bluuebunny/crossref_metadata_2025_split huggingface dataset:
Successful Implementation of the Randomized Discontinuation Trial Design: An Application to the Study of the Putative Antiangiogenic Agent Carboxyaminoimidazole in Renal Cell Carcinoma—CALGB 69901
Authors: Stadler Walter M. , Rosner Gary , Small Eric , Hollis Donna , Rini Brian , Zaentz S. Donald , Mahoney John , Ratain Mark J. 
Published: May 2005

Purpose To assess the disease-stabilizing activity of carboxyaminoimidazole (CAI) in patients with metastatic renal cell cancer (RCC) using a randomized discontinuation trial (RDT) design. Patients and Methods Recruited patients had a performance status of 0 to 2, minimal neuropathy or cerebellar dysfunction, measurable disease, and normal organ function. Treatment with 250 mg/d CAI was initiated in all patients and continued until disease progression in those with an objective response. Protocol treatment was discontinued for unacceptable toxicity or progressive disease; patients with stable disease at the 16-week evaluation point were randomly assigned in a double-blind manner to continued CAI or placebo. The primary end point was the stable disease rate in the randomized groups. Results A total of 368 patients were accrued and received therapy. Ninety percent had a performance status of 0 or 1, 80% underwent a prior nephrectomy, and 41% had received no prior systemic therapy. Serious or life-threatening toxicity was experienced by 34%, with asthenia (15%) and neuropsychiatric difficulties (7%) being most common. At the randomization point, 51% of patients had progressed, 30% withdrew, 1% experienced a partial response, and 17% had stable disease and were randomly assigned. A Bayesian futility analysis utilizing the first 49 randomly assigned patients suggested that the probability of demonstrating a higher stable disease rate in the experimental group was less than 9% even under the most optimistic a priori assumptions, and further trial accrual was halted. Conclusion CAI is inactive in RCC. The RDT design should be further explored for evaluating activity of putative disease stabilizing agents.
Multiple Signaling Defects in the Absence of RIP140 Impair Both Cumulus Expansion and Follicle Rupture
Authors: Tullet Jennifer M. A. , Pocock Victoria , Steel Jennifer H. , White Roger , Milligan Stuart , Parker Malcolm G. 
Published: May 2005

AbstractThe nuclear receptor corepressor RIP140 is essential in the ovary for ovulation, but is not required for follicle growth and luteinization. To identify genes that may be subject to regulation by RIP140 or play a role in ovulation, we compared ovarian gene expression profiles in untreated immature wild-type and RIP140 null mice and after treatment with pregnant mare serum gonadotropin and human chorionic gonadotropin. Many genes involved in signaling, extracellular matrix formation, cell-cell attachment, and adhesion were aberrantly regulated in the absence of RIP140, varying according to the hormone status of the mice. Notable among these was the reduced expression of a number of genes that encode components of signaling pathways and matrix proteins required for cumulus expansion, a key remodeling process necessary for ovulation. Histological analysis confirmed that cumulus expansion in RIP140 null mice is reduced, oocyte detachment from the mural cell wall is impaired, and follicles fail to rupture in response to LH. Although the expression of many genes involved in cumulus cell expansion was reduced, there was a subset of genes involved in extracellular matrix formation and cell-cell interactions that was up-regulated and may interfere with ovarian tissue remodeling. We propose that widespread gene dysregulation in ovarian tissues in the absence of RIP140 leads to the anovulatory phenotype. This helps to define an important role for RIP140 in the regulation of multiple processes leading to ovulation.
Minireview: The Role of Oxidative Stress in Relation to Caloric Restriction and Longevity
Authors: Gredilla Ricardo , Barja Gustavo 
Published: May 2005

Abstract
Reduction of caloric intake without malnutrition is one of the most consistent experimental interventions that increases mean and maximum life spans in different species. For over 70 yr, caloric restriction has been studied, and during the last years the number of investigations on such nutritional intervention and aging has dramatically increased. Because caloric restriction decreases the aging rate, it constitutes an excellent approach to better understand the mechanisms underlying the aging process. Various investigations have reported reductions in steady-state oxidative damage to proteins, lipids, and DNA in animals subjected to restricted caloric intake. Most interestingly, several investigations have reported that these decreases in oxidative damage are related to a lowering of mitochondrial free radical generation rate in various tissues of the restricted animals. Thus, similar to what has been described for long-lived animals in comparative studies, a decrease in mitochondrial free radical generation has been suggested to be one of the main determinants of the extended life span observed in restricted animals. In this study we review recent reports of caloric restriction and longevity, focusing on mitochondrial oxidative stress and the proposed mechanisms leading to an extended longevity in calorie-restricted animals.
Minireview: Role of the Growth Hormone/Insulin-Like Growth Factor System in Mammalian Aging
Authors: Bartke Andrzej 
Published: May 2005

Abstract
The important role of IGF and insulin-related signaling pathways in the control of longevity of worms and insects is very well documented. In the mouse, several spontaneous or experimentally induced mutations that interfere with GH biosynthesis, GH actions, or sensitivity to IGF-I lead to extended longevity. Increases in the average life span in these mutants range from approximately 20–70% depending on the nature of the endocrine defect, gender, diet, and/or genetic background. Extended longevity of hypopituitary and GH-resistant mice appears to be due to multiple mechanisms including reduced insulin levels, enhanced insulin sensitivity, alterations in carbohydrate and lipid metabolism, reduced generation of reactive oxygen species, enhanced resistance to stress, reduced oxidative damage, and delayed onset of age-related disease. There is considerable evidence to suggest that the genetic and endocrine mechanisms that influence aging and longevity in mice may play a similar role in other mammalian species, including the human.
Automatisierung der Anästhesie: Ansätze zur Regelung der Analgesie (Automation of Anaesthesia: Approaches to Control Analgesia)
Authors: Stadler Konrad Shedden , Bänziger Bertram , Leibundgut Daniel , Schumacher Peter Matthias 
Published: May 2005

Abstract
Das Schmerzempfinden (Analgesie) eines anästhesierten Patienten ist schwer quantifizierbar und kann sich über die Zeit ändern. Der Blutdruck wird klinisch oft als Indikator verwendet. In den meisten Operationen wird dieser aber nicht kontinuierlich gemessen, sondern meist nur alle fünf Minuten (nichtinvasiv). Dieser Beitrag beschreibt Ansätze zur Regelung der Analgesie, die die nichtinvasive Messung mit Information aus der kontinuierlichen Herzfrequenzmessung ergänzt, um damit schneller auf Störungen reagieren zu können. Abschließend werden klinische Versuche vorgestellt.
HyGLEAM – eine neue Methode zur Leistungssteigerung Evolutionärer Algorithmen (HyGLEAM – A New Method for Increasing the Performance of Evolutionary Algorithms)
Authors: Jakob Wilfried 
Published: May 2005

Abstract
Nahezu alle praktischen Anwendungen Evolutionärer Algorithmen sind so genannte Hybride, die in irgendeiner Form anwendungsspezifisches Wissen in das evolutionäre Verfahren integrieren, wodurch eine problemspezifische Lösung entsteht. Dieser Beitrag konzentriert sich auf zwei Fragen: Wie hybridisiert man so, dass das resultierende Verfahren allgemein anwendbar bleibt und welches ist die beste Art der Hybridisierung? Die Ergebnisse der umfangreichen Untersuchungen sind viel versprechend: Die Anzahl der Berechnungen der Qualitätsfunktion konnte um einen Faktor von bis zu 100 reduziert werden.
Der mehrfädige Komodo-Mikrocontroller (The Multithreaded Komodo Microcontroller)
Authors: Brinkschulte Uwe , Uhrig Sascha , Ungerer Theo 
Published: May 2005

Zusammenfassung
Im Komodo-Projekt wurde ein mehrfädiger Java-Mikrocontroller mit hardwarebasiertem Echtzeit-Scheduling und hardwarebasiertem Energiemanagement als FPGA-Prototyp und als ASIC-Entwurf realisiert und bewertet. Dabei wurden die Scheduling-Algorithmen FPP, EDF, LLF und das neu entwickelte, nur bei mehrfädigen Prozessorkernen anwendbare Guaranteed-Percentage (GP) Scheduling in den Prozessorkern integriert. Auf der Grundlage des prozessorintegrierten GP- bzw. EDF-Scheduling wurden zwei neuartige hardwarebasierte Energiemanagement-Techniken für mehrfädige Prozessorarchitekturen entworfen, die den Energiebedarf des Prozessorkerns durch Frequenz- und Spannungsanpassung gemäß des benötigten Rechenzeitbedarfs reduzieren.
Parallel Processing in Network Processor Architectures (Parallelverarbeitung in Netzwerkprozessorarchitekturen)
Authors: Hagenau Rainer , Albrecht Carsten , Maehle Erik , Döring Andreas C. 
Published: May 2005

Summury
Parallel processing is well established in high-performance computing. Currently, network processors as new emerging, special-purpose processors are targeted at the exploitation of parallelism to meet the requirements in data-plane processing with wire-speed. The achievable level of parallelism is determined by decisions in the architecture design and by the characteristics of the data-plane applications executed. We discuss two basic approaches in parallel processing, namely pipelining and concurrency, which establish basic models for parallel network processor organization. The features and constraints of these models are studied. Using this background some existing network processor architectures are reviewed and characterized regarding their potential in parallel data-plane processing.
Nichtstandardfehlermodelle für digitale Logikschaltkreise: Simulation, prüfgerechter Entwurf, industrielle Anwendungen (On Non-standard Fault Models for Logic Digital Circuits: Simulation, Design for Testability, Industrial Applications)
Authors: Polian Ilia 
Published: May 2005

Zusammenfassung
Konventionelle Testverfahren für integrierte Schaltungen sind zunehmend nicht mehr in der Lage, akzeptable Produktqualität zu gewährleisten. Ein möglicher Ausweg ist der Einsatz von verbesserten Modellen für Fertigungsdefekte (Nichtstandardfehlermodelle). Der erste Teil der Dissertation beschäftigt sich deshalb mit der Modellierung von Brückenfehlern. Insbesondere die Berücksichtigung des Einflusses des Brückenwiderstandes spiegelt die Gegebenheiten moderner Nanoscale-Technologien wider. Obwohl ein Kontinuum von Defekten unter Berücksichtigung nichttrivialer elektrischer Zusammenhänge modelliert wird, sind effiziente diskrete Simulationsalgorithmen möglich. Die einfachsten der vorgestellten Modelle wurden für den industriellen Einsatz optimiert; die Integration der komplexeren resistiven Modelle in die Werkzeuge eines führenden Entwurfsautomatisierungssoftware-Herstellers wird derzeit durchgeführt. Der zweite Teil der Dissertation befasst sich mit Entwurfsmethoden, welche die Testbarkeit des Schaltkreises auf dynamische Defekte erhöhen. Ein Ansatz zur Festlegung mehrerer Prüfpfade und eine Selbsttestarchitektur werden vorgestellt. Zwei Anhänge beschreiben den Zusammenhang zwischen den Nichtstandardfehlermodellen und dem konventionellen stuck-at-Modell und ihren Einsatz in der formalen Verifikation.
Efficacy of intravenous phenytoin in the treatment of status epilepticus: Kinetics of central nervous system penetration
Authors: Wilder B. Joe , Ramsay R. Eugene , Willmore L. James , Feussner George F. , Perchalski Robert J. , Shumate Jack B. 
Published: May 2005

AbstractIntravenous phenytoin (mean dose, 13.0 mg per kilogram of body weight) was administered to 14 patients at a rate not exceeding 100 mg per minute. Twelve hours after infusion the mean plasma phenytoin concentration was 10.2 μg per milliliter, and a therapeutic plasma concentration was found in 9 of the 14 patients. In 3 additional patients, during removal of a primary brain tumor, cortical samples were obtained after intravenous infusion of phenytoin (mean dose, 9.2 mg/kg). Rapid penetration of the brain was found. Concentrations at the end of infusion (16 μg/gm) and 60 minutes after infusion (23 μ/gm) were not significantly different. Six other patients received intravenous phenytoin (mean dose, 10.9 mg/kg) during pneumoencephalography. The cerebrospinal fluid phenytoin concentration gradually increased over 50 minutes. The plasma/cerebrospinal fluid ratio at 50 minutes was 11.0, which is approximately the ratio of total/free phenytoin in the plasma. An additional 10 patients in generalized convulsive status epilepticus were treated with intravenous phenytoin (mean dose, 12.2 mg/kg); status was controlled in 9 within 30 minutes. No major side‐effects were noted. Intravenous phenytoin rapidly enters the central nervous system and results in prompt and effective treatment of status epilepticus without suppressing higher cortical function or cardiorespiratory centers.
Morphological characteristics of central demyelination and remyelination: A single‐fiber study
Authors: Gledhill R. F. , McDonald W. I. 
Published: May 2005

AbstractThe characteristics of demyelination and remyelination in the central nervous system of the cat were examined using quantitative single‐fiber analysis. Internodal length, fiber diameter, and nodal gap length were measured in single fibers teased from the spinal cord of normal animals and of animals with transient experimental cord compression. Demyelination was primarily paranodal, but longer extents of myelin loss occurred. New myelin sheaths were formed by oligodendrocytes and organized into segments bounded by nodes. The internodal length remained inappropriately short for fiber diameter 6 months after compression. The findings demonstrate that the spinal cord is capable of remyelinating after injury, but whether this contributes to functional recovery remains unknown.
Visual evoked potentials in Leber's hereditary optic neuropathy
Authors: Dorfman L. J. , Nikoskelainen E. , Rosenthal A. R. , Sogg R. L. 
Published: May 2005

AbstractPattern‐reversal visual evoked potentials (VEPs) were measured serially in two brothers with Leber's hereditary optic neuropathy during the active phase of the disease. VEP latency and configuration were normal prior to the onset of visual symptoms. The earliest abnormalities consisted of either prolongation of VEP latency or unusual VEP morphology characterized by a double positive peak. As visual acuity declined progressively over a period of months, there was a parallel progressive prolongation of VEP latency accompanied by less consistent diminution of VEP amplitude. In two eyes, VEP ultimately could no longer be measured. VEP latency was normal in most of the asymptomatic family members, including the maternal presumptive carrier. These findings suggest that VEP measurements do not distinguish the presymptomatic or carrier states but do permit quantitative assessment of the activity and progression of the disease.
Particle morphology and NMR structure of polymethylmethacrylate/polystyrene emulsifier‐free core–shell cationic latices in the presence of DBMEA
Authors: Zhang Jinzhi , Li Xiaoqin , Chai Shigan , Wang Shimin , Cheng Shiyuan 
Published: May 2005

AbstractIn the absence of emulsifier, we prepared stable emulsifier‐free polymethylmethacrylate/polystyrene (PMMA/PSt) copolymer latex by batch method with comonomer N,N‐dimethyl, N‐butyl, N‐methacryloloxylethyl ammonium bromide (DBMEA) by using A1BN as initiator. The size distribution of the latex particles was very narrow and the copolymer particles were spherical and very uniform. Under the same recipe and polymerization conditions, PMMA/PSt and PSt/PMMA composite polymer particle latices were prepared by a semicontinuous emulsifier‐free seeded emulsion polymerization method. The sizes and size distributions of composite latex particles were determined both by quasi‐elastic light scattering and transmission electron microscopy (TEM). The effects of feeding manner and staining agents on the morphologies of the composite particles were studied. The results were as follows: the latex particles were dyed with pH 2.0 phosphotungestic acid solution and with uranyl acetate solution, respectively, revealing that the morphologies of the composite latex particles were obviously core–shell structures. The core–shell polymer structure of PMMA/PSt was also studied by 1H, 13C, 2D NMR, and distortionless enhancement by polarization transfer, or DEPT, spectroscopy. Results showed that PMMA/PSt polymers are composed of PSt homopolymer, PMMA homopolymer, and PMMA‐g‐PSt graft copolymers; results by NMR are consistent with TEM results. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 97: 1681–1687, 2005
Studies on engineering properties of PVC–PMMA semi‐interpenetrating polymer networks
Authors: Chakrabarti Rupa , Chakraborty Debabrata 
Published: May 2005

AbstractSemi1 and semi2 interpenetrating polymer networks (IPNs) of PVC and in situ formed PMMA have been synthesized using diallyl phthalate and ethylene glycol dimethacrylate as the crosslinkers of PVC and PMMA, respectively. These two types of IPNs have been compared w.r.t their physical, mechanical, and thermal properties and an endeavor has been made to find a correlation of these properties with the morphology generated in these systems. The semi1 IPNs displayed a decrease in their mechanical parameters and the physical properties as well, while in contrast, the semi2 IPNs exhibited a marginal increase in the corresponding values after an initial drop upto about 15% of crosslinked PMMA incorporation when compared to the crosslinked PVC in the case of semi1 IPN and linear PVC in the case of semi2 IPN. The various samples of semi1 and semi2 IPNs showed a two‐stage degradation typical of PVC, while confirming the increased stability with the samples having higher percentages of PMMA. The influence of crosslinking of the major matrix in semi1 IPN was almost counterbalanced by the influence of crosslinking in the dispersed PMMA phase in the case of semi2 IPN. The softening characteristics as detected by the extent of penetration of the probe, as has been detected by thermomechanical analysis, are in conformity with their mechanicals. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 97: 1725–1735, 2005
An indirect bioluminescence method for the quantitative measurement of polymorphonuclear cell chemotaxis
Authors: Partsch Gerald , Schwarzer Christine 
Published: May 2005

AbstractA method is presented which allows the quantification of the effects of chemotactic factors on polymorphonuclear leukocytes on the basis of a sensitive ATP measurement using bioluminescence. The assay measures those cells which have migrated through a commercial 3 μm filter system (Transwell™). The assay was tested under standardized conditions with different chemotactic agents (leukotriene B4 [LTB4], N‐formyl‐methionyl‐leucyl‐phenylalanine [FMLP], N‐formyl‐methionyl‐leucyl‐phenylalanine‐methyl ester [M‐FMLP]). Under appropriate conditions the migration of PMN‐cells is time‐dependent and linear for 60 minutes. Spontaneous migration of PMN cells is simultaneously quantified in a simple way, and the value obtained allows a determination of the actual chemotactic stiuation of the PMN cells. In healthy humans the spontaneous migration varied between 4.2% and 14.4% of the total number of PMN cells. An optimal chemotactic activity was detected at 10−8/mol/I for FMLP and 10−7 mol/l for M‐FMLP in PMN leukocytes, which correlates with literature values. It was also found that in contrast to EDTA blood, heparinized blood lowers the ATP level of PMN cells (by about 50%) and therefore heparinized blood is not recommended for chemotactic experiments. This assay is a simple tool for quantification of the spontaneous migration, and the chemotactic response to specific factors and their inhibitors in particular for pharmacological experiments. In contrast to the ‘classical’ chemotactic assays this method also permits the simultaneous testing of the influence of chemotactic substances on cellular ATP levels.
Expression and quantification of firefly luciferase under control of Rhizobium meliloti symbiotic promoters
Authors: Cebolla Angel , Ruiz‐Berraquero Francisco , Palomares Antonio J. 
Published: May 2005

AbstractWe have tested the use of firefly luciferase for monitoring regulated symbiotic nitrogen fixation gene expression. Broad‐host‐range plasmids carrying translational fusions of Rhizobium meliloti nifH, fixA and nifA promoters were constructed. Despite low levels of promoter activity the absence of Escherichia coli endogenous luminescence and the high sensitivity of the bioluminescent assay for firefly luciferase allowed rapid screening for functional luciferase expression. Plasmids containing symbiotic promoter‐luc fusions were established in R. meliloti. Luciferase activity was detected and measured in both vegetative and symbiotic cells giving comparable results with those obtained by beta‐galactosidase assays. In addition, the luciferase assay was quicker, more sensitive and could be carried out with unrestricted cells. Furthermore, bioluminescence was high enough in alfalfa nodules containing nifH—luc fusion to be observed by a dark‐adapted eye and photographed.
Chemiluminescence intensities and spectra of luminol oxidation by sodium hypochlorite in the presence of hydrogen peroxide
Authors: Arnhold J. , Mueller S. , Arnold K. , Grimm E. 
Published: May 2005

AbstractHydrogen peroxide amplifies the chemiluminescence in the oxidation of luminol by sodium hypochlorite. A linear relationship between concentration of hydrogen peroxide and light intensity was found in the concentration range 5 × 10−8−7.5 × 10−6 mol/l. At 7.5 × 10−6 mol/l H2O2 the chemiluminescence is amplified 550—fold. The chemiluminescence spectra of these reactions have a wavelength maximum at 431 nm independent of the concentration of hydrogen peroxide. The results indicate that hydrogen peroxide is a necessary component in the chemiluminescent oxidation of the luminol by sodium hypochlorite.
Quantitative generation of singlet (1Δg) oxygen from acidified aqueous peroxynitrite produced by the reaction of nitric oxide and superoxide anion
Authors: Khan Ahsan Ullah 
Published: May 2005

AbstractSimple acidification of aqueous alkaline peroxynitrite quantitatively generates singlet (1Δg) molecular oxygen, detected and quantitated spectroscopically (1270 nm). This observation provides a chemical basis for physiological cytotoxicity of ONOO− generated in the diffusion ‐ controlled reaction of cellular NO• and O. The experiments consist of (i) chemical generation of ONOO− from NO• gas and KO2 powder in alkaline aqueous solution; (ii) absorption spectral identification of ONOO− in the near‐UV with maximum at 302 nm; (iii) spectroscopic identification of 1O2 by its emission band at 1200–1340 nm with maximum at 1275 nm; and (iv) quantitation of 1O2 generated in ONOO−/H+ reaction by comparison of the chemiluminescence intensity at 1270 nm with that from H2O2/OCl− reaction that generates 1O2 with unit efficiency at alkaline pH. 1O2 was generated with unit efficiency with respect to ONOO− concentration by the ONOO−/H+ reaction.