bluuebunny/crossref_metadata_2025 huggingface dataset:
Jesus Taught His Atonement
Authors: Swinburne Richard
Published: October 2003

Jesus sought to replace the system of Temple worship in which atonement was made by animal sacrifice. This is shown by, among other things, the accusation at his trial that he would destroy ‘this temple that is made with hands’. At the Last Supper he instituted a ceremony with the words ‘my body’ and ‘my blood’, implying that what was to be commemorated was the sacrifice of himself. Many strands of the New Testament contain the idea of the death of Jesus as an atoning sacrifice, so that it is natural to look for a common source of this in the actions and teaching of Jesus.
Jesus Founded a Church
Authors: Swinburne Richard
Published: October 2003

Jesus forming a community based on 12 leaders could only be regarded in first‐century Palestine as founding a new Israel, a church. His instituting the Eucharist at the Last Supper implied that he expected that church would continue after his death. While he may have hoped that it would absorb the old Israel and that the latter would convert the Gentiles, however, the result was to be achieved, Jesus intended his church for all peoples. He did not teach explicitly that the Parousia (his second coming) would occur in his lifetime, but he did warn his disciples to be ready for its coming. The later church, in teaching the three central Christian doctrines of the Trinity, the Incarnation, and the Atonement, developed the teaching of Jesus.
The Empty Tomb and the Observance of Sunday
Authors: Swinburne Richard
Published: October 2003

The first‐century Jewish understanding of ‘resurrection’ implied bodily resurrection. St. Paul did not mention that the tomb of Jesus was empty, because that was obviously implied by his claim that Jesus was risen. That Christians believed from the earliest days that women disciples had found the tomb empty on the third day (a Sunday) after Jesus’ burial is evidenced by the fact that all Christians subsequently celebrated the Eucharist on a Sunday. Their use of the phrase ‘on the third day’ to date the Resurrection was not due to the fact that Hosea prophesied a resurrection for Israel on the third day; rather they used Hosea's phrase to describe what they believed on other grounds to be the date of Jesus’ Resurrection.
Rival Theories of What Happened
Authors: Swinburne Richard
Published: October 2003

If Jesus was not raised bodily, some rival theory of what happened to his body must be true. The only possible theories are that Jesus was not dead when taken down from the cross, the body remained in the tomb but the disciples misidentified the tomb, enemies stole the body, grave robbers stole the body, friends of Jesus (probably the ‘women at the tomb’ on the Sunday morning) stole the body. The latter is the least improbable of these alternatives to the traditional account. But it involves great deceit, which would probably have been recognized by the Christian leaders, and it involves those friends giving the body an improper burial. And it would still not account for the large number of appearances, some of them to many disciples together. The traditional account is certainly the simplest.
The Significance of the Resurrection
Authors: Swinburne Richard
Published: October 2003

If the Resurrection of Jesus occurred, it was a miracle in the sense of a violation of laws of nature brought about by God. Other cultures than those of the modern world, including first‐century Judaism, while not having the concept of a law of nature, had a concept corresponding to the modern concept of miracle as an event that could be brought about only by God. The Resurrection, if it occurred, would be such an event. It would also have been seen as God's signature of acceptance of Jesus’ atoning sacrifice, and his approval of life and teaching; and it was so seen by some New Testament writers.
The Balance of Probability
Authors: Swinburne Richard
Published: October 2003

Summarizes the argument of the book. Given only a moderate amount of evidence from natural theology in favour of the existence of God and his having reason to become incarnate among humans, there is far more evidence that Jesus led the sort of life that God Incarnate would lead, and that that life was culminated by a super‐miracle, than there is for any other prophet in human history. In consequence, the overall balance of evidence in favour of the Resurrection having occurred is very strong. This is elucidated in the formalism of the probability calculus by Bayes's theorem.
Introduction: Centering Sexual Orientation Politics
Authors: Calhoun Cheshire
Published: October 2003

This introductory chapter lays the groundwork for future chapters by suggesting that feminist theorizing must make a methodological shift from thinking that heterosexism is just a by‐product of sexism, to thinking of lesbian and gay subordination as a separate axis of oppression that intersects with gender, race, and class axes of oppression. It also introduces the two central features of lesbian and gay subordination. The first of these is that the principal damaging effect of a heterosexist system is that it displaces lesbians and gays from both the public and private spheres of civil society so that they have no legitimated social location. The second is that the principal ideologies rationalizing lesbian and gay displacement are that there are only two natural and normal sexes/genders; that lesbian and gay sexuality is excessive, compulsive, and disconnected from romantic love; and that, for a variety of reasons, lesbians and gays are unfitted for marital and family life. The last part of the chapter makes general remarks on how the book fits into the essentialist–constructionist controversy.
Separating Lesbian Theory from Feminist Theory
Authors: Calhoun Cheshire
Published: October 2003

This chapter focuses largely on lesbian feminist theorizing in the 1980s. It is argued that feminist theorizing on gender oppression has worked to conceal, rather then reveal, lesbian specificity. An attempt is made to determine what it is in feminist thinking that makes it difficult to see the lesbian in the feminist subject of woman, so that she is regarded as a ‘not‐woman’, and also as the quintessential form of feminist revolt against patriarchy because she refuses to be heterosexual. It is argued that this placement of resistance to patriarchy at the heart of what it means to be a lesbian is wrong.
The Shape of Lesbian and Gay Subordination
Authors: Calhoun Cheshire
Published: October 2003

It is argued that lesbian and gay subordination differs substantially in form from gender and racial oppression. In particular, it does not materialize in a disadvantaged place that would sharply reduce the access of lesbians and gay men as a group to basic social goods. Instead, lesbians and gays are systematically displaced to the outside of civil society so that they have no legitimized place, not even a disadvantaged one. The displacement occurs because of the requirement that all citizens adopt at least the appearance of a heterosexual identity as a condition of access to the public sphere. Various aspects of this displacement are addressed in detail.
Constructing Lesbians and Gay Men as Family's Outlaws
Authors: Calhoun Cheshire
Published: October 2003

The first two sections of this chapter summarize feminist and lesbian critiques of the family, marriage, and motherhood. The third section critiques lesbian‐feminist reasons for eschewing a political agenda that endorses family, marriage, and mothering. The fourth section traces the historical construction of lesbians and gays as outlaws to the family. In the concluding section, it is argued that making the family a political priority is not, as sometimes argued, a conservative move.
Boundaries and Allegiances
Authors: Scheffler Samuel
Published: October 2003

This book is a collection of 11 essays written from a perspective that is at once sympathetic towards, and critical of, liberalism and liberal political philosophy. The essays explore the capacity of liberal thought, and of the moral traditions on which it draws, to accommodate a variety of challenges posed by the changing circumstances of the modern world. Scheffler considers how, in an era of rapid globalization, we can best conceive of the responsibilities of individual agents and the normative significance of people's diverse commitments and allegiances. Some of the essays are primarily concerned with the role of individual desert in liberal theory. Others focus on the nature of people's special responsibilities to their families, communities, and societies, and assess the compatibility of such responsibilities with liberal ideas of justice and equality. Still others deal with the possibility of developing a liberal conception of justice that acknowledges the normative significance of social and global interdependencies, while reaffirming the values of personal life and the continuing importance of ideas of individual responsibility.
Responsibility, Reactive Attitudes, and Liberalism in Philosophy and Politics
Authors: Scheffler Samuel
Published: October 2003

During the 1980s, political liberalism in America came under heavy attack from conservatives, who claimed that liberal policies and programmes rested on a reduced conception of individual responsibility. Noting this trend, Scheffler examines the four major strands of American political philosophy since the 1970s and finds that the most prominent liberal theorists of this period—and, indeed, their most prominent critics—avoid any appeal to a pre‐institutional conception of desert. Scheffler proposes that the influence of naturalism may help to explain this surprising degree of convergence. He goes on to argue that philosophical liberalism, like political liberalism, appears to be in tension with ordinary notions of desert and responsibility. He examines the implications of this tension for liberal politics, for liberal philosophy's professed neutrality among conceptions of the good, and for the moral psychology of liberalism.
Liberalism, Nationalism, and Egalitarianism
Authors: Scheffler Samuel
Published: October 2003

Liberalism today is criticized from the opposing standpoints of particularism and globalism, the former claiming that liberalism underestimates the importance of national, cultural, and communal ties, and the latter claiming that liberalism is not sensitive enough to questions of international morality. Each of these criticisms points to a different tension within liberal theory—the particularist criticism to the tension between liberalism's explicit voluntarism and its implicit nationalism, and the globalist criticism to the tension between liberalism's commitment to egalitarianism and its commitment to particularism about political responsibility. These tensions within liberal theory are explored through Scheffler's discussion of debates about associative duties. The two tensions reflect liberalism's difficulty in jointly accommodating the three values of autonomy, moral equality, and loyalty.
The Conflict Between Justice and Responsibility
Authors: Scheffler Samuel
Published: October 2003

Members of affluent societies are often resistant to claims of global justice, and their resistance is frequently expressed in normative terms, in the claim that one has special responsibilities towards the members of one's family, community, or society. In this essay, Scheffler develops one argument, the distributive objection, which might be offered in support of claims of global justice and against the idea of special responsibilities. He then considers four possible responses to the distributive objection and concludes that the objection does not serve to invalidate all claims of special responsibility. Nevertheless, both the distributive objection and the idea of global justice are rooted in a commitment to the equal worth of persons, and the objection does demonstrate that the relationship between that commitment and the recognition of special responsibilities is more problematic than is often supposed.
Relationships and Responsibilities
Authors: Scheffler Samuel
Published: October 2003

In opposition to the voluntarist view that special responsibilities must be based on consent or some other voluntary act, this essay sketches a non‐reductionist account of such responsibilities. The non‐reductionist account begins with the idea that to value non‐instrumentally one's relationship to another person is to see that person's needs, interests, and desires as providing one with reasons for action and thus, in effect, to see the relationship as a source of special responsibilities. Scheffler then argues that one's relationships to other people do in fact give rise to special responsibilities when they are relationships that one has reason to value. Towards the end of the essay, he considers how a non‐reductionist might respond to two objections to special responsibilities, the voluntarist objection and the distributive objection. In meeting both objections, the non‐reductionist could concede that there are other moral values in addition to special responsibilities while still maintaining that special responsibilities must be part of any adequate moral scheme.
Conceptions of Cosmopolitanism
Authors: Scheffler Samuel
Published: October 2003

Distinguishes between cosmopolitanism about justice and cosmopolitanism about culture, identifying moderate and extreme forms of each of the two views. The extreme versions of cosmopolitanism, Scheffler argues, are implausible because they conflict with a notion of special responsibility that is deeply embedded in common‐sense moral thought. In arguing that a commitment to the equality of persons is neither substantively or conceptually incompatible with the recognition of special responsibilities, Scheffler seeks to undermine the case for these extreme forms of cosmopolitanism and to build the case for the moderate forms. But he notes that the moderate forms of cosmopolitanism, despite being much more plausible than the extreme versions, still face a number of philosophical and practical challenges, among them that of devising institutions and practices that take seriously both equality and special responsibilities.
The Appeal of Political Liberalism
Authors: Scheffler Samuel
Published: October 2003

Attempts to ground liberal toleration in pluralism about value, in scepticism about value, or in the simple need for a modus vivendi are all subject to various difficulties. John Rawls, in his book Political Liberalism, develops a fourth proposal, one that aims to give toleration and other liberal institutions a basis in moral reasons without presupposing any controversial moral outlook. In this essay, Scheffler critically examines Rawls's argument that the principles of justice can rest on an overlapping consensus of comprehensive moral and religious doctrines. Among the issues Scheffler discusses are the possibility of including classical utilitarianism in an overlapping consensus, the relationship between such a consensus and the ideal of public reason, and the relevance of political liberalism for societies that lack liberal, democratic traditions.
Justice and Desert in Liberal Theory
Authors: Scheffler Samuel
Published: October 2003

Scheffler identifies and interprets the core ideas in John Rawls's discussion of desert in A Theory of Justice. The conjunction of these ideas, which Scheffler terms the ‘Liberal Theory’ of desert, denies that the principles of distributive justice make reference to a ‘prejusticial’ notion of desert but allows a place for prejusticial desert in our thinking about retributive justice and the criminal law. Scheffler investigates this asymmetry between distributive and retributive justice, noting that desert is an individualistic notion that may not fit into a holistic theory of distributive justice. But retributive justice, concerned with the imposition of punishment on particular human beings, can perhaps accommodate such an individualistic notion.
Morality through Thick and Thin: A Critical Notice of Ethics and the Limits of Philosophy
Authors: Scheffler Samuel
Published: October 2003

In Ethics and the Limits of Philosophy, Bernard Williams criticizes the ‘morality system’ and the associated philosophical enterprise of constructing ethical theories. Williams argues that we would be better off replacing the ‘thin’ concepts favoured by the morality system and its theorists, concepts such as ‘right’ and ‘good’, with ‘thick’ concepts of the sort that were prevalent in the ethical thought of ancient Greece, such as ‘courage’ and ‘treachery’. In this critical essay, Scheffler presents several arguments against Williams's view; among them is the argument that the distinction between thick and thin concepts is not a clear one, and that the elimination of ethical theory would leave Williams without adequate conceptual resources to engage in the kind of social criticism that he himself regards as necessary.
Liberal Theory and Education Policy
Authors: Brighouse Harry
Published: October 2003

Provides a brief sketch of liberalism, explaining the key commitments to individualism, rights, and autonomy. It explains how political philosophy should be applied to education policy, and offers a brief account of the place of the family in liberal justice.
Three Red Herrings
Authors: Brighouse Harry
Published: October 2003

Examines, and refutes, three a priori arguments against school choice: the argument from commodification, the argument from democracy, and the argument from the common good. It argues that markets are inevitably involved in the delivery of educational services, and that although democracy is valuable its value does not justify the level of local control many critics of vouchers favour. It argues that a defensible notion of the common good cannot do the work required to ground a theory of justice for education, and is therefore not immediately pertinent to the evaluation of school reform.
The Case for Autonomy‐Facilitating Education
Authors: Brighouse Harry
Published: October 2003

The first potentially powerful objection to school choice is that it might efface the right a child has to personal autonomy. This chapter argues for the right to an autonomy‐facilitating education on the child‐centred grounds that it is highly instrumental for individual flourishing. It also explores the educational requirements of the liberal legitimacy, which dovetail with the demands of an autonomy‐facilitating education. It contrasts these requirements with Amy Gutmann's curricular proposals.
Objections to Autonomy‐Facilitating Education
Authors: Brighouse Harry
Published: October 2003

Responds to a series of objections to the argument for autonomy‐facilitating education, including objections from parental rights (put by Charles Fried), from religious freedom, from cultural rights, and from neutrality. It discusses further objections, which take the need for autonomy seriously, from William Galston and Shelley Burtt. It contains a detailed discussion of the Yoder versus Wisconsin case, in which Old Order Amish parents successfully claimed the right to withdraw their children from any form of schooling at the age of 14.
The Case for Educational Equality
Authors: Brighouse Harry
Published: October 2003

The second potential argument against choice is grounded in the value of educational equality. This chapter establishes the case for the principle of educational equality, which nests in the general value of equality of opportunity. It develops the principle to show what it implies concerning what resources should be devoted to students with disabilities and what the implications are for inclusion, and contrasts it with conceptions of educational equality grounded in multiculturalism.
Objections to Educational Equality
Authors: Brighouse Harry
Published: October 2003

Responds to a series of objections to the principle of educational equality, including the argument from elitism, the argument from the value of the family, libertarian arguments that reject redistribution even in the service of equal opportunity, and arguments that claim that only an adequate education is required as a matter of justice.
Social Justice and Existing School Choice Programmes
Authors: Brighouse Harry
Published: October 2003

Looks in detail at two existing school choice programmes, the Milwaukee Parental Choice Program, which distributes school vouchers to low‐income families, and the national choice program that has been in operation since 1988 in the UK. It evaluates them according to the criteria of justice elaborated in the previous chapters (the principle of autonomy and the principle of educational equality), showing that neither of them does well with respect to those criteria. The purpose is to identify what sorts of mechanisms cause them to do badly, and to illustrate that it is not choice but other features of the schemes that are to blame.
School Choice for Social Justice?
Authors: Brighouse Harry
Published: October 2003

Elaborates an ideal school choice scheme that, using vouchers, would succeed in meeting the constraints set by the principles of educational equality and personal autonomy. The scheme is modelled on a similar proposal made by Herbert Gintis. The chapter goes on to propose a series of reforms in existing choice schemes that would move them closer to meeting the demands of social justice.
Elemental distribution in summer fruits of Pakistan
Authors: Zahoor A. , Jaffar M. , Saqib M.
Published: October 2003

Levels of the selected major and minor elements (Na, K, Ca, Mg, Ni, Cr, Cd, Pb, Zn and Fe) in 11 summer fruits grown in Pakistan were estimated by the flame AAS method based on HNO3/HClO4 wet‐digestion method. The metal concentrations are expressed as X for triplicate sub‐samples with a standard deviation of ±1.0‐1.5 per cent. Of all the minor elements analyzed, Fe was found to be the dominant metal on mean basis as compared with other metals in fruits, its concentration being 14.25mg/kg. The increasing order of minor‐element concentration was: Cd<Pb<Zn<Cr<Ni<Fe. While for major elements, K concentration was found to be maximum as 409.7mg/kg and increasing order was: Ca<Na<Mg<K. In general, minor‐element concentrations were found to surpass the safe limit laid down by the World Health Organization. Fruits were found to be a rich resource of major elements.
Opportunities and constraints in the functional food market
Authors: Gray Jennifer , Armstrong Gillian , Farley Heather
Published: October 2003

Reviews the main food choice trends driving consumer demand for functional foods and the constraints limiting market development. Considers previous research activity in the functional food arena and subsequently identifies paramount research priorities that may facilitate the development of products that will help satisfy consumer demands for convenience, health and sensory pleasure.
Risk reduction: an insight from the UK poultry industry
Authors: Yeung Ruth M.W. , Yee Wallace M.S.
Published: October 2003

Consumer perception of a harmful and hazardous food risk and the strategies to reduce the exposure to such a risk are examined. A survey of 172 respondents confirmed the perceived risk theory and risk reducing strategies commonly used for the downside risk, and that expectations of negative utility are relevant to understand consumer perception of food safety risk. This study also shows that consumers are able to assess the uncertainty and the negative consequence of a perceived hazardous risk, and take action to reduce their exposure to the perceived risk. The findings seem to support the quality assurance scheme, useful information, brand, or product origin, which are the important risk reducing strategies of microbiological risk. Being a pilot study, this framework should be tested by using a product with which the risk is perceived to be beyond the control of consumers.
Food taboos and their nutritional implications on developing nations like Nigeria – a review
Authors: Onuorah C.E. , Ayo J.A.
Published: October 2003

This paper examined briefly the background to food taboos and food habits. These food taboos and habits have great impact on the health of the Nigerian community. Sometimes, the taboos continue even among the educated members of the society. Most of the foods tabooed in Nigeria work against the least privileged and immunocompromised, i.e. women, pregnant women, children and the elderly. These groups of people are deprived of sometimes the cheapest source of protein. This paper had collected some of these taboos and where possible the reason(s) why the foods are avoided. For some of the foods, the area where the avoidance is rampant is indicated. The list will help agencies and individuals effectively fight these food taboos. Possible solutions were also suggested. Taking or consuming these foods will improve the nutritional status of Nigerians.
Action: the most critical phase in outsourcing information technology
Authors: Fink Dieter , Shoeib Ashraf
Published: October 2003

The paper examined the nature of information technology (IT) outsourcing decision making and developed a theoretical framework consisting of five phases of decision making. The phases augmented those of Simon and consisted of intelligence, analysis and planning, strategy selection, action, and evaluation and monitoring. Australia's largest organisations and government agencies were surveyed by questionnaire to establish the importance of tasks and subtasks to be performed when completing each of the five phases. Participants possessed high experiences with IT in general and IT outsourcing in particular. When the importance of phases vis‐à‐vis each other were established, the action phase and evaluation and monitoring phase were found to be more significant than the other phases. For the action phase, which was statistically the most significant phase, the tasks of selecting an IT‐outsourcing vendor and determining a suitable IT‐outsourcing contract were dominant and strongly correlated. Findings from the study should help organisations identify and therefore better manage critical decision‐making activities during IT outsourcing particularly those related to vendors and contracts.
The implementation of online information and communication technology (ICT) on remote construction projects
Authors: Weippert A. , Kajewski S.L. , Tilley P.A.
Published: October 2003

In an attempt to bring the unique talents of various construction industry project participants together in a more productive and integrated manner, the Online Remote Construction Management (ORCM) project commenced in July 1999 proposing to test, field trial and/or evaluate the implementation of various Internet‐based construction project management (ICPM) systems and information and communication technologies (ICT) on four case study projects over a two‐year period, aiming, in general, to demonstrate leadership in facilitating the use of online technologies for the design, management and construction of building and civil construction projects. This paper provides the final results and a list of “best practice guidelines” that are critical in helping ensure successful implementation of ICT tools and/or ICPM systems on geographically dispersed (remote) civil and building construction projects..
Managing knowledge in business requirements identification
Authors: Alshawi S. , Al‐Karaghouli W.
Published: October 2003

This paper reflects on experiences when traditional IT approaches were used to design large IT systems and ended in failure. The main reflections focus on the reasons for system failure and how they relate to the diversity of knowledge, managing knowledge, and the understanding gaps that may exist between the business and the system developers. The study reveals that the understanding gaps mainly result from lack of knowledge of business operations on the developer side, matched by lack of technical appreciation and knowledge on the user side. To help address the knowledge‐gap problem, a practical approach employing soft‐systems, diagramming and set mapping techniques is proposed and described.
E‐fulfillment: the strategy and operational requirements
Authors: Tarn J. Michael , Razi Muhammad A. , Wen H. Joseph , Perez Angel A.
Published: October 2003

An e‐fulfillment system is designed to meet the high order volume and stringent customer service requirements of global business‐to‐consumer e‐commerce. The system converts the traditional warehouse into a multi‐channel e‐fulfillment center. In the e‐commerce environment, some of the toughest decisions must be made on little or no hard information. In this study, the nature of e‐business and the typical fulfillment process are discussed. The authors further examine the strategy and operational requirements for e‐fulfillment. This article is concluded with the implication of a successful e‐fulfillment system, a suggested design of an e‐fulfillment center, and the future research focuses.
Complexity, uniqueness, and similarity in between‐bundle choice
Authors: Agarwal Manoj K. , Chatterjee Subimal
Published: October 2003

When offering product/service bundles to customers, marketers must decide how best to configure the bundles such that consumers do not find the bundle‐choice particularly difficult. This paper examines perceived decision difficulty in selecting from a menu of bundles, where the bundles vary on the number of component services, the number of unique services between competing bundles, and their perceived similarity. It is found that larger bundles make decisions more difficult, more unique services between the competing bundles increases decision difficulty for small, but not large, bundles and similar bundles pose greater choice difficulty than dissimilar bundles. Implications of the results are discussed.
Brand equity’s influence on responses to event sponsorships
Authors: Roy Donald P. , Bettina Cornwell T.
Published: October 2003

Recent research into consumer responses to sponsorships has examined the role of sponsor‐event fit on cognitive and affective responses. However, influences on sponsor‐event fit have received little consideration. In this study, a sponsor’s brand equity is evaluated as a facilitator of sponsor‐event fit. Six sponsors (three high equity/three low equity) were paired with six events. Results of hypothesis testing indicated that sponsors with high brand equity were perceived as more congruent sponsors than sponsors with low brand equity even though the events sponsored were identical. Also, a positive relationship was found between sponsor‐event congruence and favorable attitudes toward the sponsor. Results of this study suggest that consumers’ attitudes toward sponsors are comprised of associations other than the sponsor‐event association. While lesser known brands can use sponsorship as a brand‐building vehicle, they may not attain the same level of results as their high equity counterparts.
Promotional evaluation and response among variety seeking segments
Authors: Trivedi Minakshi , Morgan Michael S.
Published: October 2003

Research conducted over the last decade, on the influence of brand inertia or variety seeking on promotional response, has yielded mixed results. Variety seekers have been found to be more price‐sensitive by one set of researchers, while another stream of work finds them to be less sensitive. Reconciling the two findings, the current study empirically addresses the proposition that variety seekers use price promotions strategically, as a way to experiment with different brands over time. Although consumers evaluate price promotions differently according to whether the promoted brand is more or less intrinsically favored than a reference brand, high and low variety seekers respond to brand comparisons differently, leading to differences in evaluation and responsiveness to price promotion offers. The empirical results confirm that high variety seekers are less sensitive to the preference order of considered brands, but only within a limited range of intrinsic brand favorability. Once differences in brand favorability are accounted for, moreover, finds that high variety seekers are more sensitive to promotional effort. This is compatible with the notion that, within an acceptable set of brands, variety seekers use price promotions as a low‐cost strategy for experiencing different brands over time. This understanding of the relationship among promotional offers, specific brands and consumer segments, provides valuable insights to brand managers as they consider their strategic promotional options, and design an effective promotional strategy.
Protein self‐association in solution: The bovine β ‐lactoglobulin dimer and octamer
Authors: Gottschalk Michael , Nilsson Hanna , Roos Helena , Halle Bertil
Published: October 2003

We have used proton magnetic relaxation dispersion (MRD) to study the self‐association of bovine β‐lactoglobulin variant A (BLG‐A) as a function of temperature at pH 4.7 (dimer–octamer equilibrium) and as a function of NaCl concentration at pH 2.5 (monomer–dimer equilibrium). The MRD method identifies coexisting oligomers from their rotational correlation times and determines their relative populations from the associated dispersion amplitudes. From MRD‐derived correlation times and hydrodynamic model calculations, we confirm that BLG‐A dimers associate to octamers below room temperature. The tendency for BLG‐A dimers to assemble into octamers is found to be considerably weaker than in previous light scattering studies in the presence of buffer salt. At pH 2.5, the MRD data are consistent with an essentially complete transition from monomers in the absence of salt to dimers in 1 M NaCl. Because of an interfering relaxation dispersion from nanosecond water exchange, we cannot determine the oligomer populations at intermediate salt concentrations. This nanosecond dispersion may reflect intersite exchange of water molecules trapped inside the large binding cavity of BLG‐A.
H‐bonding mediates polarization of peptide groups in folded proteins
Authors: Juranić Nenad , Macura Slobodan , Prendergast Franklyn G.
Published: October 2003

The carbon‐nitrogen J‐couplings in the hydrogen bonding chains of proteins show that H‐bonding mediates peptide‐group polarization, which results in the general reduction of peptide‐group polarity of folded proteins in solution. The net effect is to make large regions of protein secondary structure, especially β‐sheets, intrinsically more hydrophobic, contributing thereby to overall stability of the tertiary structure.
Free‐energy landscape of a chameleon sequence in explicit water and its inherent α/β bifacial property
Authors: Ikeda Kazuyoshi , Higo Junichi
Published: October 2003

A sequence in yeast MATα2/MCM1/DNA complex that folds into α‐helix or β‐hairpin depending on the surroundings has been known as “chameleon” sequence. We obtained the free‐energy landscape of this sequence by using a generalized‐ensemble method, multicanonical molecular dynamics simulation, to sample the conformational space. The system was expressed with an all‐atom model in explicit water, and the initial conformation for the simulation was a random one. The free‐energy landscape demonstrated that this sequence inherently has an ability to form either α or β structure: The conformational distribution in the landscape consisted of two α‐helical clusters with different packing patterns of hydrophobic residues, and four β‐hairpin clusters with different strand–strand interaction patterns. Narrow pathways connecting the clusters were found, and analysis on the pathways showed that a compact structure formed at the N‐terminal root of the chameleon sequence controls the cluster‐cluster transitions. The free‐energy landscape indicates that a small conditional change induces α‐β transitions. Additional unfolding simulations done with replacing amino acids showed that the chameleon sequence has an advantage to form an α‐helix. Current study may be useful to understand the mechanism of diseases resulting from abnormal chain folding, such as amyloid disease.
Initial structural and dynamic characterization of the M2 protein transmembrane and amphipathic helices in lipid bilayers
Authors: Tian Changlin , Gao Philip Fei , Pinto Lawrence H. , Lamb Robert A. , Cross Timothy A.
Published: October 2003

Amphipathic helices in membrane proteins that interact with the hydrophobic/hydrophilic interface of the lipid bilayer have been difficult to structurally characterize. Here, the backbone structure and orientation of an amphipathic helix in the full‐length M2 protein from influenza A virus has been characterized. The protein has been studied in hydrated DMPC/DMPG lipid bilayers above the gel to liquid‐crystalline phase transition temperature by solid‐state NMR spectroscopy. Characteristic PISA (Polar Index Slant Angle) wheels reflecting helical wheels have been observed in uniformly aligned bilayer preparations of both uniformly 15N labeled and amino acid specific labeled M2 samples. Hydrogen/deuterium exchange studies have shown the very slow exchange of some residues in the amphipathic helix and more rapid exchange for the transmembrane helix. These latter results clearly suggest the presence of an aqueous pore. A variation in exchange rate about the transmembrane helical axis provides additional support for this claim and suggests that motions occur about the helical axes in this tetramer to expose the entire backbone to the pore.
Identification of transglutaminase‐mediated deamidation sites in a recombinant α‐gliadin by advanced mass‐spectrometric methodologies
Authors: Mazzeo Maria Fiorella , De Giulio Beatrice , Senger Stefania , Rossi Mauro , Malorni Antonio , Siciliano Rosa Anna
Published: October 2003

Celiac disease is a permanent immune‐mediated food intolerance triggered by ingestion of wheat gliadins in genetically susceptible individuals. It has been reported that tissue transglutaminase plays an important role in the onset of celiac disease by converting specific glutamine residues within gliadin fragments into glutamic acid residues. This process increases binding affinity of gliadin peptides to HLA‐DQ2/DQ8 molecules, thus enhancing the immune response. The aim of the present study was to achieve a detailed structural characterization of modifications induced by transglutaminase on gliadin peptides. Therefore, structural analyses were carried out on a recombinant α‐gliadin and on a panel of 26 synthetic peptides, overlapping the complete protein sequence. Modified glutamine residues were identified by means of advanced mass‐spectrometric methodologies on the basis of MALDI‐TOF‐MS and tandem mass spectrometry. Results led to the identification of 19 of 94 glutamine residues present in the recombinant α‐gliadin, which were converted into glutamic acid residues by a transglutaminase‐mediated reaction. This allowed us to achieve a global view of the modifications induced by the enzyme on this protein. Furthermore, results gathered could likely be utilized as relevant information for a better understanding of processes leading to T‐cell recognition of gliadin peptides involved in celiac disease.
Allosteric transition pathways in the lactose repressor protein core domains: Asymmetric motions in a homodimer
Authors: Flynn Terence C. , Swint‐Kruse Liskin , Kong Yifei , Booth Christopher , Matthews Kathleen S. , Ma Jianpeng
Published: October 2003

The crystal structures of lactose repressor protein (LacI) provide static endpoint views of the allosteric transition between DNA‐ and IPTG‐bound states. To obtain an atom‐by‐atom description of the pathway between these two conformations, motions were simulated with targeted molecular dynamics (TMD). Strikingly, this homodimer exhibited asymmetric dynamics. All asymmetries observed in this simulation are reproducible and can begin on either of the two monomers. Asymmetry in the simulation originates around D149 and was traced back to the pre‐TMD equilibrations of both conformations. In particular, hydrogen bonds between D149 and S193 adopt a variety of configurations during repetitions of this process. Changes in this region propagate through the structure via noncovalent interactions of three interconnected pathways. The changes of pathway 1 occur first on one monomer. Alterations move from the inducer‐binding pocket, through the N‐subdomain β‐sheet, to a hydrophobic cluster at the top of this region and then to the same cluster on the second monomer. These motions result in changes at (1) side chains that form an interface with the DNA‐binding domains and (2) K84 and K84', which participate in the monomer–monomer interface. Pathway 2 reflects consequent reorganization across this subunit interface, most notably formation of a H74‐H74rsquo; π‐stacking intermediate. Pathway 3 extends from the rear of the inducer‐binding pocket, across a hydrogen‐bond network at the bottom of the pocket, and transverses the monomer–monomer interface via changes in H74 and H74rsquo;. In general, intermediates detected in this study are not apparent in the crystal structures. Observations from the simulations are in good agreement with biochemical data and provide a spatial and sequential framework for interpreting existing genetic data.
High‐resolution crystal structures of ribonuclease A complexed with adenylic and uridylic nucleotide inhibitors. Implications for structure‐based design of ribonucleolytic inhibitors
Authors: Leonidas Demetres D. , Chavali Gayatri B. , Oikonomakos Nikos G. , Chrysina Evangelia D. , Kosmopoulou Magda N. , Vlassi Metaxia , Frankling Claire , Acharya K. Ravi
Published: October 2003

The crystal structures of bovine pancreatic ribonuclease A (RNase A) in complex with 3′,5′‐ADP, 2′,5′‐ADP, 5′‐ADP, U‐2′‐p and U‐3′‐p have been determined at high resolution. The structures reveal that each inhibitor binds differently in the RNase A active site by anchoring a phosphate group in subsite P1. The most potent inhibitor of all five, 5′‐ADP (Ki = 1.2 μM), adopts a syn conformation (in contrast to 3′,5′‐ADP and 2′,5′‐ADP, which adopt an anti), and it is the β‐ rather than the α‐phosphate group that binds to P1. 3′,5′‐ADP binds with the 5′‐phosphate group in P1 and the adenosine in the B2 pocket. Two different binding modes are observed in the two RNase A molecules of the asymmetric unit for 2′,5′‐ADP. This inhibitor binds with either the 3′ or the 5′ phosphate groups in subsite P1, and in each case, the adenosine binds in two different positions within the B2 subsite. The two uridilyl inhibitors bind similarly with the uridine moiety in the B1 subsite but the placement of a different phosphate group in P1 (2′ versus 3′) has significant implications on their potency against RNase A. Comparative structural analysis of the RNase A, eosinophil‐derived neurotoxin (EDN), eosinophil cationic protein (ECP), and human angiogenin (Ang) complexes with these and other phosphonucleotide inhibitors provides a wealth of information for structure‐based design of inhibitors specific for each RNase. These inhibitors could be developed to therapeutic agents that could control the biological activities of EDN, ECP, and ANG, which play key roles in human pathologies.
Multiple structural alignment by secondary structures: Algorithm and applications
Authors: Dror Oranit , Benyamini Hadar , Nussinov Ruth , Wolfson Haim J.
Published: October 2003

We present MASS (Multiple Alignment by Secondary Structures), a novel highly efficient method for structural alignment of multiple protein molecules and detection of common structural motifs. MASS is based on a two‐level alignment, using both secondary structure and atomic representation. Utilizing secondary structure information aids in filtering out noisy solutions and achieves efficiency and robustness. Currently, only a few methods are available for addressing the multiple structural alignment task. In addition to using secondary structure information, the advantage of MASS as compared to these methods is that it is a combination of several important characteristics: (1) While most existing methods are based on series of pairwise comparisons, and thus might miss optimal global solutions, MASS is truly multiple, considering all the molecules simultaneously; (2) MASS is sequence order‐independent and thus capable of detecting nontopological structural motifs; (3) MASS is able to detect not only structural motifs, shared by all input molecules, but also motifs shared only by subsets of the molecules. Here, we show the application of MASS to various protein ensembles. We demonstrate its ability to handle a large number (order of tens) of molecules, to detect nontopological motifs and to find biologically meaningful alignments within nonpredefined subsets of the input. In particular, we show how by using conserved structural motifs, one can guide protein–protein docking, which is a notoriously difficult problem. MASS is freely available at http://bioinfo3d.cs.tau.ac.il/MASS/.
On the properties and sequence context of structurally ambivalent fragments in proteins
Authors: Kuznetsov Igor B. , Rackovsky S.
Published: October 2003

The goal of this work is to characterize structurally ambivalent fragments in proteins. We have searched the Protein Data Bank and identified all structurally ambivalent peptides (SAPs) of length five or greater that exist in two different backbone conformations. The SAPs were classified in five distinct categories based on their structure. We propose a novel index that provides a quantitative measure of conformational variability of a sequence fragment. It measures the context‐dependent width of the distribution of (ϕ,ξ) dihedral angles associated with each amino acid type. This index was used to analyze the local structural propensity of both SAPs and the sequence fragments contiguous to them. We also analyzed type‐specific amino acid composition, solvent accessibility, and overall structural properties of SAPs and their sequence context. We show that each type of SAP has an unusual, type‐specific amino acid composition and, as a result, simultaneous intrinsic preferences for two distinct types of backbone conformation. All types of SAPs have lower sequence complexity than average. Fragments that adopt helical conformation in one protein and sheet conformation in another have the lowest sequence complexity and are sampled from a relatively limited repertoire of possible residue combinations. A statistically significant difference between two distinct conformations of the same SAP is observed not only in the overall structural properties of proteins harboring the SAP but also in the properties of its flanking regions and in the pattern of solvent accessibility. These results have implications for protein design and structure prediction.
Revisiting the Ramachandran plot: Hard‐sphere repulsion, electrostatics, and H‐bonding in the α‐helix
Authors: Ho Bosco K. , Thomas Annick , Brasseur Robert
Published: October 2003

What determines the shape of the allowed regions in the Ramachandran plot? Although Ramachandran explained these regions in terms of 1–4 hard‐sphere repulsions, there are discrepancies with the data where, in particular, the αR, αL, and β‐strand regions are diagonal. The αR‐region also varies along the α‐helix where it is constrained at the center and the amino terminus but diffuse at the carboxyl terminus. By analyzing a high‐resolution database of protein structures, we find that certain 1–4 hard‐sphere repulsions in the standard steric map of Ramachandran do not affect the statistical distributions. By ignoring these steric clashes (N···Hi+1 and Oi−1···C), we identify a revised set of steric clashes (Cβ···O, Oi−1···Ni+1, Cβ···Ni+1, Oi−1···Cβ, and Oi−1···O) that produce a better match with the data. We also find that the strictly forbidden region in the Ramachandran plot is excluded by multiple steric clashes, whereas the outlier region is excluded by only one significant steric clash. However, steric clashes alone do not account for the diagonal regions. Using electrostatics to analyze the conformational dependence of specific interatomic interactions, we find that the diagonal shape of the αR and αL‐regions also depends on the optimization of the N···Hi+1 and Oi−1···C interactions, and the diagonal β‐strand region is due to the alignment of the CO and NH dipoles. Finally, we reproduce the variation of the Ramachandran plot along the α‐helix in a simple model that uses only H‐bonding constraints. This allows us to rationalize the difference between the amino terminus and the carboxyl terminus of the α‐helix in terms of backbone entropy.