101 results on '"Alexander, Larry"'
Search Results
2. Michael Perry and Disproportionate Racial Impact.
- Author
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ALEXANDER, LARRY
- Subjects
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RACE discrimination , *DISPARATE impact (Law) , *FESTSCHRIFTEN , *HUMAN rights - Published
- 2022
3. "Under Color of Law"? Rogue Officials and the Real State Action Problem.
- Author
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ALEXANDER, LARRY
- Subjects
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STATE action (Civil rights) , *EQUAL rights amendments , *EQUAL rights , *CONSTITUTIONAL law - Published
- 2022
4. Formalist Textualism and the Cernauskas Problem.
- Author
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ALEXANDER, LARRY
- Subjects
- *
TEXTUALISM (Legal interpretation) , *CONSTITUTIONAL law , *CIVIL rights , *SEX discrimination , *HOMOSEXUALITY - Published
- 2021
5. The Need to Attend to Probabilities--For Purposes of Self-Defense and Other Preemptive Actions.
- Author
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ALEXANDER, LARRY
- Subjects
- *
SELF-defense (Law) , *LEGAL justification , *ASSAULT & battery , *VIOLENCE (Law) , *CRIMINAL law - Published
- 2018
6. BREXIT AND THE FUTURE OF LIBERAL DEMOCRACY.
- Author
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Alexander, Larry
- Subjects
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BREXIT Referendum, 2016 , *DEMOCRACY , *LIBERTY , *BUREAUCRACY , *MULTICULTURALISM - Abstract
The article discusess the impact of Brexit Referendum and appointment of Donald Trump as U.S. President on liberal democracy. Topics discussed include delegation of legislative authority; challenges surrounding uncontrollable bureaucracies and hyper-regulation; and role of multiculturalism in caring out liberal democracy.
- Published
- 2018
7. LAW AND POLITICS: WHAT IS THEIR RELATION?
- Author
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ALEXANDER, LARRY
- Subjects
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LAW & politics , *SOCIAL norms , *RULES , *STATUTORY interpretation , *LEGAL positivism , *LEGAL sanctions , *PARTICULARISM (Political science) , *POLITICAL attitudes , *LAW - Abstract
The article discusses the relationship between law and politics in America, and it mentions legal norms, rules, and legal interpretation. Rational legislators' first-order reasoning is examined, along with legal scholar Frederick "Fred" Schauer's presumptive positivism theory and sanctions for rule violators. Deception and protest are assessed, as well as Schauer's rule-sensitive particularism concept.
- Published
- 2018
8. Brettschneider and 'democratic persuasion'.
- Author
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Alexander, Larry
- Subjects
- *
LIBERALISM , *SUBSIDIES , *GOVERNMENT speech , *TAXATION - Published
- 2017
- Full Text
- View/download PDF
9. Alexander on Koppelman on Alexander.
- Author
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ALEXANDER, LARRY
- Subjects
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LIBERALISM , *POLITICAL doctrines , *POLITICAL attitudes , *POLITICAL science ,SOCIAL aspects - Published
- 2017
10. Introduction to the Symposium.
- Author
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SMITH, STEVEN D. and ALEXANDER, LARRY
- Subjects
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RELIGIOUS conferences ,CONSCIENCE & religion - Abstract
The article offers an introduction to a section of articles on papers presented at the conference "Is Religion Outdated (as a Constitutional Category)" held at University of San Diego in California in 2014 on topics including religion as a legal proxy, religion and conscience, and legal autonomy.
- Published
- 2014
11. Galston on Religion, Conscience, and the Case for Accommodation.
- Author
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ALEXANDER, LARRY
- Subjects
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ESTABLISHMENT clause (Constitutional law) , *FREE exercise clause (Constitutional law) , *CONSTITUTIONAL history of the freedom of religion , *CONSCIENCE , *DUE process of law - Abstract
The article focuses on approaches of professor William A. Galston on religion, conscience, and accommodation. Topics discussed include special existence of religion under the Establishment Clause of the U.S. constitution, Galston's views on free exercise clause for special place of religion, and the importance of Fourteenth Amendment of the constitution in signifying the freedom of religion. He further discusses the constitutional history of religion.
- Published
- 2014
12. Angiotensin II stimulates fibronectin protein synthesis via a Gβγ/arachidonic acid-dependent pathway.
- Author
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Alexander, Larry D., Ding, Yaxian, Alagarsamy, Suganthi, and Cui, Xiaolan
- Subjects
- *
ANGIOTENSIN II , *PROTEIN synthesis , *CELLULAR signal transduction , *ARACHIDONIC acid , *MITOGEN-activated protein kinases , *EPIDERMAL growth factor receptors - Abstract
In rabbit proximal tubular cells, ANG II type 2-receptor (AT2)-induced arachidonic acid release is PLA2 coupled and dependent of G protein βγ (Gβγ) subunits. Moreover, ANG II activates ERK1/2 and transactivates EGFR via a c-Src-dependent mechanism. Arachidonic acid has been shown to mimic this effect, at least in part, by an undetermined mechanism. In this study, we determined the effects of ANG II on fibronectin expression in cultured rabbit proximal tubule cells and elucidated the signaling pathways associated with such expression. We found that ANG II and transfection of Gβγ subunits directly increased fibronectin protein expression, and this increase was inhibited by overexpression of β-adrenergic receptor kinase (βARK)-ct or DN-Src. Moreover, ANG II-induced fibronectin protein expression was significantly abrogated by the AT2 receptor antagonist PD123319. In addition, inhibition of cystolic PLA2 diminished ANG II-induced fibronectin expression. Endogenous arachidonic acid mimicked ANG II-induced fibronectin expression. We also found that overexpression of Gβγ subunits induced c-Src, ERK1/2, and EGFR tyrosine phosphorylation, which can be inhibited by overexpression of βARK-ct or DN-Src. Gβγ also induced c-Src SH2 domain association with the EGFR. Supporting these findings, in rabbit proximal tubular epithelium, immunoblot analysis indicated that βγ expression was significant. Interestingly, arachidonic acid- and eicosatetraenoic acid-induced responses were preserved in the presence of βARK-ct. This is the first report demonstrating the regulation of EGFR, ERK1/2, c-Src, and fibronectin by Gβγ subunits in renal epithelial cells. Moreover, this work demonstrates a role for Gβγ heterotrimeric proteins in ANG II, but not arachidonic acid, signaling in renal epithelial cells. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
13. Constitutional Theories: A Taxonomy and (Implicit) Critique.
- Author
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ALEXANDER, LARRY
- Subjects
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CONSTITUTIONAL reform , *ETHICISTS , *LAND reform laws , *PRACTICAL politics , *PHILOSOPHERS - Abstract
In this article, the author talks about several constitutional theories. He first talks about moralists theorists who view the constitution as an invitation to implement favorite moral theory as the law of the land. He further highlights that constitutional theorists contains people interpreting the constitution as the implementation of a political theory. Information on practice theorists who view constitutional law as what we do when we do constitutional law, is also offered.
- Published
- 2014
14. The Ontology of Consent.
- Author
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Alexander, Larry
- Subjects
- *
METAMORPHOSIS in literature , *NORMATIVITY (Ethics) , *MORTALITY , *CONSENT (Law) , *ANALYTIC philosophy - Abstract
An essay on the topic "The Ontology of Consent" is presented. Topics discussed include importance of the consent in the concept of mortality and law, effect of the consent on the legal and moral transformation and its consideration as the normative power to alter the normative consent, and limitations of the consent and transformative power.
- Published
- 2014
- Full Text
- View/download PDF
15. THE OBJECTIVITY OF MORALITY, RULES, AND LAW: A CONCEPTUAL MAP.
- Author
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Alexander, Larry
- Subjects
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OBJECTIVITY , *ETHICS , *LAW - Abstract
The article discusses the objectivity of morality, rules and law and explains that legal rules and decisions are metaphysically objective. It analyzes the challenges to the objectivity of legal rules and reflects on legal principles as the directly posited and as the joint product of legal rules. It presents the perspectives of philosophers Jules Coleman and Brian Leiter on legal objectivity.
- Published
- 2014
16. Other People's Errors.
- Author
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Alexander, Larry
- Subjects
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ERROR , *HUMAN behavior , *RULES , *DUTY , *ETHICS - Abstract
The question of when other people's bad acts belong on our moral ledger arises in a number of different scenarios. Each scenario has received some philosophical attention, but no one has noted the structural similarities of these various scenarios or the implications of a proposed approach to one for how the others should be approached. That is the ambition of this article. In it, seemingly disparate moral phenomena-blunt rules, preemptive restrictions, moral blackmail, complicity, retreat and proportional response, and the duty to rescue from a peril one has caused-are shown to have similar structures and thus to require similar moral approaches. [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
17. YAFFE ON ATTEMPTS.
- Author
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Alexander, Larry
- Subjects
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CRIMINAL law philosophy , *CRIMINAL attempt , *CRIME , *PUNISHMENT - Abstract
Gideon Yaffe's Attempts is a masterfully executed philosophical investigation of what it means to attempt something. Yaffe is obviously motivated by the fact that the criminal law punishes attempted crimes, and he believes that his philosophical analysis can shed light on and be used to criticize the law's understanding of those crimes. I focus exclusively on the relevance of Yaffe's philosophical analysis of attempts to the criminal law of attempts. I assume that Yaffe's account of what it is to attempt something is basically correct and ask whether the criminal law uses “attempt” in the way Yaffe uses it, and whether it should use Yaffe's conception of an attempt. I conclude that a lot of criminal-law doctrine, including, very importantly, the influential Model Penal Code's treatment of attempts, is inconsistent with Yaffe's conception of attempts. Because Yaffe is principally interested in what it means to attempt something rather than in the criminal law's treatment of attempts, I believe he misanalyzes the problem of factual versus legal impossibility. And Yaffe's chapter on inherently impossible attempts concludes by positing a quite paradoxical type of criminal attempt, one that is indeed an attempt but for which the defendant should not be convicted because the evidence of its commission is insufficient. I find Yaffe's argument to this effect opaque and therefore unconvincing. [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
18. Disparate Impact : Fairness or Efficiency?
- Author
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ALEXANDER, LARRY
- Subjects
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DISPARATE impact (Law) , *EMPLOYMENT test laws , *JOB vacancies , *SEX discrimination in employment laws , *RACE discrimination laws , *JOB qualifications - Abstract
The article evaluates the constitutionality of disparate impact discrimination, which consists of deploying an employment test in order to screen out preferred candidates from non-preferred ones disproportionately of their sexes and races. It discusses the reasons to implement disparate impact discrimination cause of action including inherent unfairness of disproportionate impact and unfairness of inefficient job qualifications. It concludes that none of the reasons justify the action.
- Published
- 2013
19. REDISH ON FREEDOM OF SPEECH.
- Author
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Alexander, Larry
- Subjects
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FREEDOM of speech , *CRIME , *FEDERAL jurisdiction , *LAW teachers , *PUNISHMENT , *ATTITUDE (Psychology) ,SCHENCK v. United States (Supreme Court case) - Abstract
My contribution to this Festschrift for Marry Redish looks at two of his most important articles on freedom of speech, both published in 1982. One article deals with free speech and advocacy of crime, while the other presents Marty's general justificatory theory of freedom of speech. Although I agree and disagree with various parts of Marty's analysis in the former, I am unpersuaded that Marty's general theory can succeed either positively or normatively. Marty Redish is an important scholar in several domains, displaying enviable versatility as well as depth. Although he is perhaps the leading contemporary expositor of the law of federal jurisdiction, he is almost as important a figure in the vastly more crowded field in which his and my scholarship overlap. Redish on Freedom of Speech is my modest contribution to this richly deserved Festschrift. [ABSTRACT FROM AUTHOR]
- Published
- 2013
20. THERE IS NO FIRST AMENDMENT OVERBREADTH(BUTTHEREARE VAGUE FIRST AMENDMENT DOCTRINES); PRIOR RESTRAINTS AREN'T "PRIOR"; AND "AS APPLIED" CHALLENGES SEEK JUDICIAL STATUTORY AMENDMENTS.
- Author
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Alexander, Larry
- Subjects
- *
POLITICAL doctrines , *LAWYERS , *JUDGES , *LAW teachers - Abstract
The author clarifies three doctrines that have been a reason of huge confusion among lawyers, judges, and academic commentators including the doctrines of first amendment overbreadth, prior restraint, and as-applied versus facial challenges. He tries to resolve the confusion by recognizing these doctrines as analytically coherent and normatively attractive. He states that the proposal of the law professor Kevin C. Walsh on severability does not contradict his analyses of severability.
- Published
- 2011
21. TELEPATHIC LAW.
- Author
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Alexander, Larry
- Subjects
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STATUTORY interpretation , *JUDICIAL process , *AMERICAN law - Abstract
The article discusses the argument of originalists that the U.S. Constitution should be interpreted according to the meaning intended by the author and the improbability of promulgating a law telepathically. Possible objections to telepathic law include the impossibility of anticipating all possible applications of the law to different norms, the deviation of interpreters from the meaning intended by lawmakers and the fallibility of lawmakers. It also notes that lawmakers communicate through texts and not telepathically.
- Published
- 2010
22. PLASTIC TREES AND GLADIATORS: LIBERALISM AND AESTHETIC REGULATION.
- Author
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Alexander, Larry
- Subjects
- *
LIBERALISM , *AVERSION , *LIBERALS , *LIBERTY , *DELEGATED legislation , *SOCIAL sciences - Abstract
The hallmark of modern liberalism is its embrace of the Millian harm principle and its antipathy to legal moralism. In this article I consider whether aesthetic regulations can be justified under the harm principle as that principle has been elaborated by Joel Feinberg. I conclude that aesthetic and other regulations that most liberals regard as unproblematic are actually instances of legal moralism. [ABSTRACT FROM AUTHOR]
- Published
- 2010
- Full Text
- View/download PDF
23. Constitutions, International Law, and the Settlement Function of Law: A Schema for Further Reflection.
- Author
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Alexander, Larry
- Subjects
- *
HUMAN settlements , *INTERNATIONAL law , *TREATIES , *CONSTITUTIONS , *CUSTOMARY international law - Abstract
The article discusses the necessity for the authoritative settlement of moral controversies within a community and its application to the field of international law in the U.S. It explores the nature of international treaties and their association to the boundaries of the U.S. Constitution. Furthermore, it offers insights on the norms of customary international law.
- Published
- 2009
24. TEMPEST IN AN EMPTY TEAPOT: WHY THE CONSTITUTION DOES NOT REGULATE GERRYMANDERING.
- Author
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Alexander, Larry and Prakash, Saikrishna B.
- Subjects
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ELECTIONS , *CONSTITUTIONS , *GERRYMANDERING , *LEGISLATIVE bodies , *JUDICIAL elections - Abstract
Judges and scholars are convinced that the Constitution forbids gerrymandering that goes "too far"-legislative redistrictings that are too partisan, too focused on race, etc. Gerrymanders are said to be unconstitutional for many reasons-they dilute votes, they are anti-democratic, and they generate uncompetitive elections won by extremist candidates. Judges and scholars cite numerous clauses that gerrymanders supposedly violate-the Equal Protection Clause, the Guarantee Clause, and even the First Amendment. We dissent from this orthodoxy. Most of these claims rest on the notion that the Constitution establishes certain ideals about representation in legislatures and about the outcome and conduct of elections. Yet the Constitution nowhere provides that a party's strength in the legislature should roughly mirror its strength in the populace, as the partisan gerrymandering cases suppose. Nor does the Constitution favor competition in legislative races, thereby forcing legislators to draw districting lines that maximize the number of competitive elections. In maintaining that the Constitution establishes districting and election ideals, the critics of gerrymandering have supposed that the Constitution incorporates their preferences about what is fair and just with respect to electoral contests and outcomes. But as we show, there are innumerable reasonable preferences about the composition of districts and legislatures, not all of which can be satisfied simultaneously. More importantly, there is no reason to think that the Constitution enshrines any of these preferences about districting and election outcomes, let alone the critics' particular preferences. We believe that the critics of gerrymandering have made the mistake of imagining that the Constitution incorporates their particular preferences. That is to say, they have sought a constitutional resolution to a matter of ordinary politics. Unfortunately, the search is futile, for the Constitution does not address the ills, real or imagined, associated with drawing district lines. The Constitution no more regulates gerrymandering than it regulates pork-barrel spending or the many advantages of incumbency. [ABSTRACT FROM AUTHOR]
- Published
- 2008
25. KENT GREENAWALT AND THE DIFFICULTY (IMPOSSIBILITY?) OF RELIGION CLAUSE THEORY.
- Author
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Alexander, Larry
- Subjects
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RELIGION & politics , *FAIRNESS - Abstract
The article presents a critique of the book "Religion and the Constitution: Establishment and Fairness," by Kent Greenawalt. It discusses the view of Greenawalt on the originally intended meaning of the U.S. Constitution (USC), how Greenawalt differentiates religion from nonreligion and their relation to the meaning and doctrine of the establishment clause in the USC. The author explores the logic on the role of fundamental beliefs in views about the proper relation of government to religion.
- Published
- 2008
26. Scalar Properties, Binary Judgments.
- Author
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ALEXANDER, LARRY
- Subjects
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DEONTIC logic , *JUDGMENT (Psychology) , *VALUES (Ethics) , *PUZZLES , *THEORY of knowledge , *RIDDLES - Abstract
In the moral realm, our deontic judgments are usually (always?) binary. An act (or omission) is either morally forbidden or morally permissible. 1 Yet the determination of an act's deontic status frequently turns on the existence of properties that are matters of degree. In what follows I shall give several examples of binary moral judgments that turn on scalar properties, and I shall claim that these examples should puzzle us. How can the existence of a property to a specific degree demarcate a boundary between an act's being morally forbidden and its not being morally forbidden? Why aren't our moral judgments of acts scalar in the way that the properties on which those judgments are based are scalar, so that acts, like states of affairs, can be morally better or worse rather than right or wrong? I conceive of this inquiry as operating primarily within the realm of normative theory. Presumably it will give aid and comfort to consequentialists, who have no trouble mapping their binary categories onto scalar properties. For example, a straightforward act utilitarian, for whom one act out of all possible acts is morally required (and hence permissible) and all others morally forbidden, can, in theory at least, provide an answer to every one of the puzzles I raise. And, in theory, so can all other types of act and rule consequentialists. They will find nothing of interest here beyond embarrassment for their deontological adversaries. The deontologists, however, must meet the challenges of these puzzles. And for them, the puzzles may raise not just normative questions, but questions of moral epistemology and moral ontology. Just how do we know that the act consequentialist's way of, say, trading off lives against lives is wrong? For example, do we merely intuit that taking one innocent, uninvolved person's life to save two others is wrong? Can our method of reflective equilibrium work if we have no theory by which to rationalize our intuitions? And what things in the world make it true, if it is true, that one may not make the act consequentialist's tradeoff? I do not provide any answers to these questions any more than I provide answers to the normative ones. But they surely lurk in the background. [ABSTRACT FROM AUTHOR]
- Published
- 2008
- Full Text
- View/download PDF
27. IS POLICY WITHIN LAW'S LIMITED DOMAIN?
- Author
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Alexander, Larry and Schauer, Frederick
- Subjects
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AMERICAN law , *GOVERNMENT policy , *PHILOSOPHY , *SOCIAL policy , *ETHICS - Abstract
In this article, the authors take a philosophical look at the connection between policy and law in the U.S. and the extent to which the former can, should and must, be limited by the latter. The authors posit that incorporation of policy may present one aspect of the question whether the part can ever incorporate the whole. They also explain the existence of law against a background of moral, factual, and policy disagreement. They conclude that law may in some cases make poor policy decisions, but those poor decisions are part of a larger policy determination in a world of empirical uncertainty and policy disagreement.
- Published
- 2007
28. How to Understand Legislatures: A Comment on Boudreau, Lupia, McCubbins, and Rodriguez.
- Author
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Alexander, Larry
- Subjects
- *
STATUTES , *STATUTORY interpretation , *LEGISLATIVE histories , *LEGISLATIVE bodies , *CONFLICT of laws - Abstract
The article discusses the understanding on legal interpretation with a focus on the works of Cheryl Boudreau, Arthur Lupia, Mathew D. McCubbins and Daniel B. Rodriguez. It is pointed out that the axioms including statutes are ways of communication from the legislature and statutes communicate commands that are constitutionally privileged. It is noted that the main focus of the analysis is on whether and which parts of a statute's legislative history will be a reliable evidence for decoding its meaning. It is ended that the problem on statutory interpretation lies on the multiplicity of legislators.
- Published
- 2007
29. DELEGATION REALLY RUNNING RIOT.
- Author
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Alexander, Larry and Prakash, Saikrishna
- Subjects
- *
DELEGATION of powers , *STATUTORY interpretation , *TAXATION , *STATUTES - Abstract
The article examines certain problems regarding the structure and statutes of conventional delegations in the U.S. The positive theory offered by the accounts of conventional delegations is taken into account. Key information about the provision of the Article I, Section 8 of the statutory delegations to increase tax and regulate commerce is presented.
- Published
- 2007
30. LAWS LIMITED DOMAIN CONFRONTS MORALITY'S UNIVERSAL EMPIRE.
- Author
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Alexander, Larry and Schauer, Frederick
- Subjects
- *
LAW , *ETHICS , *EQUALITY , *FREEDOM of religion , *FREEDOM of speech , *SEARCHES & seizures (Law) , *PUNISHMENT - Abstract
The article examines whether properly conceived law is capable of incorporating morality. Lawyers and scholars argue whether the guarantees of equal protection, freedom of speech, free exercise of religion, prohibitions on cruel and unusual punishments and unreasonable searches and seizures, require courts and other governmental decision makers to adhere to the correct moral principles regarding equality, freedom of speech, freedom of religion, punishment and privacy.
- Published
- 2007
31. The Hateful and the Obscene.
- Author
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Alexander, Larry
- Published
- 2006
- Full Text
- View/download PDF
32. COMPELLED SPEECH.
- Author
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Alexander, Larry
- Subjects
- *
ACTIONS & defenses (Law) , *WEST Virginia State Board of Education v. Barnette , *CIVIL rights ,WOOLEY v. Maynard (Supreme Court case) - Abstract
The article examines several U.S. Supreme Court cases that have been referred to as compelled speech cases and discusses the possible harms that an individual might suffer as a result of being compelled to utter propositions in which he does not believe. Details related to the West Virginia State Board of Education v. Barnette case and the Wooley v. Maynard case are provided. Compelled speech harms an individual by undermining one's own beliefs and personal integrity.
- Published
- 2006
33. "Is That English You're Speaking?" Why Intention Free Interpretation is an Impossibility.
- Author
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Alexander, Larry and Prakash, Saikrishna
- Subjects
- *
HERMENEUTICS , *INTERPRETATION (Philosophy) , *CONCEPTUALISM , *AUTHORS , *INTENTION (Logic) , *LITERATURE - Abstract
In this article, authors consider an especially strong form of conceptual textualism, the position that texts can be interpreted without any references, express or implied, to the meaning intended by the author of the text. The defining feature of this form of textualism is the insistence that intentions play no role in the production of meaning, and so one can call this view intention free (IF) textualism. According to the author of this article, in any event, whether or not IF textualists actually exist, it is useful to drive a stake through the heart of IF interpretation.
- Published
- 2004
34. The Jurisdiction of Justice: Two Conceptions of Political Morality.
- Author
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Alexander, Larry
- Subjects
- *
POLITICAL ethics , *JUSTICE , *LIBERALS , *JURISDICTION , *OBLIGATIONS (Law) , *CONCEPTS - Abstract
The topic of this article is a major fault line within normative theory that deals with the content of the moral obligations to others. According to the author, moral obligations are candidates for legal enforcement. The author argues that dividing liberal conceptions of justice into two major camps can usefully illumine much of what is debated within liberal political/moral theory. In this article, the author's aim is to paint two conceptions: unrestricted impartialism and restricted impartialism, and their strengths and weaknesses using a very broad brush.
- Published
- 2004
35. GRUTTER OR OTHERWISE: RACIAL PREFERENCES AND HIGHER EDUCATION.
- Author
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Alexander, Larry and Schwarzschild, Maimon
- Subjects
- *
RACE , *HIGHER education , *UNIVERSITIES & colleges , *UNITED States education system - Abstract
Discusses racial preferences and higher education in the U.S. Information on Supreme Court decisions on affirmative action; Views on the finding that Michigan's interest in maintaining an elite law school is a compelling interest sufficient to justify a racial classification; Culture of racial preferences in higher education; Requirement of racial preferences at public universities.
- Published
- 2004
36. Cyclic stretch-induced cPLA2 mediates ERK 1/2 signaling in rabbit proximal tubule cells.
- Author
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Alexander, Larry D, Alagarsamy, Suganthi, and Douglas, Janice G
- Abstract
Background: Recent evidence from this laboratory have demonstrated a critical role of phospholipase A2 (PLA2) and arachidonic acid in angiotensin II type 2 (AT2) receptor-mediated kinase activation in renal epithelium independent of phosphoinositide- specific phospholipase C (PLC) and without the necessity of eicosanoid biosynthesis. In the present study, we investigated whether cyclic stress phosphorylates and activates the mitogen-activated protein kinase (MAPK) pathway and whether PLA2 activation mediates mechanotransduction in renal epithelial cells. The rational for studying kidney epithelial cells relates to their similarity to podocytes, which undergo mechanical stretch related to changes in intraglomerular pressure.Methods: To produce strain or stretch, primary cultures of rabbit proximal tubular cell cells are grown in tissue culture wells having a collagen-coated Silastic deformable membrane bottoms and applying vacuum to the well to generate alternating cycles of stretch and relaxation (30 cycles/min).Results: We found that cyclic stretching of rabbit proximal tubular cells caused a time- and intensity-dependent activation of extracellular signal-regulated kinases 1 and 2 (ERK 1/2) in proximal tubular cells as detected by its phosphorylation. In addition, mechanical stretch induced PLA2 activation and a subsequent rapid release of arachidonic acid. Inhibition of PLA2 by mepacrine and methyl arachidonyl fluorophosphonate ketone (AACOCF3) attenuated both arachidonic acid release and ERK 1/2 activation by cyclic stretch, supporting the importance of PLA2 as a mediator of mechanotransduction in renal proximal tubular cells. A requirement for extracellular Ca2+ and stretch-activated Ca2+ channels was also documented. Complete inhibition of ERK 1/2 by PD98059, a MAPK kinase (MEK) inhibitor, did not suppress stretch- induced PLA2 activation and arachidonic acid release, suggesting the later events were upstream of ERK 1/2. Cyclic stretch also caused rapid phosphorylation of the EGF receptor kinase and c-Src. Furthermore, arachidonic acid itself induced time- and dose-dependent phosphorylation of c-Src. In addition, the c-Src inhibitor PP2 and selective EGF receptor kinase inhibitor AG1478 attenuated both ERK 1/2 and EGF receptor phosphorylation by cyclic stretch.Conclusion: PLA2 dependence for ERK 1/2 activation in response to cyclic stretch in proximal tubular epithelial cells was established in this report. In addition, these findings indicate cyclic stretch increased the tyrosine phosphorylation of the EGF receptor and c-Src and that c-Src acts upstream of the EGF receptor to mediate its phosphorylation, whereby both are critical for stretch- induced ERK 1/2 activation in rabbit proximal tubular cells. These observations documents for the first time a mechanism of mechanical stretch-induced kinase activation mediated by stretch activated Ca2+ channels and PLA2-dependent release of arachidonic acid. [ABSTRACT FROM AUTHOR]- Published
- 2004
- Full Text
- View/download PDF
37. VASCULAR BIOLOGY - HEMODYNAMICS - HYPERTENSION Cyclic stretch-induced cPLA2 mediates ERK 1/2 signaling in rabbit proximal tubule cells.
- Author
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Alexander, Larry D., Alagarsamy, Suganthi, and Douglas, Janice G.
- Subjects
- *
KIDNEY tubules , *CELLS , *PHOSPHOLIPASE A2 , *ARACHIDONIC acid , *ANGIOTENSIN II , *BIOSYNTHESIS , *PROTEIN kinases - Abstract
Cyclic stretch-induced cPLA2 mediates ERK 1/2 signaling in rabbit proximal tubule cells. Background. Recent evidence from this laboratory have demonstrated a critical role of phospholipase A2 (PLA2) and arachidonic acid in angiotensin II type 2 (AT2) receptor-mediated kinase activation in renal epithelium independent of phosphoinositide- specific phospholipase C (PLC) and without the necessity of eicosanoid biosynthesis. In the present study, we investigated whether cyclic stress phosphorylates and activates the mitogen-activated protein kinase (MAPK) pathway and whether PLA2 activation mediates mechanotransduction in renal epithelial cells. The rational for studying kidney epithelial cells relates to their similarity to podocytes, which undergo mechanical stretch related to changes in intraglomerular pressure. Methods. To produce strain or stretch, primary cultures of rabbit proximal tubular cell cells are grown in tissue culture wells having a collagen-coated Silastic deformable membrane bottoms and applying vacuum to the well to generate alternating cycles of stretch and relaxation (30 cycles/min). Results. We found that cyclic stretching of rabbit proximal tubular cells caused a time- and intensity-dependent activation of extracellular signal-regulated kinases 1 and 2 (ERK 1/2) in proximal tubular cells as detected by its phosphorylation. In addition, mechanical stretch induced PLA2 activation and a subsequent rapid release of arachidonic acid. Inhibition of PLA2 by mepacrine and methyl arachidonyl fluorophosphonate ketone (AACOCF3) attenuated both arachidonic acid release and ERK 1/2 activation by cyclic stretch, supporting the importance of PLA2 as a mediator of mechanotransduction in renal proximal tubular cells. A requirement for extracellular Ca2+ and stretch-activated Ca2+ channels was also documented. Complete inhibition of ERK 1/2 by PD98059, a MAPK kinase (MEK) inhibitor, did not suppress stretch- induced PLA2 activation and arachidonic acid release, suggesting the later events were upstream of ERK 1/2. Cyclic stretch also caused rapid phosphorylation of the EGF receptor kinase and c-Src. Furthermore, arachidonic acid itself induced time- and dose-dependent phosphorylation of c-Src. In addition, the c-Src inhibitor PP2 and selective EGF receptor kinase inhibitor AG1478 attenuated both ERK 1/2 and EGF receptor phosphorylation by cyclic stretch. Conclusion. PLA2 dependence for ERK 1/2 activation in response to cyclic stretch in proximal tubular epithelial cells was established in this report. In addition, these findings indicate cyclic stretch increased the tyrosine phosphorylation of the EGF receptor and c-Src and that c-Src acts upstream of the EGF receptor to mediate its phosphorylation, whereby both are critical for stretch- induced ERK 1/2 activation in rabbit proximal tubular cells. These observations documents for the first time a mechanism of mechanical stretch-induced kinase activation mediated by stretch activated Ca2+ channels and PLA2-dependent release of arachidonic acid. [ABSTRACT FROM AUTHOR]
- Published
- 2004
- Full Text
- View/download PDF
38. Reports of the Nondelegation Doctrine's Death Are Greatly Exaggerated.
- Author
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Alexander, Larry and Prakash, Saikrishna
- Subjects
- *
CONSTITUTIONAL law , *POLITICAL doctrines , *LEGISLATIVE bodies - Abstract
This article focuses on the nondelegation doctrine in legislative power. The nondelegation doctrine has roots that extend as far back as three centuries. In "The Second Treatise of Government," John Locke listed four constraints on the legislative power. In their recent article, Interring the Nondelegation Doctrine, professors Eric Posner and Adrian Vermeule reconsider the meaning of Locke's epigram and reassess the foundations of the nondelegation doctrine. In their view, the "legislative power" generally references the right to vote on bills in a legislature along with the other "de jure" powers of legislators. Moreover, Locke's maxim means no more than that the legislature cannot make third parties "legislators" by giving them the power to vote in the legislature. So when Article 1 of the constitution speaks of "legislative powers," it refers to those powers individually held by federal legislators, including most prominently the right to vote on bills. Furthermore, under their "naive" nondelegation doctrine, these are the legislative powers that cannot be delegated to third parties. Under their view, neither Locke's epigram nor the U.S. Federal Constitution goes further and prohibits broad delegations of discretion to third parties because such delegations do not create legislators and hence cannot delegate legislative power.
- Published
- 2003
- Full Text
- View/download PDF
39. The Supreme Court, the Florida Vote, and Equal Protection.
- Author
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Alexander, Larry
- Subjects
- *
UNITED States elections , *EQUAL rights - Abstract
Discusses the Supreme Court's ruling on Florida's election count in the 2000 presidential race in the United States. Criticism on the court and its ruling; Information on the basic point of the equal protection clause.
- Published
- 2001
40. Arachidonic acid directly activates members of the mitogen-activated protein kinase superfamily in rabbit proximal tubule cells.
- Author
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Alexander, Larry D., Cui, Xiao-Lan, Falck, John R., and Douglas, Janice G.
- Subjects
- *
EICOSANOIC acid derivatives , *ARACHIDONIC acid , *PROTEIN kinases - Abstract
Arachidonic acid directly activates members of the mitogen-activated protein kinase superfamily in rabbit proximal tubule cells. Background. To explore the roles of eicosanoids in arachidonic acid-induced mitogen-activated protein kinase (MAPK) signal transduction, we have shown that exposure of proximal tubular cells to arachidonic acid induces phosphorylation of c-Jun NH2 -terminal kinase (JNK) and extracellular signal-regulated kinase (ERK), two members of the MAPK superfamily. We observed that ketoconazole, an inhibitor of the cytochrome P450 pathway, blocked ERK but not JNK activation. Methods. Direct regulation of arachidonic acid on mitogen-activated protein kinase (MAPK) signaling pathways was evaluated more directly by utilizing specific enzyme inhibitors of the cytochrome P450 metabolic pathway and by comparing the relative efficacy of arachidonic acid versus its cytochrome P450 metabolites (exogenous and endogenous), eicosatetraynoic acid (ETYA), and other fatty acids on the phosphorylation of members of the MAPK superfamily (ERKs, JNK, and p38MAPK ), by utilizing early passage rabbit proximal tubular epithelial cells. Results. Arachidonic acid activated p38MAPK , a third member of the MAPK superfamily, in a time- and concentration-dependent manner. Studies designed to evaluate the ability of arachidonic acid and its cytochrome P450 metabolites (endogenously and exogenously) to stimulate ERKs, JNK, and p38MAPK found four conclusions. First, the metabolites of arachidonic acid generated endogenously by cytochrome P450 2C1 significantly augmented basal ERK activity, whereas the metabolites generated by the 2C2 isozyme significantly augmented basal p38MAPK activity. However, their effects were less profound than arachidonic acid itself. In contrast, there were no significant effects with transfection of either isozyme on basal JNK activity. Second, a variety of exogenous cytochrome P450 products were less potent than arachidonic acid on a molar basis in stimulating the activity of all three MAPKs. Third, ketoconazole and 17-octadecynoic acid, inhibitors of the cytochrome P450 pathway, as well as PPOH and DDMS, inhibitors of the epoxygenase and ω-hydroxylase pathways, respectively, failed to significantly reduce the effects of arachidonic acid to activate ERK and p38MAPK (JNK was not evaluated). Finally, arachidonic acid, its inactive analog ETYA, and other fatty acids with differing chain lengths and degrees of saturation stimulated the activity of all three MAPKs. Conclusions. These observations substantiate a role for arachidonic acid and other fatty acids in signaling linked to the MAPK superfamily in rabbit proximal tubular epithelium without the necessity of conversion to cytochrome P450 metabolites. [ABSTRACT FROM AUTHOR]
- Published
- 2001
- Full Text
- View/download PDF
41. DEFENDING JUDICIAL SUPREMACY: A REPLY.
- Author
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Alexander, Larry and Schauer, Frederick
- Subjects
- *
CONSTITUTIONAL law - Abstract
Discusses the judicial supremacy in the task of interpreting the United States (U.S.) Constitution. View of the critics on the claims of judicial supremacy; Nature of the question on whether the U.S. Supreme Court should be the supreme interpreter of the Constitution; Conclusion.
- Published
- 2000
42. Deontology at the Threshold.
- Author
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Alexander, Larry
- Subjects
- *
DUTY , *RESPONSIBILITY , *CONSEQUENTIALISM (Ethics) , *ETHICS - Abstract
Raises doubts about the threshold deontologist's picture of morality through the examination of its structure. Overview of the structure of threshold deontology; Examination of the arbitrariness of deontological thresholds; Conceptualization of the conflict between deontology and consequentialism.
- Published
- 2000
43. Theory's a What Comes Natcherly.
- Author
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Alexander, Larry
- Subjects
- *
LAW , *THEORY (Philosophy) - Abstract
Comments on the articles presented in the June 2000 issue of `San Diego Law Review' about the nature of legal theory. Types of theorizing done in law; Discussion on symmetries; Analysis of an article by Michael Moore on taxonomy of theories of law.
- Published
- 2000
44. Insufficient Concern: A Unified Conception of Criminal Culpability.
- Author
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Alexander, Larry
- Subjects
- *
CRIMINAL law , *CRIME - Abstract
Discusses the subject of criminal culpability. Recklessness as a form of criminal culpability and its problems; Unified theory of criminal culpability and problem cases for the unified conception.
- Published
- 2000
- Full Text
- View/download PDF
45. Subversive Thoughts on Freedom and the Common Good.
- Author
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Alexander, Larry and Schwarzschild, Maimon
- Subjects
- *
LIBERTARIANISM , *COMMON good - Abstract
Examines the book `Principles for a Free Society: Reconciling Individual Liberty With the Common Good.' Principles of freedom and the common good; How a climate of regulation and redistribution can create perverse incentives and social costs; Why government programs for redistribution and compulsary cross-subsidization do not benefit all.
- Published
- 1999
- Full Text
- View/download PDF
46. `With Me, It's All er Nuthin': Formalism in Law and Morality.
- Author
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Alexander, Larry
- Subjects
- *
LAW , *ETHICS , *FORMALITIES (Law) , *POLITICAL science - Abstract
Argues that the law is essentially formalistic, and morality is not in the slightest degree formalistic. Discussion on formalism; Dilemma of formalistic law; Nonformalistic nature of morality.
- Published
- 1999
- Full Text
- View/download PDF
47. On extrajudicial constitutional interpretation.
- Author
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Alexander, Larry and Schauer, Frederick
- Subjects
- *
CONSTITUTIONAL law , *STATUTORY interpretation - Abstract
Discusses issues on extrajudicial constitutional interpretation in the United States. Settlement of uncontested issues as a crucial component of constitutionalism; Understandings of non-deference; Discussion on the settlement function of law.
- Published
- 1997
- Full Text
- View/download PDF
48. Phospholipase A2-mediated activation of mitogen-activated protein kinase by angiotensin II.
- Author
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Dulin, Nickolai O., Alexander, Larry D., Harwalkar, Subash, Falck, John R., and Douglas, Janice G.
- Subjects
- *
PHOSPHOLIPASE A2 , *MITOGENS , *ARACHIDONIC acid , *BIOCHEMICAL mechanism of action - Abstract
Proposes a phospholipase A2 (PLA-2)-dependent mechanism of activation of mitogen-activated protein kinase (MAPK) in proximal tubule epithelium, mediated by arachidonic acid (AA). Experimental procedures used to conduct the study; What is angiotensin II (Ang II); Functions of Ang II; Reference to previous studies describing a protein kinase C dependent mechanism of Ang II; Results and discussion on the study.
- Published
- 1998
- Full Text
- View/download PDF
49. Discrimination by proxy.
- Author
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Alexander, Larry and Cole, Kevin
- Subjects
- *
DISCRIMINATION in education , *CONSTITUTIONAL law , *LAW school admission - Abstract
Considers the three well-settled principles of constitutional law in the United States in relation to the admission policies of three hypothetical state-supported law schools. Relationship among the principles; Anti-discrimination principle and types of racial classifications; Issue of rational discrimination.
- Published
- 1997
50. Are Smith and Hialeah reconcilable?
- Author
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Alexander, Larry,
- Subjects
- *
EMPLOYMENT Division, Dept. of Human Resources of Oregon v. Smith , *FREEDOM of religion - Abstract
Discusses the relevance of the ruling in the case of `Employment Division of Oregon versus Smith' and the ban by the citizens of Hialeah, Florida on the Santerian sect's practice of sacrificing chickens. Paradigm case of a law of general applicability; Ruling that the Free Exercise Clause does not mandate religious exemptions from the general applicability law.
- Published
- 1996
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