Seminal Event Research Articles

Milton's Words by Annabel Patterson

1140 Reviews Milton, warts and all. Thus, while the book remains a hero's life' (p. 4), itdoes not stint in exposing him as 'flawed, self-contradictory, self-serving, arrogant [...] and cunning (p. 3). Such even-handedness permeates an impressively comprehensive re-examination ofMilton's prose works. For instance, while his alignment in the 1640s with the influential credo of Protestant tolerationism is fulsomely extolled, his expressed perspective on Catholicism remained inimical and vengeful' (p. 172); and though TheDoctrine and Discipline of Divorce (1643) marks him as a 'heterodox thinker of growing confidence', whose 'exegetical skills [are] both subtle and bold' (pp. 161,164), by contrast his ideas for a radical overhaul of the nation's education system, set out in Of Education (1644), are 'Repressive, prescriptive, elitist, masculinist, militaristic, dustily pedantic, class-ridden, and affectionless' (p. 181). The explicitly chronological structure of the book?Milton's shifting age range is printed at the top of each page?might, in other biographies, have seemed unnecessarily rigid. Here, however, it complements one of the overriding objectives of the authors: to trace the specific trajectory ofMilton's radicalization. The governing paradigm of a Milton who was somehow always predisposed towards the revolutionary ideas on Church and state thatwould ultimately lead to the Civil War is persuasively challenged. Drawing with profit on the records relating to his upbringing and to his student years at Christ's College, Cambridge, Campbell and Corns command assent to the notion thatMilton's early decades were, in fact, ideologically conformist. The catalyst for his political volte-face, they postulate, were national and local events of 1637, when the twenty-eight-year-old Milton was living with his parents in the small Buckinghamshire village ofHorton. The public mutilation ofWilliam Prynne, Henry Burton, and John Bastwick for sedition against the Laudian Church 'demonstrated that the lives of the middling sort were [. . .] as fragile as those of the unpropertied' (p. 95); while the episcopal visitation ofHorton in thatyear directly impinged onMilton's family: its report reprovingly noting that some of the parish church seats, including his father's,were too high, and that the tombstone of his recently buried mother, Sara, was wrongly oriented. These seminal events give fascinating context to the sense of injustice and mission which sustained Milton through to and beyond his poetic magnum opus, Paradise Lost (1667), bywhen he was 'speaking for theGod whose conduit he had become' (p? 346). This is an assiduously researched and delicately calibrated studywhich, in vividly fleshing out its subject and his changing modes of thought and argument, both questions and affirmshis iconic status. Birkbeck, University of London Philip Major Milton's Words. By Annabel Patterson. Oxford: Oxford University Press. 2009. viii+212 pp. ?18.99. ISBN 978-0-19-957346-2. Few Miltonists can claim to be as committed, experienced, or productive as Annabel Patterson. For this reason alone it comes as no surprise that this disarmingly brief and ostensibly unprepossessing book carries the unmistakable MLR, 105.4, 2010 1141 stamp of scholarly heft. Cohering the work around close analyses of individual words employed by Milton, the author's stated aim, consonant with the recent academic trend (as exemplified in Gordon Campbell and Thomas Corns's John Milton: Life,Work, and Thought from the same publisher (2008), reviewed above), is threefold: to rehabilitate her subject's neglected prose works; to encourage, confident in its canonical status, a less deferential attitude towards theMilton corpus in general; and relatedly, to emphasize its contingency, the 'series of changes of direction, impulsive gestures, apologies, revisions, and thoughts worked out in the very process ofwriting them down' (p. 14). An engaging chapter on the divorce pamphlets argues plausibly thatMilton presents a logical case for reform of the divorce law, superimposed on a subtext of emotional chaos' (p. 48), the latter evidenced by the copious deployment of metaphor and euphemism in the Doctrine and Discipline ofDivorce (1643) which underscores his apparent physical and intellectual difficulties with sexual intercourse at this time. The most diverting?and important?chapter, however, concerns the still under-studied Paradise Regained (1671). In it,Patterson argues for, among other things, the significant influence on Milton's epic of JohnBale's Temptacyon of Christ...

Mitochondrial Mislocalization Underlies Aβ42-Induced Neuronal Dysfunction in a Drosophila Model of Alzheimer's Disease

The amyloid-β 42 (Aβ42) is thought to play a central role in the pathogenesis of Alzheimer's disease (AD). However, the molecular mechanisms by which Aβ42 induces neuronal dysfunction and degeneration remain elusive. Mitochondrial dysfunctions are implicated in AD brains. Whether mitochondrial dysfunctions are merely a consequence of AD pathology, or are early seminal events in AD pathogenesis remains to be determined. Here, we show that Aβ42 induces mitochondrial mislocalization, which contributes to Aβ42-induced neuronal dysfunction in a transgenic Drosophila model. In the Aβ42 fly brain, mitochondria were reduced in axons and dendrites, and accumulated in the somata without severe mitochondrial damage or neurodegeneration. In contrast, organization of microtubule or global axonal transport was not significantly altered at this stage. Aβ42-induced behavioral defects were exacerbated by genetic reductions in mitochondrial transport, and were modulated by cAMP levels and PKA activity. Levels of putative PKA substrate phosphoproteins were reduced in the Aβ42 fly brains. Importantly, perturbations in mitochondrial transport in neurons were sufficient to disrupt PKA signaling and induce late-onset behavioral deficits, suggesting a mechanism whereby mitochondrial mislocalization contributes to Aβ42-induced neuronal dysfunction. These results demonstrate that mislocalization of mitochondria underlies the pathogenic effects of Aβ42 in vivo.

Three-Part Inventions: The Novels of Thomas Bernhard (review)

Reviewed by: Three-Part Inventions: The Novels of Thomas Bernhard James Martin Cousineau, Thomas. Three-Part Inventions: The Novels of Thomas Bernhard. Newark, DE: University of Delaware Press, 2008. 181 pp. $48.50. The critically acclaimed adaptation of Thomas Bernhard’s novel The Lime Works (Das Kalkwerk) by Polish director Krystian Lupa as part of the Lincoln Center Festival in the summer of 2009 marked an important moment in the reception of the author’s works in the United States. For many Americans, the New York stage adaptation of this early novel was their first introduction to the works of one of Austria’s most influential writers of the late twentieth-century, rivaled only by Nobel Prize winner Elfriede Jelinek and the erstwhile enfant terrible of Austrian literature, Peter Handke. Bernhard, who died in 1989, shared these authors’ passion for theatricality, critique of language, and scathing caricatures of Austrian parochialism, which differentiates them from their German counterparts north of the Alps. Despite a self-declared ban on the publication of his works in Austria during his lifetime, Bernhard gained renown as one of Europe’s great modernist writers and was duly celebrated during his lifetime; yet he remains virtually unknown to American audiences. Three-Part Inventions by Thomas Cousineau, a Beckett scholar and professor of English literature, is thus a timely critical introduction to the novels of Thomas Bernhard for English-language readers seeking to understand the formal structures of Bernhard’s writing and to situate his work within the broader tradition of Anglo-American and European literary modernism. Cousineau’s study begins with an exposition of the seminal events of Bernhard’s life that shaped his character as a writer, relying on biographical information and assessments by literary critics and reviewers. In particular, he focuses on Bernhard’s development of a performative art of exaggeration that “revives in his readers the insane fury of Nazi rhetoric while transforming it into an art that safely ‘fails,’ as it were, to harm its designated victims” (26). While Cousineau is not a German speaker and thus must rely primarily upon English-language criticism with an occasional German, French, or even Italian source, he does offer a thorough and astute discussion of recent Bernhard criticism written within the purview of American German Studies. What he lacks in detailed background knowledge of Austrian literature and history, he more than makes up for in his insightful analysis of Bernhard’s “transformative” techniques from the rhetorical level to the metafictional. Throughout his analyses, Cousineau refers to the triangular relationship of protagonist–adversary–scapegoat [End Page 494] developed by Rene Girard as a touchstone for understanding Bernhard’s patterns of repetition and permutation that are more akin to motivic development in the musical invention, hence the title Three-Part Inventions, than traditional models of narrative development. Rather than expounding at length on Girard’s theories in a methodological prologue at the beginning of the book, the author reserves his discussion of the efficacy of his theoretical model for the afterword and proceeds with a direct investigation of Girard’s triadic structure and variations thereof in six of Bernhard’s major novels: The Lime Works (Das Kalkwerk), Correction (Korrektur), The Loser (Der Untergeher), Woodcutters (Holzfällen), Old Masters (Alte Meister), and Extinction (Auslöschung). Tracing the development of Bernhard’s narrative technique chronologically across his novelistic output, the chapters start with “fugal beginnings” in reference to The Lime Works and the establishment of the Girardian tripartite model of mimetic desire that creates a need for a scapegoat. The author provides an equal mix of close textual readings backed up with discussions of secondary literature on Bernhard, including numerous articles from journals like Modern Austrian Literature and English-language monographs on Bernhard where available. He also discusses the role of the visual arts, theater, and music in Bernhard’s writing, for example the influence of Bach and Beethoven as models, and he draws illuminating literary connections to Greek myth, Dante, Shakespeare, and various Anglo and European modernists including Proust, Joyce, Woolf, and T.S. Eliot. This is where Cousineau’s argument is at its strongest in both explicating Bernhard’s highly idiosyncratic writing style and successfully placing it within...

Buried in the unremissive ground: reading Richmond's subterranean signs

Like the forgotten memories of seminal events that purportedly lurk in the mind's subconscious, the buried substrata of a city can contain unresolved pasts, forgotten incidents that have shaped the present. And like memories, these buried artifacts can be painful once unearthed. Using Richmond, Virginia as a case, this article explores how the public reaction to a city's buried past serves as a map to the social worth of its citizens. Modern reactions to what is underground signal the relative status of modern groups; the treatment of the dead can be read as a code for modern race and class relations.

The Encyclopedia of the Spanish-American and Philippine-American wars: a political, social, and military history

A comprehensive overview of the wars that saw the United States emerge as a world power; one that had immense implications for America, especially in Latin America and Asia. ABC-CLIO, acclaimed publisher of superior references on the United States at war, revisits a pivotal moment in America's coming-of-age with The Encyclopedia of the Spanish-American and Philippine-American Wars: A Political, Social, and Military History. Again under the direction of renowned scholar Spencer Tucker, the encyclopedia covers the conflict between the United States and Spain with a depth and breadth no other reference works can match. The encyclopedia offers two complete volumes of alphabetically organized entries written by some of the world's foremost historians, covering everything from the course of the wars to relevant economic, social, and cultural matters in the United States, Spain, and other nations. Featuring a separate volume of primary-source documents and a wealth of images and maps, the encyclopedia portrays the day-to-day drama and lasting legacy of the war like never before, guiding readers through a seminal event in America's transition from the Gilded Age to the Progressive Era. * Over 600 alphabetically organized entries in two volumes, covering leading individuals, battles, weapons systems, and events in the United States, Spain, and other nations, as well as economic, cultural, and social topics * Written by expert contributors, with distinguished scholars of American military history and of the era in which the Spanish-American War took place * Over 150 primary-source documents in a separate volume giving readers firsthand access to the way the Spanish-American War unfolded and was experienced * 350 photographs and illustrations, as well as 16 maps, providing a rich array of images to help readers visualize the war's key events and lasting impact * An exceptionally extensive bibliography guiding readers to significant additional resources in print

Navigating ECM Barriers at the Invasive Front: The Cancer Cell–Stroma Interface

A seminal event in cancer progression is the ability of the neoplastic cell to mobilize the necessary machinery to breach surrounding extracellular matrix barriers while orchestrating a host stromal response that ultimately supports tissue-invasive and metastatic processes. With over 500 proteolytic enzymes identified in the human genome, interconnecting webs of protease-dependent and protease-independent processes have been postulated to drive the cancer cell invasion program via schemes of daunting complexity. Increasingly, however, a body of evidence has begun to emerge that supports a unifying model wherein a small group of membrane-tethered enzymes, termed the membrane-type matrix metalloproteinases (MT-MMPs), plays a dominant role in regulating cancer cell, as well as stromal cell, traffic through the extracellular matrix barriers assembled by host tissues in vivo. Understanding the mechanisms that underlie the regulation and function of these metalloenzymes as host cell populations traverse the dynamic extracellular matrix assembled during neoplastic states should provide new and testable theories regarding cancer invasion and metastasis.

Organ Trafficking: Global Solutions for a Global Problem

The organ trafficking market is on the rise worldwide. Numerous unfortunate stories of networks of brokers, physicians, and hospitals engaged in illegal trade have been featured in high-profile media. The profitable enterprises facilitating these unregulated services exploit the poor in underresourced countries and offer substandard medical care with unacceptable outcomes to the rich recipients. Despite efforts to boost altruistic organ donation and resolutions to curb transplant tourism, their implementation has been compromised. At the same time, the worldwide escalation in the number of patients with kidney failure coupled with a shortage in the supply of organs continues to fuel this trade. Thus, measures to enhance the donor pool in well-resourced countries to meet their own needs will act as a strong deterrent to the proliferation of transplant tourism in impoverished nations. Regulated schemes that include reimbursement for removing potential disincentives to organ donation and ensure the long-term safety of donors and their families are likely to increase living donations. Such socially responsible programs should be tested in both developed and developing countries for their own populations. It also is vital that developing countries establish a regulated, standardized, and ethical system of organ procurement; create awareness in physicians and the public; upgrade facilities and standardize medical care; and enforce legislation for transplantation. The World Health Organization, National Kidney Foundation, and international transplant and nephrology societies can have an instrumental role in facilitating initiatives in these critical areas. There should be clearly defined codes of conduct for health care facilities and professionals' roles in unregulated paid organ donations and transplants. Ultimately, physicians and transplant surgeons have the responsibility to ensure to the best of their ability that the organs they transplant were obtained upholding the highest standards of ethics.

New Orleans’s Unique School Reform Effort and Its Potential Implications for Special Education

Four years following the decimation of the New Orleans Public Schools by Hurricane Katrina the city has been described as the center of a unique urban public school reform effort. This effort is a combination of events that transpired just before the storm and those that have occurred as a result of it. In particular some claim that the emerging public school configuration seeks to be one that is comprised entirely of charter schools, thereby allowing public schools in New Orleans to become a “system of schools” as opposed to a traditional school system. While a fundamental operating principle of charter schools is increased student academic achievement in exchange for school autonomy and innovative practices, an additional responsibility of the charter schools in New Orleans is identical to that of their counterpart traditional public schools: the provision of special education services in accordance with the Individuals with Disabilities Education Improvement Act. Accordingly, this article presents an overview of the seminal reform events that have occurred to date and discusses the potential implications of this reform effort with respect to the provision of special education services.

NATO's “Humanitarian Intervention” in Kosovo: Legal Precedent or Aberration?

NATO's intervention in Kosovo in 1999 (Operation Allied Force) is one of the seminal events in contemporary international relations. While the humanitarian aspect of this intervention was widely endorsed the dominant view is that NATO acted illegally. Many who acknowledged this illegality, however, argued that because Operation Allied Force had so emphatically illustrated deficiencies with the existing legal regime that legal reform would subsequently follow. This article examines whether 10 years on Operation Allied Force can be considered a legal precedent. It is argued that while Operation Allied Force was unquestionably of significant political importance it does not constitute a legal precedent. While the intervention sparked much legal debate it did not did not lead to any significant addition or amendment to positive law nor does it constitute a precedent for customary international law.

Fifty Years of Things Fall Apart (1958)

Chinua Achebe is considered to be the most influential African novelist of the modern period and the publication of Things Fall Apart in 1958 was a seminal event in the history of African letters. ...

Discovering Event Evolution Graphs From News Corpora

Given the advance of Internet technologies, we can now easily extract hundreds or thousands of news stories of any ongoing incidents from newswires such as CNN.com, but the volume of information is too large for us to capture the blueprint. Information retrieval techniques such as topic detection and tracking are able to organize news stories as events, in a flat hierarchical structure, within a topic. However, they are incapable of presenting the complex evolution relationships between the events. We are interested to learn not only what the major events are but also how they develop within the topic. It is beneficial to identify the seminal events, the intermediary and ending events, and the evolution of these events. In this paper, we propose to utilize the event timestamp, event content similarity, temporal proximity, and document distributional proximity to model the event evolution relationships between events in an incident. An event evolution graph is constructed to present the underlying structure of events for efficient browsing and extracting of information. Case study and experiments are presented to illustrate and show the performance of our proposed technique. It is found that our proposed technique outperforms the baseline technique and other comparable techniques in previous work.

Hear All About It

To examine the content of human papillomavirus (HPV)-related vaccination information presented during nightly national television news broadcasts in the United States. A retrospective content analysis of HPV vaccination coverage on 5 major nightly US television networks from 2002 to 2007. The Vanderbilt Television News Archive was searched for keywords "Gardasil," "cervical cancer vaccination," "human papillomavirus vaccine," and "HPV vaccination." Each television news broadcast was categorized as follows: segment length (in seconds), network (American Broadcasting Company, Columbia Broadcasting Company, National Broadcasting Company, Cable News Network, or Fox Broadcasting Company), year of broadcast (2002-2007), and (4) presentation type. Air dates were plotted on a timeline to depict trends and linkages to 5 seminal events surrounding the development, efficacy, and controversy regarding HPV vaccination. During the 6-year period, a total of 27 HPV-related vaccination news broadcasts aired. News broadcasts ranged from 10 to 250 seconds, lasting an average of close to 2 minutes (mean +/- SD, 127.0 +/- 66.1 seconds). Most broadcasts presented information pertaining to HPV and cervical cancer, information on vaccine labeling, impact of the vaccine, and raised issues or concerns about the vaccine. More than half (66.7%) of news broadcasts were directly related to 5 seminal events surrounding the development, efficacy, and controversy regarding HPV vaccination. All 5 networks included within the Vanderbilt Television News Archive aired HPV vaccination content, with National Broadcasting Company and Columbia Broadcasting Company broadcasting most of the news stories during this time period. As compared with other medical-related information presented on national nightly television news during this time period, HPV vaccination received a modest amount of coverage.

The Finer Points of Filopodia

The development of a single-cell zygote into an adult organism depends on highly coordinated, complex processes that control how and when cells divide, move, and change shape. The regulation of cell shape and motility is critical for the formation of functionally distinct tissues and organs and underlies a seminal event during the early development of multicellular organisms called gastrulation—when cells of different tissue types undergo large-scale rearrangements in relation to one another [1]. These processes also play an important role in the adult organism, for example, in wound healing, when fibroblasts and other cells migrate to the site of the injury to begin the process of healing [2], and in pathological situations. For instance, cancer cells migrate from their tissue of origin to populate distinct regions and organs in a process called metastasis [3], which often leads to organ failure and death in cancer patients. Cells move and change shape at the direction of signals from surrounding tissues, though the molecular mechanisms that drive these signals remain obscure. A new study reported in this issue of PLOS Biology sheds light on these processes by describing a novel molecular mechanism that links extracellular signals to cell shape changes in the nervous system [4]. The developing nervous system is a useful model for investigating such mechanisms, because a wide variety of extracellular cues direct neurons as they form the structures and functional connections that make up the central nervous system [5]–[7]. Nascent neurons often migrate from their origin in the lumen of the neural tube to populate distinct distal layers of their target tissues, resulting in the layering of neurons in the spinal cord and cerebral and cerebellar cortices. Neurons must also extend axons to specific regions of the nervous system or periphery to make synapses with the correct partners (e.g., muscles or other neurons), and they remain capable of remodeling throughout adulthood. For example, in the brain, synaptic contacts are dynamically formed, lost, and modified in size and strength in response to neuronal activity, a process referred to as synaptic plasticity [8]. These physical changes in neuronal and synaptic shape are thought to be a basis of learning and memory. Each of these cell motility events—gastrulation, neuronal migration, axon outgrowth, wound healing, and metastasis—share common cellular features. When observed in the process of development and migration, cells exhibit dynamic extension and retraction of plasma membrane protrusions called lamellipodia and filopodia that are fundamental to cell shape and motility events (Figure 1A) [9],[10]. Lamellipodia (from Latin, “thin plate protrusions”) extend dynamically from the leading edge of migrating cells and axonal growth cones, the specialized structures at the distal tips of developing axons that explore the environment and drive axon extension (Figure 1A). Filopodia (from Latin, “thread protrusions”) also emanate from the leading edges of migrating cells and growth cones, often from the edges of lamellipodia (Figure 1A). Dynamic lamellipodial protrusions are thought to generate the force required for cell and growth cone migration, whereas filopodia are thought to mediate the ability of migrating cells and growth cones to navigate their environments and sense cues as to their direction of migration and destination. Furthermore, filopodia along the shaft of dendrites are thought to be the initiating step in the formation of a new neuronal synapse, a process important in synaptic plasticity, learning, and memory. In this issue of PLoS Biology, the Research Article by Menna et al. [4] describes a signaling pathway beginning with an extracellular cue and ending with an actin-binding protein that regulates axonal filopodia formation. Figure 1 The actin cytoskeleton in lamellipodia and filopodia.

Praxis, memory and cognition in Journalism Contributions to the periodization of Journalistic Knowledge in Brazil

The aim of this article is to rescue the seminal event of the Brazilian Journalistic Research. By reviewing authorship, thesis and arguments of the study written by Fernandes Pinheiro (1859) it also explains the role played by the main research agents. Another focus is the social impact caused by the historical recognition of Dutch colonizers as early introducers of typography in Brazil.

Cardiopulmonary Bypass in 2009: Achieving and Circulating Best Practices

Cardiopulmonary Bypass in 2009: Achieving and Circulating Best Practices

A Temporal Topic Model for New Event Detection

As an important task in Topic Detection and Tracking (TDT), New Event Detection (NED) aims to monitor the stream of news stories and detect new events reported by the first story of a topic. This paper proposes a Temporal Topic Model (TTM) to describe a topic as a series of events corresponding to different time. NED, based on TTM, firstly identifies whether a story includes the same time expressions with old topics, and then it verifies whether the story and the topics include relevant events corresponding to the expressions. Thus, a story will be determined as a new event, if it includes much few simultaneous relevant events of old topics. Additionally, this paper analyzes the distribution of time expressions to identify both seminal and novel events, by which NED modifies the probabilities of stories to be new events based on whether they include seminal or novel events of old topics. We compare our methods with some existing NED systems on TDT4 corpus, which demonstrate our methods substantially improve the efficiency and accuracy of NED.

Photo-Induced Cross-Linking of Unmodified Proteins (PICUP) Applied to Amyloidogenic Peptides

The assembly of amyloidogenic proteins into toxic oligomers is a seminal event in the pathogenesis of protein misfolding diseases, including Alzheimer's, Parkinson's, and Huntington's diseases, hereditary amyotrophic lateral sclerosis, and type 2 diabetes. Owing to the metastable nature of these protein assemblies, it is difficult to assess their oligomer size distribution quantitatively using classical methods, such as electrophoresis, chromatography, fluorescence, or dynamic light scattering. Oligomers of amyloidogenic proteins exist as metastable mixtures, in which the oligomers dissociate into monomers and associate into larger assemblies simultaneously. PICUP stabilizes oligomer populations by covalent cross-linking and when combined with fractionation methods, such as sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) or size-exclusion chromatography (SEC), PICUP provides snapshots of the oligomer size distributions that existed before cross-linking. Hence, PICUP enables visualization and quantitative analysis of metastable protein populations and can be used to monitor assembly and decipher relationships between sequence modifications and oligomerization(1). Mechanistically, PICUP involves photo-oxidation of Ru(2+) in a tris(bipyridyl)Ru(II) complex (RuBpy) to Ru(3+) by irradiation with visible light in the presence of an electron acceptor. Ru(3+) is a strong one-electron oxidizer capable of abstracting an electron from a neighboring protein molecule, generating a protein radical(1,2). Radicals are unstable, highly-reactive species and therefore disappear rapidly through a variety of intra- and intermolecular reactions. A radical may utilize the high energy of an unpaired electron to react with another protein monomer forming a dimeric radical, which subsequently loses a hydrogen atom and forms a stable, covalently-linked dimer. The dimer may then react further through a similar mechanism with monomers or other dimers to form higher-order oligomers. Advantages of PICUP relative to other photo- or chemical cross-linking methods(3,4) include short (<or=1 s) exposure to non-destructive visible light, no need for pre facto modification of the native sequence, and zero-length covalent cross-linking. In addition, PICUP enables cross-linking of proteins within wide pH and temperature ranges, including physiologic parameters. Here, we demonstrate application of PICUP to cross-linking of three amyloidogenic proteins the 40- and 42-residue amyloid beta-protein variants (Abeta40 and Abeta42), and calcitonin, and a control protein, growth-hormone releasing factor (GRF).

Photo-Induced Cross-Linking of Unmodified Proteins (PICUP) Applied to Amyloidogenic Peptides

The assembly of amyloidogenic proteins into toxic oligomers is a seminal event in the pathogenesis of protein misfolding diseases, including Alzheimer's, Parkinson's, and Huntington's diseases, hereditary amyotrophic lateral sclerosis, and type 2 diabetes. Owing to the metastable nature of these protein assemblies, it is difficult to assess their oligomer size distribution quantitatively using classical methods, such as electrophoresis, chromatography, fluorescence, or dynamic light scattering. Oligomers of amyloidogenic proteins exist as metastable mixtures, in which the oligomers dissociate into monomers and associate into larger assemblies simultaneously. PICUP stabilizes oligomer populations by covalent cross-linking and when combined with fractionation methods, such as sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) or size-exclusion chromatography (SEC), PICUP provides snapshots of the oligomer size distributions that existed before cross-linking. Hence, PICUP enables visualization and quantitative analysis of metastable protein populations and can be used to monitor assembly and decipher relationships between sequence modifications and oligomerization1. Mechanistically, PICUP involves photo-oxidation of Ru2+ in a tris(bipyridyl)Ru(II) complex (RuBpy) to Ru3+ by irradiation with visible light in the presence of an electron acceptor. Ru3+ is a strong one-electron oxidizer capable of abstracting an electron from a neighboring protein molecule, generating a protein radical1,2. Radicals are unstable, highly-reactive species and therefore disappear rapidly through a variety of intra- and intermolecular reactions. A radical may utilize the high energy of an unpaired electron to react with another protein monomer forming a dimeric radical, which subsequently loses a hydrogen atom and forms a stable, covalently-linked dimer. The dimer may then react further through a similar mechanism with monomers or other dimers to form higher-order oligomers. Advantages of PICUP relative to other photo- or chemical cross-linking methods3,4 include short (≤1 s) exposure to non-destructive visible light, no need for pre facto modification of the native sequence, and zero-length covalent cross-linking. In addition, PICUP enables cross-linking of proteins within wide pH and temperature ranges, including physiologic parameters. Here, we demonstrate application of PICUP to cross-linking of three amyloidogenic proteins the 40- and 42-residue amyloid β-protein variants (Aβ40 and Aβ42), and calcitonin, and a control protein, growth-hormone releasing factor (GRF).

Educational Restructuring and the Policy Process: The Toronto District School Board 1997-2003

This paper will examine the seminal events leading up to passage of the Fewer School Boards Act (Bill104), and its impact on the newly created Toronto District School Board (TDSB). While the focus of thispaper will be on Bill 104, it is important to note that significant structural changes needed to occur inToronto and its neighbouring municipalities before Bill 104 could take effect. To facilitate thesechanges, the Ontario government introduced and passed Bill 148 An Act to Establish a New City ofToronto. Bill 148 amalgamated the City of Toronto with the surrounding cities of East York, Etobicoke,North York, Scarborough, and York to create the "New" City of Toronto with a combined population of2.5 million citizens. Passage of Bill 148 cleared a path for the Ontario government to then pursuepassage of Bill 104. Passage of the Fewer School Boards Act amalgamated Toronto’s Public SchoolBoard with its five neighbouring cities but it also terminated the Metropolitan Toronto Public SchoolBoard. Where 74 trustees had represented citizens in Metropolitan Toronto, the newly elected 22-member TDSB became responsible for over 300,000 students, 21,000 employees, and almost 600schools. Each trustee represents a ward containing nearly 100,000 residents (Bedard and Lawton2000). While this study will focus on Toronto, both Bills 148 and 104 were part of a larger agenda bythe Ontario Progressive Conservative government to restructure a number of Ontario sectors, witheducation being the most predominant. As Leithwood, Fullan, and Watson note, the latter half of the1990s in Ontario can be viewed as "the most tumultuous in the province’s history" (2003, 1).

Wordsworth's sensibility inheritance: the Evening Sonnets and the “Miscellaneous Sonnets”

This essay reconsiders the early influences on Wordsworth as sonneteer. More specifically, it questions the pre‐eminence of the familiar story of Miltonic conversion by focusing on the vital role played by Wordsworth's contemporaries in shaping his voice. I propose that eighteenth‐century sensibility modes had substantive importance for Wordsworth's development as a sonnet writer, and functioned concomitantly with the Miltonic mode. The argument builds on recent scholarship that has positioned Wordsworth within the sensibility tradition, and does so by seeing the emergence of a distinct sonnet voice – indebted to the sonnet writers of his own day – as occurring prior to the seminal event of “rediscovering” Milton in 1802. I trace the evolution and maturation of Wordsworth's early sonnet voice from his youthful experiments through the important Evening Sonnets series and into the “Miscellaneous Sonnets,” where the strain of sensibility reaches its apotheosis. In so doing, I argue that the evening setting of these early sonnets enables Wordsworth both to articulate a process of mourning and to work towards a poetics of epiphany.