New genetic markers for treatment personalization in pediatric acute lymphoblastic leukemia

La Leucemia Linfoblástica Aguda (LLA) es el cáncer pediátrico más común. Es un desorden de las células linfoblásticas, que son las precursoras de las células linfáticas, y se caracteriza por la acumulación en médula ósea y sangre de pequeñas células blásticas con poco citoplasma y cromatina dispersa. En las últimas décadas, se ha conseguido aumentar la supervivencia del 10% al 80% pero todavía hay un 20% de pacientes que no responden al tratamiento. Esta mejoría se ha conseguido mediante la implantación de terapias combinadas y la adecuación de la terapia a grupos de riesgo. Los pacientes se separan en tres grupos de riesgo, Riesgo Estándar (RE), Alto Riesgo (AR) y Muy Alto Riesgo (MAR), en base a marcadores pronósticos, entre los que se incluyen alteraciones citogenéticas. Sin embargo, a lo largo del tratamiento, nos encontramos con dos problemas:1) Por un lado, algunos de los pacientes incluidos en el grupo de RE y AR no responden bien al tratamiento y pasan AR y MAR respectivamente. Esto quiere decir que los grupos de riesgo no están bien definidos. Por lo tanto, sería de interés poder caracterizar los pacientes que realmente son RE y AR y aquéllos que desde un principio deberían haber sido considerados como de mayor riesgo.2) Por otro lado, un alto porcentaje de pacientes experimenta toxicidad, que puede llegar a ser muy grave en algunos casos, siendo necesario parar el tratamiento. Por este motivo, sería altamente beneficioso poder reconocer a los pacientes que van a ser más sensibles al tratamiento para, de ese modo, poder ajustar la dosis.Por todo esto, creemos que una mejor asignación de los pacientes de LLA a grupos de riesgo y la personalización de la dosis, mediante nuevos marcadores genéticos, permitiría mejorar la respuesta al tratamiento.En este estudio nos planteamos, por lo tanto, dos objetivos: 1) Llevar a cabo la identificación de nuevas alteraciones genéticas presentes en el tumor para una mejor caracterización del riesgo y 2) Realizar una caracterización genética del individuo que permita predecir la respuesta al tratamiento.

An environmental assessment of the John Pennekamp Coral Reef State Park and the Key Largo Coral Reef Marine Sanctuary (Unpublished 1983 Report)

The Pennekamp Coral Reef State Park was established in 1960 and the Key Largo National Marine Sanctuary in 1975. Field studies, funded by NOAA, were conducted in 1980 - 1981 to determine the state of the coral reefs and surrounding areas in relation to changing environmental conditions and resource management that had occurred over the intervening years. Ten reef sites within the Sanctuary and seven shallow grass and hardbottom sites within the Park were chosen for qualitative and quantitative studies. At each site, three parallel transects not less than 400 m long were run perpendicular to the reef or shore, each 300 m apart. Observations, data collecting and sampling were done by two teams of divers. Approximately 75 percent of the bottom within the 18-m isobath was covered by marine grasses, predominantly turtle grass. The general health of the seagrasses appeared good but a few areas showed signs of stress. The inner hardbottom of the Park was studied at the two entrances to Largo Sound. Though at the time of the study the North Channel hardbottom was subjected to only moderate boat traffic, marked changes had taken place over the past years, the most obvious of which was the loss of the extensive beds of Sargassum weed, one of the most extensive beds of this alga in the Keys. Only at this site was the green alga Enteromorpha encountered. This alga, often considered a pollution indicator, may denote the effects of shore run off. The hardbottom at South Channel and the surrounding grass beds showed signs of stress. This area bears the heaviest boat traffic within the Park waters causing continuous turbidity from boat wakes with resulting siltation. The offshore hardbottom and rubble areas in the Sanctuary appeared to be in good health and showed no visible indications of deterioration. Damage by boat groundings and anchors was negligible in the areas surveyed. The outer reefs in general appear to be healthy. Corals have a surprising resiliency to detrimental factors and, when conditions again become favorable, recover quickly from even severe damage. It is, therefore, a cause for concern that Grecian Rocks, which sits somewhat inshore of the outer reef line, has yet to recover from die-off in 1978. The slow recovery, if occurring, may be due to the lower quality of the inshore waters. The patch reefs, more adapted to inshore waters, do not show obvious stress signs, at least those surveyed in this study. It is apparent that water quality was changing in the keys. Water clarity over much of the reef tract was observed to be much reduced from former years and undoubtedly plays an important part in the stresses seen today over the Sanctuary and Park. (PDF contains 119 pages)

Guide to the meso-scale production of the copepod Acartia tonsa

This manual is intended as a guide for the daily production of a few million A. tonsa nauplii for feeding to marine vertebrates and invertebrates. This scale of production is greater than most research would require, but smaller than commercial production, hence the term meso-scale production. This manual will briefly describe the biology of Acartia tonsa Dana that is relevant to culture, the culture methodology for meso-scale production of their eggs and nauplii, the system components utilized in production, and how to construct a few simple tools useful for this scale of production. Commercial production of copepods requires much greater feed production than is described, or the development of an efficient artificial feed, and, therefore, is not the focus of this manual. (PDF conatains 29 pages.)

Educação para cidadania na simulação parlamentar : o caso do programa “deputado por um dia” da ALRS

Analisa o projeto "Deputado por um Dia", mantido desde 1999 pela Assembleia Legislativa do Rio Grande do Sul, que promove para os jovens estudantes a vivência da rotina dos deputados estaduais. A partir da recuperação de documentos e de entrevistas, analisa efeitos do programa sobre os jovens. Conclui-se que a experiência da decisão coletiva ajuda na percepção da complexidade do processo deliberativo e na criação de uma visão menos ingênua da política.

Oceanographic results during VERTEX particle interceptor trap experiment 17 August to 8 September 1980

This report presents oceanographic data supporting the detailed chemical studies in the VERTEX Particle Interceptor Trap (PIT) experiment off the central California coast. Prior to the deployment of the PITs, an oceanographic survey of the intended study area was made on R/V CAYUSE from 17 to 21 August 1980. During this cruise, twenty CTD stations (Fig. 1) were occupied in a grid centered about the PIT site selected earlier based on archival oceanographic data. During the second leg of the VERTEX experiment from 25 August to 3 September, CTO profiles were taken as time permitted. In addition, a short survey near the PITs was made on 2 September. The intent of the pre-deployment cruise was to obtain data characterizing the vertical and horizontal variability of physical and chemical properties and to map the geostrophic flow field. Toward this end, vertical profiles of salinity, temperature and dissolved oxygen were made using a Plessey 9040 CTOa profiler. Considerable effort was expended to make vertical beam attenuation profiles to

Simulación de sistemas Multi-Agente mediante un esquema Monte Carlo basado en ecuaciones diferenciales ordinarias

[ES] En este trabajo se expone una metodología para modelar un sistema Multi-Agente (SMA), para que sea equivalente a un sistema de Ecuaciones Diferenciales Ordinarias (EDO), mediante un esquema basado en el método de Monte Carlo. Se muestra que el SMA puede describir con mayor riqueza modelos de sistemas dinámicos con variables cuantificadas discretas. Estos sistemas son muy acordes con los sistemas biológicos y fisiológicos, como el modelado de poblaciones o el modelado de enfermedades epidemiológicas, que en su mayoría se modelan con ecuaciones diferenciales. Los autores piensan que las ecuaciones diferenciales no son lo suficientemente apropiadas para modelar este tipo de problemas y proponen que se modelen con una técnica basada en agentes. Se plantea un caso basado en un modelo matemático de Leucemia Mieloide Crónica (LMC) que se transforma en un SMA equivalente. Se realiza una simulación de los dos modelos (SMA y EDO) y se compara los resultados obtenidos.

Mejora en la eficiencia en el uso del agua y los nutrientes minerales en las plantas

Duración (en horas): Más de 50 horas. Destinatario: Estudiante y Docente

Role of G protein coupled inwardly rectifier K+ channels (GIRK) on the neurobiology depression

353 págs.

Processing NOAA Spectroradiometric Data

This report outlines the NOAA spectroradiometer data processing system implemented by the MLML_DBASE programs. This is done by presenting the algorithms and graphs showing the effects of each step in the algorithms. [PDF contains 32 pages]

Oceanographic Profiling and Spectroradiometer Observations from the MOCE-1 Cruise: 28 August to 8 October 1992

This report contains the frrst observations made for the Modis Optical Characterization Experiment (MOCE). Data presented here were obtained on the R/V DeSteiguer between 28 August and 8 October along the central California coast and in Monterey Bay. Three types of data are reported here: high spectral resolution radiometry at three depths for seven stations; salinity, temperature, fluorescence and beam attenuation profiles at the same stations; and total suspended matter and suspended organic carbon and nitrogen. [PDF contans 164 pages]

Histogénèse et structure de la glande hermaphrodite d'Helix pomatia (Linn.)

(PDF contains 267 pages)

Bularreko minbizia izan duten emakumeak jarduera fisikora itzultzeko jarduera fisikoaren programa baten garapena

Artikulu eta gida askoren literatura azterketa bat burutu da, patologiari buruzko beharrezko informazioa bilatzeko, bularreko minbizia izan dutenengan burutu behar den jarduera fisikoa ezagutzeko eta azkenik, programa fisiko baten garapena burutzeko. Lan honen helburu nagusia, osasunerako eta ongizaterako jarduera fisikoaren eremuan, bularreko minbizia izan duten emakumeentzako jarduera fisikora itzultzeko programa bat sortzea da.

Physical investigations of small particles : (I) aerosol particle charging and flux enhancement and (II) whispering gallery mode sensing

Part I

Particles are a key feature of planetary atmospheres. On Earth they represent the greatest source of uncertainty in the global energy budget. This uncertainty can be addressed by making more measurement, by improving the theoretical analysis of measurements, and by better modeling basic particle nucleation and initial particle growth within an atmosphere. This work will focus on the latter two methods of improvement.

Uncertainty in measurements is largely due to particle charging. Accurate descriptions of particle charging are challenging because one deals with particles in a gas as opposed to a vacuum, so different length scales come into play. Previous studies have considered the effects of transition between the continuum and kinetic regime and the effects of two and three body interactions within the kinetic regime. These studies, however, use questionable assumptions about the charging process which resulted in skewed observations, and bias in the proposed dynamics of aerosol particles. These assumptions affect both the ions and particles in the system. Ions are assumed to be point monopoles that have a single characteristic speed rather than follow a distribution. Particles are assumed to be perfect conductors that have up to five elementary charges on them. The effects of three body interaction, ion-molecule-particle, are also overestimated. By revising this theory so that the basic physical attributes of both ions and particles and their interactions are better represented, we are able to make more accurate predictions of particle charging in both the kinetic and continuum regimes.

The same revised theory that was used above to model ion charging can also be applied to the flux of neutral vapor phase molecules to a particle or initial cluster. Using these results we can model the vapor flux to a neutral or charged particle due to diffusion and electromagnetic interactions. In many classical theories currently applied to these models, the finite size of the molecule and the electromagnetic interaction between the molecule and particle, especially for the neutral particle case, are completely ignored, or, as is often the case for a permanent dipole vapor species, strongly underestimated. Comparing our model to these classical models we determine an “enhancement factor” to characterize how important the addition of these physical parameters and processes is to the understanding of particle nucleation and growth.

Part II

Whispering gallery mode (WGM) optical biosensors are capable of extraordinarily sensitive specific and non-specific detection of species suspended in a gas or fluid. Recent experimental results suggest that these devices may attain single-molecule sensitivity to protein solutions in the form of stepwise shifts in their resonance wavelength, \lambda_{R}, but present sensor models predict much smaller steps than were reported. This study examines the physical interaction between a WGM sensor and a molecule adsorbed to its surface, exploring assumptions made in previous efforts to model WGM sensor behavior, and describing computational schemes that model the experiments for which single protein sensitivity was reported. The resulting model is used to simulate sensor performance, within constraints imposed by the limited material property data. On this basis, we conclude that nonlinear optical effects would be needed to attain the reported sensitivity, and that, in the experiments for which extreme sensitivity was reported, a bound protein experiences optical energy fluxes too high for such effects to be ignored.

Watershed monitoring and the TMDL modeling to assess bacterial loading in estuarine environments to improve management

Shellfish bed closures along the North Carolina coast have increased over the years seemingly concurrent with increases in population (Mallin 2000). More and faster flowing storm water has come to mean more bacteria, and fecal indicator bacterial (FIB) standards for shellfish harvesting are often exceeded when no source of contamination is readily apparent (Kator and Rhodes, 1994). Could management reduce bacterial loads if the source of the bacteria where known? Several potentially useful methods for differentiating human versus animal pollution sources have emerged including Ribotyping and Multiple Antibiotic Resistance (MAR) (US EPA, 2005). Total Maximum Daily Load (TMDL) studies on bacterial sources have been conducted for streams in NC mountain and Piedmont areas (U.S. EPA, 1991 and 2005) and are likely to be mandated for coastal waters. TMDL analysis estimates allowable pollutant loads and allocates them to known sources so management actions may be taken to restore water to its intended uses (U.S. EPA, 1991 and 2005). This project sought first to quantify and compare fecal contamination levels for three different types of land use on the coast, and second, to apply MAR and ribotyping techniques and assess their effectiveness for indentifying bacterial sources. Third, results from these studies would be applied to one watershed to develop a case study coastal TMDL. All three watershed study areas are within Carteret County, North Carolina. Jumping Run Creek and Pettiford Creek are within the White Oak River Basin management unit whereas the South River falls within the Neuse River Basin. Jumping Run Creek watershed encompasses approximately 320 ha. Its watershed was a dense, coastal pocosin on sandy, relic dune ridges, but current land uses are primarily medium density residential. Pettiford Creek is in the Croatan National Forest, is 1133 ha. and is basically undeveloped. The third study area is on Open Grounds Farm in the South River watershed. Half of the 630 ha. watershed is under cultivation with most under active water control (flashboard risers). The remaining portion is forested silviculture.(PDF contains 4 pages)

Structural and mechanistic motifs in membrane proteins: the three-dimensional modelling of rhodopsin, band 3, and the nicotinic acetylcholine receptor

Because so little is known about the structure of membrane proteins, an attempt has been made in this work to develop techniques by which to model them in three dimensions. The procedures devised rely heavily upon the availability of several sequences of a given protein. The modelling procedure is composed of two parts. The first identifies transmembrane regions within the protein sequence on the basis of hydrophobicity, β-turn potential, and the presence of certain amino acid types, specifically, proline and basic residues. The second part of the procedure arranges these transmembrane helices within the bilayer based upon the evolutionary conservation of their residues. Conserved residues are oriented toward other helices and variable residues are positioned to face the surrounding lipids. Available structural information concerning the protein's helical arrangement, including the lengths of interhelical loops, is also taken into account. Rhodopsin, band 3, and the nicotinic acetylcholine receptor have all been modelled using this methodology, and mechanisms of action could be proposed based upon the resulting structures.

Specific residues in the rhodopsin and iodopsin sequences were identified, which may regulate the proteins' wavelength selectivities. A hinge-like motion of helices M3, M4, and M5 with respect to the rest of the protein was proposed to result in the activation of transducin, the G-protein associated with rhodopsin. A similar mechanism is also proposed for signal transduction by the muscarinic acetylcholine and β-adrenergic receptors.

The nicotinic acetylcholine receptor was modelled with four trans-membrane helices per subunit and with the five homologous M2 helices forming the cation channel. Putative channel-lining residues were identified and a mechanism of channel-opening based upon the concerted, tangential rotation of the M2 helices was proposed.

Band 3, the anion exchange protein found in the erythrocyte membrane, was modelled with 14 transmembrane helices. In general the pathway of anion transport can be viewed as a channel composed of six helices that contains a single hydrophobic restriction. This hydrophobic region will not allow the passage of charged species, unless they are part of an ion-pair. An arginine residue located near this restriction is proposed to be responsible for anion transport. When ion-paired with a transportable anion it rotates across the barrier and releases the anion on the other side of the membrane. A similar process returns it to its original position. This proposed mechanism, based on the three-dimensional model, can account for the passive, electroneutral, anion exchange observed for band 3. Dianions can be transported through a similar mechanism with the additional participation of a histidine residue. Both residues are located on M10.