90 research outputs found
The molecular pathogenesis of myeloproliferative neoplasms
No full textMyeloproliferative neoplasms (MPNs) are a heterogeneous group of haematological stem cellmalignancies characterised by proliferation of one or more cells of the myeloid lineage. The molecularinvestigation of MPN was revolutionized in 2005 by the finding that approximately 95% of cases withpolycythaemia vera (PV) and 50-60% of cases of essential thrombocythaemia (ET) and primarymyelofibrosis (PMF) are characterised by a single acquired mutation, JAK2 V617F. My study hasfocused on four principal areas:(i) Involvement of V617F in other myeloid disorders. After developing sensitive methods todetect and quantify V617F, this mutation was identified in 17% of cases of atypical chronic myeloidleukaemia (17/99) as well as other atypical MPN, thus demonstrating that it was more widelyinvolved in myeloid disorders that initially thought. Homozygosity of V617F was shown to have arisenby acquired uniparental disomy (UPD) and examination of two cases with V617F plus either KITD816V or BCR-ABL demonstrated that the mutations had arisen in independent clones.(ii) In vitro assays to predict imatinib sensitivity. Haemopoietic colony and liquid cultures wereused to determine if peripheral blood or bone marrow cells from atypical MPN cases (n=200) weresensitive to imatinib. Of those that responded in one or both cultures (n=185) some had knownabnormalities of PDGFRA or PDGFRB, but a significant minority proved negative for all molecular testssuggesting the presence of uncharacterised imatinib-sensitive mutations.(iii) V617F as a marker of response to therapy. JAK2 V617F was used as a molecular marker tomonitor the response of PV patients (n=21) to therapy with imatinib and interferon-?. Neithertherapy eradicated V617F but there was a modest reduction in %V617F which correlated withhaematological response. By contrast, in those patients that did not respond (n=13) the %V617Fmarginally increased.(iv) Genetic predisposition to MPN. Whilst investigating the possible contribution of JAK2 singlenucleotide polymorphisms to the phenotypic diversity associated with V617F, marked skewing ofalleles associated with the mutation was observed. Further investigation revealed that V617Fassociateddisease is strongly associated with a specific constitutional JAK2 haplotype, designated46/1, in all three disease entities compared to healthy controls (PV, n=192, P=2.9x10-16; ET, n=78,P=8.2x10-9 and MF, n=41, P=8.0x10-5). Furthermore, allele-specific PCR demonstrated that V617Fspecifically arises on the 46/1 allele in most cases. The 46/1 JAK2 haplotype thus predisposes to thedevelopment of V617F associated MPNs (OR=3.7; 95% CI 3.1-4.3) and provides a model whereby aconstitutional genetic factor is associated with an increased risk of acquiring a specific somaticmutation
Performances of the HL (Hyperloop) transport system
No full textThis paper deals with an analysis of performances of the HL (Hyperloop) transport system considered as an advanced transport alternative to the existing APT (Air Passenger Transport) and HSR (High Speed Rail) systems. The considered performances are operational, financial, social and environmental. The operational performance include capacity and quality of service provided to the system’s users-passengers with attributes such as door-to-door travel time consisting of the access and egress time, schedule delay, in-vehicle time, and interchange time. The economic performances embrace the costs and revenues of operating the system. The costs include that for infrastructure, vehicles, traffic management facilities and equipment, and employees. The revenues embrace earnings from pricing users/passengers. The environmental performances include energy consumption and related emissions of GHGs (Green House Gases), and land use. The social performances are considered to be noise and safety. The analytical models of indicators of these performances are developed and applied to the scenario of operating the HL system on the short- to medium-haul travel distances/routes. These are then compared to the corresponding performances of the HSR and APT. This comparison has shown that the HL system may possess some advantages but also disadvantages regarding particular performances.Transport and PlanningOLD Urban and Regional Developmen
James McCune Smith Predicted African American Preeminence in U.S. Art and Culture
No full textJames McCune Smith (1813–1865) was an African American physician, author, intellectual, community leader, and antislavery activist. He believed that the racial caste system of the United States was perpetuated not only by the slave system but by widely entrenched negative attitudes towards people of African descent, both outside and within the African American community. To counteract popular prejudice and to promote African American confidence and unity, he wrote widely on the abilities, accomplishments, and contributions of people of African descent, both historical and contemporary. This article examines McCune Smith’s theory that African Americans would play a formative and outsize role in the development of United States artistic and intellectual culture. From his time to ours, McCune Smith’s striking prediction was fulfilled to a degree that even he, inspired with the confidence his 1841 lecture “The Destiny of the People of Color” (published 1843) reveals, might marvel at
Life and work of James McCune Smith (1813-1865)
No full textJames McCune Smith (1813-1865) was the first African American physician to practice in the United States with a medical degree. He was among the most educated African Americans of his day, having earned three degrees at the University of Glasgow. McCune Smith was also the first African American to have work published in European and US medical journals; an early and central leader in the Colored Convention Movement; author of a series of experimental essays foundational to African American literature; and among the most prolific authors in the antebellum African American press. His immense influence is revealed in myriad primary and secondary sources relating to the African American struggle for freedom before and during the US Civil War and to the African American literary tradition. Yet while he is so often cited by contemporaries and later scholars as a leader and major influence in African American intellectual, cultural, and civil rights history, McCune Smith has yet to be the subject of a full-length dedicated biography. This thesis is written with the view that McCune Smith is among the most significant figures in American history to lack a full biography. It seeks, among other things, to remedy this lack, filling in gaps in existing literature on McCune Smith’s origins and on major events and themes in his life. It will do so in a series of six chapters. Chapter One explores McCune Smith’s origins and life in New York City and argues that this context is vital for understanding McCune Smith’s lifetime of achievement and activism. Chapter Two argues that McCune Smith was the first full-fledged African American polymath as well as the preeminent African American intellectual of the 19th century. Chapter Three argues that the significance of McCune Smith’s pioneering medical career may lie more in the holistic nature of the practice he established than in the fact that he broke multiple racial barriers that African Americans faced in that field. Chapter Four argues that that McCune Smith played a more central and enduring role in the history of the African American press than is generally recognized in the relevant literature; that the subtle, complex, and often controversial ideas he expressed in his articles may have caused him to be marginalized by scholars; and that these ideas represent significant contributions to many arenas of thought. Chapter Five argues that McCune Smith’s broad conception of slavery drove his lifelong opposition to it in all its forms, from what he described as the caste system which oppressed African Americans in the North to the legalised system of chattel slavery in the South. Chapter Six traces the origins and development of McCune Smith as a scientific thinker and author. It argues that his thinking in these fields was centered on one foundational theory: that humankind consisted of a single race, classifiable into groups or ‘races’ only according to mutable characteristics caused by local circumstances. It also argues that among McCune Smith’s most significant contributions to what he called the ‘dawning science of race-history’ was his development of the theory that African Americans had arisen as an indigenous American people
The Antwerp Jesuit Cornelius Hazart as an author of dialogue pamphlets
No full textThe Antwerp Jesuit Cornelius Hazart as an author of dialogue pamphlets
Cornelius Hazart (1617-1690) was a prolific author. Amongst many another things, he published a monumental four volume Church History (De Kerckelyke Historie vanden Gheheelen Wereldt, 1667-1671) and dozens of pamphlets in which he argued that only roman Catholics could expect salvation and that their church was by far superior to the various competing protestant institutions (Martens, 2012). Many of these pamphlets were presented as imaginary, but seemingly realistic dialogues between various characters.
In recent years, Dutch scholars have paid attention to the genre of dialogue pamphlets (Dingemanse 2008). They have argued that such dialogue pamphlets were a typical feature of the ‘discussion culture’ that characterized the Dutch Republic (Frijhoff and Spies, 1999). In the Habsburg Netherlands power relations were more vertically structured than in the Dutch Republic. But just as in the Republic, literacy levels in these regions remained high and a reading culture was firmly rooted amongst urban populations (Jacobs and Verberckmoes, 2006). Therefore authorities made use of pamphlets to win over public opinion. Due to their realistic settings, dialogue pamphlets were particularly suited to enact power relations and to enhance the confessionalisation process.
In this paper, I shall analyze Hazart’s dialogue pamphlets. As a preacher of the Antwerp St Ignatius church he was a well-known polemicist. In particular, after the Peace of Munster, when relationships with the Dutch Republic were restored, Hazart used this form. Apparently, he and his fellow clergymen feared that Catholics, who had frequent contacts with northerners, would be lured into Protestantism. Not surprisingly, a detailed reading of Hazart’s dialogue pamphlets reveals that he emphasized the catholic stance on controversial points of doctrine. Moreover, and maybe more importantly, he ridiculed his counterparts, the protestant ministers. Thereby he created powerful stereotypes that would be deeply rooted in the collective imagery of the post Tridentine Catholic Netherlands.
Source material
A corpus of dialogue pamphlets by Cornelius Hazart has been compiled by searches into the STCV-database.
Basic references
C. Dingemanse, Rap van tong, scherp van pen: Literaire discussiecultuur in Nederlandse praatjespamfletten (circa 1600-1750). (Hilversum, 2008).
W. Frijhoff and M. Spies, 1650. Bevochten eendracht (The Hague, 1999).
M. Jacobs and J. Verberckmoes, ‘Populair drukwerk’ in P. Janssens ed. België in de 17de eeuw. De Spaanse Nederlanden en het Prinsbisdom Luik. Band II: Cultuur en Leefwereld (Brussels and Gent, 2006) 106-110.
B. Martens, ‘Nederlandse religieuze controversepublicaties en de kunst van het argumenteren in de Zuidelijke Nederlanden (ca. 1591-c. 1688)’, in Trajecta, 19-20 (2012), 241-272.status: Publishe
Heat recovery from molten CuCl in the Cu–Cl cycle of hydrogen production
No full textThe copper–chlorine (Cu–Cl) cycle of thermochemical hydrogen production requires heat recovery from molten CuCl at various points within the cycle. This paper examines the convective heat transfer between molten CuCl droplets and air in a counter-current spray flow heat exchanger. This direct contact heat exchanger is analyzed as a proposed new method of recovering heat from the solidified molten CuCl. Effective thermal management within the Cu–Cl cycle is crucial for achieving high thermal efficiency. The cycle’s efficiency is improved drastically when all heat released by the products of reactions is recycled internally. Recovering heat from molten CuCl is very challenging due to the phase transformations of molten CuCl, as it cools from liquid to different solid states. In this paper, a spray column direct contact heat exchanger is analyzed for the heat recovery process. A predictive model of heat transfer and droplet flow is developed and then solved numerically. The results indicate that full heat recovery is achieved with a heat exchanger diameter of 0.13 m, and heights of 0.6 and 0.8 m, for a 1 and 0.5 mm droplet diameter, respectively. Additional results are presented and discussed for heat recovery from molten CuCl in the thermochemical Cu–Cl cycle.Atomic Energy of Canada LimitedOntario Research Fun
Newton polygons and curve gonalities
No full textWe give a combinatorial upper bound for the gonality of a curve that is defined by a bivariate Laurent polynomial with given Newton polygon. We conjecture that this bound is generically attained, and provide proofs in a considerable number of special cases. One proof technique uses recent work of M. Baker on linear systems on graphs, by means of which we reduce our conjecture to a purely combinatorial statement.sponsorship: We are very grateful to an anonymous referee for his valuable comments, which led to the proof of Theorem 11. We would also like to thank Marc Coppens, Hendrik Hubrechts, Bjorn Poonen, Jan Schepers, Jan Tuitman and Wim Veys for some helpful discussions. The first author thanks the Massachusetts Institute of Technology for its hospitality. Both authors where supported by the Fund for Scientific Research Flanders (F.W.O. Vlaanderen). (Fund for Scientific Research Flanders (F.W.O. Vlaanderen))status: Publishe
Mesoscale boundary layer development over mountainous terrain
No full textNovember 1985.Also issued as author's dissertation (Ph.D.) -- Colorado State University, 1985.The diurnal evolution of the mesoscale boundary layer ( ~ 50 km) over gently sloping terrain upwind of a high mountain barrier is described using both observational data and results from numerical model simulations . Atmospheric sounding data are presented from two nights , one during the summer and the second during the winter, when the mesoscale nocturnal boundary layer development was observed . Subsequently, a series of two and three-dimensional numerical model experiments are presented which identify the important physical processes responsible for the observed features. A conceptual model of mesoscale boundary layer evolution is then presented that accounts for the principle dynamic mechanisms discerned from analysis of the observational and simulated cases. Observational data from both nights reveal that the nocturnal boundary layer (NBL) extends 200-500 m above the valley ridgetops and plateaus and cools 1-4 K. Found within this layer are topographically induced thermal winds of 1-5 m s-l which either produce mesoscale circulations or influence the prevailing synoptic wind fields. The summer night data reveal that when the prevailing geostrophic wind is less than 7-10 m s-l at 500 mb and contains ro component into the high barrier, a complete mountain-plain circulation forms over the plateaus and ridges and down valley winds in ·the underlying valleys are strong. Contrasted with this is the winter case in which a much stronger geostrophic wind ( ~ 15 m s-l at 500 mb) directed into the barrier inhibited the mountain-plain circulation . In this case, there was a wide mesoscale variability in nocturnal boundary layer structure . One numerical experiment realistically simulated the diurnal evolution of the mesoscale boundary layer through a complete cycle encompassing the evening and morning transition periods. Additional simulations reveal that surface cooling and the shear between low-level thermal f lows and the overlying winds produce a 300 -500 m deep NBL 3-5 h after sunset. The nocturnal stable layer contains decoupled wind regions and can form a blocked wind region upwind of the barrier. In all cases, the nocturnal thermal wind component was 4-5 m s-l directed away from the barrier. It is also demonstrated that full three-dimensional model configuration are necessary to adequately describe the evolution of three-dimensional boundary layer structure.Sponsored by the National Science Foundation ATM-83-04328
Resonant space: religion, theatre, and the Chinese martial arts
No full textResonant Space constellates the martial, ritual, and theatrical elements of the Chinese martial arts with the practice of contemporary theatre and dance. This interdisciplinary approach blends the embodied experiences of the author, a lifelong student of the Chinese martial arts and a theatre director and dance dramaturg, with the study of Chinese cultural history. This is a work for scholars and practitioners of the Chinese martial arts, of contemporary dance and theatre, and for scholars of Chinese religion and cultural history
Dopamine restores reward prediction errors in old age
No full textSenescence affects the ability to utilize information about the likelihood of rewards for optimal decision-making. Using functional magnetic resonance imaging in humans, we found that healthy older adults had an abnormal signature of expected value, resulting in an incomplete reward prediction error (RPE) signal in the nucleus accumbens, a brain region that receives rich input projections from substantia nigra/ventral tegmental area (SN/VTA) dopaminergic neurons. Structural connectivity between SN/VTA and striatum, measured by diffusion tensor imaging, was tightly coupled to inter-individual differences in the expression of this expected reward value signal. The dopamine precursor levodopa (L-DOPA) increased the task-based learning rate and task performance in some older adults to the level of young adults. This drug effect was linked to restoration of a canonical neural RPE. Our results identify a neurochemical signature underlying abnormal reward processing in older adults and indicate that this can be modulated by L-DOPA
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