The estimation of statistical parameters for local alignment score distributions

The distribution of optimal local alignment scores of random sequences plays a vital role in evaluating the statistical significance of sequence alignments. These scores can be well described by an extreme-value distribution. The distribution’s parameters depend upon the scoring system employed and the random letter frequencies; in general they cannot be derived analytically, but must be estimated by curve fitting. For obtaining accurate parameter estimates, a form of the recently described ‘island’ method has several advantages. We describe this method in detail, and use it to investigate the functional dependence of these parameters on finite-length edge effects.

Regulation of c-maf gene expression by Pax6 in cultured cells

c-Maf is a bZip transcription factor expressed in developmental and cellular differentiation processes. Recently, a c-maf knockout mouse model, showing abnormal lens development, has been reported. In order to study the regulation mechanisms of c-maf gene expression during the differentiation process we have cloned and functionally characterized the rat c-maf (maf-2) gene. The rat c-maf gene is an intronless gene, covering a length of 3.5 kb. Transient transfection analysis of the 5′-flanking region of the c-maf gene using luciferase as the reporter gene shows that Pax6, a master transcription factor for lens development, strongly activates the c-maf promoter construct. Endogenous c-maf is also activated by the Pax6 expression vector. Electrophoresis mobility shift assay and DNase I footprinting analysis show that at least three Pax6-binding sites are located in the 5′-flanking and 5′-non-coding regions of the rat c-maf gene. The c-maf gene was also markedly activated by its own product, c-Maf, through the MARE (Maf recognition element), suggesting that a positive autoregulatory mechanism controls this gene. In situ hybridization histochemical detection of Pax6 and c-Maf in the E14 lens showed that both mRNAs are expressed in the lens equator where lens epithelial cells are differentiating to lens fiber cells. These results suggest that a Pax6/c-Maf transcription factor cascade is working in lens development.

The RDP-II (Ribosomal Database Project)

The Ribosomal Database Project (RDP-II), previously described by Maidak et al. [Nucleic Acids Res. (2000), 28, 173–174], continued during the past year to add new rRNA sequences to the aligned data and to improve the analysis commands. Release 8.0 (June 1, 2000) consisted of 16 277 aligned prokaryotic small subunit (SSU) rRNA sequences while the number of eukaryotic and mitochondrial SSU rRNA sequences in aligned form remained at 2055 and 1503, respectively. The number of prokaryotic SSU rRNA sequences more than doubled from the previous release 14 months earlier, and ~75% are longer than 899 bp. An RDP-II mirror site in Japan is now available (http://wdcm.nig.ac.jp/RDP/html/index.html). RDP-II provides aligned and annotated rRNA sequences, derived phylogenetic trees and taxonomic hierarchies, and analysis services through its WWW server (http://rdp.cme.msu.edu/). Analysis services include rRNA probe checking, approximate phylogenetic placement of user sequences, screening user sequences for possible chimeric rRNA sequences, automated alignment, production of similarity matrices and services to plan and analyze terminal restriction fragment polymorphism experiments. The RDP-II email address for questions and comments has been changed from curator@cme.msu.edu to rdpstaff@msu.edu.

BAliBASE (Benchmark Alignment dataBASE): enhancements for repeats, transmembrane sequences and circular permutations

BAliBASE is specifically designed to serve as an evaluation resource to address all the problems encountered when aligning complete sequences. The database contains high quality, manually constructed multiple sequence alignments together with detailed annotations. The alignments are all based on three-dimensional structural superpositions, with the exception of the transmembrane sequences. The first release provided sets of reference alignments dealing with the problems of high variability, unequal repartition and large N/C-terminal extensions and internal insertions. Here we describe version 2.0 of the database, which incorporates three new reference sets of alignments containing structural repeats, trans­membrane sequences and circular permutations to evaluate the accuracy of detection/prediction and alignment of these complex sequences. BAliBASE can be viewed at the web site http://www-igbmc.u-strasbg.fr/BioInfo/BAliBASE2/index.html or can be downloaded from ftp://ftp-igbmc.u-strasbg.fr/pub/BAliBASE2/.

Vitamin B12 and hepatitis C: Molecular biology and human pathology

Cobalamins are stored in high concentrations in the human liver and thus are available to participate in the regulation of hepatotropic virus functions. We show that cyanocobalamin (vitamin B12) inhibited the HCV internal ribosome entry site (IRES)-dependent translation of a reporter gene in vitro in a dose-dependent manner without significantly affecting the cap-dependent mechanism. Vitamin B12 failed to inhibit translation by IRES elements from encephalomyocarditis virus (EMCV) or classical swine fever virus (CSFV). We also demonstrate a relationship between the total cobalamin concentration in human sera and HCV viral load (a measure of viral replication in the host). The mean viral load was two orders of magnitude greater when the serum cobalamin concentration was above 200 pM (P < 0.003), suggesting that the total cobalamin concentration in an HCV-infected liver is biologically significant in HCV replication.

Nitric oxide partitioning into mitochondrial membranes and the control of respiration at cytochrome c oxidase

An emerging and important site of action for nitric oxide (NO) within cells is the mitochondrial inner membrane, where NO binds to and inhibits members of the electron transport chain, complex III and cytochrome c oxidase. Although it is known that inhibition of cytochrome c oxidase by NO is competitive with O2, the mechanisms that underlie this phenomenon remain unclear, and the impact of both NO and O2 partitioning into biological membranes has not been considered. These properties are particularly interesting because physiological O2 tensions can vary widely, with NO having a greater inhibitory effect at low O2 tensions (<20 μM). In this study, we present evidence for a consumption of NO in mitochondrial membranes in the absence of substrate, in a nonsaturable process that is O2 dependent. This consumption modulates inhibition of cytochrome c oxidase by NO and is enhanced by the addition of exogenous membranes. From these data, it is evident that the partition of NO into mitochondrial membranes has a major impact on the ability of NO to control mitochondrial respiration. The implications of this conclusion are discussed in the context of mitochondrial lipid:protein ratios and the importance of NO as a regulator of respiration in pathophysiology.

Diferentes olhares acerca dos processos de participação docente na construção da política curricular em Itatiba (2001-2012)

A presente dissertação é fruto da pesquisa que teve como objetivo investigar a participação docente, do Ensino Fundamental II, no processo de formação continuada e principalmente na construção da política curricular do município de Itatiba, o qual tem o ensino municipalizado do 1º ao 9º ano desde 1999. Vale ressaltar que o estudo discorreu entre a gestão municipal de 2001 a 2008 e a gestão de 2009 até 2012. A investigação se desenvolveu a partir das seguintes fontes: entrevista com o Secretário de Educação que atuou entre 2001 e 2008 e com a Secretária de 2009 a 2012; entrevista com duas supervisoras que participaram de todo o processo de 2001 a 2012; entrevista com duas diretoras que atuaram desde a municipalização até 2012; entrevista com quatro professores que se efetivaram após a municipalização (2001), atuam até hoje e participaram do processo de formação até 2012; documentos oficiais: Constituição Federal de 1988, LDB (9394/96), Diretrizes Curriculares Nacionais, FUNDEF (1997), FUNDEB (2007), Deliberação CEE nº73/2008, Lei da municipalização (3110/99), Lei do Sistema de Ensino do município de Itatiba (3485/2001), Projeto Político Pedagógico da SE de 2008, assim como os documentos curriculares do município: de 2001 a 2008 Orientações Curriculares e de 2009 a 2012 Currículo do Ensino Fundamental do 6º ao 9º de todas as disciplinas. É por meio de uma pesquisa qualitativa que esta dissertação se delineia. Desse modo, com entrevistas semiestruturadas bem como roteiros previamente elaborados, tivemos como critérios de escolha dos sujeitos: profissionais da educação que atuaram desde a municipalização até 2012, que participaram de todo o processo de formação continuada e da construção da política curricular. Nessa perspectiva, as entrevistas foram gravadas em áudio e, posteriormente, transcritas para o processo de análise. Dessa forma, o processo de análise consistiu na organização dos dados em categorias e subcategorias, estas estabelecidas pelo próprio conteúdo das entrevistas colhidas dos sujeitos, como também no entrecruzamento do conteúdo das entrevistas com os dados documentais das diferentes fontes utilizadas, que foram, por sua vez, analisados e discutidos à luz do referencial teórico que fundamentou a pesquisa. O estudo foi realizado com base em contribuições de autores que discutem o currículo (Veiga, Silva, Apple, Moreira, Sacristán), os saberes docentes (Tardif), a formação continuada de professores (Nóvoa, Hargreaves), a municipalização (Azanha, Arelaro).Os resultados do trabalho revelam, entre outras coisas, que a participação docente ocorreu no ponto de vista principalmente dos professores na gestão de 2009 a 2012, uma vez que esses se sentiram parte de todo o processo de discussão e construção.

MINLP Model for the Synthesis of Heat Exchanger Networks with Handling Pressure of Process Streams

This paper introduces a new mathematical model for the simultaneous synthesis of heat exchanger networks (HENs), wherein the handling pressure of process streams is used to enhance the heat integration. The proposed approach combines generalized disjunctive programming (GDP) and mixed-integer nonlinear programming (MINLP) formulation, in order to minimize the total annualized cost composed by operational and capital expenses. A multi-stage superstructure is developed for the HEN synthesis, assuming constant heat capacity flow rates and isothermal mixing, and allowing for streams splits. In this model, the pressure and temperature of streams must be treated as optimization variables, increasing further the complexity and difficulty to solve the problem. In addition, the model allows for coupling of compressors and turbines to save energy. A case study is performed to verify the accuracy of the proposed model. In this example, the optimal integration between the heat and work decreases the need for thermal utilities in the HEN design. As a result, the total annualized cost is also reduced due to the decrease in the operational expenses related to the heating and cooling of the streams.

Electrochemical reactions of catechol, methylcatechol and dopamine at tetrahedral amorphous carbon (ta-C) thin film electrodes

The electrochemical reactions of dopamine, catechol and methylcatechol were investigated at tetrahedral amorphous carbon (ta-C) thin film electrodes. In order to better understand the reaction mechanisms of these molecules, cyclic voltammetry with varying scan rates was carried out at different pH values in H2SO4 and PBS solutions. The results were compared to the same redox reactions taking place at glassy carbon (GC) electrodes. All three catechols exhibited quasi-reversible behavior with sluggish electron transfer kinetics at the ta-C electrode. At neutral and alkaline pH, rapid coupled homogeneous reactions followed the oxidation of the catechols to the corresponding o-quinones and led to significant deterioration of the electrode response. At acidic pH, the extent of deterioration was considerably lower. All the redox reactions showed significantly faster electron transfer kinetics at the GC electrode and it was less susceptible toward surface passivation. An EC mechanism was observed for the oxidation of dopamine at both ta-C and GC electrodes and the formation of polydopamine was suspected to cause the passivation of the electrodes.

Retrofit of heat exchanger networks with pressure recovery of process streams at sub-ambient conditions

This paper presents a new mathematical programming model for the retrofit of heat exchanger networks (HENs), wherein the pressure recovery of process streams is conducted to enhance heat integration. Particularly applied to cryogenic processes, HENs retrofit with combined heat and work integration is mainly aimed at reducing the use of expensive cold services. The proposed multi-stage superstructure allows the increment of the existing heat transfer area, as well as the use of new equipment for both heat exchange and pressure manipulation. The pressure recovery of streams is carried out simultaneously with the HEN design, such that the process conditions (streams pressure and temperature) are variables of optimization. The mathematical model is formulated using generalized disjunctive programming (GDP) and is optimized via mixed-integer nonlinear programming (MINLP), through the minimization of the retrofit total annualized cost, considering the turbine and compressor coupling with a helper motor. Three case studies are performed to assess the accuracy of the developed approach, including a real industrial example related to liquefied natural gas (LNG) production. The results show that the pressure recovery of streams is efficient for energy savings and, consequently, for decreasing the HEN retrofit total cost especially in sub-ambient processes.

A Quantile-Based Probabilistic Mean Value Theorem

For non-negative random variables with finite means we introduce an analogous of the equilibrium residual-lifetime distribution based on the quantile function. This allows us to construct new distributions with support (0, 1), and to obtain a new quantile-based version of the probabilistic generalization of Taylor's theorem. Similarly, for pairs of stochastically ordered random variables we come to a new quantile-based form of the probabilistic mean value theorem. The latter involves a distribution that generalizes the Lorenz curve. We investigate the special case of proportional quantile functions and apply the given results to various models based on classes of distributions and measures of risk theory. Motivated by some stochastic comparisons, we also introduce the “expected reversed proportional shortfall order”, and a new characterization of random lifetimes involving the reversed hazard rate function.

Worcester, Massachusetts, ca. 1860 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Map of the city of Worcester, Mass. : from actual surveys under the direction of P. Ball, C.E. It was published by Smith & Mc.Kinney, between 1850 and 1860. Scale [ca. 1:3,600]. The image inside the map neatline is georeferenced to the surface of the earth and fit to the Massachusetts State Plane Coordinate System, Mainland Zone (in Feet) (Fipszone 2001) coordinate system. All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. This map shows features such as roads, railroads and stations, drainage, public buildings, schools, industry locations (e.g. mills, factories, etc.), selected private buildings with names of property owners, town and ward boundaries, cemeteries, and more. Includes also engravings of important buildings and advertisements in margins. This layer is part of a selection of digitally scanned and georeferenced historic maps from the Harvard Map Collection. These maps typically portray both natural and manmade features. The selection represents a range of originators, ground condition dates, scales, and map purposes.

World Map, ca. 1774 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: An accurate chart of the world with the new discoveries : also a view of the general &c coasting trade winds, monsoons or shifting trade winds & the variations of the compass ; from the latest and best authorities by T. Kitchin, Geographer for the Lond. Mag. It was published ca. 1774. Scale [ca. 1:90,000,000]. The image inside the map neatline is georeferenced to the surface of the earth and fit to the 'World Mercator' projection. All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. This map shows features such as drainage, cities and other human settlements, trade winds, magnetic variations, shoreline features, and more. Relief shown pictorially. Includes text and notes. This layer is part of a selection of digitally scanned and georeferenced historic maps from the Harvard Map Collection and the Harvard University Library as part of the Open Collections Program at Harvard University project: Organizing Our World: Sponsored Exploration and Scientific Discovery in the Modern Age. Maps selected for the project correspond to various expeditions and represent a range of regions, originators, ground condition dates, scales, and purposes.

World Map Showing Routes of Exploration and Discovery, 1790 (Image 1 of 8) (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Chart of the world on Mercators projection : exhibiting all the new discoveries to the present time, with the tracks of the most distinguished navigators since the year 1700 carefully collected from the best charts, maps, voyages, &c. extant and regulated from the accurate astronomical observations made in three voyages performed under the command of Captn. James Cook in the years 1768, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79 & 80, compiled and published by A. Arrowsmith, geographer; by permission of Simon McTavish Esq[r] is correctly delineated the discoveries of Mr. McKenzie laid down from his original journal in the year 1789. It was published by A. Arrowsmith, April 1, 1790. Scale [ca. 1:20,000,000]. This layer is image 1 of 8 total images of the seven sheet source map. Covers portions of eastern Asia, Siberia, Russia, Pacific Islands, and western portions of Canada and the United States including Alaska. The image inside the map neatline is georeferenced to the surface of the earth and fit to a non-standard 'World Mercator' projection, with the central meridian at 180 degrees west. All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. Note: The central meridian of this map is not the same as the Prime Meridian and may wrap the International Date Line or overlap itself when displayed in GIS software. This map shows features such as drainage, cities and other human settlements, territorial boundaries, shoreline features, and more. Relief shown by hachures. Depths shown by soundings. Includes routes, locations, and dates of James Cook's voyages. This layer is part of a selection of digitally scanned and georeferenced historic maps from the Harvard Map Collection and the Harvard University Library as part of the Open Collections Program at Harvard University project: Organizing Our World: Sponsored Exploration and Scientific Discovery in the Modern Age. Maps selected for the project correspond to various expeditions and represent a range of regions, originators, ground condition dates, scales, and purposes.

World Map Showing Routes of Exploration and Discovery, 1790 (Image 2 of 8) (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Chart of the world on Mercators projection : exhibiting all the new discoveries to the present time, with the tracks of the most distinguished navigators since the year 1700 carefully collected from the best charts, maps, voyages, &c. extant and regulated from the accurate astronomical observations made in three voyages performed under the command of Captn. James Cook in the years 1768, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79 & 80, compiled and published by A. Arrowsmith, geographer; by permission of Simon McTavish Esq[r] is correctly delineated the discoveries of Mr. McKenzie laid down from his original journal in the year 1789. It was published by A. Arrowsmith, April 1, 1790. Scale [ca. 1:20,000,000]. This layer is image 2 of 8 total images of the seven sheet source map. Covers portions of Europe, Northern Africa, and Asia. The image inside the map neatline is georeferenced to the surface of the earth and fit to the 'World Mercator' projection. All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. This map shows features such as drainage, cities and other human settlements, territorial boundaries, shoreline features, and more. Relief shown by hachures. Depths shown by soundings. Includes routes, locations, and dates of James Cook's voyages. This layer is part of a selection of digitally scanned and georeferenced historic maps from the Harvard Map Collection and the Harvard University Library as part of the Open Collections Program at Harvard University project: Organizing Our World: Sponsored Exploration and Scientific Discovery in the Modern Age. Maps selected for the project correspond to various expeditions and represent a range of regions, originators, ground condition dates, scales, and purposes.