bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of becaplermin in the closure of pharyngocutaneous fistulas
Authors: Jakubowicz David M. , Smith Richard V.
Published: March 2005

Background.

We report on the contribution of recombinant platelet‐derived growth factor‐BB (becaplermin) in treating recalcitrant postlaryngectomy fistulas in two patients with head and neck cancer.

Methods.

Topical becaplermin was applied daily, with periodic wound assessment and photodocumentation.

Results.

The two patients with persistent fistula refractory to conventional management have demonstrated rapid improvement after topical application of becaplermin. Each wound exhibited an exuberant granulation response, with a 50% decrease in the size of wound at 1 week. The patients experienced eventual closure, with none having local recurrence of their cancer at 2 years' follow‐up.

Conclusions.

Becaplermin seems to be a promising addition to traditional methods of treatment for postlaryngectomy fistulas. In patients with delayed healing, future studies will be required to determine the overall efficacy of such biologic response modifiers in the treatment of pharyngocutaneous fistulas and other chronic wounds of the head and neck. © 2005 Wiley Periodicals, Inc. Head Neck 27: XXX–XXX, 2005
Inhibition of monocyte adhesion on brain‐derived endothelial cells by NF‐kappaB decoy/polyethylenimine complexes
Authors: Fischer Dagmar , Bhattacharya Raktima , Osburg Berit , Bickel Ulrich
Published: March 2005

Background

The nuclear factor (NF)‐κB plays a key role in inflammatory reactions of the endothelium by controlling the expression of surface‐adhesion molecules and other inflammatory mediators, which facilitate the attachment of monocytes and lymphocytes to the endothelial surface. We investigated the inhibition of monocyte adhesion by NF‐κB transcription factor decoys complexed with polyethylenimines (PEIs) of different molecular weights and structures (800, 25, and 2.7 kDa PEI).

Methods

Formation, size and stability of the PEI/decoy complexes were investigated by polyacrylamide gel electrophoresis and photon correlation spectroscopy. The efficiency of the complexes was studied in a cell adhesion assay using the murine brain‐derived endothelial cell line bEnd5, activated with lipopolysaccharide as inflammatory model. U‐937 monocytes were fluorescently labeled with BCECF‐AM to permit quantitative measurement of adhesion. Expression of endothelial cell adhesion molecules was determined at the mRNA level by RT‐PCR and at the protein level by ELISA.

Results

Depending on the N/P ratio, decoys formed complexes of <200 nm in size with all PEIs, which were stable against degradation by nucleases and dissociation by albumin. Treatment of bEnd5 and U‐937 cells with NF‐κB decoys complexed with 25 and 2.7 kDa PEI reduced the number of adherent U‐937 cells and decreased the levels of ICAM‐1 and VCAM‐1 mRNA and protein. The effects were specific, time‐dependent and increased with higher N/P ratios of complexes and lower cytotoxicity of polymers. In contrast, the efficiency of the 800 kDa PEI was much lower compared to the other polymers.

Conclusions

Complexes of NF‐κB decoy and PEIs effectively inhibited the adherence of monocytes on endothelial cells, which could be a promising strategy for the treatment of inflammatory diseases. Copyright © 2005 John Wiley & Sons, Ltd.
Dynamic Mechanical and Thermal Properties of Phenylethynyl‐Terminated Polyimide Composites Reinforced With Expanded Graphite Nanoplatelets
Authors: Cho Donghwan , Lee Sangyeob , Yang Gyeongmo , Fukushima Hiroyuki , Drzal Lawrence T.
Published: March 2005

Summary: This article reports on the dynamic mechanical and thermal properties of thermosetting phenylethynyl‐terminated polyimide (PETI‐5) composites reinforced with expanded graphite (EG) nanoplatelets having various average particle sizes and content. The EG nanoplatelets with varying particle sizes were prepared by different pulverization techniques through intercalation and exfoliation of natural graphite flakes. The effect of the EG particle size and concentration of the thermal behavior of PETI‐5/EG composites was investigated with several thermal analysis methods (DMA, TMA, and DSC). The storage modulus dynamic mechanical properties and glass transition temperature significantly increased with increasing concentration of EG nanoreinforcements regardless of size. The coefficient of thermal expansion significantly decreased, especially in the glass transition region.

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An Investigation of Friction and Wear Behaviors of Polyimide/Attapulgite Hybrid Materials
Authors: Lai Shi‐Quan , Yue Li , Li Tong‐Sheng , Liu Xu‐Jun , Lv Ren‐Guo
Published: March 2005

Summary: PI/AT hybrid materials were prepared by blending of poly(amic acid) and purified AT as a type of fibrillar clays. The friction and wear behaviors of the PI hybrids were evaluated on a ball‐on‐disc wear tester. The particle size of AT in the hybrid containing 5 wt.‐% AT was about 10–100 nm in diameter and 100–1 000 nm in length. Tensile tests on the PI hybrids showed that the strength and the toughness of PI/AT hybrid materials were improved simultaneously when the content of AT was less than 5 wt.‐%. The friction coefficient and wear rate of the PI hybrids first decreased and then increased with increasing content of AT. The wear rate of the hybrid containing 3 wt.‐% AT was more than 6 times lower than that of pure PI. SEM examination of worn surfaces showed that type of wear changed from adhesive wear of pure PI into abrasive wear of the PI hybrids with adding AT to PI matrix. Debris analysis suggested that AT as filler inside the PI matrix could prevent the formation of bigger debris and a chemical reaction that occurred during the friction process of pure PI but not in the hybrids.

A plot of the calculated wear rate versus filler content.

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A plot of the calculated wear rate versus filler content.
Cover: Macromol. Mater. Eng. 3/2005
Authors: Hirao Yoshitoshi , Ohkawa Kousaku , Yamamoto Hiroyuki , Fujii Toshihiro
Published: March 2005

Cover: The picture on the cover shows morphological comparisons of the gellan chitosan hybrid fiber (left( and the novel human hair protein‐gellan‐chitosan hybrid fiber (right(, which were prepared by new combined technologies of (i( “Shindai method” for high‐efficiency extraction of human hair protein and (ii( “Watery hybridization spinning” that allows to produce the water‐insoluble hybrid fibers from two aqueous solutions of counter‐charged polymers.

Further details can be found in the Full paper by Y. Hirao, K. Ohkawa, H. Yamamoto, and T. Fujii* on page 165.
Efficient finite element formulation for geothermal heating systems. Part I: steady state
Authors: Al‐Khoury R. , Bonnier P. G. , Brinkgreve R. B. J.
Published: March 2005

This paper presents the development of a computationally efficient finite element tool for the analysis of 3D steady state heat flow in geothermal heating systems. Emphasis is placed on the development of finite elements for vertical borehole heat exchangers and the surrounding soil layers. Three factors have contributed to the computational efficiency: the proposed mathematical model for the heat exchanger, the discretization of the spatial domain using the Petrov–Galerkin method and the sequential numerical algorithm for solving the resulting system of non‐linear equations. These have contributed in reducing significantly the required number of finite elements necessary for describing the involved systems. Details of the mathematical derivations and some numerical examples are presented. Copyright © 2005 John Wiley & Sons, Ltd.
Modified immunohistological staining allows detection of Ziehl–Neelsen‐negative Mycobacterium tuberculosis organisms and their precise localization in human tissue
Authors: Ulrichs Timo , Lefmann Michael , Reich Maja , Morawietz Lars , Roth Andreas , Brinkmann Volker , Kosmiadi George A , Seiler Peter , Aichele Peter , Hahn Helmut , Krenn Veit , Göbel Ulf B , Kaufmann Stefan HE
Published: March 2005

The diagnosis of mycobacterial infection depends on the Ziehl–Neelsen (ZN) stain, which detects mycobacteria because of their characteristic acid‐fast cell wall composition and structure. The histological diagnosis of tuberculosis (TB) comprises various aspects: (1) sensitive detection of mycobacteria; (2) precise localization of mycobacteria in the context of granulomatous lesions; (3) ‘staging’ of disease according to mycobacterial spread and granulomatous tissue integrity. Thus, detection of minute numbers of acid‐fast bacteria in tissue specimens is critical. The conventional ZN stain fails to identify mycobacteria in numbers less than 104 per ml. Hence many infections evade diagnosis. PCR is highly sensitive, but allows neither localization within tissues nor staging of mycobacterial disease, and positive findings frequently do not correlate with disease. In this study, an anti‐Mycobacterium bovis bacille Calmette–Guérin polyclonal antiserum (pAbBCG) was used to improve immunostaining, which was compared to the ZN stain in histological samples. Screening of tissue samples including lungs, pleural lesions, lymph nodes, bone marrow, and skin for mycobacterial infection revealed that pAbBCG staining detects infected macrophages harbouring intracellular mycobacteria or mycobacterial material as well as free mycobacteria that are present at low abundance and not detected by the ZN stain. The positive pAbBCG staining results were confirmed either by PCR analysis of microdissected stained tissue or by culture from tissue. This immunostaining approach allows precise localization of the pathogen in infected tissue. Copyright © 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Transdifferentiation of smooth muscle cells into chondrocytes in atherosclerotic arteries in situ: implications for diffuse intimal calcification
Authors: Bobryshev Yuri V
Published: March 2005

Several hypotheses have been offered to explain the occurrence of arteriosclerotic calcification but the mechanisms involved are still not well understood. Using a combination of electron microscopy and immunohistochemistry, atherosclerotic plaques from human arteries as well as atherosclerotic‐like lesions from aortas of apo‐E‐deficient mice were examined to identify cell type(s) associated with calcification. Electron microscopic analysis showed that, in human atherosclerotic plaques, chondrocyte‐like cells were present in areas surrounding the necrotic cores. In these areas, some smooth muscle cells displayed features of their transdifferentiation into chondrocyte‐like cells. Immunohistochemical analysis confirmed that smooth muscle cells with a reduced content of α‐smooth muscle actin expressed Sox‐9. Destruction of chondrocytes resulted in the accumulation of numerous membrane‐bound vesicles in the extracellular space. Membrane‐bound vesicles originating from chondrocytes were found to undergo calcification. Similar processes were found to occur in atherosclerotic‐like lesions in apo‐E‐deficient mice. These observations suggest that transdifferentiation of smooth muscle cells into chondrocytes contributes to atherosclerotic calcification. Copyright © 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Six Sigma Applied Throughout the Lifecycle of an Automated Decision System
Authors: Patterson Angie , Bonissone Piero , Pavese Marc
Published: March 2005

Automated decision‐making systems have been deployed in many industrial, commercial, and financial applications. The needs for such systems are usually motivated by requirements for variation reduction, capacity increase, cost and cycle time reduction, and end‐to‐end traceability of the transaction or product. Before we can use any automated decision‐making system in a production environment we must develop a strategy to insure high quality throughout its entire lifecycle. We need to guarantee its performance through a rigorous Design for Six Sigma process (DFSS). This process includes validation, tuning, and production testing of the system. Once the system is in production we must monitor and maintain its performance over its lifecycle. In this paper we will outline the Six Sigma process that led to the deployment of an automated decision‐making system in one of the General Electric Financial Assurance businesses. Copyright © 2005 John Wiley & Sons, Ltd.
Six Sigma: is it Really Different?
Authors: Walters Larry
Published: March 2005

This article explores the similarities and differences between Six Sigma and other ‘Quality Improvement’ programs. The overwhelming success of Six Sigma is attributable to something, but what is it? The ‘tools’ of Six Sigma have been used for generations by educators and practitioners. Why does Six Sigma work better for some companies than others? What pitfalls should be avoided? What can I really expect to achieve from a Six Sigma initiative? Copyright © 2005 John Wiley & Sons, Ltd.
Six Sigma and Business Excellence: Strategic and Tactical Examination of IT Service Level Management at the Office of the Chief Technology Officer of Washington, DC
Authors: Edgeman Rick L. , Bigio David , Ferleman Thomas
Published: March 2005

During the period January through May 2003 ten teams of student consultants from the Quality Enhancement Systems & Teams (QUEST) Interdisciplinary Honors Program, the Robert H. Smith School of Business and the A. James Clark School of Engineering at the University of Maryland conducted a quality analysis of Information Technology Service Level Management (ITSLM) for the Office of the Chief Technology Officer (OCTO) of the Government of the District of Columbia. OCTO is largely funded by the United States Congress and is the key IT provider for various public sector agencies in Washington, DC including Metropolitan Police, the Department of Motor Vehicles, Fire and Rescue, Public Works, and DC Public Schools. Five areas of ITSLM were examined through two lenses with a student consulting team assigned to each area and lens. These areas of ITSLM were Availability Management, Capacity Management, Financial Management, Service Continuity, and Service Level Management with Service Continuity essentially referring to ‘disaster recovery’. The two lenses were Six Sigma Strategies and Methods and Business Excellence. Six Sigma is a highly structured approach to process improvement and design while Business Excellence holds to the principles and criteria that are foundational to various international quality awards such as America's Malcolm Baldrige National Quality Award or the European Quality Award. In either case, at its most fundamental level, the goal is to advance a public or private sector entity on the path to excellence. While analysis indicated that OCTO is on the path towards making Washington, DC the ‘City of Access’, a number of strategic and tactical improvement suggestions were identified that will further enable OCTO in this endeavor. Presented herein are selected results from applying the two approaches to performance improvement. In all, the results are synergistic, suggesting that the two lenses can be coordinated to accomplish more in conjunction than can either employed in isolation. Projections by OCTO of potential cost‐savings resulting from application of selected suggestions range from $2 million to $3 million. Copyright © 2005 John Wiley & Sons, Ltd.
Derivatisation of carboxylic acid groups in pharmaceuticals for enhanced detection using liquid chromatography with electrospray ionisation tandem mass spectrometry
Authors: Cartwright Andrew J. , Jones Phil , Wolff Jean‐Claude , Evans E. Hywel
Published: March 2005

Tris(2,4,6‐trimethoxyphenyl)phosphonium propylamine bromide (TMPP) has been used for the derivatisation of maleic, fumaric, sorbic and salicylic acids to facilitate determination using liquid chromatography/electrospray ionisation tandem mass spectrometry (LC/ESI‐MS/MS) in positive ion mode. Detection limits, achieved using multiple reaction monitoring mode, were 2, 4, 0.4 and 540 fmol (5 μL injection) for derivatised fumaric, sorbic, maleic and salicylic acids, respectively. In comparison, detection limits achieved in negative ion mode for the underivatised acids were 24, 51, 2, and 117 fmol, respectively. The method was successfully used for the determination of sorbic acid in a sample of Panadol™. The derivatisation of salicylic acid was not as successful, probably due to poor reaction efficiency. Copyright © 2005 John Wiley & Sons, Ltd.
Estimation of gas‐phase acidities of a series of dicarboxylic acids by the kinetic method
Authors: Ravi Kumar M. , Prabhakar S. , Nagaveni V. , Vairamani M.
Published: March 2005

The gas‐phase acidities (GA) of a series of dicarboxylic acids were estimated by applying the extended kinetic method. Proton‐bound heterodimeric anions [A−H+B−] of a series of dicarboxylic acids (A) and reference compounds (B) were generated under electrospray ionization conditions, and the dissociation of these cluster ions was examined using a triple‐quadrupole mass spectrometer. The mass‐selected proton‐bound heterodimeric anions were fragmented to yield individual monomer anions as the only product ions, and the abundance ratios of these anions were used to estimate the GA values of the dicarboxylic acids. The experiment was performed over a range of collision energies in order to more accurately determine GA values and to estimate the differences in the entropy of deprotonation of the dicarboxylic acids and the reference compounds. The trends in GA values obtained for the dicarboxylic acids could imply cyclization of the structures via intramolecular hydrogen bonding. The lower homologues show higher GA values than the higher homologues. The GA order for lower homologues is comparable with that of their solution‐phase pKa1 values. Copyright © 2005 John Wiley & Sons, Ltd.
Spatial distribution of bacterivorous nematodes in a Chinese Ecosystem Research Network (CERN) site
Authors: Liang Wenju , Jiang Yong , Li Qi , Liu Yanjun , Wen Dazhong
Published: March 2005

Geostatistics was applied to assess the spatial distribution of bacterivorous nematodes in a Chinese Ecosystem Research Network (CERN) site in northeast China. A 42×30 m plot was divided into grids with 7×5 m spacing that included 49 sampling points. Soil samples were collected from depths of 0–10 cm and 10–20 cm. The results showed thatCephalobusandPanagrolaimuswere the most dominant bacterivores, which together represented 74 and 82% of total bacterivorous nematodes on average at depths of 0–10 cm and 10–20 cm, respectively. Within‐site variability was high for these nematode genera. Geostatistical analysis indicated that a major part of this variability was spatially dependent; variograms suggest that 55–100% of sample population variance was related to spatial autocorrelation over ranges of 9–91 m. The mean numbers of total bacterivores andPanagrolaimuspopulations were higher at 0–10 cm depth than at 10–20 cm depth. Between the two depths, different distribution patterns were found forPanagrolaimus, whereas similar patterns were found forCephalobus. The maps obtained by kriging well illustrated horizontal distribution patterns of bacterivorous nematodes at two depths at field scale.
The Behavioural Responses to Illness Questionnaire (BRIQ): a new predictive measure of medically unexplained symptoms following acute infection
Authors: SPENCE MEAGAN , MOSS-MORRIS RONA , CHALDER TRUDIE
Published: March 2005

Background. The aim of this study was to design a self-report measure of behavioural responses during the acute phase of an illness, in order to assess the importance of these behaviours in the development of ongoing medically unexplained syndromes.

Method. An initial pool of items derived from theoretical models and clinical observation, was piloted on a group of 312 university students to assess the factor structure of the scale and the best fit items. The scale was further validated in a second study of 758 patients who were experiencing Campylobacter gastroenteritis. At 3 months post-infection, patients were sent a second questionnaire assessing symptoms of irritable bowel syndrome (IBS).

Results. Principal components analysis of the items in the student sample yielded a four-factor solution, labelled all-or-nothing behaviour, limiting behaviour, emotional support seeking and practical support seeking. The factor structure was confirmed in the Campylobacter sample, and internal reliability was good. All-or-nothing behaviour was associated with IBS at 3 months post-infection. In contrast, limiting behaviour and practical support seeking at the time of infection appeared to be protective.

Conclusion. The results suggest that this is a valid and reliable measure that can predict the development of a medically unexplained syndrome after acute infection. Overdoing things at the time of infection and then needing to rest for prolonged periods (all-or-nothing behaviour), appears to be a particular risk factor for the development of IBS. Targeted interventions at the time of infection may improve coping and prevent symptoms from becoming chronic.
Reversed diurnal variation in depression: associations with a differential antidepressant response, tryptophan:large neutral amino acid ratio and serotonin transporter polymorphisms
Authors: JOYCE PETER R. , PORTER RICHARD J. , MULDER ROGER T. , LUTY SUZANNE E. , McKENZIE JANICE M. , MILLER ALLISON L. , KENNEDY MARTIN A.
Published: March 2005

Background. Although diurnal variation of mood is a widely recognized symptom of depression, the clinical, neurobiological and psychopharmacological significance of this symptom has not previously been reported.

Method. A total of 195 depressed out-patients underwent a detailed clinical and neurobiological assessment, and were then randomized to treatment with either fluoxetine or nortriptyline.

Results. Of the 195 depressed patients, 62 had a pattern of reversed diurnal variation (i.e. worse in the evening). Those with reversed diurnal variation had a poorer response to a serotonergic antidepressant, were less likely to have bipolar II disorder, had a higher tryptophan:large neutral amino acid ratio and had different allele frequencies of the polymorphisms in the promoter region of the serotonin transporter.

Conclusions. These findings raise the possibility of serotonergic influence on diurnal variation, and that the symptom of reversed diurnal variation is of relevance to antidepressant prescribing.
Morphological brain changes associated with Schneider's first-rank symptoms in schizophrenia: an MRI study
Authors: SUZUKI M. , ZHOU S.-Y. , HAGINO H. , NIU L. , TAKAHASHI T. , KAWASAKI Y. , MATSUI M. , SETO H. , ONO T. , KURACHI M.
Published: March 2005

Background. Schneider's first-rank symptoms involve an alienated feature of the sense of one's own mental or physical activity. To clarify the brain morphological basis for the production of these symptoms, volumes of the frontal and medial temporal regions and their clinical correlates were examined in patients with schizophrenia.

Method. Twenty-two patients with schizophrenia and 44 age- and gender-matched healthy control subjects were included. All patients were in their psychotic episodes with definite Schneiderian symptoms, rated by using the Scale for Assessment of Positive Symptoms. Volumetric measurements of high-resolution magnetic resonance imaging were performed in the prefrontal area, cingulate gyrus, and precentral gyrus, and the medial temporal structures such as the amygdala, hippocampus, and parahippocampal gyrus.

Results. Patients had significantly decreased volumes in the cingulate gray matter and the amygdala compared to controls. In the patient group, Schneiderian symptom severity showed significant inverse correlations with volumes of the right posterior cingulate gray matter and of the left anterior parahippocampal gyrus.

Conclusions. Schneiderian symptoms may be associated with morphological abnormalities in the limbic-paralimbic regions such as the cingulate gyrus and parahippocampal gyrus, which possibly serve the self-monitoring function and the coherent storage and reactivation of information.
8 Welfare state transformation in small open economies
Authors: OBINGER HERBERT , LEIBFRIED STEPHAN , BOGEDAN CLAUDIA , GINDULIS EDITH , MOSER JULIA , STARKE PETER
Published: March 2005

We examine whether a fundamental change in the core dimension of modern 20th century statehood, the welfare state, has become evident in response to changed exogenous and endogenous challenges. By combining quantitative and qualitative approaches we take stock of social policy development in four advanced welfare states – Austria, Denmark, New Zealand and Switzerland – over the last 30 years. Neither spending patterns nor structural changes support a ‘race to the bottom thesis’, according to which the changed environment of welfare state policies has led to a downward spiral in benefit provision. On the contrary, we show that social spending levels have risen, mainly due to a catch-up of former welfare state laggards. In structural terms, a blurring of welfare regimes can be observed. This twofold process can be described as dual convergence.
A New Cognitive Behavioural Parenting Intervention for Families of Young Anxious Children: A Pilot Study
Authors: Cartwright-Hatton Sam , McNally Deborah , White Caroline
Published: March 2005

Childhood anxiety disorders often have a poor prognosis. Despite this, there are currently no published treatment protocols for young children with anxiety difficulties. Individually focused therapies (e.g. CBT) are useful for older children, but likely to be less so for this group. This paper describes a pilot investigation of a new CBT based parenting intervention for the treatment of children aged 9 years and under. Sixteen parents of 11 anxious children took part in a 10-week intervention, completing the Child Behaviour Checklist at three time points. The intervention was based on a new cognitively enhanced parenting package, with an emphasis on coping with internalizing symptoms, and with additional modules on the specific skills needed for managing anxiety. All children were reported to experience substantial decreases in their internalizing symptoms by the end of the study. Parents' satisfaction with the intervention was high. This is a promising new intervention for the treatment of a currently neglected group.
Dipyridophenazine Complexes of Cobalt(III): DNA Photocleavage and Photobiology
Authors: Funston Alison M. , Cullinane Carleen , Ghiggino Kenneth P. , McFadyen W. David , Stylli Stanley S. , Tregloan Peter A.
Published: March 2005

The UV-visible spectroscopy and photochemistry of [Co(en)2(DPPZ)](ClO4)3 (DPPZ = dipyrido[3,2-a:2´,3´-c]-phenazine) in the presence of plasmid DNA and the nucleoside 2´-deoxygaunosine have been investigated. Evidence for the intercalation of the complex with DNA and photoinduced DNA strand breakage is found. The structurally related complexes [Co(en)2(DPPN)]Cl3 and [Co(en)2(DPPA)]Cl2, where DPPN = benzo[i]dipyrido[3,2-a:2´,3´-c]phenazine and DPPA = dipyrido[3,2-a:2´,3´-c] phenazine-11-carboxylic acid, have also been synthesized and characterized. In vitro cytotoxicity studies and photocytotoxicity studies of the complexes using the C6 rat glioma cell line are reported and indicate significant increases in toxicity following irradation.
Relationships between EGFR Signaling–competent and Endocytosis-competent Membrane Microdomains
Authors: Puri Claudia , Tosoni Daniela , Comai Riccardo , Rabellino Andrea , Segat Daniela , Caneva Federico , Luzzi Paola , Di Fiore Pier Paolo , Tacchetti Carlo
Published: March 2005

Membrane microdomains, the so-called lipid rafts, function as platforms to concentrate receptors and assemble the signal transduction machinery. Internalization, in most cases, is carried out by different specialized structures, the clathrin-coated pits. Here, we show that several endocytic proteins are efficiently recruited to morphologically identified plasma membrane lipid rafts, upon activation of the epidermal growth factor (EGF) receptor (EGFR), a receptor tyrosine kinase. Analysis of detergent-resistant membrane fractions revealed that the EGF-dependent association of endocytic proteins with rafts is as efficient as that of signaling effector molecules, such as Grb2 or Shc. Finally, the EGFR, but not the nonsignaling transferrin receptor, could be localized in nascent coated pits that almost invariably contained raft membranes. Thus, specialized membrane microdomains have the ability to assemble both the molecular machineries necessary for intracellular propagation of EGFR effector signals and for receptor internalization.
Active Control and Causation
Authors: Clarke Randolph
Published: March 2005

Noncausal libertarian accounts allow that a basic free action may be uncaused and have no internal causal structure. Views of this type advanced by Carl Ginet and Hugh McCann are evaluated here. These views fail to provide adequate accounts of the active control that is exercised when one acts freely and of the reason-explanation of free actions. Any satisfactory account of these phenomena must invoke causation.
The Problem of Diminished Control
Authors: Clarke Randolph
Published: March 2005

This chapter examines the charge that the indeterminism required by standard event-causal libertarian accounts would diminish the control that is exercised in acting. The objection has been advanced with an ensurance argument and an argument from luck. Both arguments are rejected; nondeterministic causation of an action by its immediate causal antecedents need not diminish at all the type of control relevant to free action. This chapter further assesses the account of free will advanced by Robert Kane, which imposes certain special requirements meant to address the problem of diminished control. These special requirements provide no help; but, in any case, none is needed.
Agent Causation and Control
Authors: Clarke Randolph
Published: March 2005

Agent-causal accounts aim to secure greater control than can be secured by any event-causal libertarian account. Assuming that all it requires is possible, an integrated agent-causal view succeeds at this goal and adequately characterizes free will. Such a view captures well the common idea that free agents are originators of their free actions. Responses are offered to Peter van Inwagen’s challenge to agent-causal views and to Galen Strawson’s argument that free will is impossible. A claim that free will requires downward causation—of a sort involving the supersession of microlevel laws—is rejected.
Substance and Cause
Authors: Clarke Randolph
Published: March 2005

The chief difficulty for agent-causal accounts lies in defending the notion of agent causation. Either of two types of realist account of causation can be drawn on to explicate the claim that enduring substances are among the causes of things. But there remains the objection that, although this claim is intelligible, it is necessarily false. Several objections to the possibility of substance causation are considered, and it is concluded that there are, on balance, good reasons to reject this possibility.
Nietzsche on Resentment, Love, and Pity
Authors: Solomon Robert C.
Published: March 2005

In this chapter, I discuss why resentment (ressentiment) is so important to Nietzsche’s theory and what is wrong with it. I also discuss Nietzsche on love and pity and his several metaphors of strength and weakness, masters and slaves, eagles and lambs, health and illness.
Nietzsche's Existentialism
Authors: Solomon Robert C.
Published: March 2005

Is Nietzsche an existentialist? He is often included in existentialism courses and collections. But Nietzsche’s views on freedom are by no means so clear (as, say, those of Kierkegaard and Sartre), and his celebration of fatalism (amor fati) seems to go against the existentialist celebration of freedom. In this chapter, I examine Nietzsche’s views on freedom and fatalism, and I argue that Nietzsche’s classic slogan, “Become Who You Are,” suggests a strong stance on responsibility as well as an intelligible acceptance of fatalism, largely based on the ancient philosopher Heraclitus.
Meditating on the Creatures in Early American Life and Letters
Authors: Gatta John
Published: March 2005

The longstanding European tradition of meditating on creatures of the phenomenal world carried both religious and ecological significance for New England Puritans, who were peculiarly disposed to ponder the relation between earth’s visible and invisible domains. This disposition is exemplified by the poetry of meditation composed by colonial writers such as Edward Taylor and Anne Bradstreet. Bradstreet’s meditative poem “Contemplations” is interpreted ecocritically, so as to probe not only the spirituality of the world that the poet sets forth, but also the discretely material spirit of place that helped inspire her reflections. Outside the Puritan colonies, other forms of ecospirituality can be discerned in the Quaker-inspired prose writings of naturalist William Bartram and social reformer John Woolman. Both exponents of Middle Atlantic Quaker piety envisioned a divine love that encompasses animals as well as humans, and that thereby extends humanity’s ethical responsibility beyond social boundaries to the “brute creatures.”
Intimations of an Environmental Ethic in the Writings of Jonathan Edwards
Authors: Gatta John
Published: March 2005

Although the renowned Calvinist divine Jonathan Edwards scarcely fits the conventional image of a nature writer, his work embodies a theology of Creation that has important implications for environmental ethics. As such, his ethical philosophy anticipates--in several surprising but instructive ways—the twentieth-century “land ethic” set forth by Aldo Leopold in his Sand County Almanac. Edwards’s notion of “benevolence to Being in general,” as articulated in The Nature of True Virtue, is a theocentric ideal that resists the anthropocentric assumption that nature exists solely to fulfill human needs and desires. Edwards’s vision of Creation as an all-encompassing and sacred beauty thus anticipates the modern sense of “ecology” that likewise affirms the interactive unity of all living and nonliving things.
Variations on Nature
Authors: Gatta John
Published: March 2005

Among the divergent forms of nature writing that flourished in nineteenth-century America, the “Old Manse” preface by Hawthorne reflects a distinctive mood of contentment about the author’s residence in Concord, Massachusetts. This essay’s conception of nature is based not on a wilderness aesthetic, but on a pastoral sense of human interaction with the green world—a sense that Hawthorne associates in turn with Christian theological terms of grace and incarnation. The holiness of gardening likewise informs writing of this period by women such as Celia Thaxter and Margaret Fuller. The religious intensity of Walt Whitman’s ecopoetic worldview, epitomized by “Song of Myself,” ranges from the astronomical heights to the lowly plants mentioned in section 5 of this poem. Unlike Whitman’s oceanic poems, Herman Melville’s portrayal of the sea in Moby-Dick exposes nature’s underlying savagery and vulturism—but also raises deep questions about the divinely inscrutable freedom of Creation embodied by the great white whale.
“Rare and Delectable Places”
Authors: Gatta John
Published: March 2005

Walden Pond, the obvious focal point of Thoreau’s worship and spiritual discovery, qualifies thereby as a sacred place in the author’s celebrated account of “where he lived.” Thoreau’s place-centered spirituality is both active and contemplative, with the contemplative dimension vividly conveyed through his description of morning meditation in the chapter “Sounds.” Thoreau, despite his elusive and inconsistent theology, sometimes confirms belief in a personal Deity and typically envisions nature as a divine Creation. In the famous sandbank cosmogony that appears at the climax of the chapter “Spring,” Thoreau combines a numinous vision of continuous creation with an evolutionary dynamic informed by recent scientific discoveries in biology, geography, and geology. Thoreau imagined nature’s wildness, which enables us to “witness our own limits transgressed,” as wedded thereby to our sense of the sacred.
Post-Darwinian Visions of Divine Creation
Authors: Gatta John
Published: March 2005

Beginning in the latter half of the nineteenth century, Darwinism had a varied impact on American sensibilities. John Muir, for example, studied science and accepted the transmutative premise of evolutionary theory--but retained a biblically colored piety that saw God’s presence inscribed “in magnificent capitals” at places like Yosemite. During this extended period, writings by Mary Austin and Black Elk reflect their encounters with versions of naturalistic piety lying outside Euro-American ethnic traditions. Still, the written form in which Black Elk expressed his ecological vision of holiness, as imaged in the great hoop of the Lakota nation, was decidedly influenced by his contact with non-Indian culture. Although Rachel Carson was a committed scientist whose work presupposed belief in organic evolution, her writing also reflects a robust spirituality founded upon reverence for life and for the mystery of things unseen.
Marxism and the City
Authors: Katznelson Ira
Published: March 2005

Defeated in the East and discredited in the West, Marxism has broken down as an ideology and as a guide to governance. However, for all its flaws, it remains an important tool for understanding and raising questions about key aspects of modern life. In Marxism and the City, Ira Katznelson critically assesses the scholarship on cities that has developed within Marxism in the past quarter century to show how some of the most important weaknesses in Marxism as a social theory can be remedied by forcing it to engage seriously with cities and spatial concerns. He argues that such a Marxism still has a significant contribution to make to the discussion of historical questions such as the transition from feudalism to a world composed of capitalist economies and nation‐states and the acquiescence of the western working classes to capitalism. Katznelson demonstrates how a Marxism that embraces complexity and is open to engagement with other social–theoretical traditions can illuminate understanding of cities and of the patterns of class and group formation that have characterized urban life in the West.
From Feudalism to Capitalism: The Place of the City
Authors: Katznelson Ira
Published: March 2005

One area where Marxism has dealt with the city is the transition from feudalism to capitalism, although this discussion has been satisfactory only in part, since too much is compressed in the very idea of this epochal transformation. Marxism's conception of feudalism has been too narrow: it has treated some 500 years of history in terms of a single direction of change, and it has flattened the dimensions and varieties of transition. Further, Marxism's insistence on parallel treatment as modes of production for feudalism (which fused sovereignty and property), and for capitalism (which did not), is misplaced. Yet even if Marxism's discussion of the transition has been flawed, it is here that some of the most important attempts to make cities a constitutive part of a key historical and theoretical problem are found. This chapter broadens and shifts the terms of this engagement of Marxism with the city – by so doing, it is possible to shed some light on the impact cities had on large‐scale change in early modern Europe, and, in turn, on the ways cities as places were altered by the demise of feudalism.
Interpreting Kant's Critiques
Authors: Ameriks Karl
Published: March 2005

This volume contains essays on all three main areas of Kant’s work: theoretical philosophy (the first Critique), practical philosophy (the second Critique), and aesthetics (the third Critique). It begins with a substantial, specially written introduction that sets out main themes in the structure and interpretation of Kant’s Critical philosophy. The first part of the book (Chs. 1–5) includes several of the author’s well-known essays on the Critique of Pure Reason, emphasizing Kant’s central theoretical notions of a transcendental deduction and transcendental idealism, and providing an extensive review of recent English and German scholarship in this area. Part II (Chs. 6–11) includes new discussions of the Critique of Practical Reason and its relation to Kant’s other main work in moral theory, the Groundwork of the Metaphysics of Morals. Part III (Chs. 12–14) focuses on taste and the Critique of Judgment and on the controversial hypothesis that even in this area Kant’s position is fundamentally objective and conceptual. This collection demonstrates in detail how, for understanding the basic structure of any one of Kant’s Critiques, it is extremely helpful to remember its logical and historical relation to Kant’s other Critiques. This book also makes interpretation itself a central issue. Not only does it offer a series of interrelated interpretations of Kant’s main works but it also argues that the difficulty of interpretation itself is a central feature of the Critical philosophy, and that the difficulties of that philosophy have become paradigmatic for modern philosophy in general.
Kant's Deduction of Freedom and Morality
Authors: Ameriks Karl
Published: March 2005

Concerns a pivotal development in Kant’s practical philosophy, one that confirms the central role of judgement and experience in Kant’s philosophy. Kant’s first major work in practical philosophy, the Groundwork of the Metaphysics of Morals (1785), suggests a very intriguing but ultimately unsatisfying argument for the validity of morality, one that starts at first from a mere consideration of the general nature of human judgement. For a wide variety of inadequately appreciated considerations having to do with refinements in his epistemology and theory of mind between the two editions of the first Critique, Kant’s second major work in practical philosophy, the Critique of Practical Reason (1788), adopts a very different and explicitly more regressive strategy. Argues that there is a ‘great reversal’ in Kant’s position here, contrary to the readings of scholars such as Paton, Beck, and Henrich, who have contended in effect that there exists a deep continuity in these major texts, either because there is also something like a regressive strategy already in the Groundwork or because there is also a non-regressive strategy carried forward into the second Critique. Kant’s discussion in the second Critique makes fully explicit, for the first time, that the ‘experience’ lying at the basis of his practical philosophy is not anything as general as the apparent spontaneity of the mind in the process of judging or willing as such, but instead involves a kind of absolute freedom that can be grounded only regressively through the specific premise of a binding form of moral experience (called ‘the fact of reason’).
Kant on the Good Will
Authors: Ameriks Karl
Published: March 2005

Focuses on a normative question central to the beginning of Kant’s Groundwork, the concept of a good will. After distinguishing three varieties of the concept that can be constructed from Kant’s writings and criticizing several recent readings concerning them, it concludes that one can make the best sense of Kant’s intentions here by connecting the good will not to an individual act or perfect attitude but to the entirety of one’s character. Once this is done, however, there remain some very hard to understand basic features of Kant’s notion of character: his account of temptation, and his claim that we all can and should go through a fundamental moral conversion.
Kant's Groundwork III Argument Reconsidered
Authors: Ameriks Karl
Published: March 2005

Provides a detailed critical account of the beginning of the argument of part III of Kant’s Groundwork, the section of his writing in which he seems to come closest to offering a direct proof of our absolute freedom. It contends that there are several ambiguities and missteps in what seems to be Kant’s main line of argument here, but these need not count again Kant’s ultimate position. On the contrary, realizing that there may be such fundamental flaws in this part of the Groundwork is the easiest way to understand why Kant never directly refers back to it and why he reversed his method of presentation so dramatically in the second Critique.
‘Pure Reason of Itself Alone Suffices to Determine the Will’
Authors: Ameriks Karl
Published: March 2005

Provides a more detailed account of how the treatment of the ‘fact of reason’ in the second Critique can be read as an explicit reversal of Kant’s earlier procedure. In now clearly insisting on disallowing any route to a claim of absolute freedom that does not rest on the moral law, Kant reaches a position that puts the least strain on the theme that came to dominate the final version of his first Critique (1787), the claim that we have no privileged theoretical knowledge of the self, not even of its absolute spontaneity. The downside of this result is that Kant also calls freedom the ‘keystone’ of his Critical philosophy, the centre of his effort to help rebuild all philosophy, life, and culture around the notion of autonomy. Without any theoretical argument or uncontroversial practical foundation for this keystone concept, Kant’s insistence on autonomy can appear vulnerable and so it is no surprise that Kant’s system was heavily revised by his immediate successors who were desperate to find new and stronger ways to undergird the autonomy that they were even more enthusiastic about than Kant himself.
How to Save Kant's Deduction of Taste as Objective
Authors: Ameriks Karl
Published: March 2005

Combines two earlier articles that argue that there is a way of reconstructing Kant’s account of taste such that it has a plausible deduction, but one that involves understanding natural beauty as an objective feature disclosed in a particular kind of pure appreciation of sensible forms.
The English School and International Theory
Authors: Suganami Hidemi
Published: March 2005

The author outlines and assesses the contribution the English School of International Relations to theory in the study of world politics by discussing in turn each of three aspects of theorizing: ‘explanatory’, ‘normative’, and ‘international’. Explanatory theory aims to help understanding of how it is that the realm of world politics works out the ways it appears to do, while normative theory elucidates the steps through which some fundamental normative presuppositions lead to conclusions regarding what should be done in world politics. The author uses the term ‘international theory’ in Martin Wight's specific sense of the term as ‘a tradition of speculation about relations between states, a tradition imagined as the twin of speculation about the state to which the name “political theory” is appropriated’. As the discussion progresses, some other senses of the word ‘theory’ are also brought to attention to elucidate the activities of the English School. In sum, the author argues that the English School's explanatory theory is woefully underdeveloped, its normative theory is in need of further reflection, while its international theory offers a useful way of interpreting world politics.