Seminal Event Research Articles

The 1883 F.A. Cup Final: working class representation, professionalism and the development of modern football in England

The 1883 F.A. Cup Final has long been viewed as a seminal event in the rise of professional football and an example of the class/culture conflict thought to characterized later Victorian sport. Recent scholarship has improved understandings of the larger contexts surrounding the match but diminish the importance of the 1883 Final as a catalyst for wider change. Little has been done to reconcile traditional understandings with this new, and more complex, view of the motivations for cultural change within the F.A. Utilizing new perspectives on the traditions and character of English sporting culture more generally, this article seeks to recast the 1883 Final within a post-colonial discourse concerning identity and representation. Through this perspective, traditional interpretations can be reconciled with contemporary understandings and the 1883 Final can be re-imbued with a sociocultural significance that more recent perspectives tend to neglect.

Cybersonic arts: adventures in American new music

Composer, performer, instrument builder, teacher, and writer Gordon Mumma has left an indelible mark on the American contemporary music scene. A prolific composer and innovative French horn player, Mumma is recognized for integrating advanced electronic processes into musical structures, an approach he has termed Cybersonics. Musicologist Michelle Fillion curates a collection of Mumma's writings, presenting revised versions of his classic pieces as well as many unpublished works from every stage of his storied career. Here, through words and astonishing photos, is Mumma's chronicle of seminal events in the musical world of the twentieth century: his cofounding the Cooperative Studio for Electronic Music; his role in organizing the historic ONCE Festivals of Contemporary Music; performances with the Sonic Arts Union; and working alongside John Cage and David Tudor as a composer-musician with the Merce Cunningham Dance Company. In addition, Mumma describes his collaborations with composers, performers, dancers, and visual artists ranging from Robert Ashley and Pauline Oliveros to Marcel Duchamp and Robert Rauschenberg. Candid and insightful, Cybersonic Arts is the eye-opening account of a broad artistic community by an active participant and observer.

Text, Representation and Revision: Re-visioning Partition Violence in Khushwant Singh’s Train to Pakistan and Bhisham Sahni’s Tamas

Partition is a complex historical reality that continues to puzzle the minds of scholars, historians and imaginative writers, who, ever since its occurrence, have endeavored to comprehend, through their numerous texts and writings, the subtle nuances of the complex strands that shaped the making of this seminal event. The present study attempts to examine, through a comparative analysis of Singh’s Train to Pakistan and Sahni’s Tamas, how the profoundly sensitive and deeply perceptive imagination of both Singh and Sahni create texts which re-enact, with sheer clarity and force, the happenings of partition and hence enable the readers to re-vision the complexities involved in its occurrence, create awareness/consciousness in them regarding those historical blunders, the consequences of which are still borne by the people and also urge them to revise/reform their attitudes, thinking and practices so that their present as well future is safeguarded against such catastrophic events.

Reconstruction Following EEA: A 0.5% CSF Leak Rate in 200 Consecutive Cases

Introduction: Reconstruction of the ventral skull base after the Expanded Endonasal Approach (EEA) remains a controversial issue. The development of the pedicled nasoseptal flap (NSF) has been a seminal event in the maturation of EEA, resulting in a marked reduction in cerebrospinal fluid (CSF) leak rates after the procedure. However, other reconstructive options exist, including the use of non-vascularized tissue such as autografts of fat or fascia lata, homografts and tissue adhesives. In addition, many centers now use a hybrid approach, reserving the use of the NSF for high risk cases, and using non-vascularized reconstructions for low risk situations or when the NSF is unavailable because of previous resections or tumor involvement. Our group has routinely used the NSF when available for all EEA cases, with resections of the nasopharynx and drainage of skull base infections and cholesterol granulomas being the most notable exceptions. In addition, we have used other vascularized reconstructions (including the lateral vault flap and, in one case, free tissue transfer) in situations where the NSF is unavailable. This paper will report on our protocol for ventral skull base reconstruction after EEA and examine our CSF leak rate over our last 200 consecutive cases.

The Politics of Remembrance: Commemorating 1916

In remembering critical events, history; memory; and commemoration often cause confusion and dissention. In this decade of centenaries, seminal events in modern Irish history contend for pre-eminence, but 1916 is clearly the most important. Scholars are competing with journalists and politicians for control of the agenda for establishing the meaning and importance of the Rising 100 years later. The continuing problems associated with commemorating 1916 are at least partly caused by the fact that partition has hindered nationalists from achieving their aspirations of a 32 county republic. We contend that it is this failure that accounts for much of the conflict in Ireland over the last century and which is now highlighted by the politics of commemoration of 1916. Despite the inevitable efforts of politicians and parties, the Easter Rising should be understood in the context of larger and broader movements that began decades earlier: the quest for Home Rule and the search for Irish identity.

Enterprise Computer Security: A Literature Review

Information technology (IT) is a global phenomenon that provides organizations of all types the ability to achieve enterprise objectives. One IT component is computer security, sometimes referred to as cybersecurity, the detection and prevention of a rapidly evolving collection of threats and vulnerabilities capable of introducing significant IT risk to an organization. Seminal events such as the creation of U.S. Cyber Command in 2009 acknowledging cyberspace as the fifth domain of war, and the 2015 recall by Fiat Chrysler of 1.4 million vehicles to mitigate an Internet enabled threat, serve as bookends framing the rapid evolution of cybersecurity threats and the need for organizations to better understand the collective vulnerabilities that enable computer security risk. However, a recent literature review of a major information systems (IS) research journal suggests publication of academic research associated with management of computer security from an enterprise perspective is limited. Given the relevance of computer security in today’s IT environment, this finding suggests that enterprise computer security is an under studied research topic. This article addresses this finding and the research gaps with the intent of encouraging new research in this domain.

A Journey in Science: The Privilege of Exploring the Brain and the Immune System.

Real innovations in medicine and science are historic and singular; the stories behind each occurrence are precious. At Molecular Medicine we have established the Anthony Cerami Award in Translational Medicine to document and preserve these histories. The monographs recount the seminal events as told in the voice of the original investigators who provided the crucial early insight. These essays capture the essence of discovery, chronicling the birth of ideas that created new fields of research; and launched trajectories that persisted and ultimately influenced how disease is prevented, diagnosed, and treated. In this volume, the Cerami Award Monograph is by Lawrence Steinman, MD, of Stanford University in California. A visionary in the field of neurology, this is the story of Dr. Steinman's scientific journey.

A Journey in Science: "Not Lost in Translation".

Real innovations in medicine and science are historic and singular; the stories behind each occurrence are precious. At Molecular Medicine we have established the Anthony Cerami Award in Translational Medicine to document and preserve these histories. The monographs recount the seminal events as told in the voice of the original investigators who provided the crucial early insight. These essays capture the essence of discovery, chronicling the birth of ideas that created new fields of research; and launched trajectories that persisted and ultimately influenced how disease is prevented, diagnosed, and treated. In this volume, the Cerami Award Monograph is by Tak Mak, PhD, Professor, The Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, Princess Margaret Cancer Centre in Toronto. A visionary in the field of cancer, this is the story of Dr. Mak's scientific journey.

Dylan goes electric!: Newport, Seeger, Dylan, and the night that split the sixties

One of the music world's pre-eminent critics takes a fresh and much-needed look at the day Dylan went at the Newport Folk Festival, timed to coincide with the event's fiftieth anniversary. On the evening of July 25, 1965, Bob Dylan took the stage at Newport Folk Festival, backed by an electric band, and roared into his new rock hit, Like a Rolling Stone. The audience of committed folk purists and political activists who had hailed him as their acoustic prophet reacted with a mix of shock, booing, and scattered cheers. It was the shot heard round the world-Dylan's declaration of musical independence, the end of the folk revival, and the birth of rock as the voice of a generation-and one of the defining moments in twentieth-century music. In Dylan Goes Electric!, Elijah Wald explores the cultural, political and historical context of this seminal event that embodies the transformative decade that was the sixties. Wald delves deep into the folk revival, the rise of rock, and the tensions between traditional and groundbreaking music to provide new insights into Dylan's artistic evolution, his special affinity to blues, his complex relationship to the folk establishment and his sometime mentor Pete Seeger, and the ways he reshaped popular music forever. Breaking new ground on a story we think we know, Dylan Goes Electric! is a thoughtful, sharp appraisal of the controversial event at Newport and a nuanced, provocative, analysis of why it matters.

Enhanced targeting of mitochondrial peroxide defense by the combined use of thiosemicarbazones and inhibitors of thioredoxin reductase

Peroxiredoxin-3 (Prx3) accounts for about 90% of mitochondrial peroxidase activity, and its marked upregulation in many cancers is important for cell survival. Prx3 oxidation can critically alter peroxide signaling and defense and can be a seminal event in promoting cell death. Here it is shown that this mechanism can be exploited pharmacologically by combinations of clinically available drugs that compromise Prx3 function in different ways. Clinically relevant levels of the thiosemicarbazone iron chelators triapine (Tp) and 2,2′-Dipyridyl-N,N-dimethylsemicarbazone (Dp44mT) promote selective oxidation of mitochondrial Prx3, but not cytosolic Prx1, in multiple human lung and ovarian cancer lines. Decreased cell survival closely correlates with Prx3 oxidation. However, Prx3 oxidation is not merely an indicator of cell death as cytotoxic concentrations of cisplatin do not cause Prx3 oxidation. The siRNA-mediated suppression of either Prx3 or thioredoxin-2, which supports Prx3, enhances Tp’s cytotoxicity. Tp-mediated Prx3 oxidation is driven by enhanced peroxide generation, but not by nitric oxide. Many tumors overexpress thioredoxin reductase (TrxR) which supports Prx activity. Direct inhibitors of TrxR (e.g. auranofin, cisplatin) markedly enhanced Tp’s cytotoxicity, and auranofin enhanced Prx3 oxidation by low dose Tp. Together, these results support an important role for Prx3 oxidation in the cytotoxicity of Tp, and demonstrate that TrxR inhibitors can significantly enhance Tp’s cytotoxicity. Thiosemicarbazone-based regimens could prove effective for targeting Prx3 in a variety of cancers.

Breaking Dogma on the Hypothalamic-Pituitary Anatomical Relations in Vertebrates.

The hypothalamus and pituitary are present in all vertebrates from agnathans (jawless fishes) to mammals. The hypothalamus is located below the thalamus, just above the brain stem and forms the ventral part of the diencephalon. The appearance of the pituitary was a seminal event in the evolution of vertebrates (1, 2). The pituitary is not present in protochordates or other invertebrates. The pituitary consists of the same 2 principal divisions, the neurohypophysis and adenohypophysis. The neurohypophysis develops from the floor of the diencephalon as an infundibular extension, whereas the adenohypophysis develops from the oral epithelium that comes in contact with this infundibulum. In vertebrates, the evolution of a complex pituitary with dual developmental origin along with the more highly developed tripartite brain added another layer of control leading to the neuroendocrine control of many complex physiological functionssuchasgrowth,reproduction,developmentand metabolism among others. These functionally adaptive conditions may then have contributed to the expansion of vertebrates into new environments. The acquisition of the vertebrate pituitary probably resulted from wholegenome duplications that occurred early in vertebrate evolution (3). The adenohypophysis of the pituitary gland secretes a number of protein hormones that regulates a variety of the physiological processes of vertebrates. The adenohypophysialhormonescanbeclassified,onthebasis of structural and functional similarity, into 3 groups, the proopiomelanocortin family, the GH/prolactin/somatolactin family, and theglycoprotein hormone family (gonadotropins, thyroid-stimulating hormone, and a novelhormonecalledthyrostimulin).Somatolactinisonly found in teleosts. Each family is believed to have evolved fromanancestralgenebyduplicationandsubsequentmutations (4). During the evolution of the vertebrates, structural features of the pituitary and hypothalamus also evolved that perhaps optimized the communication between these tissuesasvertebratesbecamelargerandmorecomplicatedin form and distance between the hypothalamus and pitu

ChemInform Abstract: Polymer Mechanochemistry: From Destructive to Productive

AbstractReview: 76 refs.

Book Review: American Civil War: A State-by-State Encyclopedia

Obviously there is no shortage of available resources on the American Civil War. Nor is there a shortage of encyclopedias covering this seminal event from numerous perspectives and vantage points. However, there are not many sources looking specifically at the war from a state-by-state viewpoint. Two separate books with the same title have covered this territory previously. The Civil War State by State by Paul Brewer (Thunder Bay 2004), and more recently, Chester G. Hearn’s unrelated work by the same name (BlueRedPress 2013) take the state approach. However, neither work is nearly as in-depth and detailed as this new release edited by the senior fellow in military history at ABC-CLIO, who has authored or edited a long list of military history books and encyclopedias. Also, the previous editions mentioned have a great emphasis on color graphics and appealing layout, and are not intended as a starting point for scholarly research. This latest release, however, is clearly focused on providing historical background information while also pointing the user to further research and analysis by way of Further Reading lists and a “Select Bibliography.”

Der Bauernjörg: Feldherr im Bauernkrieg

The German Peasants War (1524–6) is a seminal event that has long attracted scholarly attention. While interpretations have often changed, the interest has remained squarely focused on the peasants rather than the war , despite this being one of the bloodiest conflicts of premodern German history. The only substantial military history of the war remains a short book by Manfred Bensing and Siegfried Hoyer published by the East German Militärverlag in the anniversary year of 1975. Peter Blickle, one of the foremost scholars of the early modern German peasantry, addresses this deficit in his new study of Georg Truchsess von Waldburg (1488–1531), who commanded the army of the Swabian League and played a decisive role in winning the war for the established authorities. Blickle was given access to the extensive private archive of Waldburg’s descendants, which has remained largely unused for this topic since the nineteenth century. These rich sources are supplemented by material from across south-west Germany, as well as the insight gained through a career studying peasants and, above all, the political dimension of the Peasants War, which Blickle terms ‘the Revolution of 1525’.

The Maristan "Sidi Fredj" in Fez, Morocco.

One of the seminal events in the history of diagnosis and treatment of severe psychiatric illnesswas the understanding of psychotic symptoms such as hallucinations, delusions, and paranoid ideas as resulting from “sickness” rather than from supernatural causes. With this realization, patients were treated with medications, not tortured or killed or jailed. Among the earliest psychiatric hospitals in theworldwas one in northern Africa. The word “maristan” is a contraction of a Persian word (bimarstan) meaning “the locus of sick people.” Maristans were medical institutions with four specialties: internal medicine, ophthalmology, traumatology, andpsychiatry.Over the centuries, they progressively restricted their work to mental patients only. As far as we know, the first historically known maristan in the Arab-Islamic region is the one in Baghdad during the reign of Harun Al Rashid. In Morocco, the first was built inMarrakech during the Almohad dynasty in the 12th century. It was described by Abdelwahad Al Murrakushi, a contemporary historian, as an exceptional medical institution, supported personally by the sultans. In Fez, during the Merinid dynasty another maristan, called “Sidi Fredj,”was built in the 13th century by the sultan AbuYaqub (1286–1307). LeoAfricanus (hisoriginal namewas Hassan Al Wazzan) worked in this maristan for 2 years as a secretary at the end of the 15th century. Adjacent to the Sidi Fredj maristan, herb shops allowed the preparation of many kinds of medications for centuries, and they still exist today. Medicine at that time was completely Hippocratic and never mentioned irrational causes of diseases, as is evident in medical books of famous physicians such as Ibn Rushd (Averroes) or Ibn Zohr (Avenzoar), who lived inMarrakech during the 12th and 13th centuries. Father Galaberto Jofre, a Spanish priest, came to “Africa” twice at the beginning of the 15th century to pay ransoms for Christian war prisoners and bring them back to Spain. He most probably visited Fez, which was the capital of Morocco

Structural characterization and modeling of the Borrelia burgdorferi hybrid histidine kinase Hk1 periplasmic sensor: A system for sensing small molecules associated with tick feeding.

Two-component signal transduction systems are the primary mechanisms by which bacteria perceive and respond to changes in their environment. The Hk1/Rrp1 two-component system (TCS) in Borrelia burgdorferi consists of a hybrid histidine kinase and a response regulator with diguanylate cyclase activity, respectively. Phosphorylated Rrp1 catalyzes the synthesis of c-di-GMP, a second messenger associated with bacterial life-style control networks. Spirochetes lacking either Hk1 or Rrp1 are virulent in mice but destroyed within feeding ticks. Activation of Hk1 by exogenous stimuli represents the seminal event for c-di-GMP signaling. We reasoned that structural characterization of Hk1's sensor would provide insights into the mechanism underlying signal transduction and aid in the identification of activating ligands. The Hk1 sensor is composed of three ligand-binding domains (D1-3), each with homology to periplasmic solute-binding proteins (PBPs) typically associated with ABC transporters. Herein, we determined the structure for D1, the most N-terminal PBP domain. As expected, D1 displays a bilobed Venus Fly Trap-fold. Similar to the prototypical sensor PBPs HK29S from Geobacter sulfurreducens and VFT2 from Bordetella pertussis, apo-D1 adopts a closed conformation. Using complementary approaches, including SAXS, we established that D1 forms a dimer in solution. The D1 structure enabled us to model the D2 and D3 domains. Differences in the ligand-binding pockets suggest that each PBP recognizes a different ligand. The ability of Hk1 to recognize multiple stimuli provides spirochetes with a means of distinguishing between the acquisition and transmission blood meals and generate a graded output response that is reflective of the perceived environmental threats.

The Southern Manifesto: Massive Resistance and the Fight to Preserve Segregation

On March 13, 1956, ninety-nine members of the United States Congress promulgated the Declaration of Constitutional Principles, popularly known as the Southern Manifesto. Reprinted here, the Southern Manifesto formally stated opposition to the landmark United State Supreme Court decision Brown v. Board of Education, and the emergent civil rights movement. This statement allowed the white South to prevent Brown's immediate full-scale implementation and, for nearly two decades, set the slothful timetable and glacial pace of public school desegregation. The Southern Manifesto also provided the Southern Congressional Delegation with the means to stymie federal voting rights legislation, so that the dismantling of Jim Crow could be managed largely on white southern terms. In the wake of the Brown decision that declared public school segregation unconstitutional, seminal events in the early stages of the civil rights movement--like the Emmett Till lynching, the Montgomery bus boycott, and the Autherine Lucy riots at the University of Alabama brought the struggle for black freedom to national attention. Orchestrated by United States Senator Richard Brevard Russell Jr. of Georgia, the Southern Congressional Delegation in general, and the United States Senate's Southern Caucus in particular, fought vigorously and successfully to counter the initial successes of civil rights workers and maintain Jim Crow. The South's defense of white supremacy culminated with this most notorious statement of opposition to desegregation. The Southern Manifesto: Massive Resistance and the Fight to Preserve Segregation narrates this single worst episode of racial demagoguery in modern American political history and considers the statement's impact upon both the struggle for black freedom and the larger racial dynamics of postwar America.

Disaggregases, molecular chaperones that resolubilize protein aggregates.

The process of folding is a seminal event in the life of a protein, as it is essential for proper protein function and therefore cell physiology. Inappropriate folding, or misfolding, can not only lead to loss of function, but also to the formation of protein aggregates, an insoluble association of polypeptides that harm cell physiology, either by themselves or in the process of formation. Several biological processes have evolved to prevent and eliminate the existence of non-functional and amyloidogenic aggregates, as they are associated with several human pathologies. Molecular chaperones and heat shock proteins are specialized in controlling the quality of the proteins in the cell, specifically by aiding proper folding, and dissolution and clearance of already formed protein aggregates. The latter is a function of disaggregases, mainly represented by the ClpB/Hsp104 subfamily of molecular chaperones, that are ubiquitous in all organisms but, surprisingly, have no orthologs in the cytosol of metazoan cells. This review aims to describe the characteristics of disaggregases and to discuss the function of yeast Hsp104, a disaggregase that is also involved in prion propagation and inheritance.

GWAS of longitudinal amyloid accumulation on 18F-florbetapir PET in Alzheimer's disease implicates microglial activation gene IL1RAP.

Brain amyloid deposition is thought to be a seminal event in Alzheimer's disease. To identify genes influencing Alzheimer's disease pathogenesis, we performed a genome-wide association study of longitudinal change in brain amyloid burden measured by (18)F-florbetapir PET. A novel association with higher rates of amyloid accumulation independent from APOE (apolipoprotein E) ε4 status was identified in IL1RAP (interleukin-1 receptor accessory protein; rs12053868-G; P = 1.38 × 10(-9)) and was validated by deep sequencing. IL1RAP rs12053868-G carriers were more likely to progress from mild cognitive impairment to Alzheimer's disease and exhibited greater longitudinal temporal cortex atrophy on MRI. In independent cohorts rs12053868-G was associated with accelerated cognitive decline and lower cortical (11)C-PBR28 PET signal, a marker of microglial activation. These results suggest a crucial role of activated microglia in limiting amyloid accumulation and nominate the IL-1/IL1RAP pathway as a potential target for modulating this process.

Polymer mechanochemistry: from destructive to productive.

When one brings "polymeric materials" and "mechanical action" into the same conversation, the topic of this discussion might naturally focus on everyday circumstances such as failure of fibers, fatigue of composites, abrasion of coatings, etc. This intuitive viewpoint reflects the historic consensus in both academia and industry that mechanically induced chemical changes are destructive, leading to polymer degradation that limits materials lifetime on both macroscopic and molecular levels. In the 1930s, Staudinger observed mechanical degradation of polymers, and Melville later discovered that polymer chain scission caused the degradation. Inspired by these historical observations, we sought to redirect the destructive mechanical energy to a productive form that enables mechanoresponsive functions. In this Account, we provide a personal perspective on the origin, barriers, developments, and key advancements of polymer mechanochemistry. We revisit the seminal events that offered molecular-level insights into the mechanochemical behavior of polymers and influenced our thinking. We also highlight the milestones achieved by our group along with the contributions from key comrades at the frontier of this field. We present a workflow for the design, evaluation, and development of new "mechanophores", a term that has come to mean a molecular unit that chemically responds in a selective manner to a mechanical perturbation. We discuss the significance of computation in identifying pairs of points on the mechanophore that promote stretch-induced activation. Attaching polymer chains to the mechanophore at the most sensitive pair and locating the mechanophore near the center of a linear polymer are thought to maximize the efficiency of mechanical-to-chemical energy transduction. We also emphasize the importance of control experiments to validate mechanochemical transformations, both in solution and in the solid state, to differentiate "mechanical" from "thermal" activation. This Account offers our first-hand perspective of the change-in-thinking in polymer mechanochemistry from "destructive" to "productive" and looks at future advances that will stimulate this growing field.