Síntese e testes in vitro de novas pirimido[5,4-d] pirimidinas em células resistentes do cancro coloretal

Dissertação de mestrado em Química Medicinal

A teoria ideal da justiça num mundo não ideal

Dissertação de mestrado em Filosofia (área de especialização em Filosofia Política)

A comunicação e a imagem do Gabinete de Apoio a Projectos: um estudo de caso

Dissertação de mestrado em Ciências da Comunicação (área de especialização em Publicidade e Relações Públicas)

Sistemas de Tipos para Verificación de Programas Concurrentes. Type Systems for Concurrent Programs Verification.

La programación concurrente es una tarea difícil aún para los más experimentados programadores. Las investigaciones en concurrencia han dado como resultado una gran cantidad de mecanismos y herramientas para resolver problemas de condiciones de carrera de datos y deadlocks, problemas que surgen por el mal uso de los mecanismos de sincronización. La verificación de propiedades interesantes de programas concurrentes presenta dificultades extras a los programas secuenciales debido al no-determinismo de su ejecución, lo cual resulta en una explosión en el número de posibles estados de programa, haciendo casi imposible un tratamiento manual o aún con la ayuda de computadoras. Algunos enfoques se basan en la creación de lenguajes de programación con construcciones con un alto nivel de abstración para expresar concurrencia y sincronización. Otros enfoques tratan de desarrollar técnicas y métodos de razonamiento para demostrar propiedades, algunos usan demostradores de teoremas generales, model-checking o algortimos específicos sobre un determinado sistema de tipos. Los enfoques basados en análisis estático liviano utilizan técnicas como interpretación abstracta para detectar ciertos tipos de errores, de una manera conservativa. Estas técnicas generalmente escalan lo suficiente para aplicarse en grandes proyectos de software pero los tipos de errores que pueden detectar es limitada. Algunas propiedades interesantes están relacionadas a condiciones de carrera y deadlocks, mientras que otros están interesados en problemas relacionados con la seguridad de los sistemas, como confidencialidad e integridad de datos. Los principales objetivos de esta propuesta es identificar algunas propiedades de interés a verificar en sistemas concurrentes y desarrollar técnicas y herramientas para realizar la verificación en forma automática. Para lograr estos objetivos, se pondrá énfasis en el estudio y desarrollo de sistemas de tipos como tipos dependientes, sistema de tipos y efectos, y tipos de efectos sensibles al flujo de datos y control. Estos sistemas de tipos se aplicarán a algunos modelos de programación concurrente como por ejemplo, en Simple Concurrent Object-Oriented Programming (SCOOP) y Java. Además se abordarán propiedades de seguridad usando sistemas de tipos específicos. Concurrent programming has remained a dificult task even for very experienced programmers. Concurrency research has provided a rich set of tools and mechanisms for dealing with data races and deadlocks that arise of incorrect use of synchronization. Verification of most interesting properties of concurrent programs is a very dificult task due to intrinsic non-deterministic nature of concurrency, resulting in a state explosion which make it almost imposible to be manually treat and it is a serious challenge to do that even with help of computers. Some approaches attempts create programming languages with higher levels of abstraction for expressing concurrency and synchronization. Other approaches try to develop reasoning methods to prove properties, either using general theorem provers, model-checking or specific algorithms on some type systems. The light-weight static analysis approach apply techniques like abstract interpretation to find certain kind of bugs in a conservative way. This techniques scale well to be applied in large software projects but the kind of bugs they may find are limited. Some interesting properties are related to data races and deadlocks, while others are interested in some security problems like confidentiality and integrity of data. The main goals of this proposal is to identify some interesting properties to verify in concurrent systems and develop techniques and tools to do full automatic verification. The main approach will be the application of type systems, as dependent types, type and effect systems, and flow-efect types. Those type systems will be applied to some models for concurrent programming as Simple Concurrent Object-Oriented Programming (SCOOP) and Java. Other goals include the analysis of security properties also using specific type systems.

Design of a bifurcated stent graft, with its accompanying delivery system.

Abdominal Aortic Aneurysms (AAA) haemorhaging is a life-threatening disease. An aneurysm is a permanent swelling of an artery due to a weakness in its wall. Current surgical repair involves opening the chest or abdomen, gaining temporary vascular control of the aorta and suturing a prosthetic graft to the healthy aorta within the aneurysm itself The outcome of this surgical approach is not perfect, and the quality of life after this repair is impaired by postoperative pain, sexual dysfunction, and a lengthy hospital stay resulting in high health costs. All these negative effects are related to the large incision and extensive tissue dissection. Endovascular grafting is an alternative to the standard surgical method. This treatment is a less invasive method of treating aortic aneurysms. It involves a surgical exposure of the common femoral arteries where the stent graft can be inserted through by an over-the-wire technique. All manipulations are controlled from a remote place by the use of a catheter and this technique avoids the need to directly expose the diseased artery through a large incision or an extensive dissection. The proposed design method outlined in this project is to develop the endovascular approach. The main aim is to design an unitary bifurcated stent graft (1 e- bifurcated graft as a single component) to treat these Abdominal Aortic Aneurysms. This includes the delivery system and deployment mechanism necessary to first accurately position the stent graft across the aneurysm sac and also across the iliac bifurcation, and secondly fix the stent graft in position by using expandable metal stents. Thus, excluding the aneurysm from the circulation and therefore preventing rupture. Miniaturisation is a critical aspect of this design, as the smaller the crimped stent graft the easier to guide through the vascular system to the desired location. Biocompatibility is an important aspect. The preferred materials for this prosthesis are to use Shape Memory Alloys for the stent and a multifilament fabric for the graft. A taper design is applied for the geometry as this gives a favourable flow characteristic and reduced wave reflections. Adequate testing of the stent graft to prove its durability and the ease of the method of deployment is a prerequisite. A bench test facility has being designed and build to replicate the cardiovascular system and the disease in question aortic aneurysms at the iliac bifurcation. The testing here shows the feasibility of the proposed delivery system and the durability of the stent graft across the aneurysm sac. Finally, these endovascular treatments offer the economic advantage of short hospital stays or even treatment as an outpatient, as well as elimination of the need for postoperative intensive care The risk of developing an aneurysm increases with age, that is one of the mam reasons to look for less invasive ways of treating aneurysms. Consequently, there is enormous pressure to develop and use these devices rapidly.

Hereditariedade da homeose

A preliminary account on the normal development of the imaginai discs in holometabolic Insects is made to serve as an introduction to the study of the hereditary homoeosis. Several facts and experimental data furnished specially by the students of Drosophila are brought here in searching for a more adequate explanation of this highly interesting phenomenon. The results obtained from the investigations of different homoeotic mutants are analysed in order to test Goldschmidt's theory of homoeosis. Critical examination of the basis on which this theory was elaborated are equally made. As a result from an extensive theoretical consideration of the matter and a long discussion of the most recent papers on this subject the present writer concludes that the Goldschmidt explanation of the homoeotic phenomena based on the action of diffusing substances produced by the genes, the "evocators", and on the alteration of the normal speed of maturation of the imaginai discs equally due to the activity of the genes, could not be proved and therefore should be abandoned. In the same situation is any other explanation like that of Waddington or Villee considered as fundamentally identical to that of Goldschmidt. In order to clear the problem of homoeosis in terms which seem to put the phenomenon in complete agreement with the known facts the present writer elaborated a theory first published a few years ago (1941) based entirely on the assumption that the imaginai discs are specifically determined by some kind of substances, probably of chemical nature, contained in the cytoplam of the cells entering in the consti- tution of each individual disc. These substances already present in the blastem of the egg in which they are distributed in a definite order, pass to different cells at the time the blastem is transformed into blastoderm. These substances according to their organogenic potentiality may be called antenal-substance, legsubstance, wing-substance, eye-substance, etc. The hipoderm of the embryo resulting from the multiplication of the blastoderm cells would be constituted by a series of cellular areas differing from each other in their particular organoformative capacity. Thus the hypoderm giving rise to the imaginai discs, it follows that each disc must have the same organogenic power of the hypodermal area it came from. Therefore the discs i*re determinated since their origin by substances enclosed in the cytoplasm of their cells and consequently can no longer alter their potentiality. When an antennal disc develops into a leg one can conclude that this disc in spite of its position in the body of the larva is not, properly speaking, an antennal disc but a true leg disc whose cells instead of having in their cytoplasm the antennal substance derived from the egg blastem have in its place the leg-substance. Now, if a disc produces a tarsus or an antenna or even a compound appendage partly tarsus-like, partly antenna-like, it follows tha,t both tarsal and antennal substances are present in it. The ultimate aspect of the compound structure depends upon the reaction of each kind of substance to the different causes influencing development. For instance, temperature may orient the direction of development either lowards arista or tarsus, stimulating, or opposing to the one or the other of these substances. Confering to the genes the faculty of altering the constitution of the substances containing in the cytoplasm forming the egg blastem or causing transposition of these substances from one area to another or promoting the substitution of a given substance by a different one, the hereditary homoeocis may be easily explained. However, in the opinion of the present writer cytoplasm takes the initiative in all developmental process, provoking the chromosomes to react specifically and proportionally. Accordingly, the mutations causing homoeotic phenomena may arise independently at different rime in the cytoplasm and in the chromosomes. To the part taken by the chromosomes in the manifestation of the homoeotic characters is due the mendalian ratio observed in homoeotic X normal crosses. Expression, in itself, is mainly due to the proportion of the different substances in the cells of the affected discs. Homoeotic phenomena not presenting mendelian ratio may appear as consequence of cytoplasmic mutation not accompanied by chromosomal mutation. The great variability in the morphology of the homoeotic characteres, some individual being changed towards an extreme expression of the mutant phenotype while others in spite of their homozigous constitution cannot be distinguished from the normal ones, strongly supports the interpretation based on the relative proportion of the determining substances in the discs. To the same interpretation point also asymetry and other particularities observed in the exteriorization of the phenomenon. In conformity with this new conception homoeosis should not prove homology of Insect appendages (Villee 1942) since a more replacement of substances may cause legs to develop in substitution of the wings, as it was already observed (requiring confirmation in the opinion of Bateson 1894, p. 184) and no one would conclude for the homology of these organs in the usual meaning of the term.

Formação das castas no gênero Melípona (Illiger, 1806)

The present work is destinated to prove that the castes : workers and queens, in Melipona bees are due to genetic factors and not to differences in food. 2) Material used: Hives of Melipona quadri-fasciata anthidioides (Lep. 1836), M. schenki schenki (Gribodo, 1893), M. fasciata rufiventris (Lep. 1836), M. quadri-fasciata vicina (Lep. 1836), M. marginata marginata (Lep. 1836), Apis mellifera (L. 1758). 3) It should be pointed out that in Melipona bees there are no royal cells for the queens, but all the cells are of the same size independently of being destinated for workers, queens or drones. The numerous queens which are born are killed soon after emerging from their cells. 4) Changes of feeding in quality and in quantity caused no variation of castes. The only variable factor is the size, which becomes bigger when the bee is well nourished. 5) The offsprings of 5 hives were examined : 3 of M. quadri-fasciata anthidioides (n.o 1, n.o 2 and n.o 3), 1 of M. quadri-fasciata vicina (n.o 4) and 1 of M. marginata marginata (n.o 5). Combs of about 40 cells were taken into laboratory and the type of bee registered immediately after emerging. The results of the counts were: BOX COMB WORKER QUEEN PERCENTAGE Σ X2 to 12,5% Nº 1 1th 69 8 10,4% 0, 3139 " 1 2nd 144 18 11,1% 0, 2856 " 2 1th 52 8 13,3% 0, 0384 " 3 1th 45 10 18,2% 1, 6736 " 4 1th 56 4 6,7% 1, 8686 " 4 2nd 29 4 12,1% 0,00432 Σ X2 to 25% " 5 1th 34 14 29,2% 0,44444 "5 2nd 83 27 24,5% 0, 0121 In the 4 first boxes there is a percentage of 11,63% queens and in the last there is a percentage of 25,95%. 6) These percentages are very near two genetical ratios: 12,5% or 7:1, and 25% or 3:1, which correspond to a trifactorial and a bifactorial back-cross. Carrying out a X² test no significant deviations were found ( X² to 12,5% and to 25% and table 1 to 4). 7) We suppose that the formula for the queen in the first case (11,65%) is: AaBbCc. Since the Melipona bees are arrhenotokous hymenopteres, the drones are haploid and may have any one of the following eight formulas, corresponding to the gonic segregation of the queem : ABC, ABc, Abc, Abc, AbC, aBC, aBc, abC, abc. Anyone combination of these males with the queen will give a segregation of 7 workers to 1 queen, since there is always only one triple heterozygote among the eight possible segregates (table 5). 8) In order to explain the second case, it is suffient to assume that in this species there are only two pairs of factors, the queen being the double heterozygote : AaBb, while the drones may have any one of the following constitutions: AB, Ab, aB and ab. Workers are again all diploids which are homozygous for one or both factors, for instance: AABB, AABb, AaBB, aaBb, AAbb, etc. (table 6). 9) It is suggested that the genus Melipona is an intermediary type between the solitary bees, where all females are fertile independently of their feeding, and the genera Apis and Trigona, where without special feeding all females are born sterile, while only specially fed females develop into fertile queens. 10) No speculations are put forward with regards to the evolutionary mechanism which may have been responsible for the development of the genetical determination of castes in Melipona, since it seems advisable point to extend the studies to other insects with complicated caste systems.

A influência da alimentação verde na postura

A test was conducted at Poultry Department of "Luiz de Queiroz" School of Agriculture to prove the effect of green feed on egg production. One hundred Rhode Island Red hens at plain laying period were divided in ten pens. The lot A was constituted of pens 1 to 5 and the lot B of pens 6 to 10. During 16 days the pens 1 to 5 did not receive green feed and the pens 6 to 10 received it with abundance. After and for a period of 30 days the situation was inverted. The analysis were made considering, a) the production of all chickens and b) discarding the chickens with irregular laying. In both cases the results were statistically insignificant, proving that green feed did not improve egg production.

Determinação da média aritmética e desvio padrão de quocientes de séries independentes e dependentes

The authors prove some approximate formulas for the computation of the mean and the standard error of quotients of two variates, correlated or uncorrelated, with not too high coefficient of variation. The formulas obtained are subsequently applied to some date on mensuration of horses of the Brazilian breed Mangalarga, by the eclectic system of LESBRE. The relsults obtained directly by the actual computation of the quotients as well as by means of the formulas with the aid of statistics of the numerators and the denominators are given in table 3, showing excellent agreement.

O depoimento da criança no processo civil e sua valoração probatória

O presente trabalho tem por objetivo examinar um dos meios de prova oral do processo civil, que é o depoimento da criança. Diante da existência de uma certa resistência quanto à utilização e validade deste meio de prova, foram destacados argumentos de direito probatório favoráveis à tomada do depoimento infantil, como o direito à prova no sistema da prova livre e na vertente do direito de ação e defesa, além da necessária comparação com o processo penal e o destaque aos princípios da proteção integral e do superior interesse da criança, os quais foram reforçados por outros de natureza médico-psicológica, que visaram a destacar a capacidade cognitiva da criança em recordar fatos e relatá-los. Após a desconstrução do modelo de exclusão prévia do depoimento infantil, a dissertação abordou os modelos de proteção para a audição judicial da criança, para se evitar a vitimização secundária da criança e exposição desnecessária às partes, advogados e juízes. Neste particular, foram revisados os modelos inglês do closed-circuit television - CCTV e argentino da Câmara de Gesell como paradigmas para vários outros países, inclusive o Brasil que tem incentivado o depoimento sem dano. Em derradeiro, foi examinada a valoração desse depoimento da criança, tomando-se por base a justificação lógico-racional da prova consubstanciada nos módulos de constatação, ocasião em que foi possível sublinhar que a utilização dos modelos e métodos de inquirição protetivos culminam em maior credibilidade ao depoimento da criança no processo civil e proporcionam a descoberta de falsidade voluntária ou não. Também no tópico da valoração da prova, o conteúdo do depoimento infantil vai trazer maior confiança quando conjugado com elementos intrínsecos, como a coerência do discurso e a ausência de contradições, e extrínsecos, realizado na modalidade protetiva.

Preparo de antígenos (Leprolinas Souza-Araujo) de culturas de bacilos ácido-álcool resistentes isolados de leprosos: seu emprêgo intradérmico, comparativamente com o da Lepromina, e subcutâneo ou intravenoso como tentativa terapêutica

The A. prepared five antigens from his leprosy cultures which by analogy with ROST's product he called Leprolins. The methods of its preparation and use are given. After a few tests to prove its innocuity for man the A. in cooperation with Dr. JOSÉ MARIANO, injected all five antigens intracutaneously in 120 patients. Now the products are being tested in 17 Leper Colonies of Brazil, in Argentina by Dr. SALOMON SCHUJMAN and in two leprosaria of Colombia. As antigen for skin tests the first results obtained are more or less identical with the results with Lepromin. Its use in serology for leprosy diagnosis will be made by Dr. T. PINTO of Rio, and Prof. LUIZ PRADO BARRIENTOS, of La Paz, Bolivia. As curative means the Leprolins are being injected into resistent lesions of leprosy and also by intraven injections, whose results Dr. José Mariano will publish soon. The Leprolins Souza-Araujo are put at disposal of all leprologists interested in its use.

Periodic orbits of the planar collision restricted 3-body problem

Using the continuation method we prove that the circular and the elliptic symmetric periodic orbits of the planar rotating Kepler problem can be continued into periodic orbits of the planar collision restricted 3–body problem. Additionally, we also continue to this restricted problem the so called “comets orbits”.

Clarke critical values of subanalytic Lipschitz continuous functions

We prove that any subanalytic locally Lipschitz function has the Sard property. Such functions are typically nonsmooth and their lack of regularity necessitates the choice of some generalized notion of gradient and of critical point. In our framework these notions are defined in terms of the Clarke and of the convex-stable subdifferentials. The main result of this note asserts that for any subanalytic locally Lipschitz function the set of its Clarke critical values is locally finite. The proof relies on Pawlucki's extension of the Puiseuxlemma. In the last section we give an example of a continuous subanalytic function which is not constant on a segment of "broadly critical" points, that is, points for which we can find arbitrarily short convex combinations of gradients at nearby points.

Polynomial-time complexity for instances of the endomorphism problem in free groups

We say the endomorphism problem is solvable for an element W in a free group F if it can be decided effectively whether, given U in F, there is an endomorphism Φ of F sending W to U. This work analyzes an approach due to C. Edmunds and improved by C. Sims. Here we prove that the approach provides an efficient algorithm for solving the endomorphism problem when W is a two- generator word. We show that when W is a two-generator word this algorithm solves the problem in time polynomial in the length of U. This result gives a polynomial-time algorithm for solving, in free groups, two-variable equations in which all the variables occur on one side of the equality and all the constants on the other side.

RECASTING THE ELLIOTT CONJECTURE

Let A be a simple, unital, finite, and exact C*-algebra which absorbs the Jiang-Su algebra Z tensorially. We prove that the Cuntz semigroup of A admits a complete order embedding into an ordered semigroup which is obtained from the Elliott invariant in a functorial manner. We conjecture that this embedding is an isomor phism, and prove the conjecture in several cases. In these same cases - Z-stable algebras all - we prove that the Elliott conjecture in its strongest form is equivalent to a conjecture which appears much weaker. Outside the class of Z-stable C*-algebras, this weaker conjecture has no known counterexamples, and it is plausible that none exist. Thus, we reconcile the still intact principle of Elliott's classification conjecture -that K-theoretic invariants will classify separable and nuclear C*-algebras- with the recent appearance of counterexamples to its strongest concrete form.