Top-down morphogenesis of colorectal tumors

One of the fundamental tenets of oncology is that tumors arise from stem cells. In the colon, stem cells are thought to reside at the base of crypts. In the early stages of tumorigenesis, however, dysplastic cells are routinely found at the luminal surface of the crypts whereas the cells at the bases of these same crypts appear morphologically normal. To understand this discrepancy, we evaluated the molecular characteristics of cells isolated from the bases and orifices of the same crypts in small colorectal adenomas. We found that the dysplastic cells at the tops of the crypts often exhibited genetic alterations of adenomatous polyposis coli (APC) and neoplasia-associated patterns of gene expression. In contrast, cells located at the base of these same crypts did not contain such alterations and were not clonally related to the contiguous transformed cells above them. These results imply that development of adenomatous polyps proceeds through a top-down mechanism. Genetically altered cells in the superficial portions of the mucosae spread laterally and downward to form new crypts that first connect to preexisting normal crypts and eventually replace them.

Replication infidelity during a single cycle of Ty1 retrotransposition.

Retroviruses undergo a high frequency of genetic alterations during the process of copying their RNA genomes. However, little is known about the replication fidelity of other elements that transpose via reverse transcription of an RNA intermediate. The complete sequence of 29 independently integrated copies of the yeast retrotransposon Ty1 (173,043 nt) was determined, and the mutation rate during a single cycle of replication was calculated. The observed base substitution rate of 2.5 x 10(-5) bp per replication cycle suggests that this intracellular element can mutate as rapidly as retroviruses. The pattern and distribution of errors in the Ty1 genome is nonrandom and provides clues to potential in vivo molecular mechanisms of reverse transcriptase-mediated error generation, including heterogeneous RNase H cleavage of Ty1 RNA, addition of terminal nontemplated bases, and transient dislocation and realignment of primer-templates. Overall, analysis of errors generated during Ty1 replication underscores the utility of a genetically tractable model system for the study of reverse transcriptase fidelity.

Prediction of the stability of DNA triplexes.

We present rules that allow one to predict the stability of DNA pyrimidine.purine.pyrimidine (Y.R.Y) triple helices on the basis of the sequence. The rules were derived from van't Hoff analysis of 23 oligonucleotide triplexes tested at a variety of pH values. To predict the enthalpy of triplex formation (delta H degrees), a simple nearest-neighbor model was found to be sufficient. However, to accurately predict the free energy of the triplex (delta G degrees), a combination model consisting of five parameters was needed. These parameters were (i) the delta G degrees for helix initiation, (ii) the delta G degrees for adding a T-A.T triple, (iii) the delta G degrees for adding a C(+)-G.C triple, (iv) the penalty for adjacent C bases, and (v) the pH dependence of the C(+)-G.C triple's stability. The fitted parameters are highly consistent with thermodynamic data from the basis set, generally predicting both delta H degrees and delta G degrees to within the experimental error. Examination of the parameters points out several interesting features. The combination model predicts that C(+) -G.C. triples are much more stabilizing than T-A.T triples below pH 7.0 and that the stability of the former increases approximately equal to 1 kcal/mol per pH unit as the pH is decreased. Surprisingly though, the most stable sequence is predicted to be a CT repeat, as adjacent C bases partially cancel the stability of one another. The parameters successfully predict tm values from other laboratories, with some interesting exceptions.

Voice-processing technologies--their application in telecommunications.

As the telecommunications industry evolves over the next decade to provide the products and services that people will desire, several key technologies will become commonplace. Two of these, automatic speech recognition and text-to-speech synthesis, will provide users with more freedom on when, where, and how they access information. While these technologies are currently in their infancy, their capabilities are rapidly increasing and their deployment in today's telephone network is expanding. The economic impact of just one application, the automation of operator services, is well over $100 million per year. Yet there still are many technical challenges that must be resolved before these technologies can be deployed ubiquitously in products and services throughout the worldwide telephone network. These challenges include: (i) High level of accuracy. The technology must be perceived by the user as highly accurate, robust, and reliable. (ii) Easy to use. Speech is only one of several possible input/output modalities for conveying information between a human and a machine, much like a computer terminal or Touch-Tone pad on a telephone. It is not the final product. Therefore, speech technologies must be hidden from the user. That is, the burden of using the technology must be on the technology itself. (iii) Quick prototyping and development of new products and services. The technology must support the creation of new products and services based on speech in an efficient and timely fashion. In this paper I present a vision of the voice-processing industry with a focus on the areas with the broadest base of user penetration: speech recognition, text-to-speech synthesis, natural language processing, and speaker recognition technologies. The current and future applications of these technologies in the telecommunications industry will be examined in terms of their strengths, limitations, and the degree to which user needs have been or have yet to be met. Although noteworthy gains have been made in areas with potentially small user bases and in the more mature speech-coding technologies, these subjects are outside the scope of this paper.

Contribuição ao conhecimento da malacofauna das camadas basais da Formação Corumbataí (Permiano), Estado de São Paulo

Os principais objetivos deste trabalho são: 1) estudar o material malacofaunístico de novos jazigos da região de Rio Claro - Piracicaba (SP) e de testemunhos de sondagem de Conchas (SP), referentes à porção basal da Formação Corumbataí, termo superior do Grupo Passa Dois de idade permiana e 2) determinar sua distribuição bioestratigráfica. Incluiu-se um exame parcial da provável correlação entre as faunas das bases das Formações Corumbataí (São Paulo) e Estrada Nova (Paraná) e considerações de ordem paleoecológica da malacofauna. A análise taxonômica dos bivalves da porção basal da Formação Corumbataí no Estado, forneceu apreciável diversidade genérica e específica. Duas secções colunares, uma de superfície e outra de subsuperfície são apresentadas, mostrando a distribuição bioestratigráfica dessa malacofauna. Os bivalves identificados e descritos nos diversos afloramentos foram: Angatubia cf. A. cowperesioides Mendes, Anthraconaia ? mezzalirai sp. n., Barbosaia cf. B. angulata Mendes, Barbosaia roxoi sp n., Casterella cf. C. camargoi Beurlen, Ferrazia simplicicarinata Mezzalira, Ferrazia sp., Holdhausiella elongata Mendes, Holdhausiella sp., Kidodia cf. K. stockleyi Cox, Mendesia piracicabensis gen. et sp. n., Plesiocyprinella sp., Rioclaroa cf. R. lefrevei Mezzalira. Com base na composição observada, sugeriu-se reunir as Zonas Leinzia froezi Mendes e Barbosaia angulata Mendes propostas por MEZZALIRA (1980) em uma única designada Zona Leinzia froezi - Barbosaia angulata. Os quatro níveis fossilíferos reconhecidos em subsuperfície (Poço 1-IG-Conchas) com as espécies: Casterella cf. C. gratiosa, Ferrazia cardinalis Reed e Pinzonella cf. P. illusa, a julgar pela distribuição vertical em relação à base da formação, situar-se-iam na Zona III de MEZZALIRA (1980) considerada quando definida como afossilífera. Dentre as principais conclusões, notou-se a predominância de bivalves com carenas simples e a duplas, provavelmente caráter adaptativo ao ambiente que seria provavelmente circunscrito, mixo-halino, de águas rasas, turvas e mal oxigenadas em certos intervalos.

Modelo de otimização multiobjetivo aplicado ao projeto de concepção de submarinos convencionais.

Este trabalho apresenta um modelo de otimização multiobjetivo aplicado ao projeto de concepção de submarinos convencionais (i.e. de propulsão dieselelétrica). Um modelo de síntese que permite a estimativa de pesos, volume, velocidade, carga elétrica e outras características de interesse para a o projeto de concepção é formulado. O modelo de síntese é integrado a um modelo de otimização multiobjetivo baseado em algoritmos genéticos (especificamente, o algoritmo NSGA II). A otimização multiobjetivo consiste na maximização da efetividade militar do submarino e na minimização de seu custo. A efetividade militar do submarino é representada por uma Medida Geral de Efetividade (OMOE) estabelecida por meio do Processo Analítico Hierárquico (AHP). O Custo Básico de Construção (BCC) do submarino é estimado a partir dos seus grupos de peso. Ao fim do processo de otimização, é estabelecida uma Fronteira de Pareto composta por soluções não dominadas. Uma dessas soluções é selecionada para refinamento preliminar e os resultados são discutidos. Subsidiariamente, esta dissertação apresenta discussão sucinta sobre aspectos históricos e operativos relacionados a submarinos, bem como sobre sua metodologia de projeto. Alguns conceitos de Arquitetura Naval, aplicada ao projeto dessas embarcações, são também abordados.

Digital Curation Program of the Digital Public Library of America (DPLA)

The Digital Public Library of America (DPLA) is a digital library that strives to serve the public through digital collections accumulated from a wide variety of partners. Our chosen topic for the DPLA exhibit project is Perspectives on the Vietnam War. The Vietnam War remains a controversial topic of national interest, making it a topic of depth and of many perspectives. Our goals with this exhibit were to gather different perspectives of the war through personal stories, the media, presidential administrations of the war, military personnel, and the general public, including famous figures. We strove to demonstrate the variety of perspectives on the Vietnam War through a variation of digital objects and content that will be engaging for users: both black and white and color photos, videos, and audio files. Furthermore, we wanted to ensure that our digital materials are of high quality, properly documented, and easy to search and find thus all of our objects are from DPLA and are from usable original sources. This poster will describe our processes for organizational, object selection, building our exhibit, attainment of our goals, and detailed steps of our overall operation. The poster will also include details about the minor issues and bumps that occurred while reaching our final product as well as the team members’ perspectives on the project as a whole including: problems, words to for the wise, and triumphs.

Opinions about judo athletes’ image

OBJECTIVE: The present study aimed to evaluate opinions of persons who are involved with judo about judo athletes’ personality. METHODS: For this purpose 132 coaches, athletes, students of Department of Physical Education and Sport Science (DEPESS) and students of military school answered to a 35-item questionnaire describing their image towards judo athletes, in regard to social, volition, active, physical and emotional nature. RESULTS: statistical analysis showed that all the groups rated from the average, to somewhat strong and, also, to strong, while coaches rated higher to the most items. More specifically, one way ANOVA revealed significant differences, with coaches rating significantly higher, in the items of “being healthy” in physical nature (F=2.85, p<0.05), in items “having proper manner” and “being sincere” in social nature, (F=3.41, p<0.05 and F=3.09, p<0.05 respectively), “being positive” in active nature (F=3.95, p<0.05). Also in the items “being mild” (F=3.04, p<0.05), “being cheerful” (F=3.60, p<0.05) and “being carefree” (F=2.98, p<0.05) in emotional nature. Moreover, students of military school rating significantly higher in the item of “being cautious” in active nature (F=2.51, p<0.05) and in the item of “having power of concentration” in active nature both students of military school and of DEPESS rating significantly higher (F=5.66, p<0.01). CONCLUSIONS: The high rating in the most items might be due to the nature of the attitudes provided and cultured during the judo lessons, practice time and matches. Moreover, the differences between the groups for the coaches group might be observed because they have the most real image for judo athletes.

Muro Mediterráneo: búnkeres y baterías para la defensa del litoral (1936-1939)

The Mediterranean wall, which is a collection of defensive constructions along the coast, was built during the Spanish War (1936-39) to prevent enemy attacks. It´s called this way like the Atlantic Wall, which was built after the Second World War. These group of buildings consist of batteries, bunkers and barracks placed along the coastline, sometimes next to another kind of infrastructure. Its location (typical of a military strategy) and its peculiar morphology are like another ones: the historical watchtowers ones. They were built by the Kingdom of Spain in the same geography four centuries earlier although, in our case, the buildings are updated to the conditions of contemporary wars: camouflage against air raids. A collection of anti-aircraft devices, placed along the coast since the late 1937, were risen following the instructions of the Valencian State to defend both citizens and cities from the aviation´s bombings. The following military settlements, organized from North to South, are part of the most relevant ones of the coast of Alicante: the Denia and Javea ones, the North of Alicante and Southwest of Alicante ones, the Portichol one, the Galvany´s Clot one and, finally, the Cape and Bay of Santa Pola ones. Remains of more than 60 architectural elements, that document the first concrete´s ruins, are still there. This paper tries to document all of them (providing their location, their morphological genealogy and including some drawings of the current state) to contribute to their revaluation and to help to their necessary protection. They are a legacy of architectural heritage which consolidates and increases the memory of our culture.

Voyage et campagnes au Canada / par M. le chevalier de D. L. P. : manuscript, 1757-1760

Describes his voyage to Canada from Brest, and his observations of military operations and Indians while in Louisbourg, Québec, and Fort Carillon.

Letters from Stanhope Prevost to William Tudor,

Three letters regarding the Chanca silver mine, news of Bolívar and other South American military officers, and news about mutual friends.

Bombay Harbour, India, Nautical Chart, 1806 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: A plan of Bombay harbour : principally illustrative of the entrance, constructed from measured bases, and a series of angles, taken in 1803 & 4 by James Horsburgh. It was published by James Horsburgh in 1806. Scale [ca.1:37,820].The image inside the map neatline is georeferenced to the surface of the earth and fit to the Kalianpur 1975 India Zone III projected coordinate system. All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. This map shows features such as drainage, cities and other human settlements, fortification, shoreline features (rocks, shoals, anchorage points, ports, inlets, lighthouses, etc.), and more. Relief shown by depth soundings. Includes also profile views and navigational notes.This layer is part of a selection of digitally scanned and georeferenced historic maps from the Harvard Map Collection. These maps typically portray both natural and manmade features. The selection represents a range of originators, ground condition dates, scales, and map purposes.

Maryland, West Virginia & Virginia : Civil War Telegram Map, 1862 (Raster Image)

This layer is a georeferenced raster image of the historic paper map: War telegram marking map. It was published by L. Prang & Co. in 1862. Scale [ca. 1:490,000]. Covers portions of Maryland, West Virginia, the District of Columbia, and eastern Virginia. The image inside the map neatline is georeferenced to the surface of the earth and fit to the Universal Transverse Mercator projection (WGS 1984 UTM Zone 18N). All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, or other information associated with the principal map. This map shows features such as roads, railroads, drainage, selected points of military interest, and more. Relief shown by hachures. Includes text: "Explanations.The extraordinary large scale on which this map is drawn has been adopted to make it just what we designed it to be, namely 1st. The most distinct map ever published of the whole Virginia territory, where the decisive battles for the Union will be fought. 2nd. A marking map, that is a map to mark the change of positions of the Union forces in red pencil and the rebel forces in blue, on the receipt of every telegram from the seat of war..." This layer is part of a selection of digitally scanned and georeferenced historic maps of the Civil War from the Harvard Map Collection. Many items from this selection are from a collection of maps deposited by the Military Order of the Loyal Legion of the United States Commandery of the State of Massachusetts (MOLLUS) in the Harvard Map Collection in 1938. These maps typically portray both natural and manmade features, in particular showing places of military importance. The selection represents a range of regions, originators, ground condition dates, scales, and purposes.

Charleston Harbor, South Carolina, 1863 (Raster Image)

This layer is a georeferenced raster image of the historic paper map: Charleston Harbor and its approaches showing the positions of the Rebel-batteries, [by] U.S. Coast Survey. It was published in 1863 by Lith. of J. Bien. Scale 1:30,000. Nautical chart covering Charleston Harbor and a portion of Charleston, South Carolina. The image inside the map neatline is georeferenced to the surface of the earth and fit to the South Carolina State Plane Coordinate System (in Meters) (Fipszone 3900). All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, or other information associated with the principal map. This map shows features such as roads, railroads, houses, vegetation, drainage, military batteries and fortifications, coastal features (shoals, rocks, channels, floating batteries, etc.) and more. Overprinted to show 1/4-mile concentric circles centered on St. Michaels, Charleston; positions occupied by the Union Army and Navy; "Rebel batteries in possession of National forces [and] batteries still held by the Rebels [on] Sept. 7th 1863." Union positions are based "on the authority of Maj. T.B. Brooks." Relief shown by hachures; depths shown by soundings and shading. This layer is part of a selection of digitally scanned and georeferenced historic maps of the Civil War from the Harvard Map Collection. Many items from this selection are from a collection of maps deposited by the Military Order of the Loyal Legion of the United States Commandery of the State of Massachusetts (MOLLUS) in the Harvard Map Collection in 1938. These maps typically portray both natural and manmade features, in particular showing places of military importance. The selection represents a range of regions, originators, ground condition dates, scales, and purposes.

Newport, Rhode Island, 1776 (Raster Image)

This layer is a georeferenced raster image of the historic map entitled: A plan of the town of Newport in the province of Rhode Island (sheet originally published in 1776). The map is [sheet 11] from the Atlantic Neptune atlas Vol. 3 : Charts of the coast and harbors of New England, from surveys taken by Samuel Holland and published by J.F.W. Des Barres, 1781. Scale [ca. 1:6,400]. The image is georeferenced to the surface of the earth and fit to the 'World Mercator' (WGS 84) projected coordinate system. All map collar information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, or other information associated with the principal map. This map shows features such as roads, public buildings, churches, wharves, American Revolution military defenses and structures, drainage, and more. Relief shown by hachures. Indexed for street names and points of interest. This layer is part of a selection of digitally scanned and georeferenced historic maps from The Harvard Map Collection. The entire Atlantic Neptune atlas Vol. 3 : Charts of the coast and harbors of New England has been scanned and georeferenced as part of this selection.