bluuebunny/crossref_metadata_2025 huggingface dataset:
Escherichia coli thioredoxin inhibition by cadmium
Authors: Rollin‐Genetet Françoise , Berthomieu Catherine , Davin Anne‐Hélène , Quéméneur Eric
Published: March 2004

Observations of thioredoxin inhibition by cadmium and of a positive role for thioredoxin in protection from Cd2+ led us to investigate the thioredoxin–cadmium interaction properties. We used calorimetric and spectroscopic methods at different pH values to explore the relative contribution of putative binding residues (Cys32, Cys35, Trp28, Trp31 and Asp26) within or near the active site. At pH 8 or 7.5 two binding sites were identified by isothermal titration calorimetry with affinity constants of 10 × 106 m−1 and 1 × 106 m−1. For both sites, a proton was released upon Cd2+ binding. One mole of Cd2+ per mole of reduced thioredoxin was measured by mass spectrometry at these pH values, demonstrating that the two binding sites were partially occupied and mutually exclusive. Cd2+ binding at either site totally inhibited the thiol–disulfide transferase activity of Trx. The absence of Cd2+ interaction detected for oxidized or alkylated Trx and the inhibition of the enzymatic activity of thioredoxin by Cd2+ supported the role of Cys32 at the first site. The fluorescence profile of Cd2+‐bound thioredoxin differed, however, from that of oxidized thioredoxin, indicating that Cd2+ was not coordinated with Cys32 and Cys35. From FTIR spectroscopy, we inferred that the second site might involve Asp26, a buried residue that deprotonates at a rather high and unusual pKa for a carboxylate (7.5/9.2). The pKa of the two residues Cys32 and Asp26 have been shown to be interdependent [Chivers, T. P. (1997) Biochemistry36, 14985–14991]. A mechanism is proposed in which Cd2+ binding at the solvent‐accessible thiolate group of Cys32 induces a decrease of the pKa of Asp26 and its deprotonation. Conversely, interaction between the carboxylate group of Asp26 and Cd2+ at a second binding site induces Cys32 deprotonation and thioredoxin inhibition, so that Cd2+ inhibits thioredoxin activity not only by binding at the Cys32 but also by interacting with Asp26.
Chemical foundation of the attenuation of methylmercury(II) cytotoxicity by metallothioneins
Authors: Leiva‐Presa Àngels , Capdevila Mercè , Cols Neus , Atrian Silvia , González‐Duarte Pilar
Published: March 2004

To elucidate the chemical interactions underlying the role of metallothioneins (MTs) in reducing the cytotoxicity caused by MeHg(II), we monitored in parallel by electronic absorption and CD spectroscopies the stepwise addition of MeHgCl stock solution to mammalian Zn7‐MT1 and the isolated Zn4‐αMT1 and Zn3‐βMT1 fragments. The incorporation of MeHg+ into Zn7‐MT and Zn3‐βMT entails total displacement of Zn(II) and unfolding of the protein. However, both features are only partial for Zn4‐αMT. The different behavior observed for this fragment, whether isolated or constituting one of the two domains of Zn7‐MT, indicates interdomain interactions in the whole protein. Overall, the binding properties of Zn7‐MT, Zn4‐αMT and Zn3‐βMT toward MeHg+ are unprecedented. In addition, the sequestration of MeHg+ by Zn7‐MT and the concomitant release of Zn(II) are probably two of the main contributions in the detoxifying role of mammalian MT.
Collectins
Authors: van de Wetering J. Koenraad , van Golde Lambert M. G. , Batenburg Joseph J.
Published: March 2004

Collectins are a family of collagenous calcium‐dependent defense lectins in animals. Their polypeptide chains consist of four regions: a cysteine‐rich N‐terminal domain, a collagen‐like region, an α‐helical coiled‐coil neck domain and a C‐terminal lectin or carbohydrate‐recognition domain. These polypeptide chains form trimers that may assemble into larger oligomers. The best studied family members are the mannan‐binding lectin, which is secreted into the blood by the liver, and the surfactant proteins A and D, which are secreted into the pulmonary alveolar and airway lining fluid. The collectins represent an important group of pattern recognition molecules, which bind to oligosaccharide structures and/or lipid moities on the surface of microorganisms. They bind preferentially to monosaccharide units of the mannose type, which present two vicinal hydroxyl groups in an equatorial position. High‐affinity interactions between collectins and microorganisms depend, on the one hand, on the high density of the carbohydrate ligands on the microbial surface, and on the other, on the degree of oligomerization of the collectin. Apart from binding to microorganisms, the collectins can interact with receptors on host cells. Binding of collectins to microorganisms may facilitate microbial clearance through aggregation, complement activation, opsonization and activation of phagocytosis, and inhibition of microbial growth. In addition, the collectins can modulate inflammatory and allergic responses, affect apoptotic cell clearance and modulate the adaptive immune system.
Direct electrochemistry of the Desulfovibrio gigas aldehyde oxidoreductase
Authors: Correia dos Santos Margarida M. , Sousa Patrícia M. P. , Gonçalves M. Lurdes S. , Romão M. João , Moura Isabel , Moura José J. G.
Published: March 2004

This work reports on the direct electrochemistry of the Desulfovibrio gigas aldehyde oxidoreductase (DgAOR), a molybdenum enzyme of the xanthine oxidase family that contains three redox‐active cofactors: two [2Fe‐2S] centers and a molybdopterin cytosine dinucleotide cofactor. The voltammetric behavior of the enzyme was analyzed at gold and carbon (pyrolytic graphite and glassy carbon) electrodes. Two different strategies were used: one with the molecules confined to the electrode surface and a second with DgAOR in solution. In all of the cases studied, electron transfer took place, although different redox reactions were responsible for the voltammetric signal. From a thorough analysis of the voltammetric responses and the structural properties of the molecular surface of DgAOR, the redox reaction at the carbon electrodes could be assigned to the reduction of the more exposed iron cluster, [2Fe‐2S] II, whereas reduction of the molybdopterin cofactor occurs at the gold electrode. Voltammetric results in the presence of aldehydes are also reported and discussed.
Neutral N‐glycans of the gastropod Arion lusitanicus
Authors: Gutternigg Martin , Ahrer Karin , Grabher‐Meier Heidi , Bürgmayr Sabine , Staudacher Erika
Published: March 2004

The neutral N‐glycan structures of Arion lusitanicus (gastropod) skin, viscera and egg glycoproteins were examined after proteolytic digestion, release of the glycans from the peptides, fluorescent labelling with 2‐aminopyridine and fractionation by charge, size and hydrophobicity to obtain pure glycan structures. The positions and linkages of the sugars in the glycan were analysed by two dimensional HPLC (size and hydrophobicity) and MALDI‐TOF mass spectrometry before and after digestion with specific exoglycosidases. The most striking feature in the adult tissues was the high amount of oligomannosidic and small paucimannosidic glycans terminated with 3‐O‐methylated mannoses. The truncated structures often contained modifications of the inner core by β1,2‐linked xylose to the β‐mannose residue and/or an α‐fucosylation (mainly α1,6‐) of the innermost GlcNAc residue. Skin and viscera showed predominantly the same glycans, however, in different amounts. Traces of large structures carrying 3‐O‐methylated galactoses were also detected. The egg glycans contained mainly (≈ 75%) oligomannosidic structures and some paucimannosidic structures modified by xylose or α1,6‐fucose, but in this case no methylation of any monosaccharide was detected. Thus, gastropods seem to be capable of producing many types of structures ranging from those typical in human to structures similar to those found in nematodes, and therefore will be a valuable model to understand the regulation of glycosylation. Furthermore, this opens the way for using this organism as a host for the production of recombinant proteins. The detailed knowledge on glycosylation also may help to identify targets for pest control.
Inhibition of Drosophila melanogaster acetylcholinesterase by high concentrations of substrate
Authors: Stojan Jure , Brochier Laure , Alies Carole , Colletier Jacques Philippe , Fournier Didier
Published: March 2004

Acetylcholine hydrolysis by acetylcholinesterase is inhibited at high substrate concentrations. To determine the residues involved in this phenomenon, we have mutated most of the residues lining the active‐site gorge but mutating these did not completely eliminate hydrolysis. Thus, we analyzed the effect of a nonhydrolysable substrate analogue on substrate hydrolysis and on reactivation of an analogue of the acetylenzyme. Analyses of various models led us to propose the following sequence of events: the substrate initially binds at the rim of the active‐site gorge and then slides down to the bottom of the gorge where it is hydrolyzed. Another substrate molecule can bind to the peripheral site: (a) when the choline is still inside the gorge – it will thereby hinder its exit; (b) after choline has dissociated but before deacetylation occurs – binding at the peripheral site increases deacetylation rate but (c) if a substrate molecule bound to the peripheral site slides down to the bottom of the active‐site before the catalytic serine is deacetylated, its new position will prevent the approach of water, thus blocking deacetylation.
Possible involvement of an FKBP family member protein from a psychrotrophic bacterium Shewanella sp. SIB1 in cold‐adaptation
Authors: Suzuki Yutaka , Haruki Mitsuru , Takano Kazufumi , Morikawa Masaaki , Kanaya Shigenori
Published: March 2004

A psychrotrophic bacterium Shewanella sp. strain SIB1 was grown at 4 and 20 °C, and total soluble proteins extracted from the cells were analyzed by two‐dimensional polyacrylamide gel electrophoresis. Comparison of these patterns showed that the cellular content of a protein with a molecular mass of 28 kDa and an isoelectric point of four greatly increased at 4 °C compared to that at 20 °C. Determination of the N‐terminal amino acid sequence, followed by the cloning and sequencing of the gene encoding this protein, revealed that this protein is a member of the FKBP family of proteins with an amino acid sequence identity of 56% to Escherichia coli FKBP22. This protein was overproduced in E. coli in a His‐tagged form, purified, and analyzed for peptidyl‐prolyl cis‐trans isomerase activity. When this activity was determined by the protease coupling assay using N‐succinyl‐Ala‐Leu‐Pro‐Phe‐p‐nitroanilide as a substrate at various temperatures, the protein exhibited the highest activity at 10 °C with a kcat/Km value of 0.87 µm−1·s−1. When the peptidyl‐prolyl cis‐trans isomerase activity was determined by the RNase T1 refolding assay at 10 and 20 °C, the protein exhibited higher activity at 10 °C with a kcat/Km value of 0.50 µm−1·s−1. These kcat/Km values are lower but comparable to those of E. coli FKBP22. We propose that a FKBP family protein is involved in cold‐adaptation of psychrotrophic bacteria.
Protein engineering of pyruvate carboxylase
Authors: Sueda Shinji , Islam Md. Nurul , Kondo Hiroki
Published: March 2004

Pyruvate carboxylase (PC) from Bacillus thermodenitrificans was engineered in such a way that the polypeptide chain was divided into two, between the biotin carboxylase (BC) and carboxyl transferase (CT) domains. The two proteins thus formed, PC‐(BC) and PC‐(CT+BCCP), retained their catalytic activity as assayed by biotin‐dependent ATPase and oxamate‐dependent oxalacetate decarboxylation, for the former and the latter, respectively. Neither activity was dependent on acetyl‐CoA, in sharp contrast to the complete reaction of intact PC. When assessed by gel filtration chromatography, PC‐(BC) was found to exist either in dimers or monomers, depending on the protein concentration, while PC‐(CT + BCCP) occurred in dimers for the most part. The two proteins do not associate spontaneously or in the presence of acetyl‐CoA. Based on these observations, this paper discusses how the tetrameric structure of PC is built up and how acetyl‐CoA modulates the protein structure.
Clinical efficacy of metal stents for the treatment of focal abdominal aortic stenosis
Authors: Eftekhar Kathy , Young Noel , Fletcher John , Bester Lourens , Wong Louise , Puttaswamy Vikram
Published: March 2004

Seven patients (four women and three men) who underwent primary stenting of infrarenal abdominal aortic stenosis over a 4‐year period are reported. The patients ranged between 44 and 77 years of age. All were referred for treatment of disabling claudication. Self‐expanding stents with balloon assistance were used. A single complication, a retroperitoneal haematoma, requiring surgical intervention occurred in one patient. Patients had either complete resolution of symptoms (five of seven) or a substantial decrease in their claudication symptoms. Primary stenting is a safe and effective treatment for severe abdominal aortic stenosis.
The importance of ecological research for ecosystem management: The case of browsing by swamp wallabies (Wallabia bicolor) in commercially harvested native forests
Authors: Di Stefano Julian
Published: March 2004

Summary  Ecosystem management often proceeds within the context of sub‐optimal relationships between ecologists and ecosystem managers, and management outcomes could be improved with greater collaboration between members of these disciplines. This paper identifies an ecosystem management problem resulting from the interaction between timber harvesting and browsing wallabies, and this case study is used to exemplify how ecological data and expertise can contribute to the process of ecosystem management. It is argued that appropriate use of existing ecological data, establishment of strategic new research and the implementation of management actions as experimental hypothesis tests can facilitate achievement of management objectives, but greater collaboration between ecologists and managers is required before this can occur. Reasons for sub‐optimal relationships are outlined, and the potential for structural change within large State‐run ecosystem management agencies to improve interactions between managers and ecologists is discussed.
A practical technique for non‐destructive monitoring of soil surface invertebrates for ecological restoration programmes
Authors: Bowie Mike H. , Frampton Chris M.
Published: March 2004

Summary  This study investigates the suitability of using wooden discs as facsimiles for natural fallen logs to non‐destructively monitor invertebrates. Wooden discs cut from tree trunks were placed on the ground at five sites and monitored. A diverse range of species was found under the discs including large numbers of some species. On Quail Island, Pine, Macrocarpa, Oak and Beech discs were compared. Beech discs had significantly fewer invertebrates and recognizable taxonomic units than other disc types. Pine discs had significantly more flatworms than the other three disc types. A comparison of invertebrate numbers when discs were placed directly on soil or grass indicated that larger numbers of individuals and recognizable taxonomic units were found under discs placed on bare soil compared with those on grass. Discs with a soil cavity beneath had significantly fewer individuals and recognizable taxonomic units than discs without cavities. Carabids showed considerable seasonal variation, with highest numbers in spring and lowest in winter, and larger numbers were found under discs at moist sites. Skinks over‐wintered under discs in drier open sites at Lincoln and Quail Island. Disc condition was assessed after 28 months and showed Macrocarpa had deteriorated the most of the four disc types. Wooden discs are a useful tool for the ecological management of terrestrial invertebrate fauna in restoration programmes for monitoring and considerable potential exists for discs to provide habitat for restoration of terrestrial invertebrate taxa.
The habitat hectares approach to vegetation assessment: An evaluation and suggestions for improvement
Authors: McCarthy Michael A. , Parris Kirsten M. , Van Der Ree Rodney , McDonnell Mark J. , Burgman Mark A. , Williams Nicholas S. G. , McLean Natasha , Harper Michael J. , Meyer Rachelle , Hahs Amy , Coates Terry
Published: March 2004

Summary  The habitat hectares approach is an explicit, quantitative method for assessing the quality of vegetation by adding scores that are assigned to 10 habitat attributes. We believe it will be more repeatable and transparent than other methods that rely on subjective judgement. However, we have four principal criticisms of the method as it is currently proposed: (i) measurement of some of the attributes may be subject to considerable error that varies among assessors; (ii) the comparison of each measure with a single benchmark does not accommodate appropriate disturbance regimes; (iii) the proposed combination of attributes leads to some apparent internal inconsistencies; and (iv) it is not clear how the method will actually be used in practice. We suggest modifications to address these concerns and improve the proposed method. Finally, we make additional suggestions about the method's potential application, including: separate reporting of the extent and quality of different vegetation types to avoid the inappropriate combination of measures of area and quality; valuing appropriate disturbance regimes in natural areas; and considering very carefully the application of compensation or mitigation measures.
Modelling rising groundwater and the impacts of salinization on terrestrial remnant vegetation in the Blackwood River Basin
Authors: Hodgson Geoff , Hatton Tom , Salama Ramsis
Published: March 2004

Summary  Southwest Western Australia has a particularly rich biodiversity. Clearing for agriculture has greatly reduced the extent of native vegetation in wheatbelt catchments; it also set into train hydrogeological and hydrological changes that are still evolving toward a new equilibrium. With those changes come widespread land salinization that presents a further risk to remnant vegetation, particularly in low portions of the landscape. The equilibrium position of shallow groundwater was modelled for the Blackwood Catchment, and used to assess the extent of risk to a set of remnant vegetation classes. A total of 37 368 ha of remnant vegetation was identified to be at risk of salinization when hydrological equilibrium is reached. Further hydrological modelling assessed the rate of development of these watertables (and hence the rate of impact on remnants), as well as the potential to protect remnants by controlling groundwater recharge with revegetation. The results demonstrate that only high levels of revegetation are effective at protecting high value remnants in the longer term. The timing of events is dependant on the accuracy of estimating recharge.
The development and raison d’être of ‘habitat hectares’: A response to McCarthy et al. (2004)
Authors: Parkes David , Newell Graeme , Cheal David
Published: March 2004

We welcome the constructive comments of McCarthy et al. (2004), and are grateful for the opportunity to respond.
Can there be a science of the symbolic?
Authors: Beebe John
Published: March 2004

Abstract:  Science means not just ‘knowing’, but knowing verified by replicability. Science is particularly hard to bring to depth psychology because the individual uniquenesses that can’t be repeated are what make people most deeply themselves. Everyone, including the analytic investigator, however, has a science, in the sense of a world‐view that is replicated by experience. Jung offered hermeneutics as an alternative mode to science for getting to know the psychological subject. But as Heidegger emphasized, hermeneutics always begins with the projection of a world‐view, i.e., the science of the would‐be interpreter. In the analytic situation, dialogue is available to test the world‐view and enlarge its horizon, in accord with Gadamer's expansion of hermeneutics, ‘the classical discipline concerned with the art of understanding texts’, into a method of inquiry open to the possibilities of otherness. An example is given from an analytic training seminar, in which the author began by projecting his version of the theory of psychological types onto the dream material a candidate offered in response to the seminar. A dialogue with the candidate ensued which enabled the teacher to correct his original, somewhat rigid, application of his scientific viewpoint. In such a dialogue, psyche emerges as the final interpreter of what is, generating hypotheses that can fruitfully be applied to the understanding of other cases.
Epistemological premise, developmental idea, main motivation in Jung's and Kohut's psychoanalysis: looking for some analogies
Authors: Giannoni Massimo
Published: March 2004

Abstract:  We are living the passage from the positivistic ideal to a new cultural climate which may be called post‐modernism, subjectivism or perspectivism and in which we have lost the conviction that it is possible to reach an absolute knowledge. This climate can become a strong stimulus to a dialogue and a comparison among different psychoanalytical schools and between psychoanalysis and empirical research to find some of the reference points we need in our work. In my paper I will compare self psychology and analytic psychology in order to point out several strong analogies. Firstly, they are based on the same methodological option which gathers knowledge through an empathic understanding ‘from within’. According to both Jung and Kohut the individual has within himself a psycho‐biological potential, an individual pre‐formed core that asks to evolve completely: the central motivation of human beings is the realization of their own individuality. This shared theoretical and epistemological ground conveys convergences in the clinical field between the two disciplines (interpretation of dreams, respect of resistance, diminishing attitude regarding sexual drives, etc.) and specifically determines an attitude of the analyst, which respects the individual process of development, which pays attention to the inner experience, and which gives importance to the analyst's and the patient's subjective experience.
This new science of ours: a more or less systematic history of consciousness and transcendence  Part I
Authors: Tresan David I.
Published: March 2004

Abstract:  This paper is a search for the origins and nature of human consciousness. This portion, the first part of two, takes up a signal work of Jung and one of Freud, both published in 1911 and both deriving thinking as the first embodiment of higher mental functions. Thinking and consciousness (and subsequently spirit) are elaborated in terms of the nature and vicissitudes of libido. Jung's less well understood theory regarding a quantitative libido is particularly addressed as are his non‐Cartesian ways of reasoning. Also addressed is Jung's turning away in the final analysis from a frankly metaphysical and transcendent position as compared to the pre‐Socratic philosophers with whom focused thinking began in the western world. Differentiation is made between mechanistic and energetic field dynamics in how reality is viewed.
Imagination as laboratory
Authors: Zabriskie Beverley
Published: March 2004

Abstract:  The theme, ‘Science and the Symbolic’, may be approached via either concept. From one side, we may track how imagination, fantasy, and even dreams have initiated scientific theory and lines of research. From the other, we may look to the mythopoeic musings of the human mind for themes of proto‐science and/or proto‐psychology, and attempt to discern if they follow a method which may be called scientific. Neuroscientists such as Edelman and Llinas honour imagination as the carrier of emergent properties, and depth psychoanalysts see it as a vector toward actualization. What mind imagines through what the alchemists termed ‘true imagination’ may eventually be realized through what brain and body may conceive and execute.
Becoming Pilgrims: Engaging Theory Through Practice in the Introductory World Religions Course
Authors: Hill Susan E.
Published: March 2004

Abstract. This paper explores the use of the educational pilgrimage as an active learning strategy in the introductory world religions course. As we study pilgrimages from different religious traditions throughout the semester using Victor Turner as our theoretical guide, students also plan their own campus pilgrimage, paying homage to sites that help them reach their educational goals. Using student comments and my own observations, I highlight the ways in which the educational pilgrimage both affirms and raises critical questions about Turner's theory of pilgrimage. In this way, the educational pilgrimage is an opportunity for students to enhance and clarify their understanding of theory through practice.
The Marketization of the Nonprofit Sector: Civil Society at Risk?
Authors: Eikenberry Angela M. , Kluver Jodie Drapal
Published: March 2004

The public sector has increasingly adopted the methods and values of the market to guide policy creation and management. Several public administration scholars in the United States have pointed out the problems with this, especially in relation to the impact on democracy and citizenship. Similarly, nonprofit organizations are adopting the approaches and values of the private market, which may harm democracy and citizenship because of its impact on nonprofit organizations' ability to create and maintain a strong civil society. This article reviews the major marketization trends occurring within the nonprofit sector—commercial revenue generation, contract competition, the influence of new and emerging donors, and social entrepreneurship—and surveys research on their potential impact on nonprofit organizations' contributions to civil society. The article ends with a discussion of the significance of marketization in the nonprofit sector for public administration scholars and public managers.
Devolution and Innovation: The Adoption of State Environmental Policy Innovations by Administrative Agencies
Authors: Sapat Alka
Published: March 2004

Do states act as laboratories for reform? Are state administrative agencies likely to adopt policy innovations? This study analyzes the adoption of environmental policy innovations by state administrative agencies in the area of hazardous waste regulation. Four explanations are developed to explain the factors that affect innovation adoption: the severity of the problem, the importance of institutional factors, the role played by interest groups, and contextual factors. Institutional factors, such as state wealth and administrative professionalism, are important determinants of innovation adoption. State agencies are also likely to adopt innovations to deal with problems created by hazardous waste contamination. In addition, state environmental managers are not directly influenced by interest groups, and the inclusion of all stakeholders is likely to lead to greater support for new policy initiatives. Implications for practitioners are drawn based on the study's findings.
The Regulation Dilemma: Cooperation and Conflict in Environmental Governance
Authors: Potoski Matthew , Prakash Aseem
Published: March 2004

Across the United States and around the world, businesses have joined voluntary governmental and nongovernmental environmental regulations. Such codes often require firms to establish internal environmental management systems to improve their environmental performance and regulatory compliance. Meanwhile, governments have been offering incentives to businesses that self‐police their regulatory compliance and promptly report and correct violations. This article examines how governmental regulatory enforcement can influence firms' compliance with mandatory and voluntary regulations. Cooperative regulatory enforcement—in which firms self‐police their environmental operations and governments provide regulatory relief for voluntarily disclosed violations—yields optimal win–win outcomes, but only when both sides cooperate. If firms are likely to evade compliance, governments are better off adopting a deterrence approach. If governments insist on rigidly interpreting and enforcing laws, firms may have incentives to evade regulations and not voluntary codes. Cooperation is possible through credible signals between firms and government.
Privatizing Federal Credit Programs: Why Sallie Mae?
Authors: Corder J. Kevin , Hoffmann Susan M.
Published: March 2004

The federal government subsidizes lending to a number of borrowers—notably students, farmers, and homeowners. Government‐sponsored enterprises issue the securities that channel capital to many of these privileged borrowers. One of the largest of these enterprises, the Student Loan Marketing Association (Sallie Mae), is scheduled to be wholly privatized by September 30, 2008. What explains the privatization of this enterprise? To identify distinctive features of Sallie Mae that permitted or abetted privatization, we investigate the structure, related capital market innovations, and growth of three government‐sponsored enterprises. We conclude that a unique structural feature of Sallie Mae may explain the pace of privatization. The core asset of Sallie Mae, the student loan, is guaranteed and subsidized by the government. The case of Sallie Mae is an instructive yet poorly understood example of how the federal government can leverage private‐sector assets and incentives to achieve public policy missions.
Politics and Administration in Council‐Manager Government: Differences between Newly Elected and Senior Council Members
Authors: Nalbandian John
Published: March 2004

This study examines the different attitudes of newly elected officials and senior incumbents on variables that are considered to be the building blocks of the relationship between local elected officials and professional civil service staff: council respect for the city's professional staff; a clear understanding of the roles of council and the staff; and the governing body's commitment towards working as a group and toward consensus. Governing body members who have served for eight or more years show greater respect for staff, have greater role understanding, and value teamwork among their colleagues more than their newly elected counterparts. While there are differences, the attitudes of long‐term officials appear to change little while in office. They enter office with the building blocks of their own success. These findings are based on a cross‐sectional and modest longitudinal survey research design, supplemented by in‐depth interviews.
Medicaid Managed Care for Children with Special Health Care Needs: Examining Legislative and Judicial Constraints on Privatization
Authors: Reed Christine M. , Meyer Kyle P.
Published: March 2004

Over the past decade, much has been written about the results of reinventing government. Most research has examined the effects of executive or managerial perspectives. Using David Rosenbloom's competing perspectives model, we examine Medicaid managed care programs for children with special health care needs to illustrate the influence of legislative and judicial institutional perspectives on the reinvention movement. Legislative and judicial responses to the reinvention of Medicaid managed care reveal the outer limits of what managed care and related executive reforms can accomplish in a Constitutional system that is based on checks and balances among competing institutional perspectives. Furthermore, relative to Medicaid managed care, legislative and judicial responses conserve public responsibility to society's most vulnerable populations. In the long run, the balance of institutional perspectives and values—not managerial innovation per se—will influence public administration.
Unilateral Politics
Authors: Waterman Richard W.
Published: March 2004

Phillip J. Cooper, By Order of the President: The Use and Abuse of Executive Direct Action

William G. Howell, Power without Persuasion: The Politics of Direct Presidential Action

Kenneth R. Mayer, With the Stroke of a Pen: Executive Orders and Presidential Power
Rafts: Scale‐Dependent, Active Lipid Organization at the Cell Surface
Authors: Mayor Satyajit , Rao Madan
Published: March 2004

Rafts have been conceptualized as lateral heterogeneities in the organization of cholesterol and sphingolipids, endowed with sorting and signaling functions. In this review we critically examine evidence for the main tenet of the ‘raft hypothesis’, namely lipid‐dependent segregation of specific membrane components in the plasma membrane. We suggest that conventional approaches to studying raft organization wherein membranes are treated as passive, thermally equilibrated systems are unlikely to provide an adequate framework to understand the mechanisms of raft‐organization in vivo. An emerging view of raft organization is that it is spatio‐temporally regulated at different scales by the cell. This argues that rafts must be defined by simultaneous observation of components involved in particular functions. Recent evidence from the study of glycosylphosphatidyl inositol‐anchored proteins, a common raft‐marker, supports this picture in which larger scale, more stable rafts are induced from preexisting small‐scale lipid‐dependent structures actively maintained by cellular processes.
Lipid Rafts and the Regulation of Exocytosis
Authors: Salaün Christine , James Declan J. , Chamberlain Luke H.
Published: March 2004

Exocytosis is the process whereby intracellular fluid‐filled vesicles fuse with the plasma membrane, incorporating vesicle proteins and lipids into the plasma membrane and releasing vesicle contents into the extracellular milieu. Exocytosis can occur constitutively or can be tightly regulated, for example, neurotransmitter release from nerve endings. The last two decades have witnessed the identification of a vast array of proteins and protein complexes essential for exocytosis. SNARE proteins fill the spotlight as probable mediators of membrane fusion, whereas proteins such as munc18/nsec1, NSF and SNAPs function as essential SNARE regulators. A central question that remains unanswered is how exocytic proteins and protein complexes are spatially regulated. Recent studies suggest that lipid rafts, cholesterol and sphingolipid‐rich microdomains, enriched in the plasma membrane, play an essential role in regulated exocytosis pathways. The association of SNAREs with lipid rafts acts to concentrate these proteins at defined sites of the plasma membrane. Furthermore, cholesterol depletion inhibits regulated exocytosis, suggesting that lipid raft domains play a key role in the regulation of exocytosis. This review examines the role of lipid rafts in regulated exocytosis, from a passive role as spatial coordinator of exocytic proteins to a direct role in the membrane fusion reaction.
Transmembrane Asymmetry and Lateral Domains in Biological Membranes
Authors: Devaux Philippe F. , Morris Roger
Published: March 2004

It is generally assumed that rafts exist in both the external and internal leaflets of the membrane, and that they overlap so that they are coupled functionally and structurally. However, the two monolayers of the plasma membrane of eukaryotic cells have different chemical compositions. This out‐of‐equilibrium situation is maintained by the activity of lipid translocases, which compensate for the slow spontaneous transverse diffusion of lipids. Thus rafts in the outer leaflet, corresponding to domains enriched in sphingomyelin and cholesterol, cannot be mirrored in the inner cytoplasmic leaflet. The extent to which lipids contribute to raft properties can be conveniently studied in giant unilamellar vesicles. In these, cholesterol can be seen to condense with saturated sphingolipids or phosphatidylcholine to form μm scale domains. However, such rafts fail to model biological rafts because they are symmetric, and because their membranes lack the mechanism that establishes this asymmetry, namely proteins. Biological rafts are in general of nm scale, and almost certainly differ in size and stability in inner and outer monolayers. Any coupling between rafts in the two leaflets, should it occur, is probably transient and dependent not upon the properties of lipids, but on transmembrane proteins within the rafts.
Recognition of Lumenal Prion Protein Aggregates by Post‐ER Quality Control Mechanisms Is Mediated by the Preoctarepeat Region of PrP
Authors: Gilch Sabine , Nunziante Max , Ertmer Alexa , Wopfner Franziska , Laszlo Lajos , Schätzl Hermann M.
Published: March 2004

Prion diseases are fatal transmissible neurodegenerative disorders linked to an aberrant conformation of the cellular prion protein (PrPc). We have shown previously that the chemical compound suramin induced aggregation of fully matured PrPc in post‐ER compartments, thereby, activating a post‐ER quality control mechanism and preventing cell surface localization of PrP by intracellular re‐routing of aggregated PrP from the Golgi/TGN directly to lysosomes. Of note, drug‐induced PrP aggregates were not toxic and could easily be degraded by neuronal cells. Here, we focused on determining the PrP domains mediating these effects. Using PrP deletion mutants we show that intracellular re‐routing but not aggregation depends on the N‐terminal PrP (aa 23–90) and, more precisely, on the preoctarepeat domain (aa 23–50). Fusion of the PrP N‐terminus to the GPI‐anchored protein Thy‐1 did not cause aggregation or re‐routing of the chimeric protein, indicating that the N‐terminus is only active in re‐routing when prion protein aggregation occurs. Insertion of a region with a comparable primary structure contained in the PrP paralogue prnd/doppel (aa 27–50) into N‐terminally deleted PrP re‐established the re‐routing phenotype. Our data reveal an important role for the conserved preoctarepeat region of PrP, namely controlling the intracellular trafficking of misfolded PrP.
Molecular Dynamics and Interactions for Creation of Stimulation‐Induced Stabilized Rafts from Small Unstable Steady‐State Rafts
Authors: Kusumi Akihiro , Koyama‐Honda Ikuko , Suzuki Kenichi
Published: March 2004

We have evaluated the sizes and lifetimes of rafts in the plasma membrane from the existing literature, with a special attention paid to their intrinsically broad distributions and the limited time and space scales that are covered by the observation methods used for these studies. Distinguishing the rafts in the steady state (reserve rafts) from those after stimulation or unintentional crosslinking of raft molecules (stabilized receptor‐cluster rafts) is critically important. In resting cells, the rafts appear small and unstable, and the consensus now is that their sizes are smaller than the optical diffraction limit (250 nm). Upon stimulation, the raft‐preferring receptors are clustered, inducing larger, stabilized rafts, probably by coalescing small, unstable rafts or cholesterol‐glycosphingolipid complexes in the receptor clusters. This receptor‐cluster‐induced conversion of raft types may be caused by suppression of alkyl chain isomerization and the lipid lateral diffusion in the cluster, with the aid of exclusion of cholesterol from the bulk domain and the boundary region of the majority of transmembrane proteins. We critically inspected the possible analogy to the boundary lipid concept. Finally, we propose a hypothesis for the coupling of GPI‐anchored receptor signals with lipid‐anchored signaling molecules in the inner‐leaflet raft.
Lipids as Targeting Signals: Lipid Rafts and Intracellular Trafficking
Authors: Helms J. Bernd , Zurzolo Chiara
Published: March 2004

Our view of biological membranes has evolved dramatically over the last few decades. In the bilayer model from Singer & Nicholson (Science 1972;175:720–731), both proteins and lipids freely diffuse within the plane of the membrane. Currently, however, membranes are viewed as a mosaic of different compartments or domains maintained by an active cytoskeleton network (Ritchie et al. Mol Membr Biol 2003; 20:13–18). Due to interactions between membrane components, several types of subdomains can form with different characteristics and functions. Lipids are likely to play an important role in the formation of so‐called lipid‐enriched microdomains or lipid rafts, adding another order of complexity to the membrane model. Rafts represent a type of domain wherein lipids of specific chemistry may dynamically associate with each other, to form platforms important for membrane protein sorting and construction of signaling complexes (Simons & Toomre. Nat Rev Mol Cell Biol 2000;1:31–39). Currently, there are several hypotheses concerning the nature of rafts (reviewed in (Edidin. Annu Rev Biophys Biomol Struct 2003;32: 257–283; Zurzolo et al. EMBO Rep 2003;4:1117–1121)). The most commonly cited one, proposed by Kai Simons (Simons & Ikonen. Nature 1997;387:569–572; Pralle et al. J Cell Biol 2000;148:997–1008), suggests that rafts are relatively small structures (∼ 50 nm) enriched in cholesterol and sphingolipids within which associated proteins are likely to be concentrated. Another proposal (Anderson & Jacobson. Science 2002;296:1821–1825) suggests that rafts are constructed of lipid shells. These are small dynamic assemblies wherein ‘raft’ proteins are preferentially associated with certain types of lipids. These ‘shells’ are thermodynamically stable mobile entities in the plane of the membrane that are able to target the protein they encase to preexisting rafts/caveolae domains. In this review we summarize the data suggesting a specific role for lipid domains in intracellular trafficking and sorting and present a modification of the raft model that may help explain the observed phenomena.
Reproductive and Sexual Health Among Young Adults in Uzbekistan
Authors: Buckley Cynthia , Barrett Jennifer , Asminkin Yakov P.
Published: March 2004

Since 1991, contraceptive use has risen significantly in Uzbekistan while reliance on abortion has declined; yet reproductive health improvements have not translated into better conditions for sexual health. The prevalence of sexually transmitted diseases increased significantly in the 1990s, and UN AIDS currently identifies the Central Asian region as a high HIV‐growth zone. Structural, institutional, and attitudinal factors have contributed to the disconnection between reproductive and sexual health in Uzbekistan, even though family planning programs have been well established during the HIV pandemic. Integrating state statistics, Demographic and Health Survey data, and focus‐group‐discussion results, we highlight the ways in which a heavily centralized program focusing on reproductive health did little to better sexual health, especially among young adults. The example of Uzbekistan reveals pathways by which reproductive health efforts may continue to be compartmentalized, decreasing their potential contributions to sexual health, especially among young adults.
Reassessing the Level of Unintended Pregnancy and Its Correlates in Vietnam
Authors: Cu Le Linh , Magnani Robert , Rice Janet , Speizer Ilene , Bertrand William
Published: March 2004

Despite rapidly increasing contraceptive use and rapidly declining fertility, unintended pregnancy and induced abortion remain common in Vietnam. This study reassesses the level of unintended pregnancy in Vietnam and its correlates, drawing on retrospective calendar data gathered for the Vietnam Demographic and Health Survey II. Data from 13,540 “segments” of outcomes and contraceptive practice were analyzed. Based on the calendar data, 40 percent of pregnancies during the 1994‐97 period are estimated to have been unintended, a proportion 48 percent higher than the prevailing estimate calculated from the reported intendedness of live births. When concealment of pregnancies ending in induced abortions is taken into account, the unintended pregnancy rate in Vietnam is likely to approach levels found only in developing countries. Unintended pregnancy was found to be associated with age, early marriage, spousal age difference, number of living sons, past unintended pregnancy, geographic region, contraceptive use prior to pregnancy, and the family planning supply environment. The findings suggest that broadening the method mix at the community level, targeting high‐risk and underserved groups, and expanding postabortion counseling and services are likely to have a dramatic impact on the unintended pregnancy rate in Vietnam.
Chip Morphology and Forces in End Milling of Elastomers
Authors: Shih Albert J. , Luo Jie , Lewis Mark A. , Strenkowski John S.
Published: March 2004

This paper describes chip morphology and forces in end milling of elastomers. A classification system that identifies elastomer chips based on their size and morphology is described. Optical pictures and Scanning Electron Microscopy (SEM) micrographs were used to examine and classify chips. A four-step examination procedure is developed to specify seven types of chips. Serrated chip formation with apparent adiabatic shear bands was observed for one end milling condition. The low thermal conductivity of elastomer is a possible cause for the observed shear band formation. Another type of serrated chip was found with surface wavy marks due to vibration of the workpiece. End milling force components were also recorded and analyzed. It was found that end milling of solid carbon dioxide cooled elastomers generated higher forces than the room temperature workpiece. A correlation of the maximum uncut chip thickness on averaged peak cutting force components is identified for different spindle speeds. This has indicated the potential for modeling elastomer machining processes.
Multiple Fault Diagnosis for Sheet Metal Fixtures Using Designated Component Analysis
Authors: Camelio Jaime A. , Hu S. Jack
Published: March 2004

This paper presents a new approach to multiple fault diagnosis for sheet metal fixtures using designated component analysis (DCA). DCA first defines a set of patterns based on product/process information, then finds the significance of these patterns from the measurement data and maps them to a particular set of faults. Existing diagnostics methods has been mainly developed for rigid-body-based 3-2-1 locating scheme. Here an N-2-1 locating scheme is considered since sheet metal parts are compliant. The proposed methodology integrates on-line measurement data, part geometry, fixture layout and sensor layout in detecting simultaneous multiple fixture faults. A diagnosability discussion for the different type of faults is presented. Finally, an application of the proposed method is presented through a computer simulation.
Optimal Process Planning for Laser Forming of Doubly Curved Shapes
Authors: Liu Chao , Yao Y. Lawrence , Srinivasan Vijay
Published: March 2004

There has been a considerable amount of work carried out on two-dimensional laser forming. In order to advance the process further for industrial applications, however, it is necessary to consider more general cases and especially their process planning aspect. This paper presents an optimal approach to laser scanning paths and heating condition determination for laser forming of doubly curved shapes. Important features of the approach include the strain field calculation based on principal curvature formulation and minimal strain optimization, and scanning paths and heating condition (laser power and scanning velocity) determination by combining analytical and practical constraints. The overall methodology is presented first, followed by more detailed descriptions of each step of the approach. Two distinctive types of doubly curved shape, pillow and saddle shapes are focused on and the effectiveness of the proposed approach is validated by forming experiments.