins, PSEN1 and PSEN2, have been proposed to be the catalytic components of the γ-secretase protein complex, which is an intramembranous multimeric protease involved in development, cell regulatory processes, and neurodegeneration in Alzheimer's disease. Here we describe the sequencing, chromosomal mapping, and polymorphism analysis of PSEN1 and PSEN2 in the domestic pig (Sus scrofa domesticus).

Results

The porcine presenilin proteins showed a high degree of homology over their entire sequences to the PSENs from mouse, bovine, and human. PSEN1 and PSEN2 transcription was examined during prenatal development of the brain stem, hippocampus, cortex, basal ganglia, and cerebellum at embryonic days 60, 80, 100, and 114, which revealed distinct temporal- and tissue-specific expression profiles. Furthermore, immunohistochemical analysis of PSEN1 and PSEN2 showed similar localization of the proteins predominantly in neuronal cells in all examined brain areas.

Conclusion

The data provide evidence for structural and functional conservation of PSENs in mammalian lineages, and may suggest that the high sequence similarity and colocalization of PSEN1 and PSEN2 in brain tissue reflect a certain degree of functional redundancy. The data show that pigs may provide a new animal model for detailed analysis of the developmental functions of the PSENs.
Differential regulation of iron chelator-induced IL-8 synthesis via MAP kinase and NF-κB in immortalized and malignant oral keratinocytes
Authors: Lee Hwa-Jeong , Lee Jun , Lee Sun-Kyung , Lee Suk-Keun , Kim Eun-Cheol
Published: September 2007

Background

Interleukin-8 (IL-8) is a cytokine that plays an important role in tumor progression in a variety of cancer types; however, its regulation is not well understood in oral cancer cells. In the present study, we examined the expression and mechanism of IL-8 in which it is involved by treating immortalized (IHOK) and malignant human oral keratinocytes (HN12) cells with deferoxamine (DFO).

Methods

IL-8 production was measured by an enzyme-linked immunoabsorbent assay and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. Electrophoretic mobility shift assays was used to determine NF-κB binding activity. Phosphorylation and degradation of the I-κB were analyized by Western blot.

Results

IHOK cells incubated with DFO showed increased expression of IL-8 mRNA, as well as higher release of the IL-8 protein. The up-regulation of DFO-induced IL-8 expression was higher in IHOK cells than in HN12 cells and was concentration-dependent. DFO acted additively with IL-1β to strongly up-regulate IL-8 in IHOK cells but not in HN12 cells. Accordingly, selective p38 and ERK1/2 inhibitors for both kinases abolished DFO-induced IL-8 expression in both IHOK and HN12 cells. Furthermore, DFO induced the degradation and phosphorylation of IκB, and activation of NF-κB. The IL-8 inducing effects of DFO were mediated by a nitric oxide donor (S-nitrosoglutathione), and by pyrrolidine dithiocarbamate, an inhibitor of NF-κB, as well as by wortmannin, which inhibits the phosphatidylinositol 3-kinase-dependent activation of NAD(P)H oxidase.

Conclusion

This results demonstrate that DFO-induced IL-8 acts via multiple signaling pathways in immortalized and malignant oral keratinocytes, and that the control of IL-8 may be an important target for immunotheraphy against human oral premalignant lesions.
A conserved gene family encodes transmembrane proteins with fibronectin, immunoglobulin and leucine-rich repeat domains (FIGLER)
Authors: Munfus Delicia L , Haga Christopher L , Burrows Peter D , Cooper Max D
Published: September 2007

Background

In mouse the cytokine interleukin-7 (IL-7) is required for generation of B lymphocytes, but human IL-7 does not appear to have this function. A bioinformatics approach was therefore used to identify IL-7 receptor related genes in the hope of identifying the elusive human cytokine.

Results

Our database search identified a family of nine gene candidates, which we have provisionally named fibronectin immunoglobulin leucine-rich repeat (FIGLER). The FIGLER 1–9 genes are predicted to encode type I transmembrane glycoproteins with 6–12 leucine-rich repeats (LRR), a C2 type Ig domain, a fibronectin type III domain, a hydrophobic transmembrane domain, and a cytoplasmic domain containing one to four tyrosine residues. Members of this multichromosomal gene family possess 20–47% overall amino acid identity and are differentially expressed in cell lines and primary hematopoietic lineage cells. Genes for FIGLER homologs were identified in macaque, orangutan, chimpanzee, mouse, rat, dog, chicken, toad, and puffer fish databases. The non-human FIGLER homologs share 38–99% overall amino acid identity with their human counterpart.

Conclusion

The extracellular domain structure and absence of recognizable cytoplasmic signaling motifs in members of the highly conserved FIGLER gene family suggest a trophic or cell adhesion function for these molecules.
Susceptibility of schizophrenia and affective disorder not associated with loci on chromosome 6q in Han Chinese population
Authors: Wang Zuowei , Fang Yiru , Yu Shunying , Yuan Chengmei , Hong Wu , Yi Zhenghui , Jiang Sanduo , John R Kelsoe , Wang Zucheng
Published: September 2007

Background

Several linkage studies across multiple population groups provide convergent support for susceptibility loci for schizophrenia – and, more recently, for affective disorder – on chromosome 6q. We explore whether schizophrenia and affective disorder have common susceptibility gene on 6q in Han Chinese population.

Methods

In the present study, we genotyped 45 family trios from Han Chinese population with mixed family history of schizophrenia and affective disorder. Twelve short tandem repeat (STRs) markers were selected, which covered 102.19 cM on chromosome 6q with average spacing 9.29 cM and heterozygosity 0.78. The transmission disequilibrium test (TDT) was performed to search for susceptibility loci to schizophrenia and affective disorder.

Results

The results showed STRs D6S257, D6S460, D6S1021, D6S292 and D6S1581 were associated with susceptibility to psychotic disorders. When families were grouped into schizophrenia and affective disorder group, D6S257, D6S460 and D6S1021, which map closely to the centromere of chromosome 6q, were associated with susceptibility to schizophrenia. Meanwhile, D6S1581, which maps closely to the telomere, was associated with susceptibility to affective disorder. But after correction of multiple test, all above association were changed into no significance (P > 0.05).

Conclusion

These results suggest that susceptibility of schizophrenia and affective disorder not associated with loci on chromosome 6q in Han Chinese population.
DetectiV: visualization, normalization and significance testing for pathogen-detection microarray data
Authors: Watson Michael , Dukes Juliet , Abu-Median Abu-Bakr , King Donald P , Britton Paul
Published: September 2007

DNA microarrays offer the possibility of testing for the presence of thousands of micro-organisms in a single experiment. However, there is a lack of reliable bioinformatics tools for the analysis of such data. We have developed DetectiV, a package for the statistical software R. DetectiV offers powerful yet simple visualization, normalization and significance testing tools. We show that DetectiV performs better than previously published software on a large, publicly available dataset.
Influence of Introduction of Positron Emission Tomography on Adherence to Mediastinal Staging Protocols and Performance of Mediastinoscopy
Authors: Goosens Martijn , Smulders Sietske A. , Smeenk Frank W. , Daniëls-Gooszen Alette W. , Donkers-van Rossum Astrid B. , Edelbroek Michela A. , Huysmans Dyde A. , Michels Arent-Jan , van Straten Bart A.H.M. , Postmus Pieter E.
Published: September 2007

Purpose

In this study, we investigated the impact of implementation of [18F] fluorodeoxyglucose positron emission tomography (FDG-PET) in daily practice on adherence to mediastinal staging protocols and performance of mediastinoscopy in non–small-cell lung cancer (NSCLC) patients who are possible candidates for surgical resection. Institutional review board approval was obtained.

Patients and Methods

From a nonuniversity teaching hospital and three surrounding community hospitals in Eindhoven, the Netherlands, we studied data from 143 patients with NSCLC who underwent mediastinoscopy and/or thoracotomy in three consecutive periods (1, 0 to 9 months; 2, 10 to 18 months; and 3, 19 to 31 months) after introduction of PET. Mediastinoscopy was indicated in case of enlarged and/or PET-positive nodes. Adherence to these surgical mediastinal staging guidelines and the performance of PET and mediastinoscopy were investigated and compared between the three periods and with our previous study before introduction of PET.

Results and Conclusion

Guidelines for indicating mediastinoscopy were adequately followed in significantly more instances after introduction of PET (80%), compared with the period before PET (66%). Optimal yield (lymph node stations 4, right and left, and 7) of mediastinoscopy (in 27% of patients) was not significantly different from the period before PET (39% of patients). Compared with the historical data, the percentage of positive mediastinoscopies increased from 15.5 to 17.6 (not significant). We found no significant differences between the three consecutive periods with regard to adequacy of indicating and performance of mediastinoscopy. After introduction of PET, adherence to staging guidelines with respect to mediastinoscopy improved. Although fewer mediastinoscopies had an optimal yield, more proved to be positive for metastases. Nevertheless, when a mediastinoscopy is indicated, surgeons must be encouraged to reach an optimal yield because PET positive nodes might be false negative. This occurred in 5% to 6% of all patients.
Dioxin Affects Glucose Transport via the Arylhydrocarbon Receptor Signal Cascade in Pluripotent Embryonic Carcinoma Cells
Authors: Tonack Sarah , Kind Karen , Thompson Jeremy G. , Wobus Anna M. , Fischer Bernd , Santos Anne Navarrete
Published: September 2007

Intoxication by dioxins such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) leads, among other damages, to early embryo loss, fetal malformations, and cardiovascular toxicity. Apart from binding to the arylhydrocarbon receptor (AhR), the mechanism of TCDD-mediated embryo toxicity is still unclear. We investigated possible modes of a TCDD-mediated toxicity, particularly in glucose metabolism, in pluripotent P19 mouse embryonic carcinoma cells. Undifferentiated P19 cells were exposed to 1–100 nm TCDD and characterized for AhR signaling. For studying cell differentiation, P19 cells were exposed to 10 nm TCDD at stage of embryoid body formation, and analyzed on glucose metabolism and cardiac differentiation during the next 3 wk. TCDD treatment activated the AhR-signaling cascade within 1 h, confirmed by AhR translocation, induction of cytochrome P450 1A1 expression, and activation of the xenobiotic response element. Although cell viability and transcription of the cardiac marker protein α-myosin heavy chain were affected, TCDD did not inhibit the differentiation of P19 cells to pulsating cardiomyocytes. TCDD significantly down-regulated the expression levels of the glucose transporter (GLUT) isoforms 1 and 3. After 24-h TCDD treatment, GLUT1 was no longer localized in the plasma membrane of P19 cells. The impaired GLUT expression correlated with a lower glucose uptake in 5-d-old embryoid bodies. The TCDD effects were mediated by AhR, as shown by preculture with the AhR antagonist α-naphthoflavone. Our data demonstrate that an AhR-mediated disturbance in GLUT expression and insufficient glucose uptake may be major mechanisms in TCDD embryo toxicity.