Differential Antitumor Effects of IgG and IgM Monoclonal Antibodies and Their Synthetic Complementarity-Determining Regions Directed to New Targets of B16F10-Nex2 Melanoma Cells

Malignant melanoma has increased incidence worldwide and causes most skin cancer-related deaths. A few cell surface antigens that can be targets of antitumor immunotherapy have been characterized in melanoma. This is an expanding field because of the ineffectiveness of conventional cancer therapy for the metastatic form of melanoma. In the present work, antimelanoma monoclonal antibodies (mAbs) were raised against B16F10 cells (subclone Nex4, grown in murine serum), with novel specificities and antitumor effects in vitro and in vivo. MAb A4 (IgG2ak) recognizes a surface antigen on B16F10-Nex2 cells identified as protocadherin beta(13). It is cytotoxic in vitro and in vivo to B16F10-Nex2 cells as well as in vitro to human melanoma cell lines. MAb A4M (IgM) strongly reacted with nuclei of permeabilized murine tumor cells, recognizing histone 1. Although it is not cytotoxic in vitro, similarly with mAb A4, mAb A4M significantly reduced the number of lung nodules in mice challenged intravenously with B16F10-Nex2 cells. The V(H) CDR3 peptide from mAb A4 and V(L) CDR1 and CDR2 from mAb A4M showed significant cytotoxic activities in vitro, leading tumor cells to apoptosis. A cyclic peptide representing A4 CDR H3 competed with mAb A4 for binding to melanoma cells. MAb A4M CDRs L1 and L2 in addition to the antitumor effect also inhibited angiogenesis of human umbilical vein endothelial cells in vitro. As shown in the present work, mAbs A4 and A4M and selected CDR peptides are strong candidates to be developed as drugs for antitumor therapy for invasive melanoma.

Diversity of Somatic Coliphages in Coastal Regions with Different Levels of Anthropogenic Activity in Sao Paulo State, Brazil

Bacteriophages are the most abundant and genetically diverse viruses on Earth, with complex ecology in both quantitative and qualitative terms. Somatic coliphages (SC) have been reported to be good indicators of fecal pollution in seawater. This study focused on determining the concentration of SC and their diversity by electron microscopy of seawater, plankton, and bivalve samples collected at three coastal regions in Sao Paulo, Brazil. The SC counts varied from < 1 to 3.4 x 103 PFU/100 ml in seawater (73 samples tested), from < 1 to 4.7 x 10(2) PFU/g in plankton (46 samples tested), and from < 1 to 2.2 x 10(1) PFU/g in bivalves (11 samples tested). In seawater samples, a relationship between the thermotolerant coliforms and Escherichia coli and SC was observed at the three regions (P = 0.0001) according to the anthropogenic activities present at each region. However, SC were found in plankton samples from three regions: Baixada Santista (17/20), Canal de Sao Sebastiao (6/14), and Ubatuba (3/12). In seawater samples collected from Baixada Santista, four morphotypes were observed: A1 (4.5%), B1 (50%), C1 (36.4%), and D1 (9.1%). One coliphage, Siphoviridae type T1, had the longest tail: between 939 and 995 nm. In plankton samples, Siphoviridae (65.8%), Podoviridae (15.8%), Microviridae (15.8%), and Myoviridae (2.6%) were found. In bivalves, only the morphotype B1 was observed. These SC were associated with enteric hosts: enterobacteria, E. coli, Proteus, Salmonella, and Yersinia. Baixada Santista is an area containing a high level of fecal pollution compared to those in the Canal de Sao Sebastiao and Ubatuba. This is the first report of coliphage diversity in seawater, plankton, and bivalve samples collected from Sao Paulo coastal regions. A better characterization of SC diversity in coastal environments will help with the management and evaluation of the microbiological risks for recreation, seafood cultivation, and consumption.

Orthogonal packing of identical rectangles within isotropic convex regions

A mixed integer continuous nonlinear model and a solution method for the problem of orthogonally packing identical rectangles within an arbitrary convex region are introduced in the present work. The convex region is assumed to be made of an isotropic material in such a way that arbitrary rotations of the items, preserving the orthogonality constraint, are allowed. The solution method is based on a combination of branch and bound and active-set strategies for bound-constrained minimization of smooth functions. Numerical results show the reliability of the presented approach. (C) 2010 Elsevier Ltd. All rights reserved.

An eigenvalue problem for the biharmonic operator on Z(2)-symmetric regions

In this work we show that the eigenvalues of the Dirichlet problem for the biharmonic operator are generically simple in the set Of Z(2)-symmetric regions of R-n, n >= 2, with a suitable topology. To accomplish this, we combine Baire`s lemma, a generalised version of the transversality theorem, due to Henry [Perturbation of the boundary in boundary value problems of PDEs, London Mathematical Society Lecture Note Series 318 (Cambridge University Press, 2005)], and the method of rapidly oscillating functions developed in [A. L. Pereira and M. C. Pereira, Mat. Contemp. 27 (2004) 225-241].

Cys mutants in functional regions of Sticholysin I clarify the participation of these residues in pore formation

Experimental evidence shows that the mechanism of pore formation by actinoporins is a multistep process, involving binding of the water-soluble monomer to the membrane and subsequent oligomerization on the membrane surface, leading to the formation of a functional pore. However, as for other eukaryotic pore-forming toxins, the molecular details of the mechanism of membrane insertion and oligomerization are not clear. In order to obtain further insight with regard to the structure-function relationship in sticholysins, we designed and produced three cysteine mutants of recombinant sticholysin I (rStI) in relevant functional regions for membrane interaction: StI E2C and StI F15C (in the N-terminal region) and StI R52C (in the membrane binding site). The conformational characterization derived from fluorescence and CD spectroscopic studies of StI E2C, StI F15C and StI R52C suggests that replacement of these residues by Cys in rStI did not noticeably change the conformation of the protein. The substitution by Cys of Arg(52) in the phosphocholine-binding site, provoked noticeable changes in rStI permeabilizing activity; however, the substitutions in the N-terminal region (Glu(2), Phe(15)) did not modify the toxin`s permeabilizing ability. The presence of a dimerized population stabilized by a disulfide bond in the StI E2C mutant showed higher pore-forming activity than when the protein is in the monomeric state, suggesting that sticholysins pre-ensembled at the N-terminal region could facilitate pore formation. (C) 2011 Elsevier Ltd. All rights reserved.

Simple telemedicine for developing regions: Camera phones and paper-based microfluidic devices for real-time, off-site diagnosis

This article describes a prototype system for quantifying bioassays and for exchanging the results of the assays digitally with physicians located off-site. The system uses paper-based microfluidic devices for running multiple assays simultaneously, camera phones or portable scanners for digitizing the intensity of color associated with each colorimetric assay, and established communications infrastructure for transferring the digital information from the assay site to an off-site laboratory for analysis by a trained medical professional; the diagnosis then can be returned directly to the healthcare provider in the field. The microfluidic devices were fabricated in paper using photolithography and were functionalized with reagents for colorimetric assays. The results of the assays were quantified by comparing the intensities of the color developed in each assay with those of calibration curves. An example of this system quantified clinically relevant concentrations of glucose and protein in artificial urine. The combination of patterned paper, a portable method for obtaining digital images, and a method for exchanging results of the assays with off-site diagnosticians offers new opportunities for inexpensive monitoring of health, especially in situations that require physicians to travel to patients (e.g., in the developing world, in emergency management, and during field operations by the military) to obtain diagnostic information that might be obtained more effectively by less valuable personnel.

Geoprocessing journey-to-work data : delineating commuting regions in Dalarna, Sweden

Delineation of commuting regions has always been based on statistical units, often municipalities or wards. However, using these units has certain disadvantages as their land areas differ considerably. Much information is lost in the larger spatial base units and distortions in self-containment values, the main criterion in rule-based delineation procedures, occur. Alternatively, one can start from relatively small standard size units such as hexagons. In this way, much greater detail in spatial patterns is obtained. In this paper, regions are built by means of intrazonal maximization (Intramax) on the basis of hexagons. The use of geoprocessing tools, specifically developed for the processing ofcommuting data, speeds up processing time considerably. The results of the Intramax analysis are evaluated with travel-to-work area constraints, and comparisons are made with commuting fields, accessibility to employment, commuting flow density and network commuting flow size. From selected steps in the regionalization process, a hierarchy of nested commuting regions emerges, revealing the complexity of commuting patterns.

Biophysical Regions of Maine

http://digitalcommons.colby.edu/atlasofmaine2009/1016/thumbnail.jpg

Regional subsidies and industrial prospects of lagging regions

Large and sustained differences in economic performance across regions of developing countries have long provided motivation for fiscal incentives designed to encourage firm entry in lagging areas. Empirical evidence in support of these policies has, however, been weak at best. This paper undertakes a direct evaluation of the most prominent fiscal incentive policy in Brazil, the Fundos Constitucionais de Financiamento (Constitutional Funds). In doing so, we exploit valuable features of the Brazilian Ministry of Labor's RAIS data set to address two important elements of firm location decisions that have the potential to bias an assessment of the Funds: (i) firm “family structure” (in particular, proximity to headquarters for vertically integrated firms), and (ii) unobserved spatial heterogeneity (with the potential to confound the effects of the Funds). We find that the pull of firm headquarters is very strong relative to the Constitutional Funds for vertically integrated firms, but that, with non-parametric controls for time invariant spatial heterogeneity, the Funds provide statistically and economically significant incentives for firms in many of the targeted industries.

Effect of price and in-store promotion on sales: a study of distinct regions in an emerging market

Increasing competition caused by globalization, high growth of some emerging markets and stagnation of developed economies motivate Consumer Packaged Goods (CPGs) manufacturers to drive their attention to emerging markets. These companies are expected to adapt their marketing activities to the particularities of these markets in order to succeed. In a country classified as emerging market, regions are not alike and some contrasts can be identified. In addition, divergences of marketing variables effect can also be observed in the different retail formats. The retail formats in emerging markets can be segregated in chain self-service and traditional full-service. Thus, understanding the effectiveness of marketing mix not only in country aggregated level data can be an important contribution. Inasmuch as companies aim to generate profits from emerging markets, price is an important marketing variable in the process of creating competitive advantage. Along with price, promotional variables such as in-store displays and price cut are often viewed as temporary incentives to increase short-term sales. Managers defend the usage of promotions as being the most reliable and fastest manner to increase sales and then short-term profits. However, some authors alert about sales promotions disadvantages; mainly in the long-term. This study investigates the effect of price and in-store promotions on sales volume in different regions within an emerging market. The database used is at SKU level for juice, being segregated in the Brazilian northeast and southeast regions and corresponding to the period from January 2011 to January 2013. The methodological approach is descriptive quantitative involving validation tests, application of multivariate and temporal series analysis method. The Vector-Autoregressive (VAR) model was used to perform the analysis. Results suggest similar price sensitivity in the northeast and southeast region and greater in-store promotion sensitivity in the northeast. Price reductions show negative results in the long-term (persistent sales in six months) and in-store promotion, positive results. In-store promotion shows no significant influence on sales in chain self-service stores while price demonstrates no relevant impact on sales in traditional full-service stores. Hence, this study contributes to the business environment for companies wishing to manage price and sales promotions for consumer brands in regions with different features within an emerging market. As a theoretical contribution, this study fills an academic gap providing a dedicated price and sales promotion study to contrast regions in an emerging market.

Genotype by environment interaction for birth and weaning weights of composite beef cattle in different regions of Brazil

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Evaluation of thermal stress indexes for dairy cows in tropical regions

Seis índices de estresse ambiental foram aplicados a 1.359 dados de 359 vacas Holandesas e 54 vacas Jersey em rebanhos comerciais do Ceará e Rio Grande do Norte. O critério de seleção aplicado aos índices foi sua correlação com a temperatura retal e a freqüência respiratória dos animais. O Índice de Temperatura e Umidade (THI) e o Índice de Globo e Umidade (BGHI) apresentaram os piores resultados, com correlações muito baixas com as respostas dos animais. Os índices escolhidos foram o Índice de Temperatura Equivalente (ESI), correlacionado significativamente com a temperatura retal (r = 0,293) e a freqüência respiratória (r = 0,520), e o Índice de Carga Térmica (HLI), com correlações r = 0,286 e r = 0,542 respectivamente.

Potential and costs for the production of electrolytic hydrogen in alcohol and sugar cane plants in the central and south regions of Brazil

This project verified the potential for the production of hydrogen via water electrolysis by using the exceeding electrical energy resultant from alcohol and sugar plants that use sugar cane bagasse as fuel. The studies were carried out in cogeneration plants authorized by the Electrical Energy National Agency (ANEEL). The processing history of sugar cane considered was based on the 2006/2007 harvests. The total bagasse produced, electrical energy generated and exceeding electrical energy in a year were calculated. It was obtained an average energy consumption value of 5.2 kWh Nm(-3) and the hydrogen production costs regarding the amount of sugar cane processed that ranged from US$ 0.50 to US$ 0.75 Nm(-3). The results pointed that the costs for the production of hydrogen via the bagasse exceeding energy are close to the production costs that use other sources of energy. As the energy generated from the bagasse is a renewable one, this alternative for the production of hydrogen is economical and environmentally viable. (C) 2008 International Association for Hydrogen Energy. Published by Elsevier Ltd. All rights reserved.

Water beetles in mountainous regions in southeastern Brazil

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Gene Expression Profiles Stratified according to Type 1 Diabetes Mellitus Susceptibility Regions

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)