A Phase II Biomarker-Embedded Study of Lapatinib plus Capecitabine as First-line Therapy in Patients with Advanced or Metastatic Gastric Cancer

An exploratory phase II biomarker-embedded trial (LPT109747; NCT00526669) designed to determine the association of lapatinib-induced fluoropyrimidine gene changes with efficacy of lapatinib plus capecitabine as first-line treatment for advanced gastric cancer or gastroesophageal junction adenocarcinoma independent of tumor HER2 status. Tumor biopsies obtained before and after 7-day lapatinib (1,250 mg) to analyze changes in gene expression, followed by a 14-day course of capecitabine (1,000 mg/m(2) twice daily, 14/21 days) plus lapatinib 1,250 mg daily. Blood samples were acquired for pharmacokinetic analysis. Primary clinical objectives were response rate (RR) and 5-month progression-free survival (PFS). Secondary objectives were overall survival (OS), PFS, time to response, duration of response, toxicity, and identification of associations between lapatinib pharmacokinetics and biomarker endpoints. Primary biomarker objectives were modulation of 5-FU-pathway genes by lapatinib, effects of germline SNPs on treatment outcome, and trough steady-state plasma lapatinib concentrations. Sixty-eight patients were enrolled; (75% gastric cancer, 25% gastroesophageal junction). Twelve patients (17.9%) had confirmed partial response, 31 (46.3%) had stable disease, and 16 (23.9%) had progressive disease. Median PFS and OS were 3.3 and 6.3 months, respectively. Frequent adverse events included diarrhea (45%), decreased appetite (39%), nausea (36%), and fatigue (36%). Lapatinib induced no changes in gene expression from baseline and no significant associations were found for SNPs analyzed. Elevated baseline HER3 mRNA expression was associated with a higher RR (33% vs. 0%; P = 0.008). Lapatinib plus capecitabine was well tolerated, demonstrating modest antitumor activity in patients with advanced gastric cancer. The association of elevated HER3 and RR warrants further investigation as an important player for HER-targeted regimens in combination with capecitabine

Discovery of a New Retrograde Trans-Neptunian Object: Hint of a Common Orbital Plane for Low Semimajor Axis, High-inclination TNOs and Centaurs

Although the majority of Centaurs are thought to have originated in the scattered disk, with the high-inclination members coming from the Oort cloud, the origin of the high-inclination component of trans-Neptunian objects (TNOs) remains uncertain. We report the discovery of a retrograde TNO, which we nickname “Niku,” detected by the Pan-STARRS 1 Outer Solar System Survey. Our numerical integrations show that the orbital dynamics of Niku are very similar to that of 2008 KV42 (Drac), with a half-life of ˜500 Myr. Comparing similar high-inclination TNOs and Centaurs (q > 10 au, a <100 au, and i > 60°), we find that these objects exhibit a surprising clustering of ascending node, and occupy a common orbital plane. This orbital configuration has high statistical significance: 3.8-σ. An unknown mechanism is required to explain the observed clustering. This discovery may provide a pathway to investigating a possible reservoir of high-inclination objects.

Production of Gaseous Radiotracers Ch3i and I2 Through Na123i Salt

The objective of the present work was to develop, separately, methodology for production of two gaseous tracers through the sodium iodide NaI marked with 123I. Found in the nature in form different, the iodine has been used in diverse works in the area of the industry and health. These two forms of the gaseous iodine, the methyl iodide, CH3I, and molecular iodine, I2, are very unstable and volatile in the ambient temperature and presents different problems in clean-up and monitoring systems. The syntheses were processed with sodium iodide (NaI) 1M aqueous solution marked with 123I. The production of gas I2 was realized with in chlorine acid (HCl) and sodium iodate salt (NaIO3) and the CH3I was used, the salt of NaI and the reagent (CH3)2SO4. The production of gases was initially realized through in unit in glass with an inert material and the purpose was to study the kinetic of reaction and to determine the efficiency of production. The two synthesis occurs in the reaction bottle and after of produced, the gas is stored in the collect bottle that contains a starch solution for fixed the I2, and in syntheses of CH3I contains a silver nitrate solution for your fixation. To determine the efficiency of production of gases, analytic tests were realized, where the consumption of iodide ions of the bottle of reaction are measured. The optimization of production of the each gaseous tracer was studied varying parameter as: concentration of iodide, concentration of acid and temperature. After, the syntheses of the radiotracers were realized in the compact unit, having been used as main reagent the salt radiated of sodium iodide, Na123I. The transportation of elementary iodine and methyl iodine was studied by a scintillation detector NaI (2 x 2)” positioned in the reaction bottle.

Muzyka i muzyczność prozy japońskiej okresu Heian (794-1192)

Wydział Neofilologii: Katedra Orientalistyki

Solution to reduce nonlinearity in LTE RoF system for an efficient das topology:a brief review

In this paper, a review on radio-over-fiber (RoF) technology is conducted to support the exploding growth of mobile broadband. An RoF system will provide a platform for distributed antenna system (DAS) as a fronthaul of long term evolution (LTE) technology. A higher splitting ratio from a macrocell is required to support large DAS topology, hence higher optical launch power (OLP) is the right approach. However, high OLP generates undesired nonlinearities, namely the stimulated Brillouin scattering (SBS). Three different aspects of solving the SBS process are covered in this paper, where the solutions ultimately provided an additional 4 dB link budget.

Evaluation of alkene degradation in the detailed tropospheric chemistry mechanism, MCM v3, using environmental chamber data

The representation of alkene degradation in version 3 of the Master Chemical Mechanism (MCM v3) has been evaluated, using environmental chamber data on the photo-oxidation of ethene, propene, 1-butene and 1-hexene in the presence of NOx, from up to five chambers at the Statewide Air Pollution Research Center (SAPRC) at the University of California. As part of this evaluation, it was necessary to include a representation of the reactions of the alkenes with O(3P), which are significant under chamber conditions but generally insignificant under atmospheric conditions. The simulations for the ethene and propene systems, in particular, were found to be sensitive to the branching ratios assigned to molecular and free radical forming pathways of the O(3P) reactions, with the extent of radical formation required for proper fitting of the model to the chamber data being substantially lower than the reported consensus. With this constraint, the MCM v3 mechanisms for ethene and propene generally performed well. The sensitivity of the simulations to the parameters applied to a series of other radical sources and sink reactions (radical formation from the alkene ozonolysis reactions and product carbonyl photolysis; radical removal from the reaction of OH with NO2 and β-hydroxynitrate formation) were also considered, and the implications of these results are discussed. Evaluation of the MCM v3 1-butene and 1-hexene degradation mechanisms, using a more limited dataset from only one chamber, was found to be inconclusive. The results of sensitivity studies demonstrate that it is impossible to reconcile the simulated and observed formation of ozone in these systems for ranges of parameter values which can currently be justified on the basis of the literature. As a result of this work, gaps and uncertainties in the kinetic, mechanistic and chamber database are identified and discussed, in relation to both tropospheric chemistry and chemistry important under chamber conditions which may compromise the evaluation procedure, and recommendations are made for future experimental studies. Throughout the study, the performance of the MCM v3 chemistry was also simultaneously compared with that of the corresponding chemistry in the SAPRC-99 mechanism, which was developed and optimized in conjunction with the chamber datasets.

Análisis de los cambios epigenéticos en la metilación del DNA inducidos por la diabetes y sus posibles mecanismos

Los cambios epigenéticos son responsables de la aparición de muchas patologías humanas y sus causas son debido a factores ambientales como genéticos. Se ha descrito en enfermedades crónicas como la Diabetes Mellitus tipo 2 (T2DM) que se caracteriza por los estados de hiperglucemia y el incremento en el estrés oxidativo que conlleva a complicaciones micro y macro vasculares, asociado a una desmetilación global del genoma. Nuestra hip��tesis corresponde a que los órganos diana son afectados por las alteraciones como la metilación e hidroximetilación como consecuencia del estrés oxidativo que luego repercuten en la persistencia de la enfermedad. Métodos: A partir de sangre periférica se analizaron los cambios globales en la metilación del DNA que son afectados por el estado metabólico de 60 individuos (40 pacientes, 20 controles sanos). Por técnicas de cuantificación se compararon los resultados obtenidos con los de la expresión de las enzimas involucradas. Por último, se realizó un estudio de microarreglos de metilación del DNA y de expresión obtenidos de la base de datos GEO para así comparar los resultados con nuestros datos experimentales. Resultados: Los pacientes diabéticos con pobre control metabólico presentaron mayores niveles de metilación que el grupo control y no se encontró alteración en las enzimas involucradas en este proceso. Los resultados fueron concordantes con el estudio de microarreglos. Conclusión: Los estudios experimentales y de microarreglos demostraron que la metilación es tejido específico y que existe una mayor oxidación en pacientes. Por ello proponemos una vía alterna de desmetilación no enzimática, basada en la oxidación directa de los grupos metilos generados por los estados oxidativos característicos de esta enfermedad.

Análisis del concepto de liderazgo y sus aplicaciones en el contexto empresarial

El presente trabajo se realizó con el objetivo de tener una visión completa de las teorías del liderazgo, teniendo de este una concepción como proceso y poder examinar las diversas formas de aplicación en las organizaciones contemporáneas. El tema es enfocado desde la perspectiva organizacional, un mundo igualmente complejo, sin desconocer su importancia en otros ámbitos como la educación, la política o la dirección del estado. Su enfoque tiene que ver con el estudio académico del cual es la culminación y se enmarca dentro de la perspectiva constitucional de la Carta Política Colombiana que reconoce la importancia capital que tienen la actividad económica y la iniciativa privada en la constitución de empresas. Las diversas visiones del liderazgo han sido aplicadas de distintas maneras en las organizaciones contemporáneas y han generado diversos resultados. Hoy, no es posible pensar en una organización que no haya definido su forma de liderazgo y en consecuencia, confluyen en el campo empresarial multitud de teorías, sin que pueda afirmarse que una sola de ellas permita el manejo adecuado y el cumplimiento de los objetivos misionales. Por esta razón se ha llegado a concebir el liderazgo como una función compleja, en un mundo donde las organizaciones mismas se caracterizan no solo por la complejidad de sus acciones y de su conformación, sino también porque esta característica pertenece también al mundo de la globalización. Las organizaciones concebidas como máquinas que en sentido metafórico logran reconstituirse sus estructuras a medida que están en interacción con otras en el mundo globalizado. Adaptarse a las cambiantes circunstancias hace de las organizaciones conglomerados en permanente dinámica y evolución. En este ámbito puede decirse que el liderazgo es también complejo y que es el liderazgo transformacional el que más se acerca al sentido de la complejidad.

A pointwise constrained version of the Liapunov convexity theorem for vectorial linear first-order control systems

We generalize the Liapunov convexity theorem's version for vectorial control systems driven by linear ODEs of first-order p = 1 , in any dimension d ∈ N , by including a pointwise state-constraint. More precisely, given a x ‾ ( ⋅ ) ∈ W p , 1 ( [ a , b ] , R d ) solving the convexified p-th order differential inclusion L p x ‾ ( t ) ∈ co { u 0 ( t ) , u 1 ( t ) , … , u m ( t ) } a.e., consider the general problem consisting in finding bang-bang solutions (i.e. L p x ˆ ( t ) ∈ { u 0 ( t ) , u 1 ( t ) , … , u m ( t ) } a.e.) under the same boundary-data, x ˆ ( k ) ( a ) = x ‾ ( k ) ( a ) & x ˆ ( k ) ( b ) = x ‾ ( k ) ( b ) ( k = 0 , 1 , … , p − 1 ); but restricted, moreover, by a pointwise state constraint of the type 〈 x ˆ ( t ) , ω 〉 ≤ 〈 x ‾ ( t ) , ω 〉 ∀ t ∈ [ a , b ] (e.g. ω = ( 1 , 0 , … , 0 ) yielding x ˆ 1 ( t ) ≤ x ‾ 1 ( t ) ). Previous results in the scalar d = 1 case were the pioneering Amar & Cellina paper (dealing with L p x ( ⋅ ) = x ′ ( ⋅ ) ), followed by Cerf & Mariconda results, who solved the general case of linear differential operators L p of order p ≥ 2 with C 0 ( [ a , b ] ) -coefficients. This paper is dedicated to: focus on the missing case p = 1 , i.e. using L p x ( ⋅ ) = x ′ ( ⋅ ) + A ( ⋅ ) x ( ⋅ ) ; generalize the dimension of x ( ⋅ ) , from the scalar case d = 1 to the vectorial d ∈ N case; weaken the coefficients, from continuous to integrable, so that A ( ⋅ ) now becomes a d × d -integrable matrix; and allow the directional vector ω to become a moving AC function ω ( ⋅ ) . Previous vectorial results had constant ω, no matrix (i.e. A ( ⋅ ) ≡ 0 ) and considered: constant control-vertices (Amar & Mariconda) and, more recently, integrable control-vertices (ourselves).

Do aviamento as cooperativas de beneficiamento: inovações sociais em sistemas de produção com castanha-do-brasil (Bertholletia excelsa bonpl) no estado do Amap��.

Este estudo caracteriza o extrativismo da castanha-do-brasil (Bertholletia excelsa bonpl), sua estrutura e comercialização e relações sociais na Região Sul do Amap��. este processo experimenta rápidas transformações a partir da metade da década de 1990, e, com essas mudanças diferentes representações sociais ao extrativismo são construídas, fato que no futuro implicará em novos arranjos envolvendo as agriculturas e a conservação ambiental. Para entender este processo e construir soluções tecnológicas para contribuir na manutenção dessa harmonia, a Embrapa Amap�� desenvolveu no período de 2008/2010, processos de inovações técnicas e sociais nesse sistema, usando a metodologia de pesquisa participativa, envolvendo 22 comunidades locais e 151 famílias da RESEX Rio Cajarí, RDS Iratapuru e PAE Maracá. Os resultados demonstram a necessidade de investimentos em infraestrutura e capacitação das cooperativas locais, para que de fato assuman as funções de comando e coordenação da modernização dessas relações, dentre outras, influenciando na harmonização desse tipo de extrativismo com as agriculturas, contribuindo assim com a melhoria na qualidade de vida associada com a preservação ambiental de comunidades locais do Sul do Amap��.

Produtividade da soja e densidade populacional do nematoide das lesões radiculares em função da correção do solo com calcário, gesso e potássio.

2016

Variação longitudinal do poder calorífico de clones de Eucalyptus sp.

2016

Dinâmica populacional de Tetranychus ogmophallos (Acari: Tetranychidae) em genótipos de amendoim forrageiro (Arachis spp.) no estado do Acre.

O amendoim forrageiro é uma leguminosa herbácea tropical e perene, que apresenta importância na produção de forragem em pastos consorciados com gramíneas sob sistemas pecuários intensivos. Dentre as pragas associadas ao amendoim forrageiro, o ácaro-carmim, Tetranychus ogmophallos Ferreira & Flechtmann, é uma das principais, causando injúrias pela contínua sucção de seiva. O objetivo deste trabalho foi determinar a dinâmica populacional de T. ogmophallos em dois acessos de amendoim forrageiro (Arachis pintoi e um híbrido de Arachis pintoi x Arachis appressipila) no estado do Acre. O levantamento foi realizado no período de março de 2014 a dezembro de 2015. Semanalmente, era lançado aleatoriamente, um quadrado de 100 x 100 cm, em três repetições por genótipo. Em cada lançamento eram coletadas, aleatoriamente, 20 folhas/genótipo, totalizando 60 folhas por amostragem/genótipo. Em laboratório os ácaros eram contabilizados sob microscópio estereoscópio. Os picos populacionais de T. ogmophallos foram verificados nos meses de outubro a novembro nos dois genótipos de amendoim forrageiro. Também foi observado que ataque de T. ogmophallos não causou mortalidade de plantas nos dois genótipos.