Statistical mechanics of protein complexed and condensed DNA

In this thesis I treat various biophysical questions arising in the context of complexed / ”protein-packed” DNA and DNA in confined geometries (like in viruses or toroidal DNA condensates). Using diverse theoretical methods I consider the statistical mechanics as well as the dynamics of DNA under these conditions. In the first part of the thesis (chapter 2) I derive for the first time the single molecule ”equation of state”, i.e. the force-extension relation of a looped DNA (Eq. 2.94) by using the path integral formalism. Generalizing these results I show that the presence of elastic substructures like loops or deflections caused by anchoring boundary conditions (e.g. at the AFM tip or the mica substrate) gives rise to a significant renormalization of the apparent persistence length as extracted from single molecule experiments (Eqs. 2.39 and 2.98). As I show the experimentally observed apparent persistence length reduction by a factor of 10 or more is naturally explained by this theory. In chapter 3 I theoretically consider the thermal motion of nucleosomes along a DNA template. After an extensive analysis of available experimental data and theoretical modelling of two possible mechanisms I conclude that the ”corkscrew-motion” mechanism most consistently explains this biologically important process. In chapter 4 I demonstrate that DNA-spools (architectures in which DNA circumferentially winds on a cylindrical surface, or onto itself) show a remarkable ”kinetic inertness” that protects them from tension-induced disruption on experimentally and biologically relevant timescales (cf. Fig. 4.1 and Eq. 4.18). I show that the underlying model establishes a connection between the seemingly unrelated and previously unexplained force peaks in single molecule nucleosome and DNA-toroid stretching experiments. Finally in chapter 5 I show that toroidally confined DNA (found in viruses, DNAcondensates or sperm chromatin) undergoes a transition to a twisted, highly entangled state provided that the aspect ratio of the underlying torus crosses a certain critical value (cf. Eq. 5.6 and the phase diagram in Fig. 5.4). The presented mechanism could rationalize several experimental mysteries, ranging from entangled and supercoiled toroids released from virus capsids to the unexpectedly short cholesteric pitch in the (toroidaly wound) sperm chromatin. I propose that the ”topological encapsulation” resulting from our model may have some practical implications for the gene-therapeutic DNA delivery process.

Die Bedeutung von molekularem Sauerstoff für die Evolution des genetischen Codes

Die Entstehung und Evolution des genetischen Codes, der die Nukleotidsequenz der mRNA in die Aminosäuresequenz der Proteine übersetzt, zählen zu den größten Rätseln der Biologie. Die ersten Organismen, die vor etwa 3,8 Milliarden Jahren auf der Erde auftraten, nutzten einen ursprünglichen genetischen Code, der vermutlich ausschließlich abiotisch verfügbare Aminosäuren terrestrischer oder extraterrestrischer Herkunft umfasste. Neue Aminosäuren wurden sukzessive biosynthetisiert und selektiv in den Code aufgenommen, welcher in der modernen Form aus bis zu 22 Aminosäuren besteht. Die Ursachen für die Selektion und die Chronologie ihrer Aufnahme sind bis heute unbekannt und sollten im Rahmen der vorliegenden Arbeit erforscht werden. Auf Grundlage quanten-chemischer Berechnungen konnte in dieser Arbeit zunächst ein Zusammenhang zwischen der HOMO-LUMO-Energiedifferenz (H-L-Distanz), die ein inverses quanten-chemisches Korrelat für allgemeine chemische Reaktivität darstellt, und der chronologischen Aufnahme der Aminosäuren in den genetischen Code aufgezeigt werden. Demnach sind ursprüngliche Aminosäuren durch große H-L-Distanzen und neue Aminosäuren durch kleine H-L-Distanzen gekennzeichnet. Bei einer Analyse des Metabolismus von Tyrosin und Tryptophan, bei denen es sich um die beiden jüngsten Standard-Aminosäuren handelt, wurde ihre Bedeutung als Vorläufer von Strukturen ersichtlich, die sich durch eine hohe Redox-Aktivität auszeichnen und deren Synthese gleichzeitig molekularen Sauerstoff erfordert. Aus diesem Grund wurden die Redox-Aktivitäten der 20 Standard-Aminosäuren gegenüber Peroxylradikalen und weiteren Radikalen getestet. Die Untersuchungen ergaben eine Korrelation zwischen evolutionärem Auftreten und chemischer Reaktivität der jeweiligen Aminosäure, die sich insbesondere in der effizienten Reaktion zwischen Tryptophan bzw. Tyrosin und Peroxylradikalen widerspiegelte. Dies indizierte eine potentielle Bedeutung reaktiver Sauerstoffspezies (ROS) bei der Konstituierung des genetischen Codes. Signifikante Mengen an ROS wurden erst zu Beginn der Oxygenierung der Geobiosphäre, die als Great Oxidation Event (GOE) bezeichnet wird und vor circa 2,3 Milliarden Jahren begann, gebildet und müssen zur oxidativen Schädigung vulnerabler, zellulärer Strukturen geführt haben. Aus diesem Grund wurde das antioxidative Potential von Aminosäuren beim Prozess der Lipidperoxidation untersucht. Es konnte gezeigt werden, dass lipophile Derivate von Tryptophan und Tyrosin befähigt sind, die Peroxidation von Rattenhirnmembranen zu verhindern und humane Fibroblasten vor oxidativem Zelltod zu schützen. Daraus gründete sich das in dieser Arbeit aufgestellte Postulat eines Selektionsvorteils primordialer Organismen während des GOEs, die Tryptophan und Tyrosin als redox-aktive Aminosäuren in Membranproteine einbauen konnten und somit vor Oxidationsprozessen geschützt waren. Demzufolge wurde die biochemische Reaktivität als Selektionsparameter sowie oxidativer Stress als prägender Faktor der Evolution des genetischen Codes identifiziert.

Untersuchung der Ladung des Neutrons

Die Quantisierung der elektrischen Ladung ist eine der größten Fragestellungen der Physik, die bis heute nicht verstanden ist. Im Standardmodell der Teilchenphysik ist sie beispielsweise nicht mathematisch inhärent erklärbar. Dadurch wäre es möglich, dass das Neutron eine winzige Ladung tragen kann. In dieser Arbeit wurde eine Apparatur auf Grundlage eines Vorgängerexperiments entwickelt, mit der eine Untersuchung der Ladung des Neutrons mit höchster Präzision durchgeführt werden kann. Dabei werden ultrakalte Neutronen in einem optischen System einem elektrischen Feld zwischen zwei Elektrodenplatten ausgesetzt. In der ersten Ladungsmessung mit dieser Apparatur konnte eine statistische Sensitivität von δq≈2,4∙10⁻²⁰ e/√d erreicht werden. Diese Sensitivität ist die höchste, die bisher mit ultrakalten Neutronen für eine Ladungsmessung erreicht werden konnte. In dieser Arbeit wurde das Konzept des Vorgängerexperiments grundlegend überarbeitet, um die Sensitivität der Apparatur zu erhöhen. Es wurden detaillierte Untersuchungen der Systematik der Apparatur durchgeführt und das theoretische Potential der Sensitivität von derzeit δq≈10⁻²¹ e/√d ermittelt. Mit dieser Apparatur wurde der Grundstein für die Messung einer neuen niedrigeren oberen Grenze der elektrischen Ladung des Neutrons gelegt. In nächster Zeit kann dadurch eine niedrigere obere Grenze für die Ladung des Neutrons von q≈10⁻²² e erzielt werden.

Representations of the Human/ Nonhuman Primate Divide: the Influence of Science, Fiction, and Science-Fiction on the Concept of 'Being Human'

For as far back as human history can be traced, mankind has questioned what it means to be human. One of the most common approaches throughout Western culture's intellectual tradition in attempts to answering this question has been to compare humans with or against other animals. I argue that it was not until Charles Darwin's publication of The Descent of Man and Selection in Relation to Sex (1871) that Western culture was forced to seriously consider human identity in relation to the human/ nonhuman primate line. Since no thinker prior to Charles Darwin had caused such an identity crisis in Western thought, this interdisciplinary analysis of the history of how the human/ nonhuman primate line has been understood focuses on the reciprocal relationship of popular culture and scientific representations from 1871 to the Human Genome Consortium in 2000. Focusing on the concept coined as the "Darwin-Müller debate," representations of the human/ nonhuman primate line are traced through themes of language, intelligence, and claims of variation throughout the popular texts: Descent of Man, The Jungle Books (1894), Tarzan of the Apes (1914), and Planet of the Apes (1963). Additional themes such as the nature versus nurture debate and other comparative phenotypic attributes commonly used for comparison between man and apes are also analyzed. Such popular culture representations are compared with related or influential scientific research during the respective time period of each text to shed light on the reciprocal nature of Western intellectual tradition, popular notions of the human/ nonhuman primate line, and the development of the field of primatology. Ultimately this thesis shows that the Darwin-Müller debate is indeterminable, and such a lack of resolution makes man uncomfortable. Man's unsettled response and desire for self-knowledge further facilitates a continued search for answers to human identity. As the Human Genome Project has led to the rise of new debates, and primate research has become less anthropocentric over time, the mysteries of man's future have become more concerning than the questions of our past. The human/ nonhuman primate line is reduced to a 1% difference, and new debates have begun to overshadow the Darwin-Müller debate. In conclusion, I argue that human identity is best represented through the metaphor of evolution: both have an unknown beginning, both have an indeterminable future with no definite end, and like a species under the influence of evolution, what it means to be human is a constant, indeterminable process of change.

"Brethren upon the same level" : membership and class in Calumet's Masonic Lodge

The Keweenaw Peninsula of Upper Michigan was a ethnic conglomerate of cultures and ideas, with people attracted to the area by the mineral wealth found along the Copper Range. The center of copper mining from the mid 1860s to 1968 was in the vicinity of Calumet Township, home to the world-famous Calumet and Hecla Mining Company. The township depended on the mines and the company’s president Agassiz’s strove to make the area a “model community,” that included groups such as the Free and Accepted Masons. Men from myriad backgrounds arrived in Calumet from the British Isles, Germany, Finland, Eastern and Southern Europe and the Eastern United States. As in other communities from the time period these men formed common interest groups like Masonic Lodge 271, which received its charter in 1870. Gentlemen joined with merchants and craftsmen. They became “brethren upon the same level,” and were elevated to the status of Master Mason. This symbolic transformation within the Lodge removed the men from the “profane world” outside the sanctity of Masonry, and in the ritualistic transformation of the meeting they were reborn into Masonry’s sacred mysteries. Masonry acted as a means of moral guidance to men and gave them access to a larger social and economic community through a common connection of brotherhood. As the candidates moved through the three Blue Lodge degrees of Entered Apprentice, Fellowcraft, and Master Mason they saw each other as “brethren upon the same level” – all economic classes equal within the Masonic Lodge. To examine equality within Lodge 271, this study sorted workers into classes to allow a comparison of Lodge 271’s membership. Possibly a comparison between other lodges can be drawn from the membership. The Union Building in Calumet, MI will be examined for its role in the ritualistic transformation of Masonry as it housed Masonic activities and transformations. This transformation brought men into the lodge of brothers. While Masonry professed equality between members however, to what extent did the membership of the lodge reflect this between the brethren? To what extent did economic class determine who was made “brethren upon the same level? 1 Arthur Thurner, Calumet Copper and People: History of a Michigan Mining Community, 1864-1970 (Hancock, MI: Book Concern, 1974), 122.

TB research at UT-Houston--a review of cord factor: new approaches to drugs, vaccines and the pathogenesis of tuberculosis.

Tuberculosis remains a major threat as drug resistance continues to increase. Pulmonary tuberculosis in adults is responsible for 80% of clinical cases and nearly 100% of transmission of infection. Unfortunately, since we have no animal models of adult type pulmonary tuberculosis, the most important type of disease remains largely out of reach of modern science and many fundamental questions remain unanswered. This paper reviews research dating back to the 1950's providing compelling evidence that cord factor (trehalose 6,6 dimycolate [TDM]) is essential for understanding tuberculosis. However, the original papers by Bloch and Noll were too far ahead of their time to have immediate impact. We can now recognize that the physical and biologic properties of cord factor are unprecedented in science, especially its ability to switch between two sets of biologic activities with changes in conformation. While TDM remains on organisms, it protects them from killing within macrophages, reduces antibiotic effectiveness and inhibits the stimulation of protective immune responses. If it comes off organisms and associates with lipid, TDM becomes a driver of tissue damage and necrosis. Studies emanating from cord factor research have produced (1) a rationale for improving vaccines, (2) an approach to new drugs that overcome natural resistance to antibiotics, (3) models of caseating granulomas that reproduce multiple manifestations of human tuberculosis. (4) evidence that TDM is a key T cell antigen in destructive lesions of tuberculosis, and (5) a new understanding of the pathology and pathogenesis of postprimary tuberculosis that can guide more informative studies of long standing mysteries of tuberculosis.

Review of Clément Vidal, "The Beginning and the End. The Meaning of Life in a Cosmological Perspective"

No more ground control. Dissertations ideally always have been ambitious, and this one can’t claim to be too humble in these regards. Together the pieces of this work form a world view that the author confesses to finding ‘magnificent’. The story he tells is one in which intelligence and complexity are keys to unlock the universe’s mysteries. Vidal tackles questions like ‘What is philosophy?’, ‘Where does it all come from?’, Where are we going?’, ‘Are we alone in the universe?’ and even ‘What is good and what is evil?’. Questions which philosophers for ages have tried to answer.

Path characteristics and colony arrival-departure statistics of king penguins (Aptenodytes patagonicus) on Possession and Kerguelen Island

Orientation based on visual cues can be extremely difficult in crowded bird colonies due to the presence of many individuals. We studied king penguins (Aptenodytes patagonicus) that live in dense colonies and are constantly faced with such problems. Our aims were to describe adult penguin homing paths on land and to test whether visual cues are important for their orientation in the colony. We also tested the hypothesis that older penguins should be better able to cope with limited visual cues due to their greater experience. We collected and examined GPS paths of homing penguins. In addition, we analyzed 8 months of penguin arrivals to and departures from the colony using data from an automatic identification system. We found that birds rearing chicks did not minimize their traveling time on land and did not proceed to their young (located in creches) along straight paths. Moreover, breeding birds' arrivals and departures were affected by the time of day and luminosity levels. Our data suggest that king penguins prefer to move in and out of the colony when visual cues are available. Still, they are capable of navigating even in complete darkness, and this ability seems to develop over the years, with older breeding birds more likely to move through the colony at nighttime luminosity levels. This study is the first step in unveiling the mysteries of king penguin orientation on land.

Los "ejemplares raros" de Botánica del caos de Ana María Shuan

El acercamiento crítico a “Botánica del caos" de Ana María Shua se decide, fundamentalmente, desde el análisis de su paratexto en el que, siguiendo a Genette, se pone de manifiesto la dimensión pragmática de la obra, su relación con el lector. Se intenta dar a conocer la función de algunos de los elementos constitutivos en particular y en relación con el todo integrado. Los ingredientes del paratexto se disponen a la manera de cajas chinas y contienen misterios secretos desplegados en diferentes planos y dimensiones. Las conexiones del entramado perfecto de la estructura de la obra revelan una consideración minuciosa por parte de la autora que demuestra su oficio de acuerdo con los rasgos característicos del género que practica: el microrrelato.

La telefonía móvil : el impacto social

El objetivo de este proyecto ha sido el de realizar un análisis del importante desarrollo que han sufrido las telecomunicaciones, haciendo un especial hincapié en la telefonía móvil y el impacto y repercusión que ha causado actualmente en nuestra sociedad. Para ello se hará un repaso evolutivo de las tecnologías de la información y las telecomunicaciones, y se establecerá una relación entre la gran difusión de éstas y su efecto sobre los usos, y cambios percibidos por los consumidores del nuevo siglo. Ciertamente la historia de la tecnología, nos enseña que la gente y las organizaciones acaban utilizándola para unos propósitos muy diferentes de aquellos que inicialmente fueron concebidas. Además cuanto más interactiva sea una tecnología, tanto más probable será que los usuarios se conviertan en productores o modificadores de la misma. Por tanto, la sociedad necesita resolver las incógnitas que pueda suscitar el rápido y continúo cambio de las comunicaciones. Este proyecto trata de ayudar a responder alguna de las cuestiones que actualmente se están planteando. ¿Son los teléfonos móviles una expresión de identidad, artilugios de moda, herramientas de la vida cotidiana, o todo lo anterior? ¿Existen nuevos modelos de comportamiento y conducta social? ¿La comunicación móvil está favoreciendo la aparición de una nueva cultura joven con un lenguaje propio basado en la comunicación textual y multimodal? ¿Tienen los teléfonos móviles efectos nocivos en la salud? La respuesta a estas preguntas afecta a nuestras vidas y también condiciona las políticas públicas y las estrategias de negocio, por eso requiere adquirir un conocimiento cimentado en la información, y la recopilación de datos de diversas fuentes, tanto de estadísticas provenientes de diferentes estudios e investigaciones, como de empresas consultoras, siempre basada en una perspectiva global. En conjunto, se espera dentro de los límites del conocimiento actual, contribuir a establecer las bases para el análisis y valoración de la relación existente entre comunicación, tecnología y sociedad en todo el mundo. Abstract The purpose of this project has been to analyse the significant development undergone by telecommunications, putting a special emphasis on mobile phones and the impact it has caused in society. We will go over the evolution of IT technologies and telecommunications as well as establish a relationship between its spread and effect of its uses and changes understood by the new century consumers. Technology history shows us that people and organizations use it for very different purposes from those originally thought. Furthermore, the more interactive technologies are, the more users will modify or produce it. Therefore, society needs to solve the mysteries of the quick and continuous change of communications. This project tries to help and answer some of the questions considered these days. Are mobile phones an expression of identity, fashionable devices, tools for everyday life or all at once? Are there any new models of performance and social behaviour? Is mobile communication favouring the existence of a new young culture with a typical language based on textual and multimodal communication? Are mobile phones bad for our health? The answer to these questions affects us all and conditions public politics and business strategies so it is required to get firm knowledge based on information. It is also important to compile data from various sources, from statistics of research and studies, based on a global perspective. As a whole, we hope to contribute to establish the bases for the future analysis and assessment of a fundamental trend that is redefining the relationship between communication, technology and society worldwide by transforming the wireless networks that make our lives.

Solution to Darwin's dilemma: Discovery of the missing Precambrian record of life

In 1859, in On the Origin of Species, Darwin broached what he regarded to be the most vexing problem facing his theory of evolution—the lack of a rich fossil record predating the rise of shelly invertebrates that marks the beginning of the Cambrian Period of geologic time (≈550 million years ago), an “inexplicable” absence that could be “truly urged as a valid argument” against his all embracing synthesis. For more than 100 years, the “missing Precambrian history of life” stood out as one of the greatest unsolved mysteries in natural science. But in recent decades, understanding of life's history has changed markedly as the documented fossil record has been extended seven-fold to some 3,500 million years ago, an age more than three-quarters that of the planet itself. This long-sought solution to Darwin's dilemma was set in motion by a small vanguard of workers who blazed the trail in the 1950s and 1960s, just as their course was charted by a few pioneering pathfinders of the previous century, a history of bold pronouncements, dashed dreams, search, and final discovery.

O livro infantil como ferramenta na educação artística e patrimonial : projeto editorial sobre património histórico-artístico de Lisboa

Children books can constitute an important tool to talk about art and heritage with children in preschool. The images and narrative help children to become aware that works of art can tell us stories and if they pay attention to the details they can discover their mysteries. The children book project: Ginja, um Gato Lisboeta is an example of that, revealing the history of the city through the adventures of a little girl and her cat Ginja, watching and discovering the heritage of Lisbon

Evans's Supper Rooms.

Binder's title.

Papers and addresses.

The stone mason of Cromarty -- Class-day poem -- Alchemy and the alchemists -- Twelfth-night observances -- Mysteries and masques -- The settlement of New Amsterdam -- Historical sketch of Christ church -- Ticonderoga and Crown Point -- New York in 1801 -- Mysterious disappearances and presumptions of death in insurance cases -- The law of mortmain -- The law of life insurance -- Speech at Boston, Mass. -- Speech at Savannah, Ga. -- Address to Boston life underwriters -- Speech at Wilmington, Del. -- Life insurance in its relation to legal medicine -- Speech at St. Nicholas club dinner -- Speech at dinner of alumni of Trinity College.