Crystal structures of the endoplasmic reticulum aminopeptidase-1 (ERAP1) reveal the molecular basis for N-terminal peptide trimming

Endoplasmatic reticulum aminopeptidase 1 (ERAP1) is a multifunctional enzyme involved in trimming of peptides to an optimal length for presentation by major histocompatibility complex (MHC) class I molecules. Polymorphisms in ERAP1 have been associated with chronic inflammatory diseases, including ankylosing spondylitis (AS) and psoriasis, and subsequent in vitro enzyme studies suggest distinct catalytic properties of ERAP1 variants. To understand structure-activity relationships of this enzyme we determined crystal structures in open and closed states of human ERAP1, which provide the first snapshots along a catalytic path. ERAP1 is a zinc-metallopeptidase with typical H-E-X-X-H-(X)18-E zinc binding and G-A-M-E-N motifs characteristic for members of the gluzincin protease family. The structures reveal extensive domain movements, including an active site closure as well as three different open conformations, thus providing insights into the catalytic cycle. A K 528R mutant strongly associated with AS in GWAS studies shows significantly altered peptide processing characteristics, which are possibly related to impaired interdomain interactions.

Beta-Turn Conformations In Crystal-Structures Of Model Peptides Containing Alpha,Alpha-Di-N-Propylglycine And Alpha,Alpha-Di-N-Butylglycine

The crystal state conformations of three peptides containing the alpha, alpha-dialkylated residues, alpha,alpha-di-n-propylglycine (Dpg) and alpha,alpha-di-n-butylglycine (Dbg), have been established by x-ray diffraction. Boc-Ala-Dpg-Ala-OMe (I) and Boc-Ala-Dbg-Ala-OMe (III) adopt distorted type II beta-turn conformations with Ala (1) and Dpg/Dbg (2) as the corner residues. In both peptides the conformational angles at the Dxg residue (I: phi = 66.2 degrees, psi = 19.3 degrees; III: phi = 66.5 degrees, psi = 21.1 degrees) deviate appreciably from ideal values for the i + 2 residue in a type II beta-turn. In both peptides the observed (N...O) distances between the Boc CO and Ala(3) NH groups are far too long (I: 3.44 Angstrom; III: 3.63 Angstrom) for an intramolecular 4 --> 1 hydrogen bond. Boc-Ala-Dpg-Ala-NHMe (II) crystallizes with two independent molecules in the asymmetric unit. Both molecules IIA and IIB adopt consecutive beta-turn (type III-III in IIA and type III-I in IIB) or incipient 3(10)-helical structures, stabilized by two intramolecular 4 --> 1 hydrogen bonds. In all four molecules the bond angle N-C-alpha-C' (tau) at the Dxg residues are greater than or equal to 110 degrees. The observation of conformational angles in the helical region of phi,psi space at these residues is consistent with theoretical predictions.

Childhood-as-rescue in the emergence and spread of the U.S. public school

In this volume, the editors have brought together prominent international contributors to examine the relevance of Foucauldian thought on educational theory, practice and institutional life. The result is a diverse collection that offers broad and engaging analyses of how power and knowledge are configured in the practices and norms of schooling. This text not only provides a critical examination of the significance of Foucauldian thought for education, but also discusses how Foucault's theories are arrayed in the everyday life of schools.

Solid state stacked trimers of 1,10-phenanthroline in a supramolecular tubular motif of C-methyl calix[4]resorcinarene

The self-assembly of bidentate ligand, 1,10-phenanthroline with C-methyl calix[4]resorcinarene (CMCR) in presence of coumarin results in a unique trimer stacking arrangement of phenanthroline molecules in a nanotubular motif generated by the supramolecular assembly of the host.

Approximate solution of u'=-A2u using a relation between exp(-tA2) and exp(itA)

Let A be a positive definite operator in a Hilbert space and consider the initial value problem for u(t) = -A(2)u. Using a representation of the semigroup exp(-A(2)t) in terms of the group exp(iAt) we express u in terms of the solution of the standard heat equation w(t) = W-yy, with initial values v solving the initial value problem for v(y) = iAv. This representation is used to construct a method for approximating u in terms of approximations of v. In the case that A is a 2(nd) order elliptic operator the method is combined with finite elements in the spatial variable and then reduces the solution of the 4(th) order equation for u to that of the 2(nd) order equation for v, followed by the solution of the heat equation in one space variable.

Determination of beta-turn conformation by laser Raman spectroscopy

To correlate the Raman frequencies of the amide I and III bands to beta-turn structures, three peptides shown to contain beta-turn structure by x-ray diffraction and NMR were examined. The compounds examined were tertiary (formula: see text). The amide I band of these compounds is seen at 1,668, 1,665, and 1,677 cm-1, and the amide III band appears at 1,267, 1,265, and 1,286 cm-1, respectively. Thus, it is concluded that the amide I band for type III beta-turn structure appears in the range between 1,665 and 1,677 cm-1 and the amide III band between 1,265 and 1,286 cm-1.

The validity of the Adler-Bardeen theorem in the supersymmetric U(1) gauge model

Using the dimensional reduction regularization scheme, we show that radiative corrections to the anomaly of the axial current, which is coupled to the gauge field, are absent in a supersymmetric U(1) gauge model for both 't Hooft-Veltman and Bardeen prescriptions for γ5. We also discuss the results with reference to conventional dimensional regularization. This result has significant implications with respect to the renormalizability of supersymmetric models.

A Literary Turn : Rethinking the Roles of Generalization and Theory in Anglo-American Moral Philosophy

This work investigates the role of narrative literature in late-20th century and contemporary Anglo-American moral philosophy. It aims to show the trend of reading narrative literature for purposes of moral philosophy from the 1970 s and early 80 s to the present day as a part of a larger movement in Anglo-American moral philosophy, and to present a view of its significance for moral philosophy overall. Chapter 1 provides some preliminaries concerning the view of narrative literature which my discussion builds on. In chapter 2 I give an outline of how narrative literature is considered in contemporary Anglo-American moral philosophy, and connect this use to the broad trend of neo-Aristotelian ethics in this context. In chapter 3 I connect the use of literature to the idea of the non-generalizability of moral perception and judgment, which is central to the neo-Aristotelian trend, as well as to a range of moral particularisms and anti-theoretical positions of late 20th century and contemporary ethics. The joint task of chapters 2 and 3 is to situate the trend of reading narrative literature for the purposes of moral philosophy in the present context of moral philosophy. In the following two chapters, 4 and 5, I move on from the particularizing power of narrative literature, which is emphasized by neo-Aristotelians and particularists alike, to a broader under-standing of the intellectual potential of narrative literature. In chapter 4 I argue that narrative literature has its own forms of generalization which are enriching for our understanding of the workings of ethical generalizations in philosophy. In chapter 5 I discuss Iris Murdoch s and Martha Nussbaum s respective ways of combining ethical generality and particularity in a philosophical framework where both systematic moral theory and narrative literature are taken seriously. In chapter 6 I analyse the controversy between contemporary anti-theoretical conceptions of ethics and Nussbaum s refutation of these. I present my suggestion for how the significance of the ethics/literature discussion for moral philosophy can be understood if one wants to overcome the limitations of both Nussbaum s theory-centred, equilibrium-seeking perspective, and the anti-theorists repudiation of theory. I call my position the inclusive approach .

Tyhjyyden reunalla, helvetin kannella : Yhtenäisen subjektin hajoaminen Saul Bellowin Herzogissa

The study shows that the reading paradigm derived from codes Roland Barthes presented in his S/Z exposes the postmodernic nature of Saul Bellow s Herzog (1964), and embodies in which way the novel is organized as a radical rewriting of modernism and its ideology. I explore how solid, compact and modernistic subject breaks down at every level of Herzog s narration. I actually argue that the heteroglossic novel is representative of an early American postmodern movement in literaure, and it should by no means be dissected narrowly as a realistic or naturalistic novel at all. The intertextual code verifies that the interpretation of Herzog remains inadequate if one doesn t take account of the novel s significant intertextual references to other texts. In fact, even the mind of Moses Herzog, the protagonist of the novel, is a mosaic of citations. It emerges from the dissertation that the figure of Don Quixote follows Moses Herzog as an ambiguous shadow while the professor of history struggles with his anxiety and anguish, and travels in a mentally confused state around the U.S. for five days in the early 1960s, encountering the impending atmosphere of transition as the country is on the threshold of a significant cultural and social change. There is a strong necessity for updated interpretation of Herzog partly because its centrality to Bellow s own career as a writer but mainly because it has been previously read trough modernistic lenses. I shall try to proof in my study that American Jewish Saul Bellow s (1915 2005) Herzog escapes any kind of simple, elemental or essentialistic construction or reading and in real terms it doesn t offer any comprehensive, total or coherent solution or system for those philosophical doctrines it criticizes and makes fun of. The philosophical, conceptual and cultural substance of Herzog does not constitute an independent or autonomous theoretical tract which would have a life of its own. Altough the novel reflects the continuity of Bellow s writing it is clearly some kind of conscious or unconscious experiment during his long career as a writer. He hasn t been so radical before or since the publication of Herzog. It is unarguably his most postmodern novel.The reading paradigm based on specific codes demonstrates how deep into the basic questions of his personal life and existence itself he must dive in oder to find his many ways towards authentic or primordial self in fragmented and shattered world which is constanly rewritten and which makes human being a tourist of his own life. In that ongoing process the protagonist has to accept the ultimate plurality of his mind and self. He must confront that the modernistic definition of identity as a solid, monolithic and stable entity has broken down into different, inconsistent and even contradictory possibilities of identification. Moses Herzog embodies obviously Stuart Hall s description of the postmodern self his identity has turn into a movable feast.

Renormalisation of the Fayet-Illiopoulos term in supersymmetric spontaneously broken U( 1) gauge theories

It is shown that the Fayet-Illiopoulos D term in N= 1 supersymmetric spontaneously broken U( 1) gauge theories may get one-loop corrections, even when trace U( 1) charges are zero. However, these corrections are only logarithmically divergent and hence do not affect the naturalness of the theory.

The poly dA helix: a new structural motif for high performance DNA-based molecular switches

We report a pH-dependent conformational transition in short, defined homopolymeric deoxyadenosines (dA(15)) from a single helical structure with stacked nucleobases at neutral pH to a double-helical, parallel-stranded duplex held together by AH-HA base pairs at acidic pH. Using native PAGE, 2D NMR, circular dichroism (CD) and fluorescence spectroscopy, we have characterized the two different pH dependent forms of dA(15). The pH-triggered transition between the two defined helical forms of dA(15) is characterized by CD and fluorescence. The kinetics of this conformational switch is found to occur on a millisecond time scale. This robust, highly reversible, pH-induced transition between the two well-defined structured states of dA(15)represents a new molecular building block for the construction of quick-response, pH-switchable architectures in structural DNA nanotechnology.

Supporting mindful planners in a mindless system: Limitations to the emotional turn in planning practice

Despite widespread acknowledgment within planning scholarship that emotion – both present in knowledge and a form of knowledge – is integral to lived experience and the judgement of planners, it is often sidelined within planning practice. The extent to which mainstream planning has been able or willing to accommodate emotions remains constrained and the emotions of planners and the public remain an unacknowledged but pervasive presence. Antonio Ferreira recently highlighted in this journal the importance of attending to emotions at the level of the individual planner through the concept of mindfulness. We argue this approach must be complemented by an acknowledgement of the structural and institutional limitations of including emotions in planning practice. Drawing from the emotional geographies literature to describe a social-spatial conceptualisation of emotion, we highlight ontological and practical tensions associated with the achievement of the ‘emotional turn’ and advance a more purposeful engagement with emotion in mainstream planning practice.

Illegal Immigration and the U.S. Labor Market of the 1990s

Public testimony by Prof. Briggs given before the Subcommittee on Immigration and Claims of the Committee on the Judiciary, House of Representatives, April 5, 1995.

U.S. Asylum Policy and the New World Order

"In the new world order, differences in political ideology have given way to differences in economic conditions between nation states as the prompting force for the outflow of would-be refugees and asylum seekers. In part, these pressures are associated with the political disintegration of the poorer republics of the former Soviet Union and its former satellite nations into ethnic enclaves. But the most endemic of the new contributory pressures are emanating from North-South economic differences between the "have" and "have-not" nations."

100 Years of U.S. Consumer Spending: Data for the Nation, New York City, and Boston

[From Preface] The Consumer Expenditure Survey is among the oldest publications of the Bureau of Labor Statistics. With information on the expenditures, incomes, and demographic characteristics of households, the survey documents the spending patterns and economic status of American families. This report offers a new approach to the use of Consumer Expenditure Survey data. Normally, the survey presents an indepth look at American households at a specific point in time, the reference period being a calendar year. Here, the authors use consumer expenditure data longitudinally and draw on information from decennial census reports to present a 100-year history of significant changes in consumer spending, economic status, and family demographics in the country as a whole, as well as in New York City and Boston.