Um Gavroche entre a política e a sociedade: teatro de Arthur Azevedo (1891-1898)

Arthur Azevedo viveu uma época de mudanças. Nascido em São Luís do Maranhão, em 7 de julho de 1855, na Corte, como tantos outros jovens provincianos daquela época. No Rio de Janeiro, foi jornalista, escritor, funcionário público e destacado autor teatral. Testemunhou a passagem do Império à República, fazendo desse conjunto de acontecimentos, matéria e cenário para suas crônicas, contos e peças teatrais, em especial, em suas Revistas de Ano. Partindo do conceito de cultura política, tal como foi formulado por Serge Bernstein, pretende-se analisar a produção de Arthur nos anos subseqüentes à mudança do regime, à luz do contexto social e teatral experimentado pelo autor, articulando suas escolhas políticas e a cultura da época à obra por ele deixada.

Práticas discursivas de estudantes no Facebook e em blogs: do ciberespaço à escola

As novas tecnologias da informação e da comunicação (TIC) já fazem parte da realidade de um grande quantitativo de pessoas. Mesmo aquelas menos favorecidas economicamente, leem, escrevem, fruem e se comunicam na web, incluindo nossos estudantes. No entanto, muitos educadores afirmam que esses mesmos alunos não têm interesse pela leitura e pela escrita. Geralmente, as leituras e textos produzidos no ciberespaço por esses estudantes são desconsideradas ou menosprezadas no espaço escolar. Diante desse contexto, nosso trabalho propõe compreender como os gêneros discursivos/textuais lidos e/ou produzidos por alunos no ciberespaço são configurados; e não apenas isso, busca refletir sobre possibilidades de a escola inserir gêneros, discurso(s) e linguagem (ns) construídos na Internet, não somente a partir de sua recontextualização na escola, conforme critica Bernstein (1996), mas para além, entendendo esses gêneros e toda a possibilidade que carregam como meios para a interação e para a produção de sentidos diversos. Tendo como base principal as considerações de Bernstein (1996), Bakhtin (1992; 2006; 2008) e da Análise Crítica do Discurso de Fairclough (2001), os objetivos desta dissertação são: (1) identificar traços recorrentes presentes nos gêneros discursivos/textuais com os quais nossos estudantes, alunos de duas escolas públicas, com faixa etária entre os 12 e os 19 anos, estão em contato na web, além de buscar (2) contribuir para a incorporação desses gêneros pela escola, refletindo e discutindo com os próprios alunos acerca de caminhos que podem ser trilhados para que a escola, de alguma maneira, abarque os gêneros circulantes na Internet, sem deixar de lado os gêneros já trabalhados no ambiente escolar

QM/MM simulation of liquid water with an adaptive quantum region.

The simulation of complex chemical systems often requires a multi-level description, in which a region of special interest is treated using a computationally expensive quantum mechanical (QM) model while its environment is described by a faster, simpler molecular mechanical (MM) model. Furthermore, studying dynamic effects in solvated systems or bio-molecules requires a variable definition of the two regions, so that atoms or molecules can be dynamically re-assigned between the QM and MM descriptions during the course of the simulation. Such reassignments pose a problem for traditional QM/MM schemes by exacerbating the errors that stem from switching the model at the boundary. Here we show that stable, long adaptive simulations can be carried out using density functional theory with the BLYP exchange-correlation functional for the QM model and a flexible TIP3P force field for the MM model without requiring adjustments of either. Using a primary benchmark system of pure water, we investigate the convergence of the liquid structure with the size of the QM region, and demonstrate that by using a sufficiently large QM region (with radius 6 Å) it is possible to obtain radial and angular distributions that, in the QM region, match the results of fully quantum mechanical calculations with periodic boundary conditions, and, after a smooth transition, also agree with fully MM calculations in the MM region. The key ingredient is the accurate evaluation of forces in the QM subsystem which we achieve by including an extended buffer region in the QM calculations. We also show that our buffered-force QM/MM scheme is transferable by simulating the solvated Cl(-) ion.

Tests of an adaptive QM/MM calculation on free energy profiles of chemical reactions in solution.

We present reaction free energy calculations using the adaptive buffered force mixing quantum mechanics/molecular mechanics (bf-QM/MM) method. The bf-QM/MM method combines nonadaptive electrostatic embedding QM/MM calculations with extended and reduced QM regions to calculate accurate forces on all atoms, which can be used in free energy calculation methods that require only the forces and not the energy. We calculate the free energy profiles of two reactions in aqueous solution: the nucleophilic substitution reaction of methyl chloride with a chloride anion and the deprotonation reaction of the tyrosine side chain. We validate the bf-QM/MM method against a full QM simulation, and show that it correctly reproduces both geometrical properties and free energy profiles of the QM model, while the electrostatic embedding QM/MM method using a static QM region comprising only the solute is unable to do so. The bf-QM/MM method is not explicitly dependent on the details of the QM and MM methods, so long as it is possible to compute QM forces in a small region and MM forces in the rest of the system, as in a conventional QM/MM calculation. It is simple, with only a few parameters needed to control the QM calculation sizes, and allows (but does not require) a varying and adapting QM region which is necessary for simulating solutions.

Free energy surface reconstruction from umbrella samples using Gaussian process regression

We demonstrate how the Gaussian process regression approach can be used to efficiently reconstruct free energy surfaces from umbrella sampling simulations. By making a prior assumption of smoothness and taking account of the sampling noise in a consistent fashion, we achieve a significant improvement in accuracy over the state of the art in two or more dimensions or, equivalently, a significant cost reduction to obtain the free energy surface within a prescribed tolerance in both regimes of spatially sparse data and short sampling trajectories. Stemming from its Bayesian interpretation the method provides meaningful error bars without significant additional computation. A software implementation is made available on www.libatoms.org.

Free energy surface reconstruction from umbrella samples using Gaussian process regression II: Multiple collective variables

We demonstrate how a prior assumption of smoothness can be used to enhance the reconstruction of free energy profiles from multiple umbrella sampling simulations using the Bayesian Gaussian process regression approach. The method we derive allows the concurrent use of histograms and free energy gradients and can easily be extended to include further data. In Part I we review the necessary theory and test the method for one collective variable. We demonstrate improved performance with respect to the weighted histogram analysis method and obtain meaningful error bars without any significant additional computation. In Part II we consider the case of multiple collective variables and compare to a reconstruction using least squares fitting of radial basis functions. We find substantial improvements in the regimes of spatially sparse data or short sampling trajectories. A software implementation is made available on www.libatoms.org.

Bézier曲线间最近距离的计算方法

针对Bzier曲线间最近距离计算问题,提出一种简捷、可靠的计算方法.该方法以Bernstein多项式算术运算为工具,建立Bzier曲线间最近距离的计算模型;然后充分利用Bzier曲面的凸包性质和de Casteljau分割算法进行求解.该方法几何意义明确,能有效地避免迭代初始值的选择和非线性方程组的求解,并可进一步推广应用于计算Bzier曲线/曲面间的最近距离.实验结果表明,该方法简捷、可靠且容易实现,与Newton-Raphson方法的融合可进一步提高该方法的运行速度.

精密复杂曲面重构与多轴数控加工刀位规划策略

数控加工作为现代制造中的标志性加工技术，在航空航天、运载工具、动力装备等领域的精密复杂型面加工中占据着主导地位。随着国内高速数控加工中心及高档数控机床等硬件设备的日趋成熟和普及，围绕高速数控加工的一些深层次问题便逐步显现出来，这突出表现在数控机床的高速加工特性与传统加工方法之间的矛盾。本文将主要围绕复杂型面高速数控加工中的两大关键技术：曲面造型技术与刀位规划策略，展开论述，着重解决其中的一些关键科学问题，以期为复杂型面的高速数控加工提供新的技术支持。 1. 以罐车曲面重构为例，详细论述了从不完整散乱数据到曲面精确重构的整个过程，着重解决了自由曲面重构理论在实际应用中遇到的一些问题。针对不完整散乱数据，提出一种散乱数据的有序化处理方法，同时给出了面向NURBS的数据自动参数化策略，用于构造罐车的系列截面轮廓线。然后以曲面蒙皮操作为基础实现罐车曲面的快速重构。最后利用参数曲面的离散表达，完成罐车容积的快速检定并借以验证罐车曲面重建的精确性。 2. 以Bézier曲线/曲面为基础，运用多元Bernstein多项式算术运算，将点到复杂曲线/曲面最近点的计算转化为Bernstein多项式方程的求解，进而基于Bernstein基函数的线性精度性质，给出一种新的最近点计算模型。然后通过de Casteljau快速分割算法和二叉/四叉树递归分解的搜索策略寻找最近点。该方法可以有效避免繁琐的迭代计算和对初始值的选择，并从计算效率入手，对其加以改进，成功实现了分割算法与Newton-Raphson方法的融合。再利用B样条曲线/曲面与Bézier曲线/曲面之间成熟的转换算法，将所提出的方法进一步推广到应用更为广泛的B样条曲线/曲面。 3. 通过对刀具轨迹有效性的分析，将刀具轨迹规划分为曲面上曲线族的选择和有效合理排布方式的设计两个方面，为刀具轨迹规划提供了新的设计思路。并以此为基础，对最优刀具轨迹的定义进行了重新阐述，指出今后刀具轨迹规划的研究必须综合考虑轨迹的几何、刀具的运动以及机床的动力学特性。 4. 针对数控加工中心高速加工特性，提出一种等参数螺旋轨迹生成方法。该方法以减少抬刀和路径转接为目的，并综合考虑刀具轨迹几何与运动力学性能，特别适合自由曲面的高速数控加工。同时，在刀具路径的链接、误差分析等方面，也提出了一些颇具特色的方法，从而避免了传统偏置轨迹繁琐的自交干涉检测，能够有效抑制刀具负载的波动，减小刀具的磨损。 5. 在正确重建网格模型拓扑关系的基础上，从离散微分几何学这一新的角度入手，给出了一种新的三角网格曲面微分几何特性分析方法，进而以参数曲面上曲线偏置方法为基础，结合三角网格曲面的拓扑结构和局部区域的精确拟合，建立了网格曲面上的曲线偏置模型，并将计算最近点的方法进一步推广用来计算曲面上的偏置点，从而避免了繁琐的迭代计算。以此为基础，对网格模型的边界轮廓进行等残留偏置，给出了网格曲面上的等残留刀具轨迹生成方法。可进一步利用螺旋线连接各条轨迹，生成更为光滑刀具路径。

Mutations in NGLY1 cause an inherited disorder of the endoplasmic reticulum-associated degradation pathway.

PURPOSE: The endoplasmic reticulum-associated degradation pathway is responsible for the translocation of misfolded proteins across the endoplasmic reticulum membrane into the cytosol for subsequent degradation by the proteasome. To define the phenotype associated with a novel inherited disorder of cytosolic endoplasmic reticulum-associated degradation pathway dysfunction, we studied a series of eight patients with deficiency of N-glycanase 1. METHODS: Whole-genome, whole-exome, or standard Sanger sequencing techniques were employed. Retrospective chart reviews were performed in order to obtain clinical data. RESULTS: All patients had global developmental delay, a movement disorder, and hypotonia. Other common findings included hypolacrima or alacrima (7/8), elevated liver transaminases (6/7), microcephaly (6/8), diminished reflexes (6/8), hepatocyte cytoplasmic storage material or vacuolization (5/6), and seizures (4/8). The nonsense mutation c.1201A>T (p.R401X) was the most common deleterious allele. CONCLUSION: NGLY1 deficiency is a novel autosomal recessive disorder of the endoplasmic reticulum-associated degradation pathway associated with neurological dysfunction, abnormal tear production, and liver disease. The majority of patients detected to date carry a specific nonsense mutation that appears to be associated with severe disease. The phenotypic spectrum is likely to enlarge as cases with a broader range of mutations are detected.

SELECTED AMERICAN VIOLIN WORKS AND THEIR EUROPEAN CONTEXT

For my dissertation, I did a study and performance of American violin works by Charles Ives, Aaron Copland, Leonard Bernstein, and John Corigliano, along with contemporaneous European works by Paul Hindemith, Bela Bartok, Igor Stravinsky, Sergei Prokofiev, and Francis Poulenc. The selected American violin works display the development of a distinctively American style and cover a significant formative period (1914-1963) of American classical music. I intend that the European works form a backdrop for setting in relief any distinctly American qualities possessed by the American works. This is because they cover a similar time period and have significant stylistic affinities and shared influences. My topic stems from a question, "What defines the American Sound?" I attempted to find the answer by looking at the time when American composers consciously searched for their identities, and declared their music to be distinctly American. I found that those distinctive qualities stemmed from three sources: folk music, jazz and hymns. Ives and Copland can be viewed as American in content for their inclusion of such elements, while Bernstein and Corigliano can also be considered as "ideologically American" for their adventurous and eclectic spirit. The simplicity derived from singing a hymn or crooning a popular song; the freedom inspired by jazz; the optimism of accepting all possibilities-these elements inform the common spirit that I found in the music of these four American composers. FIRST RECITAL Sonatafor Violin Solo Op.3112 (1924), Paul Hindemith (1895-1963) Suite Italiennefor Violin and Piano (1932), Igor Stravinsky (1882-1971) Sonatafor Violin and Piano (1963), John Corigliano (b.1938) SECOND RECITAL Second Sonatafor Violin and Piano (1914-17), Charles Ives (1874-1954) First Rhapsody for Violin and Piano (1928), Bela Bart6k (1881-1971) Violin Sonata No.1 infminor (1938-46), Sergei Prokofiev (1891-1953) THIRD RECITAL Nocturne for Violin and Piano (1926), Aaron Copland (1900-1990)Sonata for Violin and Piano, Op. 119 (1942-3, rev.1949), Francis Poulenc (1899-1963)Serenade (after Plato's "Symposium'') (1954) by Leonard Bernstein (1918-1990) The pianists were Sun Ha Yoon (Bart6k) and Grace Eunae Cho (all other repertoire).

SELECTED TWENTIETH-CENTURY BRITISH & AMERICAN ENGLISH SONG REPERTOIRE WRITTEN FOR SOPRANO

English language song (both British and American) is influenced by a variety of cultures, races, and musical forms and has produced a broad range of song repertoire. Like songs in all countries and throughout history, these songs can be classified into three categories: imitative songs, experimental songs, and songs of individuality. Music experimentation, necessary and welcome as it is, can hardly command broad international attention. Thus, the songs of this dissertation performance project are chosen from the first and third categories: imitative songs and individual songs in the composer's own unique style. This project concentrates its exploration on twentieth-century solo songs written in English. Although twentieth-century British & American composers also produced solos and chamber music in other languages, this dissertation focuses upon their English repertoire. This performance project consists of three programs: one British repertoire and two American. The first program titled An Evening of British Song examines twentieth-century British song written by Roger Quilter, Peter Warlock, William Walton, Benjamin Britten, Thomas F. Dunhill, Ivor Gurney, and Frank Bridge. It was presented on December 12, 2001, in Homer Ulrich Recital Hall with the collaborative pianist Meriel Owen. The second program titled An Evening of American Song I comprises music written by Dominick Argento, Samuel Barber, Ned Rorem, Leonard Bernstein, and Lee Hoiby. It was presented on October 23, 2002, in Joseph & Alma Gildenhorn Recital Hall with the collaborative pianist R. Timothy McReynolds. The third program titled An Evening of American Song II written by John Duke, John Corigliano, Charles Ives, Richard Hundley, Lori Laitman, Frederick Loewe, George Gershwin, and Jerome Kern was presented on December 18, 2003, again in Joseph & Alma Gildenhorn Recital Hall with the collaborative pianist R. Timothy McReynolds and the flutist Jessica Dunnavant. Each of these three dissertation recitals occurred at the University of Maryland in College Park and was recorded. These CD recordings are held by the Michelle Smith Performing Arts Library at the University of Maryland.

Tracing Neoclassical Influences in selected solo and chamber music for the clarinet

The musical period of Neoclassicism began in the 1920's, between the first and second world wars. It was initiated by French composers and eventually spread to other countries. One of the most important themes to emerge from the movement was to escape from the formless, rather emotional music of the Romantic era and instead, emphasize balance, order, objectivity and clarity in musical form. Many popular clarinet repertoires are enjoyed by performers and listeners because the music is enjoyable to play and easy to listen to. In particular, classically influenced clarinet music is quite interesting because it features musical elements from both the past and contemporary musical styles. For instance, some composers have integrated preexisting, more traditional styles of composition with lighter styles of modern culture such as popular music and Jazz. It is difficult to discover purely neoclassical clarinet repertoires even though many composers created their pieces during the neoclassical era. What we most commonly find are both neoclassical and non-neoclassical influences in compositions from that time period. Thus, I aim to trace the influence of neoclassicism in selected clarinet repertoires that exist today. It is my hope that increased awareness and knowledge about accessible clarinet music may encourage the general public to develop a deeper interest in a wider sphere of clarinet music, beyond what is considered popular today. The works performed and discussed in this dissertation are the following: (Recital I) Duo Concertante by Darius Milhaud; Sonata by Leonard Bernstein; Sonata for Two Clarinets by Francis Poulenc; Duos for Flute and Clarinet, Op. 34 by Robert Muczynski; Dance Preludes by Witold Lutoslawski, (Recital II) Sonatine by Arthur Honegger; Time pieces by Robert Muczynski; Suite for Clarinet, Violin and Piano by Darius Milhaud; Sonate for Clarinet, Flute and Piano by Maurice Emmanuel; Tarantelle for Flute, Clarinet and Piano, Op. 6 by Camille Saint-Saëns, (Recital III) Sonatina by Joseph Horovitz; Suite from L'histoire du Soldat for Clarinet, Violin and Piano by Igor Stravinsky; Contrasts for Clarinet, Violin and Piano by Béla Bartók The recitals that took place on December 1, 2012 and on April 25, 2013 were performed in the Ulrich Recital Hall of the Clarice Performing Arts Center in College Park, Maryland. The recital that took place on November 2, 2013 was performed at the Gildenhorn Recital Hall of the same performing arts center.

Gene therapy for glioblastoma [correction of gliobestome] multiform: in vivo tumor transduction with the herpes simplex thymidine kinase gene followed by ganciclovir.

Clinical Trial

A phase 1-2 clinical trial of gene therapy for recurrent glioblastoma multiforme by tumor transduction with the herpes simplex thymidine kinase gene followed by ganciclovir.

This study has investigated the effects of herpes simplex thymidine kinase gene (HSV-tk) transfer followed by ganciclovir treatment as adjuvant gene therapy to surgical resection in patients with recurrent glioblastoma multiforme (GBM). The study was open and single-arm, and aimed at assessing the feasibility and safety of the technique and indications of antitumor activity. In 48 patients a suspension of retroviral vector-producing cells (VPCs) was administered by intracerebral injection immediately after tumor resection. Intravenous ganciclovir was infused daily 14 to 27 days after surgery. Patients were monitored for adverse events and for life by regular biosafety assaying. Tumor changes were monitored by magnetic resonance imaging (MRI). Reflux during injection was a frequent occurrence but serious adverse events during the treatment period (days 1-27) were few and of a nature not unexpected in this population. One patient experienced transient neurological disorders associated with postganciclovir MRI enhancement. There was no evidence of replication-competent retrovirus in peripheral blood leukocytes or in tissue samples of reresection or autopsy. Vector DNA was shown in the leukocytes of some patients but not in autopsy gonadal samples. The median survival time was 8.6 months, and the 12-month survival rate was 13 of 48 (27%). On MRI studies, tumor recurrence was absent in seven patients for at least 6 months and for at least 12 months in two patients, one of whom remains recurrence free at more than 24 months. Treatment-characteristic images of injection tracks and intracavity hemoglobin were apparent. In conclusion, the gene therapy is feasible and appears to be satisfactorily safe as an adjuvant to the surgical resection of recurrent GBM, but any benefit appears to be marginal. Investigation of the precise effectiveness of this gene therapy requires prospective, controlled studies.