bluuebunny/crossref_metadata_2025 huggingface dataset:
Israel's High Court of Justice Model
Authors: Ginbar Yuval
Published: January 2009

This chapter describes and analyzes the model of legalized torture established by a 1999 Israeli Supreme Court (as High Court of Justice, HCJ) ruling, under which interrogation of suspected terrorists has been regulated in Israel between then and the present. Declaring the Landau system as illegal, since the ‘defence of necessity’ (DoN) cannot apply a priori and interrogators have no authority to torture or ill-treat, the Court nevertheless ruled that the DoN is available ex post facto to interrogators who torture (applied ‘physical methods’) in ticking bomb situations. According to official data, dozens of Palestinians were interrogated annually using ‘extraordinary measures’ in TBSs during the second Palestinian Intifadah's first two years. Human rights organizations claim much higher numbers. No interrogators have been prosecuted. Methods, pronounced by a UN expert to amount to torture, include incommunicado detention, sleep deprivation, shackling in painful positions, and other forms of violence and humiliation.
Part IV—Introduction
Authors: Ginbar Yuval
Published: January 2009

This chapter introduces Part IV, where three issues raised by the discussion of the models in Part III are to be examined. The question of whether or not the interrogation methods used in the US and Israeli models constitute torture under international legal definitions or are even unlawful at all, for instance as ‘cruel, inhuman, or degrading treatment’ is discussed first, followed by an analysis of the ‘defence of necessity’ as a putative basis for exempting torturers in ticking bomb situations from criminal responsibility. This issue will be analysed both in the context of national and international criminal law. Thirdly, in concluding this Part, the applicability of that defence and other ex post mechanisms to the reality of states facing terrorism in the early 21st century will be discussed.
The Dangers ofAmour‐Propre
Authors: Neuhouser Frederick
Published: January 2009

This chapter reconstructs Rousseau's account of why amour-propre is the principal source of the enslavement, conflict, vice, misery, and self-estrangement that pervades human reality. The first question to be addressed is how amour-propre helps make possible the evils mentioned above. The concern is not to explain why those evils are so widespread — why amour-propre so frequently gives rise to them — but merely to understand how the features of amour-propre outlined in the previous chapter make them possible. Implicit in this undertaking is the view that in the absence of amour-propre, these human evils would be non-existent or, at worst, extremely rare.
On Hart's Ways: Law as Reason and as Fact
Authors: Finnis John
Published: January 2009

This chapter criticizes Hart's account of the internal perspective of participants in institutions and practices. It maintains that the inadequacies in Hart's account are importantly connected to the inadequacy of his understanding of the reasons-for-action with which legal officials (and other moral agents) are confronted.
The Legal Entrenchment of Illegality
Authors: Lyons David
Published: January 2009

This chapter recounts a number of situations in the American South where legal officials persistently declined to impose penalties for certain crimes (committed against black people) even though the identities of the perpetrators of those crimes were generally known to the legal authorities. It adduces these harrowing facts of American history in order to question Hart's model of the ways in which the activities of legal officials sustain the existence of laws.
Fairness, Needs, and Desert
Authors: Hooker Brad
Published: January 2009

This chapter explores two major distinctions that are often deemed relevant to fairness: benefits that satisfy some need(s) versus benefits that do not satisfy any need(s), and deserved benefits versus undeserved benefits. In the course of investigating these distinctions, it argues in favour of weighted prioritarianism as one key principle in an overall account of justice.
3 Easter and the Passover Moon
Authors: Mosshammer Alden A.
Published: January 2009

Jesus was crucified at the time of the Passover. Passover is observed on the 14th day of the first month, when the springtime crop is ripe. In a lunar calendar, the 14th day of the month is a full moon. Some communities commemorated the Passion on the 14th day of the moon, regardless of the calendar date (Quartodecimans). Others observed Easter on a Sunday at the approximate time of the full moon. The Council of Nicaea (AD 325) endorsed the latter practice and provided that all should defer to the churches at Rome and Alexandria for the determination of the date. Those churches had adopted a cycle for coordinating the phases of the moon with the vernal equinox. The earliest such cycle equated eight Julian years with 99 lunar months. What ultimately became the standard cycle equated 19 Julian years with 235 lunar months.
6 The Computistical Rules
Authors: Mosshammer Alden A.
Published: January 2009

Dionysius Exiguus appended to his 95‐year table a set of rules (argumenta) for working with the data. Of the sixteen rules included in the manuscripts, only the first ten derive genuinely from Dionysius, with the possible exception of the seventh rule. In his examples, Dionysius uses what he calls the present year—the consulship of Probus, AD 525. The rules are clearly of Alexandrian origin. Dionysius has adapted them to the Roman calendar, but some of them are explicable only as formulae based on the Alexandrian calendar.
13 The Chronicon Paschale and the Origins of the Byzantine Era
Authors: Mosshammer Alden A.
Published: January 2009

The Byzantine form of the Alexandrian cycle emerged in the 7th century, with an era of creation corresponding to 5509/8 BC and a cycle that began with the 14th day of the moon on 2 April. The Byzantine cycle and its era were adaptations of an innovation proposed by the author of the Chronicon Paschale. That text uses a 19‐year cycle beginning from the 14th day of the moon on 13 April and acalendar that began on Wednesday, 21 March 5509 BC. The authors of the Byzantine cycle accepted Sunday 18 March 5509 BC as the date of creation, but numbered the years from 1 September 5509 BC, in synchronism with the civil calendar. They also moved the saltus from the end of the 19th year to the end of the 17th so as to yield a sequence of epacts in agreement with the Alexandrian cycle.
6 Excursus: Success and Choice of Competitive Strategies
Authors: Herrmann Andrea M.
Published: January 2009

This chapter explores corporate success. It addresses the question: Are pharmaceutical firms less successful if they pursue strategies that are not supported by national institutions? Given that quantitative analyses do not support this idea, the chapter examines the strategy choices of entrepreneurs. Since institutional considerations are of limited importance to this end, on which grounds do entrepreneurs base their choice of a competitive strategy? Qualitative comparisons of interviews with managers reveal that technological opportunities to transform inventions or imitations into marketable products are of major concern when entrepreneurs choose their firms' strategy. The chapter concludes by illustrating the implications that result from these findings for institutional theories.
Peremptory Norms in International Law
Authors: Orakhelashvili Alexander
Published: January 2009

This monograph analyses the questions raised by the legal effects of peremptory norms of international law (jus cogens), reflected in Article 53 of the 1969 Vienna Convention on the Law of Treaties. A comprehensive study of this problem has been lacking so far in international legal doctrine. Peremptory norms, although often criticised and even more often approached with sceptical nihilism, nevertheless attract growing doctrinal and practical attention, and have increasing importance in determining the permissible limits on the action of State and non-State actors in different areas. In view of this overriding impact on what might otherwise be instances of the law-making process, peremptory norms concern a constitutional aspect of international law. Peremptory norms are non-derogable norms, and the concept of derogation is among the key concepts analysed here. Derogation from peremptory norms can be attempted in a wide variety of situations, but if peremptory norms are to operate as norms and not merely as aspirations, they must generate consequences that are also peremptory. This effects-oriented character of peremptory norms is examined in a variety of fields. The hierarchical superiority of peremptory norms is not limited to the sphere of primary legal relations, but becomes most crucially relevant after a specific peremptory norm is breached. A norm's peremptory character is relevant not only for its substance but also for its consequences; peremptoriness consists primarily in the capacity to impact through its effects upon conflicting acts, situations and agreements.
The Effect ofJus Cogensin the Law of Treaties
Authors: Orakhelashvili Alexander
Published: January 2009

This chapter addresses the impact of jus cogens in the law of treaties. It examines the most classical or traditional case of the invalidity of treaties under Article 53 of the 1969 Vienna Convention on the Law of Treaties. It also examines the practical impact of jus cogens not directly mentioned in, but structurally admitted by, the Vienna Convention: interpretation of treaties, reservations to treaties, suspension, and modification of treaties. In some cases, the impact of jus cogens is direct while in other cases it is mediated through objective treaty obligations (see above Chapter 4). The chapter covers both conceptual aspects and State practice.
The Normative Conflict between a Security Council Resolution andJus Cogens: The Practice of the Security Council
Authors: Orakhelashvili Alexander
Published: January 2009

This chapter examines how exactly the UN Security Council acts in breach of jus cogens and what sort of normative conflicts are produced. In some cases, Security Council expressly generates, authorises or approves breaches of jus cogens; in other cases, it is seen as implicitly acquiescing to such violations; in some cases the inaction of the Council is seen as an approval of breaches. The chapter examines and assesses all these claims at the example of State practice covering multiple situations: Cyprus, Bosnia, Iraq, Libya, Kosovo, and East Timor.
Legal Consequences of the Conflict of a Security Council Resolution with Peremptory Norms
Authors: Orakhelashvili Alexander
Published: January 2009

This chapter examines a number of problems of interpretation of Security Council resolutions to construe them as not conflicting with jus cogens and so preserve their validity. As for resolutions that cannot be so interpreted, the chapter examines the issue of invalidity of resolutions; and the means of challenging illegal resolutions: protest, refusal to carry out, and judicial review. The practice of all relevant international tribunals is examined. As a follow-up on Chapters 12–14 of this monograph, the articles by this author in Max-Planck YBUNL (2007) and AJIL (2008) should be consulted.
Doctrinal Treatment of the Effectiveness of Legal Regulation
Authors: Orakhelashvili Alexander
Published: January 2009

This chapter examines how the determinacy and effectiveness of legal regulation were first focused upon, and taken as the basis for international legal reasoning, by J. L. Brierly and Sir Hersch Lauterpacht. The analysis covers the two authors' examination of the completeness of legal regulation, and separation of international law from politics. A few basic premises of legal reasoning are identified as the starting-point for analysis for the rest of the monograph.
Characteristics and Implications of the Effectiveness of Legal Regulation
Authors: Orakhelashvili Alexander
Published: January 2009

This chapter focuses on the essence of determinacy of legal rules, and the degrees of their indeterminacy as can be met in international judicial practice. If rules are indeterminate, this opens the way for arguing that law is influenced by politics, and that rules can be subjectively interpreted. This would not support the consistency and effectiveness of legal regulation. After examining how tribunals can respond to alleged indeterminacy of rules, the chapter examines in detail how legal argument relates to political argument in the international legal system, and how legal obligation relates to the residual sovereignty of States. These issues are crucial for examining how interpretation works in the subsequent chapters, from Chapter 9 onwards.
Conceptual Aspects of Interpretation
Authors: Orakhelashvili Alexander
Published: January 2009

This chapter examines starting-point conceptual issues of interpretation in international law. The basic questions relate not only to doctrinal aspects, such as the discourse between Sir Hersch Lauterpacht and Julius Stone, but also to such key issues as relationship between interpretation and application of rules; evolutive interpretation, interpretation and sovereignty, and ‘approximate application’. Identifying the basis of interpretation in reflecting the original consent and agreement, the chapter concludes that there are no radical differences in how different treaty and non-treaty instruments should be interpreted.
7 Mind and Body
Authors: Cooper Adam G.
Published: January 2009

Philosophical debate continues over the relation of mind to body. ‘Cartesian dualism’ is the dirty word, but can even a moderate materialism make proper sense of the full range of human intellectual and spiritual activity? Determining whether, what, and how we know calls for a philosophy of the flesh articulated in full consciousness of our bodily situatedness. At the same time, a philosophy of the flesh, or even a philosophy in the flesh, does not require a scepticism about the human capacity for transcendence, or agnosticism about the reality of transcendent truth.
Constitutional Principles of EU External Relations
Authors: De Baere Geert
Published: January 2009

The volume explores the marked differences between the complex and rapidly changing legal organization of EU external relations and the EU's ‘internal’ constitutional order. The European Union is unique as a polity organized along federal lines but with fully fledged States as its component political entities. The tension between the self-conscious Member States and their constitutional relationship within the EU is especially pronounced in the foreign policy field, where they remain determined to assert their status as full subjects of the international order. This book explores how foreign policy fits within the constitutional structure of the EU, characterized by the division of external relations competences between the EU and the Member States (‘the vertical axis’), and between the ‘pillars’ of which the Union is composed, in particular the division between the Community competences of the first pillar and the common foreign and security competences of the second pillar (‘the horizontal axis’). This is a study of the extent to which foreign policy is legally sui generis within the sui generis constitutional order of the EU, and of how the common foreign and security policy is in turn sui generis within the foreign policy structure of the Union. It provides both an exploration of the constitutional reality of EU foreign policy and theoretical analysis which suggests possibilities for reform.
Conclusions
Authors: De Baere Geert
Published: January 2009

This chapter begins with a summary of discussions in the preceding chapters. It then discusses EU foreign policy, identity, and law. It concludes that the development of the EU's external relations, and of the EU in general, can be seen as an extraordinary attempt to bring foreign policy more within the realm of law and thereby to constrain its possible destructive force. Having domesticated the Member States' foreign policies with regard to each other, the EU is gradually moving its focus from the inside to the outside, bringing the Member States' foreign policies with regard to third countries more and more within the constraining and enabling framework of EU law.
5 Individual Choice and Social Order
Authors: Taylor‐Gooby Peter
Published: January 2009

This chapter relates the social science traditions discussed in Chapter 4 to the assumptions of social citizenship identified in Chapter 1. It reviews evidence from the study of games, evolutionary psychology, negotiation over public goods, behaviour in markets, and other areas of research, to show that individual rational actor approaches can provide strong accounts of reciprocity and of some aspects of social inclusion. However they are much weaker in explaining the development of the kind of citizenship trust that is essential to the stability of welfare states, and unable to offer it more than a limited role in social interactions. More sociological accounts resting on norms, symbolic communication and expressive approaches to action provide good accounts of the development of welfare state citizenship (understood as embedded norms). In more recent work, structural approaches to social norms have been integrated with accounts of the experience of independent individual agency. This approach offers an explanation of the development of the values essential to social citizenship and of how they can contribute in welfare states. However, it is of declining importance in the logic that directs policy-making.
11 Welfare Under Altered Circumstances
Authors: Taylor‐Gooby Peter
Published: January 2009

Welfare states have enjoyed considerable success in containing the pressures of economic, political, and social change identified in Chapter 1. However, an important theme in their responses, the shift towards an individual rational actor approach to policy-making, risks weakening the values that sustain social citizenship. It may support reciprocity but undermines social inclusion and trust in welfare state institutions. Any response must recognise the continuing pressures for greater competitiveness arising in a more open economy. Cost-constraint is not the only factor contributing to productivity. Greater inclusiveness, more open opportunities and constraint on privilege at the top end may help to secure better mobilization of human resources. More democratic accountability will enhance trust in services. The individual rational actor approach to welfare state reform has considerable weaknesses as well as the strengths that make it attractive to governments.
Pursuing our Own Good
Authors: Kekes John
Published: January 2009

Enjoyment of one's life consists in pursuing our own good in our own way. Personal evaluation of the available possibilities on the basis of what is most important to oneself is a means to it. It leads to a complex attitude formed of beliefs, emotions, and motives expressing one's deepest concerns. Attitudes may be coherent or incoherent, reasonable or unreasonable. The attitudes of detached contemplation, creative inwardness, and shibumi are critically considered.
The Communication of Christianity
Authors: Harding Christopher
Published: January 2009

This chapter looks at the ways in which Christianity was communicated across vast expanses of rural Punjab, the reaction of missionaries once they became aware that a large-scale movement of poor rural workers towards Christianity was afoot, and the various ways in which they sought to order and teach those entering the mission-Churches. Convert perceptions about Christianity at this early stage are crucial. Was there a tendency among converts to view it as a collection of ideas and resources from which they could pick and choose, or rather as a cohesive whole that would have to be either accepted or rejected in its totality? The role played by catechists in these early years of the mission-convert relationship is examined, from their training and workload to varying perceptions among missionaries and converts about what their main duties ought to be and how satisfactorily they were executing them.
4 Concentration among the Rich
Authors: Atkinson Anthony B.
Published: January 2009

This study examines the concentration of wealth among the group of top wealth holders, defined as those with wealth in excess of a high cut‐off. The study begins by considering the definition of this cut‐off, analogous to the definition of a poverty line at the other end of the distribution. It then considers what can be learned about the proportion classified as ‘rich’ and about the concentration among the rich from four non‐survey sources: journalists' lists, estate data, wealth tax data, and investment income tax data. It starts off from the world's billionaires in 2006, but is particularly concerned with changes over time within countries, taking France, Germany, the UK, and the USA, to illustrate the different sources.
8 Household Wealth in Latin America
Authors: Torche Florencia , Spilerman Seymour
Published: January 2009

This study provides a descriptive analysis of wealth ownership and wealth inequality in Latin American countries, using diverse published sources and primary data analysis for sixteen nations. This chapter presents estimates of the distribution of home ownership, land, and financial assets, and find very high wealth concentration in all these types of assets, with the partial exception of home ownership. The relevance of informal assets and the historical patterns of wealth accumulation and concentration since colonial times are discussed. Mechanisms of intergenerational wealth transmission are analysed for the Chilean case.
16 Land Titles, Credit Markets, and Wealth Distributions
Authors: MacGee James C.
Published: January 2009

Does the existence of formal title to land and real estate matter for the distribution of wealth? This study reviews the empirical literature on the economic impact of land and real‐estate administration systems across countries. This study argues that a functioning credit market for secured credit is necessary to realize the full benefits of legal title to private real estate. This study also reviews quantitative economic theory on wealth distribution to assess the probable impact of different land‐registration systems on wealth inequality. The implication of current theory is that poor land‐administration systems may sometimes lead to lower levels of wealth inequality than better land‐registration systems.
India
Authors: Brancati Dawn
Published: January 2009

This chapter discusses the case study of India (1947–present). In India, decentralization is neither an unabashed success, as in Spain, nor a resounding failure, as in Czechoslovakia. India has experienced intermittent bouts of conflict in some regions and periods of its history more than in others. This chapter attributes India's mixed track record to the behavior of regional parties in the country and the failure of statewide parties to fully incorporate regional interests into their agenda. In India, regional parties have prompted conflict and secessionism by adopting legislation harmful to regional minorities and mobilizing groups to engage in ethnic conflict and secessionism. Regional parties have been confined to the regional level, however, until the 1990s. Statewide parties, and the Congress Party in particular, have not fully or always reduced ethnic conflict and secessionism in India because of certain conditions in the country that reduce their incentive to incorporate the interests of particular regions into their agenda (i.e. the pivotalness — or lack thereof — of certain regions and/or groups within India, the distribution of ethnolinguistic and religious groups throughout the country, the internal organization of statewide parties, as well as the leadership style of particular political leaders in the country). This chapter attributes the shape of India's party system to specific features of decentralization in the country (i.e. the proportion of national legislative seats India's many regions hold individually, the extension of decision‐making autonomy to some regions of India and not others, and the election of the upper house entirely by the country's regional legislatures).
Ethnic Conflict and Secessionism
Authors: Brancati Dawn
Published: January 2009

Through statistical analysis, this chapter tests the generalizability of its argument regarding the effect of decentralization and regional parties on ethnic conflict and secessionism. The analysis draws on an original dataset, known as the constituency‐level elections (CLE) dataset, which provides election results for national (lower and upper house) elections and regional elections from 1945 to 2002 at the constituency‐level of government, to measure systematically the electoral strength of regional parties. To measure ethnic conflict and secessionism, the chapter draws on the Minorities at Risk dataset (1985–2000), which it corrects for selection bias. The analysis supports the chapter's argument that decentralization diminishes the strength of ethnic conflict and secessionism, while regional parties intensify it, and that the ability of decentralization to reduce conflict decreases as the electoral strength of regional parties increases. The chapter controls for a number of factors that may affect regional party strength (e.g. ethnolinguistic heterogeneity, economic development, democracy, and the executive and electoral system). The chapter also uses instrumental variable regression in this chapter to disentangle the causal relationships between decentralization, regional parties, and ethnic conflict and secessionism.
Chapter 6 Retirement Distributions and the Bequest Motive
Authors: Hallman G. Victor
Published: January 2009

Managing retirement payouts generally revolves primarily around securing adequate retirement income and assuring the continuity of such income for as long as the retirees live. Many commentators have suggested that the most efficient strategy to deal with these issues for risk-averse retirees is to annuitize retirement benefits. However, these commentators recognize that relatively few retirees actually choose life annuitization (the so-called ‘annuity puzzle’). One reason for this is the bequest or inheritance motive which involves using income-tax-favored retirement plans to pass wealth to the heirs (probably children) of the retiree or to charity. This chapter discusses the concepts, strategies, and constraints on using tax-favored retirement plans as wealth transfer devices.
Chapter 10 The Impact of Health Status and Out‐of‐Pocket Medical Expenditures on Annuity Valuation
Authors: Turra Cassio M. , Mitchell Olivia S.
Published: January 2009

This chapter describes how differences in health status at retirement can influence the decision to purchase a life annuity. It extends previous research on annuitization decisions by incorporating the effect of health differentials via differences in survival throughout the latter portion of life. It then shows how precautionary savings motivated by uncertain out-of-pocket medical expenses influence annuitization decisions. Results show that annuities become less attractive to people facing uncertain medical expenses. While full annuitization would still be optimal if annuity markets were truly complete and both life- and health-contingent, lacking this, annuity equivalent wealth values are much lower for those in poor health, as compared to persons in good health.
Chapter 11 Annuity Valuation, Long‐Term Care, and Bequest Motives
Authors: Ameriks John , Caplin Andrew , Laufer Steven , Van Nieuwerburgh Stijn
Published: January 2009

Financial security in retirement has traditionally meant having a steady flow of annuity income as long as one lives — a definition enshrined in the Social Security system. Earlier research has stressed a more holistic approach, which focuses on the match between resources and spending needs. Using this formulation this chapter estimates annuity values given long-term care concerns and bequest motives, where these estimated values are consistent with low observed demand for standard annuities. The chapter extends this model to value non-standard annuities with various security-enhancing features that may be of value to retirees.
The Blasphemy of Sirmium (357) and Basil of Ancyra
Authors: Beckwith Carl L.
Published: January 2009

This chapter argues that the synod of Sirmium (357) and its theological manifesto led Hilary to recast his efforts against his Homoian opponents. Following this synod, Basil of Ancyra and his theological circle issued a letter rejecting the Homoian theology of the Sirmium manifesto and stated their own Homoiousian theology. This chapter reviews in detail both the Sirmium manifesto and the Homoiousian response to it.
The Fundamental Legal Right to Privacy
Authors: Zucca Lorenzo
Published: January 2009

This chapter deals with the fundamental right to privacy; its protean nature is exposed as well as its propensity to conflict with other fundamental rights. Lacking a common core, the fundamental right to privacy is broken down into four sub-rights: informational privacy, decisional privacy, formational privacy, and physical privacy. It is argued that there is a link between the lack of a narrow definition of privacy and its aptitude to conflict. Therefore, the fundamental right to privacy is likely to conflict with other fundamental rights in several contexts, as is shown in Chapters 6 and 7.
Taking the Law into Our Own Hands: Kant on the Right to Revolution
Authors: Korsgaard Christine M.
Published: January 2009

Kant condemned revolution as a violation of a duty of justice, yet was a supporter of the French Revolution. This chapter defends Kant's view that revolution is a violation of a duty of justice by appeal to the fact that in order to be just, revolution would have to accord with the general will, and the government speaks for the general will. The chapter then explains Kant's paradoxical attitude by appeal to the distinction between duties of justice and duties of virtue. The duties of justice require us to obey the powers that be, because only in the political state can human rights and freedom be realized. But the virtue of justice requires us to make human rights our end. When a political society itself violates human rights, the virtue of justice is turned against itself, and the person who makes human rights his end may be driven to take the law into his own hands.
Realism and Constructivism in Twentieth‐Century Moral Philosophy
Authors: Korsgaard Christine M.
Published: January 2009

This chapter traces the development of one of the central debates of late 20th-century moral philosophy — the debate between realism and what Rawls called “constructivism.” It argues that realism is a reactive position that arises in response to almost every attempt to give a substantive explanation of morality. It results from the realist's belief that such explanations inevitably reduce moral phenomena to natural phenomena. The chapter traces this belief, and the essence of realism, to a view about the nature of concepts: that it is the function of all concepts to describe reality. Constructivism may be understood as the alternative view that the function of a normative concept is to refer schematically to the solution to a practical problem. A constructivist account of a concept, unlike a traditional analysis, is an attempt to work out the solution to that problem. The chapter explains how the philosophies of Kant and Rawls can be understood on this model.
A divide-and-conquer approach to analyze underdetermined biochemical models
Authors: Kotte Oliver , Heinemann Matthias
Published: January 2009

Motivation: To obtain meaningful predictions from dynamic computational models, their uncertain parameter values need to be estimated from experimental data. Due to the usually large number of parameters compared to the available measurement data, these estimation problems are often underdetermined meaning that the solution is a multidimensional space. In this case, the challenge is yet to obtain a sound system understanding despite non-identifiable parameter values, e.g. through identifying those parameters that most sensitively determine the model's behavior.

Results: Here, we present the so-called divide-and-conquer approach—a strategy to analyze underdetermined biochemical models. The approach draws on steady state omics measurement data and exploits a decomposition of the global estimation problem into independent subproblems. The solutions to these subproblems are joined to the complete space of global optima, which can be easily analyzed. We derive the conditions at which the decomposition occurs, outline strategies to fulfill these conditions and—using an example model—illustrate how the approach uncovers the most important parameters and suggests targeted experiments without knowing the exact parameter values.

Contact:  heinemann@imsb.biol.ethz.ch

Supplementary information:  Supplementary data are available at Bioinformatics online.
A semi-analytical model for oblique impacts of elastoplastic spheres
Authors: Wu Chuan-Yu , Thornton Colin , Li Long-Yuan
Published: January 2009

Results of finite-element analysis (FEA) of oblique impacts of elastic and elastic, perfectly plastic spheres with an elastic flat substrate are presented. The FEA results are in excellent agreement with published data available in the literature. A simple model is proposed to predict rebound kinematics of the spheres during oblique impacts. In this model, the oblique impacts are classified into two regimes: (i) persistent sliding impact, in which sliding occurs throughout the impact, the effect of tangential (elastic or plastic) deformation is insignificant and the model reproduces the well-established theoretical solutions based on rigid body dynamics for predicting the rebound kinematics and (ii) non-persistent sliding impact, in which sliding does not occur throughout the impact duration and the rebound kinematics depends upon both Poisson's ratio and the normal coefficient of restitution (i.e. the yield stress of the materials). For non-persistent sliding impacts, the variation of impulse ratio with impact angle is approximated using an empirical equation with four parameters. These parameters are sensitive to the values of Poisson's ratio and the normal coefficient of restitution, but can be obtained by fitting numerical data. Consequently, a complete set of solutions is obtained for the rebound kinematics, including the tangential coefficient of restitution, the rebound velocity at the contact patch and the rebound rotational speed of the sphere during oblique impacts. The accuracy and robustness of this model is demonstrated by comparisons with FEA results and data published in the literature. The model is capable of predicting complete rebound behaviour of spheres for both elastic and elastoplastic oblique impacts.
A new integral property of inertial waves in rotating fluid spheres
Authors: Liao Xinhao , Zhang Keke
Published: January 2009

The problem of fluid motion in the form of inertial waves in an incompressible inviscid fluid contained in a rotating sphere is governed by the Poincaré equation, a second-order hyperbolic partial differential equation. Its explicit general analytical solution in terms of a double Poincaré polynomial was found by Zhang
et al
. (

Zhang
et al
. 2001

J. Fluid Mech
.
437
, 103–119), describing the pressure
p

mnK

and the velocity

u

mnK

of spherical inertial waves, where the triple indices (
mnK
) are indicative of the azimuthal, vertical and radial structures, respectively. On the basis of the general explicit solution, we reveal a new intriguing integral property of the spherical inertial waves

for all possible values of
m
,
l
and
n
, where
M
and
K
are related to the degree of the double Poincaré polynomial and

denotes the complex conjugate of

u

mlM

. A mathematical proof of the vanishing of the integral involving the construction of two auxiliary recurrence relations is presented. Furthermore, a comparison with the corresponding integral for rotating cylinders is made, showing a fundamental difference between the two systems.
Expression of the calcium‐binding protein S100P is regulated by bone morphogenetic protein in pancreatic duct epithelial cell lines
Authors: Hamada Shin , Satoh Kennichi , Hirota Morihisa , Fujibuchi Wataru , Kanno Atsushi , Umino Jun , Ito Hiromichi , Satoh Akihiko , Kikuta Kazuhiro , Kume Kiyoshi , Masamune Atsushi , Shimosegawa Tooru
Published: January 2009

We previously reported that bone morphogenetic protein (BMP)‐4 induces epithelial–mesenchymal transition in a pancreatic cancer cell line. To further investigate the detailed molecular mechanism of BMP action in pancreatic cancer, we carried out comprehensive microarray analysis in Panc‐1 cells. The microarray analysis elucidated novel BMP target genes, and among them, the calcium‐binding protein S100P was identified as an upregulated gene. S100P induction by BMP4 was confirmed by real‐time reverse transcription–polymerase chain reaction and western blot analysis in Panc‐1 and HPDE cells. Short interfering RNA‐based knockdown of S100P expression sufficiently repressed BMP4‐induced cell migration in Panc‐1 cells. Because Panc‐1 and HPDE cells express wild‐type Smad4, we hypothesized that Smad4 might be indispensable for S100P induction by BMP4. S100P induction by BMP4 was not observed in the Smad4‐null cell line BxPC3, and was sufficiently attenuated in short interfering RNA‐based Smad4‐knockdown Panc‐1 cells. Interestingly, detailed promoter analysis revealed that upregulation of S100P by BMP4 was independent of the Smad‐binding element, indicating that an additional unknown downstream factor of the Smad4‐dependent pathway is necessary for this induction. These findings are the first of their kind, and this Smad4‐dependent regulation of S100P by BMP signaling might explain the migratory mechanism of cancer cells, which is still unknown. (Cancer Sci 2009; 100: 103–110)
Patients with localized primary non‐tonsillar oral diffuse large B‐cell lymphoma exhibit favorable prognosis despite a non‐germinal center B‐cell‐like phenotype
Authors: Sato Yasuharu , Onishi Naoko , Morito Toshiaki , Takata Katsuyoshi , Mizobuchi Kohichi , Nagatsuka Hitoshi , Ichimura Kouichi , Tanaka Takehiro , Tamura Maiko , Yoshino Tadashi
Published: January 2009

Diffuse large B‐cell lymphomas are detected frequently in the oral cavity. Although tonsillar lymphomas have been rather well characterized, lymphomas originating from non‐tonsillar regions, such as the gingiva, palate, and tongue, have not been well studied. We examined the pathology of clinical samples obtained from 21 patients with localized primary non‐tonsillar oral diffuse large B‐cell lymphoma. Immunohistological examination of CD10, Bcl‐6, and MUM1 determined that 17 of 21 (81%) samples exhibited non‐germinal center B‐cell type, an increased proportion of non‐germinal center B‐cell type compared with previous reports in samples of tonsillar origin (P < 0.05). The four remaining samples exhibited germinal center B‐cell type, although one sample expressed MUM1. Follow‐up clinical survival data were obtained from the 17 patients over a range from 4 to 173 months (mean 52 months). All patients were treated with chemotherapies, irradiation, or surgical resection. Sixteen patients achieved complete remission and two patients relapsed, but no patient has died of disease. Extranodal diffuse large B‐cell lymphomas of non‐germinal center B‐cell type are generally characterized by poor prognosis, regardless of localized disease. Interestingly, our results indicate that, unlike similar lymphomas of tonsillar origin, localized primary non‐tonsillar oral diffuse large B‐cell lymphomas exhibit favorable prognosis, suggesting that these lymphomas may be clinicopathologically distinct. (Cancer Sci 2009; 100: 42–46)
Antibody epitope peptides as potential inducers of IgG antibodies against CD98 oncoprotein
Authors: Itoh Kunihiko , Ohshima Motohiro , Sonobe Momoyo , Saito Misa , Yoshida Akira , Hayashi Hideki , Inoue Kazuyuki , Masuko Takashi
Published: January 2009

An epitope is an antibody‐recognition site on a target antigen. As such, active immunization of epitope peptides may induce therapeutic efficacy equivalent to the administration of parent antibody medicines. In the present study, we designed peptides based on the epitope recognized by the tumor‐suppresive anti‐CD98 monoclonal antibody HBJ127, and investigated their efficacy for induction of antitumor immunity. The immune sera showed reactivity against the corresponding peptide–keyhole limpet hemocyanin (KLH) and peptide–bovine serum abumin (BSA) conjugates, although they did not react with CD98‐positive HeLa cells or recombinant CD98 heavy chain. To elucidate whether the epitope peptide failed to induce antitumor immunity or not, we constructed the IgG1, κ Fab phage display libraries from spleen cells of immunized mice and tried to retrieve CD98‐reactive recombinant Fab (rFab) fragments by panning against either epitope peptide–BSA conjugates or live HeLa cells. RFab fragments retrieved from peptide–BSA panning showed no reactivity to HeLa cells. Their variable‐region sequences were different from HBJ127. However, rFab fragments retrieved from HeLa cell panning showed reactivity to CD98 by indirect immunofluorescence and immunoprecipitation. Moreover, they were structurally almost identical to HBJ127. Although the immunogenicity of epitope peptides may be insufficient for induction of expected antitumor activity in vivo, we used antibody phage display to show that IgG antibodies almost identical to HBJ127 were an undetectable population in epitope peptide‐induced immune sera. (Cancer Sci 2009; 100: 126–131)
Japanese phase II study of 90Y‐ibritumomab tiuxetan in patients with relapsed or refractory indolent B‐cell lymphoma
Authors: Tobinai Kensei , Watanabe Takashi , Ogura Michinori , Morishima Yasuo , Hotta Tomomitsu , Ishizawa Kenichi , Itoh Kuniaki , Okamoto Shin‐ichiro , Taniwaki Masafumi , Tsukamoto Norifumi , Okumura Hirokazu , Terauchi Takashi , Nawano Shigeru , Matsusako Masaki , Matsuno Yoshihiro , Nakamura Shigeo , Mori Shigeo , Ohashi Yasuo , Hayashi Masaki , Endo Keigo
Published: January 2009

There is no data about the efficacy and safety of radioimmunotherapy with 90Y‐ibritumomab tiuxetan in patients with relapsed or refractory indolent B‐cell lymphoma pretreated with rituximab‐containing chemotherapy. We focused on this in a Japanese phase II study. Radioimmunotherapy with 90Y‐ibritumomab tiuxetan (11.1 and 14.8 MBq) was evaluated in patients with 100–149 × 109 and >150 × 109 platelets/L, respectively. The primary endpoint was the overall response rate. Forty patients were treated with 90Y‐ibritumomab tiuxetan (18 with 11.1 MBq/kg and 22 with 14.8 MBq/kg). Thirty‐five patients (88%) had been pretreated with rituximab, including 27 (68%) pretreated with rituximab‐containing chemotherapy. The overall response rate was 83% (33/40; 95% confidence interval, 67–93%), and the complete response rate was 68% (27/40; 95% confidence interval, 51–81%). The overall response rates in patients pretreated with rituximab‐containing chemotherapy and rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R‐CHOP) were 83% (19/23) and 94% (17/18), respectively. The median progression‐free survival time of the 40 patients who received 90Y‐ibritumomab tiuxetan was 9.6 months. Toxicity was primarily hematological and mostly transient. No grade 4 non‐hematological toxicity was observed. In conclusion, radioimmunotherapy with 90Y‐ibritumomab tiuxetan is safe and highly effective in patients with relapsed or refractory indolent B‐cell lymphoma, including those pretreated with rituximab‐containing chemotherapy. (ClinicalTrials.gov number NCT00220285) (Cancer Sci 2009; 100: 158–164)
Role of iron in carcinogenesis: Cancer as a ferrotoxic disease
Authors: Toyokuni Shinya
Published: January 2009

Iron is abundant universally. During the evolutionary processes, humans have selected iron as a carrier of oxygen inside the body. However, iron works as a double‐edged sword, and its excess is a risk for cancer, presumably via generation of reactive oxygen species. Thus far, pathological conditions such as hemochromatosis, chronic viral hepatitis B and C, exposure to asbestos fibers, as well as endometriosis have been recognized as iron overload‐associated risks for human cancer. Indeed, iron is carcinogenic in animal experiments. These reports unexpectedly revealed that there are target genes in iron‐induced carcinogenesis and that iron‐catalyzed oxidative DNA damage is not random in vivo. Several iron transporters and hepcidin, a peptide hormone regulating iron metabolism, were discovered in the past decade. Furthermore, a recent epidemiological study reported that iron reduction by phlebotomy decreased cancer risk in the apparently normal population. These results warrant reconsideration of the role of iron in carcinogenesis and suggest that fine control of body iron stores would be a wise strategy for cancer prevention. (Cancer Sci 2009; 100: 9–16)
Inverse correlation of the up‐regulation of FZD10 expression and the activation of β‐catenin in synchronous colorectal tumors
Authors: Nagayama Satoshi , Yamada Eiji , Kohno Yoshiki , Aoyama Tomoki , Fukukawa Chikako , Kubo Hajime , Watanabe Go , Katagiri Toyomasa , Nakamura Yusuke , Sakai Yoshiharu , Toguchida Junya
Published: January 2009

We investigated the immunohistochemical expression patterns of Frizzled homolog 10 (FZD10), a cell‐surface receptor for molecules in the Wnt pathway, in tissue samples derived from 104 patients with colorectal cancers (CRCs). There was no immunoreactivity for FZD10 in normal colonic mucosa, and only tumor cells in polyps and CRC tissues showed spotted immunostaining patterns in apical sides of the cytoplasm. In metastatic liver lesions, tumor cells showed cytoplasmic immunostaining similar to primary lesions, whereas normal liver parenchyma showed almost no immunostaining. Frequencies of FZD10‐immunopositive cells in tumor tissues were significantly higher in CRCs than those in polyps (3.3 ± 10.3%vs 20.5 ± 31.7%, P = 0.0016), and almost equivalent with those in metastatic liver lesions (33.2 ± 39.7%vs 26.4 ± 33.4%, P = 0.133). Analyses of paired samples (polyps and CRCs, or CRCs and metastatic liver lesions from the same patient) suggested that a subset of CRCs possessed intrinsic genetic mechanisms causing the evolution of FZD10‐positive clones during tumor progression, making FZD10 a promising candidate for molecular imaging and a target for therapy. To our surprise, cancer cells immunopositive for FZD10 showed significantly less nuclear accumulation of β‐catenin, compared to FZD10‐immunonegative cancer cells, and there was a strong inverse correlation between nuclear immunostaining scores for β‐catenin expression and expression patterns of FZD10 (P = 0.0002), suggesting that FZD10 has a distinct role from other FZDs in canonical Wnt signal transduction. (Cancer Sci 2009; 100: 405–412)