DNA unzipped under a constant force exhibits multiple metastable intermediates

Single molecule studies, at constant force, of the separation of double-stranded DNA into two separated single strands may provide information relevant to the dynamics of DNA replication. At constant applied force, theory predicts that the unzipped length as a function of time is characterized by jumps during which the strands separate rapidly, followed by long pauses where the number of separated base pairs remains constant. Here, we report previously uncharacterized observations of this striking behavior carried out on a number of identical single molecules simultaneously. When several single lphage molecules are subject to the same applied force, the pause positions are reproducible in each. This reproducibility shows that the positions and durations of the pauses in unzipping provide a sequence-dependent molecular fingerprint. For small forces, the DNA remains in a partially unzipped state for at least several hours. For larger forces, the separation is still characterized by jumps and pauses, but the double-stranded DNA will completely unzip in less than 30 min

Frederic W. Goudy Correspondence 1935-1946

American printing of the late nineteenth century was crude and commercial in the worst sense. The ideals and vitality that William Morris, Emery Walker, C. H. St. John Hornby, Charles Ricketts, T.J. Cobden-Sanderson and others injected into English printing during the last decades of the nineteenth century and into the twentieth were known to relatively few Americans. One of those few Americans was Frederic W. Goudy, March 8, 1865--May 11, 1947. Paul Johnston in an article for the Fleuron (No. VII, 1930, p. 191A) wrote, It was the part of Frederic W. Goudy to help the general printer in America to understand and to learn from the movement which began with Morris. And it is to Mr Goudy that American printing owes much of the strength and charm which may be claimed for the common, as well as the fine, work to-day. Goudy\u27s activities in printing-related fields included type design and manufacture, writing and speaking to the public about the principles of letter forms, type design and typography, and operation with his family of a private press for thirty-odd years. Through these activities Goudy\u27s influence on printing was amazingly great, yet no analytical and thorough studies of him exist. Rochester Institute of Technology received in 1975 several boxes of Goudy\u27s private correspondence. Most of the approximately 1600 letters were addressed to Goudy during the years 1936-1946. The correspondents were printers, educators, type foundry personnel, book collectors, equipment manufacturers, family and friends, and their letters deal with business as well as personal activities. This thesis has involved editing the letters into a calendar. The contents of each letter has been abstracted, with important information being quoted. Background material has been added to clarify an entry or to refer to related correspondence. Indexes of personal and company names and Goudy type faces have been prepared as reference aids to the calendar. The entries have been arranged chronologically to follow Goudy s daily life in the ten year period. It was expected that a calendar form of the correspondence would allow the material therein to be fully utilized. Further, it was hoped that the information in the letters would contribute measurably to a serious study of Frederic Goudy. It will be for future Goudy researchers to test those expectations, but confirmation seems probable

Is it cricket? : an ethical evaluation of race qoutas in sport

Includes bibliographical references (leaves 95-97).The paper begins by distinguishing the most common justifications for affirmative action and situating the use of quotas within that framework. It is suggested that the arguments evaluated in the paper are useful in attempting to justify not only the quota system, but also other policies which make use of racial preference. Both justice-based and consequentialist arguments to defend the quota system are discussed at length, with both being found to be unsatisfactory in their attempts to justify the "reverse discrimination" found in the quota system and other policies which make use of racial preference

Cinema contested: regulation of cinema in the late Ottoman Empire

Cinema Contested explores cinema regulations of the late Ottoman Empire (1890s- 1920s). The dissertation uses Ottoman Turkish, French, Turkish, and U.S. archival sources to delineate the intentions of regulators, the practises and the impact of regulation on cinema’s development across the sprawling Ottoman Empire. From the late nineteenth century, nationalist uprisings weakened the political authority of Sultan Abdülhamid II (r. 1876-1909). In the early twentieth century, oppositional political groups pressed for constitutional government, which led to a political reformation. During the final years of the Empire, the turbulent conditions of World War I (1914-1918) created territorial and demographic transformations. Films were initially exhibited in this complex context, principally by foreign itinerant exhibitors, and quickly thereafter by Ottoman merchants. Regulation followed quickly, shaped by the concerns of the political and elite classes in relation to education, Islamic morality, and politics. These regulations also addressed the material operations of cinema, including safety, zoning, and licensing procedures. Cinema came under regulatory scrutiny as did printed media and public entertainments vis-à-vis its political function. Yet, the authorities’ lax enforcement practises created a complex and ambiguous system. Ottoman legislators drafted a number of regulations over film exhibition, production and circulation. Multiple government agencies, at the central and local levels, endeavoured to control exhibition practises and venues. Regulations targeted specific audiences, notably children and women, who were seen as the ‘future of the state’ and ‘bearers of the nation’. Discourses and practises of the Ottoman dominant class became particularly visible in the attempts to limit cinemagoing, ban certain films, or promote educational and ‘harmless’ productions for ‘vulnerable’ audiences. This process was not simply repressive, but also helped shape how cinema would develop in the region. The dissertation provides a detailed historical analysis of the primary sources in order to reconstruct the multifaceted landscape of cinema regulations in this tumultuous region and period

Stretching and relaxation dynamics in double stranded DNA

We study numerically the mechanical stability and elasticity properties of duplex DNA molecules within the frame of a network model incorporating microscopic degrees of freedom related with the arrangement of the base pairs. We pay special attention to the opening-closing dynamics of double-stranded DNA molecules which are forced into non-equilibrium conformations. Mechanical stress imposed at one terminal end of the DNA molecule brings it into a partially opened configuration. We examine the subsequent relaxation dynamics connected with energy exchange processes between the various degrees of freedom and structural rearrangements leading to complete recombination to the double-stranded conformation. The similarities and differences between the relaxation dynamics for a planar ladder-like DNA molecule and a twisted one are discussed in detail. In this way we show that the attainment of a quasi-equilibrium regime proceeds faster in the case of the twisted DNA form than for its thus less flexible ladder counterpart. Furthermore we find that the velocity of the complete recombination of the DNA molecule is lower than the velocity imposed by the forcing unit which is in compliance with the experimental observations for the opening-closing cycle of DNA molecules.Comment: 21 pages, 9 figure

Investigation of Lung Structure-Function Relationships Using Hyperpolarized Noble Gases

Magnetic Resonance Imaging (MRI) is an application of the nuclear magnetic resonance (NMR) phenomenon to non-invasively generate 3D tomographic images. MRI is an emerging modality for the lung, but it suffers from low sensitivity due to inherent low tissue density and short T2*. Hyperpolarization is a process by which the nuclear contribution to NMR signal is greatly enhanced to more than 100,000 times that of samples in thermal equilibrium. The noble gases 3He and 129Xe are most often hyperpolarized by transfer of light angular momentum through the electron of a vaporized alkali metal to the noble gas nucleus (called Spin Exchange Optical Pumping). The enhancement in NMR signal is so great that the gas itself can be imaged via MRI, and because noble gases are chemically inert, they can be safely inhaled by a subject, and the gas distribution within the interior of the lung can be imaged. The mechanics of respiration is an elegant physical process by which air is is brought into the distal airspaces of the lungs for oxygen/carbon dioxide gas exchange with blood. Therefore proper description of lung function is intricately related to its physical structure, and the basic mechanical operation of healthy lungs -- from pressure driven airflow, to alveolar airspace gas kinetics, to gas exchange by blood/gas concentration gradients, to elastic contraction of parenchymal tissue -- is a process decidedly governed by the laws of physics. This dissertation will describe experiments investigating the relationship of lung structure and function using hyperpolarized (HP) noble gas MRI. In particular HP gases will be applied to the study of several pulmonary diseases each of which demonstrates unique structure-function abnormalities: asthma, cystic fibrosis, and chronic obstructive pulmonary disease. Successful implementation of an HP gas acquisition protocol for pulmonary studies is an involved and stratified undertaking which requires a solid theoretical foundation in NMR and hyperpolarization theory, construction of dedicated hardware, development of dedicated software, and appropriate image analysis techniques for all acquired data. The author has been actively involved in each of these and has dedicated specific chapters of this dissertation to their description. First, a brief description of lung structure-function investigations and pulmonary imaging will be given (chapter 1). Brief discussions of basic NMR, MRI, and hyperpolarization theory will be given (chapters 2 and 3) followed by their particular methods of implementation in this work (chapters 4 and 5). Analysis of acquired HP gas images will be discussed (chapter 6), and the investigational procedures and results for each lung disease examined will be detailed (chapter 7). Finally, a quick digression on the strengths and limitations of HP gas MRI will be provided (chapter 8)

Unzipping Dynamics of Long DNAs

The two strands of the DNA double helix can be `unzipped' by application of 15 pN force. We analyze the dynamics of unzipping and rezipping, for the case where the molecule ends are separated and re-approached at constant velocity. For unzipping of 50 kilobase DNAs at less than about 1000 bases per second, thermal equilibrium-based theory applies. However, for higher unzipping velocities, rotational viscous drag creates a buildup of elastic torque to levels above kBT in the dsDNA region, causing the unzipping force to be well above or well below the equilibrium unzipping force during respectively unzipping and rezipping, in accord with recent experimental results of Thomen et al. [Phys. Rev. Lett. 88, 248102 (2002)]. Our analysis includes the effect of sequence on unzipping and rezipping, and the transient delay in buildup of the unzipping force due to the approach to the steady state.Comment: 15 pages Revtex file including 9 figure

Cultural Technology and Sporting Value: A Philosophical Investigation

Few people would dispute that today’s world is highly technological. But what do we mean when we talk of ‘technology’, and is it possible to quantify its effect on human beings? This thesis considers the relationship between technology and humanity as being one of symbiosis - we shape our tools and in turn, our tools shape us. The nature of this relationship is described by ‘essentialist’ critics of technology as narrowing the focus of human endeavour towards a technological value-set dominated by efficiency, to the detriment of other values important to the human animal. Sport provides an excellent framework for examining the impact of technology defined in this way, as it is a ubiquitous and highly technological arena. If it can be plausibly argued that an increasingly technological and performance-centred approach to sport is detrimental to an holistic understanding of sport’s potential to benefit both the individual and society as a whole, it may be the case that sport provides accessible and irrefutable evidence for the truth of the essentialists’ claims regarding the impact on society of technology writ large. This thesis presents such an argument. Furthermore, if we grant the essentialist critics their contention and admit the impossibility of returning to an ‘untechnological’ world, we have to find some way of restoring and maintaining an holistic existence in the face of the restricted value-set imposed by our technology and our interactions with it. To this end, the latter part of this thesis promotes ‘metaphysical’ sporting values (freedom, self-affirmation and beautiful, harmonious action) as a way to counter-balance the impact of technology in sport and suggest ways to solve the ‘technological problem’ more generally