bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adenovirus-Mediated Extracellular Superoxide Dismutase Gene Therapy Reduces Neointima Formation in Balloon-Denuded Rabbit Aorta
Authors: Laukkanen Mikko O. , Kivelä Antti , Rissanen Tuomas , Rutanen Juha , Karkkainen Minna K. , Leppanen Olli , Bräsen Jan Hinrich , Yla-Herttuala Seppo 
Published: October 2002

Background—Restenosis is a frequent problem after invasive treatment of atherosclerotic vessels and is associated with intimal hyperplasia, which is primarily a result of proliferation and migration of smooth muscle cells, leading to the formation of neointima. Because there is no effective conventional medication for restenosis, gene therapy is a potential new treatment to prevent neointima formation.Methods and Results—In the present study, we analyzed the effects of adenovirus-mediated extracellular superoxide dismutase (EC-SOD) gene transfer (3×109pfu/kg AdEC-SOD versus AdLacZ control virus) on neointima formation in balloon-denuded rabbit aortas. Local catheter-mediated gene transfer to the arterial wall reduced restenosis (P<0.001) and decreased the number of macrophages in the transduced segment (P<0.001) 2 weeks and 4 weeks after the gene transfer compared with AdLacZ controls. Transgene expression was detected in the arterial wall by RT-PCR 2 weeks after the procedure, and the production of superoxide anion was reduced after the gene transfer. Recovery of the endothelial layer was enhanced in EC-SOD-transduced rabbits compared with LacZ controls (P<0.001) 2 weeks after the gene transfer. The therapeutic effect was found to be extended, affecting the gene transfer site and flanking aortic segments from the renal arteries to the bifurcation. However, systemic AdEC-SOD gene transfer to liver did not have any effects on restenosis.Conclusions—The results suggest that EC-SOD gene transfer reduces restenosis and may be useful for the prevention of intimal hyperplasia after vascular manipulations.
Population Pharmacokinetics of the Novel Anticancer Agent E7070 During Four Phase I Studies: Model Building and Validation
Authors: van Kesteren Ch. , Mathôt R. A.A. , Raymond E. , Armand J. P. , Dittrich Ch. , Dumez H. , Roché H. , Droz J. P. , Punt C. , Ravic M. , Wanders J. , Beijnen J. H. , Fumoleau P. , Schellens J. H.M. 
Published: September 2002

PURPOSE: N-(3-Chloro-7-indolyl)-1,4-benzenedisulfonamide (E7070) is a novel sulfonamide anticancer agent currently in phase II clinical development for the treatment of solid tumors. Four phase I studies have been finalized, with E7070 administered at four different treatment schedules to identify the maximum-tolerated dose and the dose-limiting toxicities. Pharmacokinetic analyses of all studies revealed E7070 to have nonlinear pharmacokinetics. A population pharmacokinetic model was designed and validated to describe the pharmacokinetics of E7070 at all four treatment schedules and to identify the possible influences of patient characteristics on the pharmacokinetic parameters. PATIENTS AND METHODS: Plasma concentration-time data of all patients (n = 143) were fitted to several pharmacokinetic models using NONMEM. Seventeen covariables were investigated for their relation with individual pharmacokinetic parameters. A bootstrap procedure was performed to check the validity of the model. RESULTS: The data were best described using a three-compartment model with nonlinear distribution to a peripheral compartment and two parallel pathways of elimination from the central compartment: a linear and a saturable pathway. Body-surface area (BSA) was significantly correlated to both the volume of distribution of the central compartment and to the maximal elimination capacity. The fits of 500 bootstrap replicates of the data set demonstrated the robustness of the developed population pharmacokinetic model. CONCLUSION: A population pharmacokinetic model has been designed and validated that accurately describes the data of four phase I studies with E7070. Furthermore, it has been demonstrated that BSA-guided dosing for E7070 is important.
Phase I Clinical and Pharmacokinetic Study of Flavopiridol Administered as a Daily 1-Hour Infusion in Patients With Advanced Neoplasms
Authors: Tan Antoinette R. , Headlee Donna , Messmann Richard , Sausville Edward A. , Arbuck Susan G. , Murgo Anthony J. , Melillo Giovanni , Zhai Suoping , Figg William D. , Swain Sandra M. , Senderowicz Adrian M. 
Published: September 2002

PURPOSE: To define the maximum-tolerated dose (MTD), dose-limiting toxicity, and pharmacokinetics of the cyclin-dependent kinase inhibitor flavopiridol administered as a daily 1-hour infusion every 3 weeks. PATIENTS AND METHODS: Fifty-five patients with advanced neoplasms were treated with flavopiridol at doses of 12, 17, 24, 30, 37.5, and 52.5 mg/m2/d for 5 days; doses of 50 and 62.5 mg/m2/d for 3 days; and doses of 62.5 and 78 mg/m2/d for 1 day. Plasma sampling was performed to characterize the pharmacokinetics of flavopiridol with these schedules. RESULTS: Dose-limiting neutropenia developed at doses ≥ 52.5 mg/m2/d. Nonhematologic toxicities included nausea, vomiting, diarrhea, hypotension, and a proinflammatory syndrome characterized by anorexia, fatigue, fever, and tumor pain. The median peak concentrations of flavopiridol achieved at the MTDs on the 5-day, 3-day, and 1-day schedule were 1.7 μmol/L (range, 1.3 to 4.2 μmol/L), 3.2 μmol/L (range, 1.7 to 4.8 μmol/L), and 3.9 μmol/L (1.8 to 5.1 μmol/L), respectively. Twelve patients had stable disease for ≥ 3 months, with a median duration of 6 months (range, 3 to 11 months). CONCLUSION: The recommended phase II doses of flavopiridol as a 1-hour infusion are 37.5 mg/m2/d for 5 days, 50 mg/m2/d for 3 days, and 62.5 mg/m2/d for 1 day. Flavopiridol as a daily 1-hour infusion can be safely administered and can achieve concentrations in the micromolar range, sufficient to inhibit cyclin-dependent kinases in preclinical models. Further studies to determine the optimal schedule of flavopiridol as a single agent and in combination with chemotherapeutic agents are underway.
Organ Preservation Therapy Using Induction Plus Concurrent Chemoradiation for Advanced Resectable Oropharyngeal Carcinoma: A University of Pennsylvania Phase II Trial
Authors: Machtay Mitchell , Rosenthal David I. , Hershock Diane , Jones Heather , Williamson Shirnett , Greenberg Michael J. , Weinstein Gregory S. , Aviles Victor M. , Chalian Ara A. , Weber Randal S. 
Published: September 2002

PURPOSE: To determine the efficacy, feasibility, and toxicity of a new regimen for locally advanced oropharyngeal carcinoma. PATIENTS AND METHODS: Patients had technically resectable stage III/IV squamous cell carcinoma of the oropharynx, exclusive of T1-2N1. Induction chemotherapy consisted of carboplatin (area under the curve formula equal to 6) and paclitaxel 200 mg/m2 for two cycles, followed by re-evaluation. Patients with major response continued to definitive radiotherapy (70 Gy over 7 weeks) plus concurrent once-weekly paclitaxel (30 mg/m2/wk). Patients with advanced neck disease also underwent post–radiation therapy neck dissection and two more chemotherapy cycles. RESULTS: Fifty-three patients were enrolled. Median follow-up was 31 months (minimum follow-up for survivors was 18 months). The major response rate to induction chemotherapy was 89%; 90% of patients had a complete response after concurrent chemoradiation. Actuarial survival at 3 years was 70%, and 3-year event-free survival was 59%. The 3-year actuarial locoregional control was 82% and the 3-year actuarial rate of distant metastases was 19%. Organ preservation was achieved in 77% of all patients. One patient (2%) died during therapy. Late grade 3 toxicity occurred in 24% of patients, consisting mainly of chronic dysphagia/aspiration and/or radiation soft tissue ulceration. The treatment-related mortality rate was 4% (two patients died from respiratory failure). CONCLUSION: Response to induction chemotherapy as studied in this trial was not useful as a predictive marker for ultimate outcome or organ conservation. Overall, however, this regimen offers good disease control and survival for patients with locally advanced oropharyngeal carcinoma, comparable with other concurrent chemoradiation programs. Further study of similar protocols is indicated.
Adjuvant Chemotherapy Use for Medicare Beneficiaries With Stage II Colon Cancer
Authors: Schrag Deborah , Rifas-Shiman Sheryl , Saltz Leonard , Bach Peter B. , Begg Colin B. 
Published: September 2002

PURPOSE: Clinical trials have not demonstrated that adjuvant chemotherapy improves survival for patients with resected stage II colon cancer. Nevertheless, patients may receive this treatment despite its uncertain benefit. The objective of this study was to determine the extent to which adjuvant chemotherapy is used for patients with stage II colon cancer. PATIENTS AND METHODS: Using the Surveillance, Epidemiology, and End Results-Medicare linked database, we identified 3,151 patients aged 65 to 75 with resected stage II colon cancer and no adverse prognostic features. The primary outcome was chemotherapy use within 3 months of surgery ascertained from claims submitted to Medicare. Relationships between patient characteristics and adjuvant chemotherapy use were measured and their significance was assessed using multivariable logistic regression. Survival for treated and untreated patients was compared using a Cox model. RESULTS: Twenty-seven percent of patients received chemotherapy during the 3 postoperative months. Younger age at diagnosis, white race, unfavorable tumor grade, and low comorbidity were each associated with a greater likelihood of receiving treatment. Sex, the number of examined lymph nodes in the tumor specimen, the urgency of the surgical admission, and median income was each unrelated to treatment. Five-year survival was 75% for untreated patients and 78% for treated patients. After adjusting for known between-group differences, the hazard ratio for survival associated with adjuvant treatment was 0.91 (95% confidence interval, 0.77 to 1.09). CONCLUSION: A substantial percentage of Medicare beneficiaries with resected stage II colon cancer receive adjuvant chemotherapy despite its uncertain benefit.
Global warming potentials modified for surface radiative forcing for use in surface energy balance models
Authors: Evans W. F. J. , Puckrin E. 
Published: October 2002

AbstractThe radiative impact of greenhouse gases in warming the Earth varies significantly, depending on whether one considers the forcing at the tropopause or at the surface. Compared to the former, the surface forcing for some greenhouse gases is reduced by the interference of water vapour. Hence, we calculate alternative surface global warming potentials (SGWPs) that are derived from the surface forcing radiation of greenhouse gases for potential use in surface radiative energy balance models (SREBMs). For gases with a large water vapour overlap, the SGWPs are typically 30% smaller than current GWPs; for gases with relatively little overlap, the SGWPs are larger by more than 33%. These results may be used in conjunction with SREBMs as an additional means of calculating climate change, and may lead to an altered emissions budget compared to that outlined by the current Kyoto agreement. Copyright © 2003 Royal Meteorological Society.
Variation in Soil-Catena Characteristics of Moraines with Time and Climate, South Island, New Zealand
Authors: Birkeland Peter W. 
Published: October 2002

AbstractSoil catenas on three moraines in each of two areas with different climate were studied to determine (a) downcatena soil differentiation with climate and time and (b) their usefulness in estimating the relative ages of the underlying deposits. In the dry area (mean annual precipitation (MAP), ca. 0.5 m) all soils have A/Bw/C profiles formed in loess/till. Their similarity in morphology and in most chemical characteristics with catena position and age suggests that the low MAP does not result in much redistribution of water, elements, or sediment downcatena. This similarity also suggests ages close to each other and correlation with the Otiran Glaciation (oxygen-isotope stages 2 and 4). In the wet area (MAP ca. 3 m) the soils also formed in loess/till and with time (a) soil morphology progresses from A/Bw/C to A/E/B/C, (h) reduced properties intensify, especially in the downcatena profiles, (c) citrate-bicarbonate-dithionite-extractable Fe displays accumulation in the youngest catena followed by loss in the older catenas, and (d) downcatena trends in total chemical data display marked losses of the more mobile elements. These data demonstrate that although catena development is rapid in a wet climate, the downcatena contrast can be muted with time due to a change from processes dominated by oxidation to those dominated by reduction. Soil catena properties in the wet area are sufficiently different to not refute age estimations suggested by Suggate (1990): youngest moraine, oxygen-isotope stage 2; intermediate moraine, isotope stage 4; and oldest moraine, isotope stage 10. An unresolved problem in both areas is the possibility of soil erosion to foul soil-age relations.
Seismic-Reflection Identification of Susquehanna River Paleochannels on the Mid-Atlantic Coastal Plain
Authors: Genau Robert B. , Madsen John A. , McGeary Susan , Wehmiller John F. 
Published: October 2002

AbstractLand-based, high-resolution seismic-reflection methods were used to image Quaternary paleochannels of the Susquehanna River system. Using a portable, 12-channel signal-enhancing seismograph, 12 accelerometers as receivers, and a 4.54-kg sledge hammer struck against an aluminum plate as a source, a sixfold, multichannel seismic profile 2.5 km long was acquired at Taylors Island, Maryland. On the processed seismic profile, pronounced high-amplitude seismic reflections delineate the unconformity between Quaternary and underlying Tertiary sediments and the disconformable contact separating Miocene and Eocene deposits. Subsurface-seismic stratigraphic relationships that clearly indicate the presence of two paleochannels were observed, one believed to be the Exmore paleochannel, projected to underlie northern Taylors Island based on marine seismic data. An overlapping sequence of fill sediments was observed on the eastern margin of the Exmore paleochannel. The second paleochannel may be a tributary of the Exmore or possibly the western edge of the younger Eastville paleochannel. Results from this study indicate that land-based, shallow, high-resolution seismic-reflection data can be used to delineate subsurface geomorphology successfully in coastal plain environments. This technique of defining erosional surfaces and depositional units beneath present land areas, when integrated with chronostratigraphic data, is a powerful tool for developing a better understanding of the Quaternary record.
Holocene Sea-Level Record on Funafuti and Potential Impact of Global Warming on Central Pacific Atolls
Authors: Dickinson William R. 
Published: October 2002

AbstractGeomorphic features inherited from the mid-Holocene glacio-hydro-isostatic sea-level highstand that affected the central Pacific region influence the susceptibility of atoll islets to potentially enhanced wave erosion associated with rise in sea level from global warming. Shoreline morphology on multiple islets of Funafuti atoll in central Tuvalu reflects a relative mid-Holocene sea-level highstand 2.2–2.4 m above modern sea level. Typical islets are composed of unconsolidated post-mid-Holocene sediment resting disconformably on cemented coral rubble formed beneath now-emergent mid-Holocene reef flats. Exposed remnants of the lithified islet foundations serve as resistant buttresses protecting the flanks of atoll islets from wave attack. Islets lacking cemented mid-Holocene deposits as part of their internal structure are migratory sand cays with unstable shorelines. Any future sea-level rise ≥0.75 m, bringing high tide above the elevation of mid-Holocene low tide, might trigger enhanced wave erosion of stable atoll islets by overtopping the indurated mid-Holocene reef platforms. As analogous threshold relations are inferred for other central Pacific atolls, the risk of future inundation of island nations cannot be evaluated solely in terms of expected sea-level rise with respect to gross islet elevations.
The description of the rate of protein and lipid growth in pigs in relation to live weight
Authors: WHITTEMORE C. T. , GREEN D. M. 
Published: October 2002

The paper seeks to compare the effectiveness of various functions as appropriate to express protein retention and lipid retention as a function of pig live weight. Linear descriptors were adequate for protein growth over the 20 to 120 kg live weight range, but not adequate when higher live weights were included. Linear descriptors were not adequate for lipid growth over any weight range. Quadratic and cubic polynomials, and the logistic function, were faulted on their failure to describe the known biology. Augmentation of the allometric function added nothing to the simple form. The Gompertz function was consistently effective for the description of daily protein retention rate. The Bridges and Richards functions are more flexible than the Gompertz with respect to the point of inflection, but when applied they resembled the Gompertz and therefore did not materially influence the descriptive outcome. The cubic polynomial, augmented allometric, Bridges and Richards functions, although favoured in other reports, were found to add nothing to the more simple functions. It is concluded that protein retention can be well expressed in relation to live weight by linear and Gompertz functions. Lipid retention could be well described by an allometric relationship with pig mass.
ATP induced MUC5AC release from human airways in vitro
Authors: Roger Patricia , Gascard Jean-Pierre , Bara Jacques , de Montpreville Vincent Thomas , Yeadon Micheal , Brink Charles 
Published: October 2002

Background: Chronic airway diseases are often associated with marked mucus production, however, little is known about the regulation of secretory activity by locally released endogenous mediators.Aim: This investigation was performed to determine the release of MUC5AC mucin from human bronchial preparations using the purinergic agonists adenosine 5′‐triphosphate (ATP) and uridine 5′‐triphosphate (UTP).Methods: Immunohistochemical and immunoradiometric assays (IRMA) were used to detect the MUC5AC mucin. Immunohistochemical analysis were performed using individual 1–13 M1 and 21 M1 MAbs recognizing a recombinant M1 mucin partially encoded by the MUC5AC gene. IRMA measurments were performed using a mixture of eight anti‐M1 mucin MAbs (PM8), which included both 1–13 M1 and 21 M1 MAbs. Lysozyme and protein were also measured in the biological fluids derived from human bronchial preparations obtained from patients who had undergone surgery for lung carcinoma.Results: The anti‐M1 monoclonal antibodies labelled epithelial goblet cells. After challenge of human bronchial preparations with ATP, the goblet cells exhibited less staining. In contrast, UTP did not alter the immunolabelling of goblet cells. MUC5AC mucin in the bronchial fluids derived from ATP‐ch allenged preparations was increased while UTP had no effect on release. ATP did not alter either the quantities of lysozyme or protein detected in the biological fluids.Conclusion: These results suggest that ATP may regulate epithelial goblet cell secretion of MUC5AC mucin from human airways in vitro.
Decompilation: the enumeration of types and grammars
Authors: Breuer Peter T. , Bowen Jonathan P. 
Published: October 2002

While a compiler produces low-level object code from high-level source code, a decompiler produces high-level code from low-level code and has applications in the testing and validation of safety-critical software. The decompilation of an object code provides an independent demonstration of correctness that is hard to better for industrial purposes (an alternative is to prove the compiler correct). But, although compiler compilers are in common use in the software industry, a decompiler compiler is much more unusual.
It turns out that a data type specification for a programming-language grammar can be remolded into a functional program that enumerates all of the abstract syntax trees of the grammar. This observation is the springboard for a general method for compiling decompilers from the specifications of (nonoptimizing) compilers.
This paper deals with methods and theory, together with an application of the technique. The correctness of a decompiler generated from a simple occam-like compiler specification is demonstrated. The basic problem of enumerating the syntax trees of grammars, and then stopping, is shown to have no recursive solution, but methods of abstract interpretation can be used to guarantee the adequacy and completeness of our technique in practical instances, including the decompiler for the language presented here.
Retargetable microcode synthesis
Authors: Mueller Robert A. , Varghese Joseph 
Published: October 2002

Most work on automating the translation of high-level microprogramming languages into microcode has dealt with lexical and syntactic analysis and the use of manually produced macro tables for code generation. We describe an approach to and some results on the formalization and automation of the more difficult problem of retargeting local code generation in a machine-independent, optimizing microcode synthesis system. Whereas this problem is similar in many ways to that of retargeting local code generation in high-level language compilers, there are some major differences that call for new approaches.
The primary issues addressed in this paper are the representation of target microprogrammable machines, the intermediate representation of local microprogram function, and general algorithmic methods for deriving local microcode from target machine and microcode function specifications. Of particular interest are the use of formal semantics and data flow principles in achieving both a general and reasonably efficient solution. Examples of the modeling of a representative horizontal machine (the PUMA) and the generation of microcode for the PUMA machine model from our working implementation are presented.
Momo, Dogen, and the Commodification of Time
Authors: Loy David , Goodhew Linda 
Published: October 2002

AbstractThe odd thing was, no matter how much time he saved, he never had any to spare; in some mysterious way, it simply vanished. Imperceptibly at first, but then quite unmistakably, his days grew shorter and shorter. (Momo 65) One of the most remarkable novels of the late twentieth century is Momo, by the German writer Michael Ende. Although apparently written for children, it contains profound insights into our modern attitude toward time. Is it a coincidence that Ende later became interested in Buddhism? He visited Japan several times: the first trip in 1977 included a discussion with a Zen priest; the second time in 1989 to marry his second wife, SATO Mariko. This essay will explore the deep resonances between Ende's view of time in Momo and the Buddhist perspective on time, particularly as expressed by the Japanese Zen master Dogen (1200-1253). These resonances are of more than literary or historical interest: understanding what Ende and Dogen have to say about time gives us important insight into how we experience time today.
Xanthoria karrooensis and X. alexanderbaai (Teloschistaceae), two new lichen species from southern Africa
Authors: Kärnefelt I. , Kondratyuk S. , Søchting U. , Frödén P. 
Published: October 2002

AbstractTwo new species, Xanthoria karrooensis S. Kondratyuk & Kärnefelt and Xanthoria alexanderbaai S. Kondratyuk & Kärnefelt, both apparently endemic to South Africa, are described and illustrated. Other xanthorioid species known from southern Africa are listed in a Table and a preliminary key is provided for the African species. The new species are compared with a number of presumably related species, and a Table is provided comparing the character states for the new species and related species.