IN-VITRO CYTOTOXICITY AND CELL CYCLE ANALYSIS OF TWO NOVEL BIS-1, 2, 4-TRIAZOLE DERIVATIVES: 1,4-BIS[5-(5-MERCAPTO-1,3,4-OXADIAZOL-2-yl-METHYL)-THIO-4-(p-TOLYL)-1, 2,4-TRIAZOL-3-yl]-BUTANE (MNP-14) AND 1,4-BIS[5-(CARBETHOXY-METHYL)-THIO-4-(p-ETHOXY PHENYL)-1,2,4-TRIAZOL-3-yl]-BUTANE (MNP-16)

In the present study, we have tested the cytotoxic and DNA damage activity of two novel bis-1,2,4 triazole derivatives, namely 1,4-bis[5-(5-mercapto-1,3,4-oxadiazol-2-yl-methyl)-thio4-(p-tolyl)-1,2 ,4-triazol-3-yl]-butane (MNP-14) and 1,4-bis[5-(carbethoxy-methyl)-thio-4-(p-ethoxy phenyl) -1,2,4-triazol-3-yl]-butane (MNP-16). The effect of these molecules on cellular apoptosis was also determined. The in-vitro cytotoxicity was evaluated by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay as well as Trypan blue dye exclusion methods against human acute lymphoblastic leukemia (MOLT4) and lung cancer cells (A549). Our results showed that MNP-16 induced significant cytotoxicity (IC50 of 3-5 mu M) compared with MNP-14. The cytotoxicity induced by MNP-16 was time and concentration dependent. The cell cycle analysis by flow cytometry (fluorescence-activated cell sorting [FACS]) revealed that though there was a significant increase in the apoptotic population (sub-G1 phase) with an increased concentration of MNP-14 and 16, there was no cell cycle arrest. Further, the comet assay results indicated considerable DNA

A Nearly Exact Reformulation of the Girsanov Linearization for Stochastically Driven Nonlinear Oscillators

The Girsanov linearization method (GLM), proposed earlier in Saha, N., and Roy, D., 2007, ``The Girsanov Linearisation Method for Stochastically Driven Nonlinear Oscillators,'' J. Appl. Mech., 74, pp. 885-897, is reformulated to arrive at a nearly exact, semianalytical, weak and explicit scheme for nonlinear mechanical oscillators under additive stochastic excitations. At the heart of the reformulated linearization is a temporally localized rejection sampling strategy that, combined with a resampling scheme, enables selecting from and appropriately modifying an ensemble of locally linearized trajectories while weakly applying the Girsanov correction (the Radon-Nikodym derivative) for the linearization errors. The semianalyticity is due to an explicit linearization of the nonlinear drift terms and it plays a crucial role in keeping the Radon-Nikodym derivative ``nearly bounded'' above by the inverse of the linearization time step (which means that only a subset of linearized trajectories with low, yet finite, probability exceeds this bound). Drift linearization is conveniently accomplished via the first few (lower order) terms in the associated stochastic (Ito) Taylor expansion to exclude (multiple) stochastic integrals from the numerical treatment. Similarly, the Radon-Nikodym derivative, which is a strictly positive, exponential (super-) martingale, is converted to a canonical form and evaluated over each time step without directly computing the stochastic integrals appearing in its argument. Through their numeric implementations for a few low-dimensional nonlinear oscillators, the proposed variants of the scheme, presently referred to as the Girsanov corrected linearization method (GCLM), are shown to exhibit remarkably higher numerical accuracy over a much larger range of the time step size than is possible with the local drift-linearization schemes on their own.

Functional Corannulene: Diverse Structures, Enhanced Charge Transport, and Tunable Optoelectronic Properties

Chemical functionalization of various hydrocarbons, such as coronene, corannulene, and so forth, shows good promise in electronics applications because of their tunable optoelectronic properties. By using quantum chemical calculations, we have investigated the changes in the corannulene buckybowl structure, which greatly affect its electronic and optical properties when functionalized with different electron-withdrawing imide groups. We find that the chemical nature and position of functional groups strongly regulate the stacking geometry, -stacking interactions, and electronic structure. Herein, a range of optoelectronic properties and structure-property relationships of various imide-functionalized corannulenes are explored and rationalized in detail. In terms of carrier mobility, we find that the functionalization strongly affects the reorganization energy of corannulene, while the enhanced stacking improves hopping integrals, favoring the carrier mobility of crystals of pentafluorophenylcorannulene-5-monoimide. The study shows a host of emerging optoelectronic properties and enhancements in the charge-transport characteristics of functionalized corannulene, which may find possible semiconductor and electronics applications.

Validation of polyvinylidene fluoride nasal sensor to assess nasal obstruction in comparison with subjective technique

Objective: The aim of this study is to validate the applicability of the PolyVinyliDene Fluoride (PVDF) nasal sensor to assess the nasal airflow, in healthy subjects and patients with nasal obstruction and to correlate the results with the score of Visual Analogue Scale (VAS). Methods: PVDF nasal sensor and VAS measurements were carried out in 50 subjects (25-healthy subjects and 25 patients). The VAS score of nasal obstruction and peak-to-peak amplitude (Vp-p) of nasal cycle measured by PVDF nasal sensors were analyzed for right nostril (RN) and left nostril (LN) in both the groups. Spearman's rho correlation was calculated. The relationship between PVDF nasal sensor measurements and severity of nasal obstruction (VAS score) were assessed by ANOVA. Results: In healthy group, the measurement of nasal airflow by PVDF nasal sensor for RN and LN were found to be 51.14 +/- 5.87% and 48.85 +/- 5.87%, respectively. In patient group, PVDF nasal sensor indicated lesser nasal airflow in the blocked nostrils (RN: 23.33 +/- 10.54% and LN: 32.24 +/- 11.54%). Moderate correlation was observed in healthy group (r = 0.710, p < 0.001 for RN and r = 0.651, p < 0.001 for LN), and moderate to strong correlation in patient group (r = 0.751, p < 0.01 for RN and r = 0.885, p < 0.0001 for LN). Conclusion: PVDF nasal sensor method is a newly developed technique for measuring the nasal airflow. Moderate to strong correlation was observed between PVDF nasal sensor data and VAS scores for nasal obstruction. In our present study, PVDF nasal sensor technique successfully differentiated between healthy subjects and patients with nasal obstruction. Additionally, it can also assess severity of nasal obstruction in comparison with VAS. Thus, we propose that the PVDF nasal sensor technique could be used as a new diagnostic method to evaluate nasal obstruction in routine clinical practice. (C) 2015 Elsevier Inc. All rights reserved.

Growth of skipjack, Katsuwonus pelamis, and yellowfin, Thunnus albacares, tunas in the Eastern Pacific Ocean, as estimated from tagging data

ENGLISH: The average linear growth rate of skipjack in the eastern Pacific is less than 1 mm per day except for fish 375 to 424 mm in length at release. The growth rate shows a decrease with increasing length and increasing time at liberty. The growth rate of fish in the length range of about 43 to 57 cm is apparently more rapid in the eastern Pacific than in the western Pacific. Dsing data for the northeastern and southeastern Pacific combined, K and ~ were estimated to be 0.658 (on an annual basis) and 885 mm, respectively, by the ungrouped method and 0.829 and 846 mm, respectively, by the grouped method. Sensitivity analyses have shown however, that the estimates of these parameters are poorly determined by the sum of squares method used to derive them. Estimates of K and ~ for the eastern Pacific tend to be lower and higher, respectively, than those for the western Pacific. The average linear growth rate of yellowfin in the eastern Pacific is a little less than 1 mm per day for fish between about 25 and 100 cm in length at release. The growth appears to be most rapid in Area 2 (Revillagigedo Islands) and slowest in Areas 1 (Baja California), 5 (Central America- Colombia), and 6 (Ecuador-Peru). There is considerable variation in the growth rates of individual fish. The growth does not show a decrease with increasing length or increasing time at liberty so realistic estimates of the parameters of the von Bertalanffy or other similar equations cannot be calculated from these data. If realistic estimates of these parameters are to be secured larger fish must be tagged and released or many more long-term returns from fish to about 100 cm in length at release must be obtained. The growth patterns for the eastern Pacific, central Pacific and eastern Atlantic found by most other investigators differ from one another and from those found in the present study. Some of these differences may be real and others may be due to deficiencies in the data or the methods of analysis. Estimates obtained from tagging data are believed to be realistic provided the tags do not inhibit the growth of the fish. It appears that the growth rates of single- and double-tagged fish are the same; this indicates, though not unequivocally, that the tags do not inhibit the growth. SPANISH: La tasa media de crecimiento lineal del barrilete en el Pacífico oriental es inferior a lmm/día, excepto en el caso de peces de entre 375y 424mm de longitud de liberación. La tasa de crecimiento disminuye a medida que aumenta la longitud y el tiempo en libertad. La tasa de crecimiento de peces de entre unos 43 y 57 cm de longitud parece ser mayor en el Pacífico oriental que en el occidental. A partir de datos del Pacífico nororiental y suroriental combinados, se estimaron K y loo en 0.658 (anual) y 885mm, respectivamente, usando el método no agrupado, y 0.829 y 846mm, respectivamente, usando el método agrupado. Sin embargo, los análisis de sensitividad han demostrado que el método de suma de cuadrados utilizado para derivar las estimaciones de estos parámetros las determina con poca precisión. Las estimaciones de K y loo para el Pacífico oriental suelen ser inferiores y superiores, respectivamente, a los del Pacífico occidental. La tasa media de crecimiento lineal del aleta amarilla en el Pacífico oriental es ligeramente inferior a lmm/día para los peces de entre unos 25y 100cmde longitud de liberación. El crecimiento parece ser más rápido en el Area 2(Islas Revillagigedo),y más lento en las Areas 1(Baja California), 5 (Centroamérica-Colombia), y 6 (Ecuador-Perú). Las tasas de crecimiento de peces individuales varían considerablemente. El crecimiento no muestra una disminuciónconun aumento en la longitud o en el tiempo en libertad, y por consecuencia no se se pueden calcular estimaciones realistas de los parámetros de la ecuación de von Bertalanffy u otras ecuaciones similares a partir de estos datos. Para obtener estimaciones realistas de estos parámetros sería necesario marcar peces mayores u obtener muchas más devoluciones a largo plazo de marcas de peces de unos 100cm de longitud de liberación. Los patrones de crecimiento correspondientes al Pacífico oriental, Pacífico central, y Atlántico oriental descubiertos por la mayoría de los investigadores son diferentes entre síy también de los del presente estudio. Es posibleque algunas de estas diferencias sean verdaderas, mientras que otras se deban a faltas en los datos on en los métodos analíticos utilizados. Se considera que las estimaciones obtenidas a partir de los datos de marcado son realistas, suponiendo siempre que las marcas no impidan el crecimiento de los peces. Parece ser que las tasas de crecimiento de peces con una marca y con dos son idénticas, lo cual indica, aunque sin certeza total, que las marcas no ejercen tal efecto. (PDF contains 76 pages.)

Dual Confocal Laser-Induced Fluorescence/Moveable Contactless Conductivity Detector For Capillary Electrophoresis Microchip

A new dual simultaneous detector was developed for capillary electrophoresis microchip. Confocal laser-induced fluorescence (LIF) and moveable contactless conductivity detection (MCCD) were combined together for the first time. The two detection systems shared a common detection cell and could respond simultaneously. They were mutually independent and advantageous in analyses of mixtures containing organic and inorganic ions. The confocal LIF had high sensitivity and the MCCD could move along the separation channel and detect in different positions of the channel. The detection conditions of the dual detector were optimized. Rhodamine B was used to evaluate the performance of the dual detector. The limit of detection of the confocal LIF was < 5 nM, and that of the MCCD was 0.1 mu M. The dual detector had highly sensitivity and could offer response easily, rapidly and simultaneously. 

照明光瞳非对称性对光刻成像质量的影响

研究了照明光瞳非对称性对光刻成像质量的影响。通过PROLITH软件计算了环形与四极照明条件下，光瞳非对称性对图形位置偏移量、曝光图形内水平线条与垂直线条的宽度差、曝光图形上密集线条与孤立线条之间线宽偏差的影响。研究结果表明，光瞳非对称性主要影响曝光图形的位置偏移量，光瞳非对称性引起的图形位置偏移量与光瞳非对称性的大小成线性关系。根据套刻精度的误差分配原则，计算得到光瞳非对称性的容限为5％。

钕玻璃、Nd：YAG和Nd：GGG热容激光特性比较

考虑固体热容激光器对工作介质的要求，对比分析了掺钕的玻璃、YAG和GGG的多种材料性能。并对三者在激光工作周期内的瞬态温度场及热应力进行了数值模拟。结果表明：在给定的边界及工作条件下，当钕玻璃激光器以热容方式工作，时间为5S时，介质最高升温超过400K，最大热致应力为25MPa，接近其断裂极限的50％。在此条件下进行冷却，当水温为283K时，需经过约120S才基本恢复到初始工作状态。而Nd：YAG和Nd：GGG两种介质在相同输入工作条件下，工作时间可达10S，且温度分布相对平坦，温差和热应力较小，经水冷约

Contributions to High-Throughput Computing Based on the Peer-to-Peer Paradigm

XII, 116 p.

A proteção jurídica dos dados clínicos de testes em medicamentos para humanos

A discussão jurídica versa acerca da proteção ou não dos dados clínicos e informações não divulgadas Data Package, obtidos através de pesquisas clinicas, a partir do desenvolvimento de um novo medicamento. È importante realizar-se uma investigação prévia para descobrir se o novo medicamento a ser comercializado, possui efeitos benéficos ou adversos, que possam afetar os seres humanos, garantindo assim a eficácia e a segurança de sua utilização. O dossiê contendo os dados clínicos é submetido à Agência Nacional de Vigilância Sanitária que, no uso de sua atribuição específica, e em função da avaliação do cumprimento de caráter jurídico-administrativo e técnico-científico relacionado com a eficácia, segurança e qualidade do medicamento conforme a Lei 6360/76 e o Decreto 79.094/77 determina o registro sanitário. A tese defendida pelas sociedades farmacêuticas de pesquisa é a de que seria vedado à ANVISA deferir registros de medicamentos genéricos e similares de mesmo princípio ativo, com base nas pesquisas clinicas realizada, enquanto vigente o período de exclusividade, com fundamento no artigo 5, inciso XXIX da Constituição Federal, artigos 39.1, 39.2, 39.3 do Acordo sobre Aspectos dos Direitos de Propriedade Intelectual Acordo TRIPS, artigo 195, XIV da Lei n 9.279/96 (Lei da Propriedade Industrial), artigo 421, 884, 885 e 886 do CC, artigo 37, caput, da CF e artigo 2, da Lei 9.784/99 e aplicação analógica da Lei 10.603/2002. A ANVISA ao permitir aos fabricantes dos medicamentos genéricos e similares a utilização do pacote de dados clínicos, fornecido pelo titular do medicamento de referencia, estaria promovendo a concorrência desleal e parasitária, ao permitir que as versões genéricas e similares, ingressem no mercado, sob custos de produção e comerciais substancialmente menores, do que os praticadas pelos medicamentos de referencia. Este argumento tem fulcro na norma do artigo 39.3 do Acordo TRIPS firmado entre os membros da Organização Mundial do Comércio OMC, em 1994, no qual o Brasil é signatário, e que se comprometeram a adotar providências no sentido de manter em sigilo e protegidos contra o uso comercial desleal os dados clínicos relativos à pesquisa clínica, necessários à aprovação da comercialização de produtos farmacêuticos. A divulgação, exploração ou a utilização dos dados clínicos, sem a autorização do respectivo titular, o qual demandou recursos materiais e humanos consideráveis e desde que estas informações tenham sido apresentadas a entidades governamentais como condição para aprovação da comercialização de um medicamento, devem ser protegidas. Os Estados membros da OMC e subscritores do acordo internacional devem assegurar que os concorrentes não tenham acesso às informações recebidas pelo ente estatal, que não as explorarem ou delas possam aferir indevidamente tanto direta quanto indiretamente de vantagens que as beneficiem do conhecimento técnico-cientifico, investimentos e esforços realizados pelo titular daquela pesquisa clínica. Dentro deste cenário, faz-se necessário que o Estado produza um marco regulatório capaz de prover uma segurança jurídica, que permita as sociedades farmacêuticas disponibilizar elevado investimento, viabilizando a realização de pesquisa clinica e introdução de novos medicamentos.