bluuebunny/crossref_metadata_2025_split huggingface dataset:
D-501036, a novel selenophene-based triheterocycle derivative, exhibits potentin vitroandin vivoantitumoral activity which involves DNA damage and ataxia telangiectasia–mutated nuclear protein kinase activation
Authors: Juang Shin-Hun , Lung Chia-Chi , Hsu Pi-Chen , Hsu Kuo-Shun , Li Yu-Chen , Hong Pao-Chiung , Shiah Her-Shyong , Kuo Ching-Chuan , Huang Ching-Wei , Wang Yu-Chin , Huang Leeyuan , Chen Tom S. , Chen Shyh-Fong , Fu Kuo-Chu , Hsu Cheng-Li , Lin Meng-Ju , Chang Ching-jer , Ashendel Curtis L. , Chan Thomas C.K. , Chou Kai-Ming , Chang Jang-Yang 
Published: January 2007

AbstractD-501036 [2,5-bis(5-hydroxymethyl-2-selenienyl)-3-hydroxymethyl-N-methylpyrrole] is herein identified as a novel antineoplastic agent with a broad spectrum of antitumoral activity against several human cancer cells and an IC50 value in the nanomolar range. The IC50 values for D-501036 in the renal proximal tubule, normal bronchial epithelial, and fibroblast cells were &gt;10 μmol/L. D-501036 exhibited no cross-resistance with vincristine- and paclitaxel-resistant cell lines, whereas a low level of resistance toward the etoposide-resistant KB variant was observed. Cell cycle analysis established that D-501036 treatment resulted in a dose-dependent accumulation in S phase with concomitant loss of both the G0-G1 and G2-M phase in both Hep 3B and A-498 cells. Pulsed-field gel electrophoresis showed D-501036–induced, concentration-dependent DNA breaks in both Hep 3B and A-498 cells. These breaks did not involve interference with either topoisomerase-I and topoisomerase-II function or DNA binding. Rapid reactive oxygen species production and formation of Se-DNA adducts were evident following exposure of cells to D-501036, indicating that D-501036–mediated DNA breaks were attributable to the induction of reactive oxygen species and DNA adduct formation. Moreover, D-501036–induced DNA damage activated ataxia telangiectasia–mutated nuclear protein kinase, leading to hyperphosphorylation of Chk1, Chk2, and p53, decreased expression of CDC25A, and up-regulation of p21WAF1 in both p53-proficient and p53-deficient cells. Collectively, the results indicate that D-501036–induced cell death was associated with DNA damage–mediated induction of ataxia telangiectasia–mutated activation, and p53-dependent and -independent apoptosis pathways. Notably, D-501036 shows potent activity against the growth of xenograft tumors of human renal carcinoma A-498 cells. Thus, D-501036 is a promising anticancer compound that has strong potential for the management of human cancers. [Mol Cancer Ther 2007;6(1):193–202]
Molecular correlates of gefitinib responsiveness in human bladder cancer cells
Authors: Shrader Marissa , Pino Maria Simona , Brown Gordon , Black Peter , Adam Liana , Bar-Eli Menahse , Dinney Colin P.N. , McConkey David J. 
Published: January 2007

AbstractWe characterized the effects of the small molecule epidermal growth factor receptor (EGFR) inhibitor gefitinib (ZD1839, Iressa) on cell proliferation in a panel of 17 human bladder cancer cell lines. Gefitinib inhibited DNA synthesis in a concentration-dependent fashion in 6 of 17 lines. Growth inhibition was associated with p27Kip1 accumulation and decreased cyclin-dependent kinase 2 activity. Gefitinib also inhibited baseline EGFR, AKT, and extracellular signal-regulated kinase (ERK) phosphorylation in the EGFR-dependent cells maintained in serum-free medium, whereas it had no effect on baseline EGFR or ERK phosphorylation in the EGFR-independent cells. Analyses of candidate markers of EGFR dependency revealed that the gefitinib-sensitive cells expressed higher surface EGFR levels than the gefitinib-resistant lines. Gefitinib-sensitive cells generally expressed higher levels of E-cadherin and lower levels of vimentin than the gefitinib-resistant cells, but these correlations were not perfect, suggesting that these markers of epithelial-mesenchymal transition cannot be used by themselves to prospectively predict EGFR-dependent growth. Together, our results show that bladder cancer cells are markedly heterogeneous with respect to their sensitivity to EGFR antagonists. Although surface EGFR levels and epithelial-mesenchymal transition status seem to roughly correlate with responsiveness, they cannot be used by themselves to identify bladder tumors that will be sensitive to EGFR-directed therapy. However, comparing levels of p27Kip1 or DNA synthesis before and after gefitinib exposure does identify the drug-sensitive cells. [Mol Cancer Ther 2007;6(1):277–85]
Dynamics of Model Error: The Role of the Boundary Conditions
Authors: Nicolis C. 
Published: January 2007

Abstract
The different modes of the early stages of the response of a forecasting model to a small error in the boundary conditions are analyzed. A general formulation of the problem based on the use of Green’s functions is developed and implemented on systems in which the operators acting on the spatial coordinates of the fields involved are diffusion-like and advection-like. It is shown that the generic behavior displays a nonanalytic structure not reducible to a power of time for short times.
Angular Momentum Conservation and Gravity Wave Drag Parameterization: Implications for Climate Models
Authors: Shaw Tiffany A. , Shepherd Theodore G. 
Published: January 2007

Abstract
The robustness of the parameterized gravity wave response to an imposed radiative perturbation in the middle atmosphere is examined. When momentum is conserved and for reasonable gravity wave drag parameters, the response to a polar cooling induces polar downwelling above the region of the imposed cooling, with consequent adiabatic warming. This response is robust to changes in the gravity wave source spectrum, background flow, gravity wave breaking criterion, and model lid height. When momentum is not conserved, either in the formulation or in the implementation of the gravity wave drag parameterization, the response becomes sensitive to the above-mentioned factors—in particular to the model lid height. The spurious response resulting from nonconservation is found to be nonnegligible in terms of the total gravity wave drag–induced downwelling.
Time Step Sensitivity of Nonlinear Atmospheric Models: Numerical Convergence, Truncation Error Growth, and Ensemble Design
Authors: Teixeira João , Reynolds Carolyn A. , Judd Kevin 
Published: January 2007

Abstract
Computational models based on discrete dynamical equations are a successful way of approaching the problem of predicting or forecasting the future evolution of dynamical systems. For linear and mildly nonlinear models, the solutions of the numerical algorithms on which they are based converge to the analytic solutions of the underlying differential equations for small time steps and grid sizes. In this paper, the authors investigate the time step sensitivity of three nonlinear atmospheric models of different levels of complexity: the Lorenz equations, a quasigeostrophic (QG) model, and a global weather prediction system (NOGAPS). It is illustrated here how, for chaotic systems, numerical convergence cannot be guaranteed forever. The time of decoupling of solutions for different time steps follows a logarithmic rule (as a function of time step) similar for the three models. In regimes that are not fully chaotic, the Lorenz equations are used to illustrate how different time steps may lead to different model climates and even different regimes. A simple model of truncation error growth in chaotic systems is proposed. This model decomposes the error onto its stable and unstable components and reproduces well the short- and medium-term behavior of the QG model truncation error growth, with an initial period of slow growth (a plateau) before the exponential growth phase. Experiments with NOGAPS suggest that truncation error can be a substantial component of total forecast error of the model. Ensemble simulations with NOGAPS show that using different time steps may be a simple and natural way of introducing an important component of model error in ensemble design.
Dynamic Radiative–Convective Equilibria Using GCM Column Physics
Authors: Held Isaac M. , Zhao Ming , Wyman Bruce 
Published: January 2007

Abstract
The behavior of a GCM column physics package in a nonrotating, doubly periodic, homogeneous setting with prescribed SSTs is examined. This radiative–convective framework is proposed as a useful tool for studying some of the interactions between convection and larger-scale dynamics and the effects of differing modeling assumptions on convective organization and cloud feedbacks.
For the column physics utilized here, from the Geophysical Fluid Dynamics Laboratory (GFDL) AM2 model, many of the properties of the homogeneous, nonrotating model are closely tied to the fraction of precipitation that is large-scale, rather than convective. Significant large-scale precipitation appears above a critical temperature and then increases with further increases in temperature. The amount of large-scale precipitation is a function of horizontal resolution and can also be controlled by modifying the convection scheme, as is illustrated here by modifying assumptions concerning entrainment into convective plumes. Significant similarities are found between the behavior of the homogeneous model and that of the Tropics of the parent GCM when ocean temperatures are increased and when the convection scheme is modified.
The Primary Nonlinear Dynamics of Modal and Nonmodal Perturbations of Monochromatic Inertia–Gravity Waves
Authors: Achatz Ulrich 
Published: January 2007

Abstract
The breaking of an inertia–gravity wave (IGW), initiated by its leading normal modes (NMs) or singular vectors (SVs), and the resulting small-scale eddies are investigated by means of direct numerical simulations of a Boussinesq fluid characterizing the upper mesosphere. The focus is on the primary nonlinear dynamics, neglecting the effect of secondary instabilities. It is found that the structures with the strongest impact on the IGW and also the largest turbulence amplitudes are the NM (for a statically unstable IGW) or short-term SV (statically and dynamically stable IGW) propagating horizontally transversely with respect to the IGW, possibly in agreement with observations of airglow ripples in conjunction with statically unstable IGWs. In both cases these leading structures reduce the IGW amplitude well below the static and dynamic instability thresholds. The resulting turbulent dissipation rates are within the range of available estimates from rocket soundings, even for IGWs at amplitudes low enough precluding NM instabilities. Thus SVs can help explain turbulence occurring under conditions not amenable for the classic interpretation via static and dynamic instability. Because of the important role of the statically enhanced roll mechanism in the energy exchange between IGW and eddies, the turbulent velocity fields are often conspicuously anisotropic. The spatial turbulence distribution is determined to a large degree by the elliptically polarized horizontal velocity field of the IGW.
Impacts of mass movement erosion on land productivity: a review
Authors: Blaschke Paul M. , Trustrum Noel A. , Hicks Douglas L. 
Published: January 2007

Wherever people gain their livelihood in mountains and steeplands, the productive capacity of the soils they use is likely to be affected by mass movement erosion. The impacts of mass movement erosion on land productivity are significant but under-rated in the scientific literature. Impacts on cropping are here reported from 15 countries in south and southeast Asia, east Africa, the Caribbean and Melanesia, but accounts are generalized or anecdotal, and do not quantify crop loss or damage attributable to mass movement separately from that due to surface or fluvial erosion. Impacts on pastoral grazing have been studied in New Zealand, where production losses of up to 80% at field scale, and up to 20% at farm scale, have been measured. Studies in the Pacific Northwest coastal forests of North America show plantation forest wood volume declines by 35-50% on eroded sites. Mass movement impacts on production from tropical forests or agroforestry appear to be as yet undocumented. The reasons for lack of documentation are, first, that most soil erosion-productivity research has been done on gently sloping cropland, which is subject to surface rather than mass movement erosion. Secondly, geomorphological research in steeplands has dealt with mass movement as a hazard to human life, settlements and infrastructure -with limited identification of its contribution to sediment loads in rivers, and disregarding its impact on land productivity. We suggest there are many other countries where significant impacts are likely to occur, and that erosion-productivity studies should pay more attention to this type of erosion. Studies should not be restricted to cropland, but also extend to grazing land, plantation forestry, agro-forestry and traditional uses of natural forest as mass movement appears to affect all these forms of land-based production, particularly in densely populated steeplands whether tropical or temperate. Topics needing study are the documentation and costing of productivity losses, ways to reduce mass movement impacts on productivity, and ways to enhance recovery of soil on eroded areas (e.g., revegetation with fertility-building shrubs and legumes).
Plant functional types: an alternative to taxonomic plant community description in biogeography?
Authors: Duckworth Jennifer C. , Kent Martin , Ramsay Paul M. 
Published: January 2007

This article critically reviews the concept of plant functional types as an alternative to the traditional taxonomic species-based approach to plant community description in biogeography and ecology. Originally formulated in the last century, there has been an acceleration in interest in the concept over the last decade. Plant functional types are nonphylogenetic groupings of species that show close similarities in their response to environmental and biotic controls. Functional classifications often cut across taxonomic classifications and may be more meaningful in terms of plant response, in addition to overcoming certain problems associated with the traditional taxonomic species-based approach. Plant functional types are derived from traits based on species morphology, physiology and/or life history, depending on the aims and scale of the research. Whilst some traits can be measured in the field, others require more detailed laboratory measurement and experimentation. A trade-off exists between the time and efficiency gained from using simple traits and those requiring more elaborate analysis, although certain ‘key traits’ may act as easily measured surrogates for others. Practical applications of plant functional types in biogeography and ecology are also reviewed. Plant functional types can aid in the understanding of ecological processes, such as the assembly and stability of communities and succession, and facilitate the detection and prediction of response to environmental change at a range of scales. Despite its potential, the plant functional type approach is probably best viewed as a complementary approach to description using traditional taxonomy.
Recent climate variability and future climate change scenarios for
Authors: Britain Great , Conway D. 
Published: January 2007

This article reviews recent climatically extreme periods in Great Britain and presents results from the latest general circulation model (GCM) experiments showing the possible spatial patterns and magnitude of future climate change for this region. During the last decade the British Isles has seen record-breaking periods of above-average temperatures, alongside periods with above and below-average precipitation, combined with an increase in winter precipitation and a decrease in summer precipitation. The impacts of these anomalies, coupled with the possibility that future climate change may increase their frequency and/or severity, have prompted the UK Department of the Environment, Transport and Regions and other organizations involved in environmental management, such as the Environment Agency, to commission a number of studies into their impacts. These have highlighted wide-ranging impacts on the natural environment of Great Britain and on human ativities to the extent of affecting the national economy. The use of GCMs for the development of future climate change scenarios is reviewed. Results from recent ensemble GCM experiments with and without the effects of sulphate aerosols are presented. These show broadly similar changes in temperature and precipitation to previous climate change scenarios prepared for Great Britain. In summary, the scenarios suggest the following: a warming of about 3 8C (3.5 8C) over the region by 2100 with (without) the effects of sulphate aerosols; slight increases in annual precipitation over northern England and Scotland, more pronounced increases over the whole of the region in winter; and slight decreases in precipitation over Wales and central England in summer. These changes are synchronous with decreases in the number of wet-days and increases in the intensity of precipitation on wet-days. The high level of uncertainty associated with regional scenarios of temperature and precipitation is discussed and emphasized
Applied physical geography in New Zealand
Authors: Kirk R. M. , Morgan R. K. , Single M. B. , Fahey B. 
Published: January 2007

Physical geographers in New Zealand have a tradition of applied research in a variety of contexts, including environmental management as well as soil, vegetation and landform systems conservation. In recent years this work has been given new impetus (with the promise of even greater involvement) as a result of economic restructuring at the national level, restructuring of government departments and agencies dealing with environmental and resource management and conservation, the introduction of new statutes relating to environmental and resource management, and major changes in the funding and management of science research in the public sector. This article provides an overview of the institutional environment within which New Zealand physical geographers now carry out applied work. The contemporary resource management and legislative contexts are described and structural changes that have taken place in New Zealand science over the last decade are reviewed. Research undertaken by the authors or their research students provides examples of the different types of work now being undertaken by physical geographers in New Zealand under the new legislative and funding regimes. Two examples are described in detail. The first is drawn from research dealing with catchment hydrology and water supply and has been undertaken by a physical geographer employed by Landcare Research, a Crown-owned research company. The second comes from work carried out by two university-based physical geographers into the environmental effects on coasts of a new mode of marine passenger transport (`fast ferries'), to meet the requirements of new environmental legislation.
Docetaxel in hepatic impairment
Authors: Kolesar Jill M 
Published: January 2007

Purpose. The primary objective of this paper is to provide a brief overview of docetaxel pharmacokinetics, pharmacodynamics, indications, and drug interactions, concentrating on their relationship with docetaxel use in patients with hepatic impairment. Data Sources. The literature was reviewed through a MEDLINE search from 1986 to 2000. Relevant articles cited in literature obtained by MEDLINE searching were also considered. The following terms were searched: hepatic impairment, liver failure, Taxotere, and docetaxel. The search was restricted to the English language. Data Extraction. The current literature is reviewed in regard to docetaxel pharmacokinetics, pharmacodynamics, dosing, efficacy, adverse effects, and drug interactions and with a special emphasis on docetaxel use in patients with hepatic impairment. Data Synthesis. Docetaxel has a wide spectrum of clinical activity and is used frequently in the treatment of metastatic breast cancer, NSCLC, ovarian cancer and cancer of the head and neck. The dose-limiting toxicity of docetaxel is neutropenia. Docetaxel is metabolized in the liver and elevations in hepatic enzymes can predict a reduced clearance of docetaxel, which is associated with an increased incidence of neutropenia. Based on population pharmacokinetic modeling, docetaxel can be safely administered in patients with elevated hepatic enzymes if the dose is reduced on the first cycle.
Establishing a baseline incidence of adverse drug reactions in hospitalised oncology patients
Authors: Poole Susan Gaye , Dooley Michael Joseph 
Published: January 2007

Objectives. To establish the incidence of adverse drug reactions (ADRs) in oncology patients hospitalised at a tertiary referral adult cancer hospital and identify areas where intervention strategies may effectively reduce their impact. Design. A prospective study was conducted in November and December 1998 at the Peter MacCallum Cancer Institute (PMCI), Melbourne, Australia. Pharmacists identified patients who had experienced an ADR contributing to the admission or occurring during the episode of care. Outcome measures. An assessment was made of causality, as definite, probably or possibly. The severity of the ADR was assessed as mild, moderate or severe. Results. Twenty-six admissions (9.6%) were related to drug therapy. One hundred and thirty-four ADRs occurred in 86 inpatient episodes of care (31.6% of admissions). One hundred and four ADRs (60.8%) were associated with active therapy for malignancy or infection. Supportive therapy, including analgesics and antiemetics, were implicated in 67 (39.2%) adverse events. Pharmacists rated the majority of reactions as definitely associated with the implicated drug and the majority of at least moderate severity. Discussion. Drug therapy contributed to 9.6% of admissions. This is higher than in other Australian studies. The majority of ADRs identified were associated with active therapy for malignancy or infection. These adverse effects are not unexpected in the setting of aggressive therapy. Other potentially preventable ADRs may be overlooked in the context of the more severe and life-threatening events occurring simultaneously. Conclusion. Approximately 37.5% of patients admitted to PMCI experienced an ADR. Many of these events may have been prevented using simple intervention strategies. There is an opportunity for clinical pharmacists to ensure preventive measures are instituted, thereby improving patient outcomes.