Predictive Biomarkers of Bacillus Calmette-Gu´erin Immunotherapy Response in Bladder Cancer: Where AreWe Now?

The most effective therapeutic option for managing nonmuscle invasive bladder cancer (NMIBC), over the last 30 years, consists of intravesical instillations with the attenuated strain Bacillus Calmette-Gu´erin (the BCG vaccine). This has been performed as an adjuvant therapeutic to transurethral resection of bladder tumour (TURBT) and mostly directed towards patients with highgrade tumours, T1 tumours, and in situ carcinomas. However, from 20% to 40% of the patients do not respond and frequently present tumour progression. Since BCG effectiveness is unpredictable, it is important to find consistent biomarkers that can aid either in the prediction of the outcome and/or side effects development. Accordingly, we conducted a systematic critical review to identify themost preeminent predictive molecular markers associated with BCG response. To the best of our knowledge, this is the first review exclusively focusing on predictive biomarkers for BCG treatment outcome. Using a specific query, 1324 abstracts were gathered, then inclusion/exclusion criteria were applied, and finally 87 manuscripts were included. Several molecules, including CD68 and genetic polymorphisms, have been identified as promising surrogate biomarkers. Combinatory analysis of the candidate predictive markers is a crucial step to create a predictive profile of treatment response.

Novel Secretion Apparatus Maintains Spore Integrity and Developmental Gene Expression in Bacillus subtilis

Plos Genetics, 5(7): ARTe1000566

Culture-dependent characterization of cyanobacterial diversity in the intertidal zones of the Portuguese coast: A polyphasic study

Cyanobacteria are important primary producers, and many are able to fix atmospheric nitrogen playing a key role in the marine environment. However, not much is known about the diversity of cyanobacteria in Portuguese marine waters. This paper describes the diversity of 60 strains isolated from benthic habitats in 9 sites (intertidal zones) on the Portuguese South and West coasts. The strains were characterized by a morphological study (light and electron microscopy) and by a molecular characterization (partial 16S rRNA, nifH, nifK, mcyA, mcyE/ndaF, sxtI genes). The morphological analyses revealed 35 morphotypes (15 genera and 16 species) belonging to 4 cyanobacterial Orders/Subsections. The dominant groups among the isolates were the Oscillatoriales. There is a broad congruence between morphological and molecular assignments. The 16S rRNA gene sequences of 9 strains have less than 97% similarity compared to the sequences in the databases, revealing novel cyanobacterial diversity. Phylogenetic analysis, based on partial 16S rRNA gene sequences showed at least 12 clusters. One-third of the isolates are potential N2-fixers, as they exhibit heterocysts or the presence of nif genes was demonstrated by PCR. Additionally, no conventional freshwater toxins genes were detected by PCR screening.

Penicillium glabrum cork colonising isolates – preliminary analysis of their genomic similari

Cork stopper manufacturing process includes an operation, known as stabilisation, by which humid cork slabs are extensively colonised by fungi. The effects of fungal growth on cork are yet to be completely understood and are considered to be involved in the so called “cork taint” of bottled wine. It is essential to identify environmental constraints which define the appearance of the colonising fungal species and to trace their origin to the forest and/or as residents in the manufacturing space. The present article correlates two sets of data, from consecutive years and the same season, of systematic biologic sampling of two manufacturing units, located in the North and South of Portugal. Chrysonilia sitophila dominance was identified, followed by a high diversity of Penicillium species. Penicillium glabrum, found in all samples, was the most frequent isolated species. P. glabrum intra-species variability was investigated using DNA fingerprinting techniques revealing highly discriminative polymorphic markers in the genome. Cluster analysis of P. glabrum data was discussed in relation to the geographical location of strains, and results suggest that P. glabrum arise from predominantly the manufacturing space, although cork resident fungi can also contrib

Every normal logic program has a 2-valued semantics: theory, extensions, applications, implementations

Trabalho apresentado no âmbito do Doutoramento em Informática, como requisito parcial para obtenção do grau de Doutor em Informática

Negative non-ground queries in well founded semantics

Dissertação apresentada na Faculdade de Ciências e Tecnologia da Universidade Nova de Lisboa para obtenção do grau de Mestre em Computational Logic

Incremental Recomputation of Pig Latin’s Nest and Unnest Operators

This master’s thesis addresses the maintenance of pre-computed structures, which store a frequent or expensive query, for the nested bag data type in the high level work-flow language Pig Latin. This thesis defines a model suitable to accommodate incremental expressions over nested bags on Pig Latin. Afterwards, the partitioned normal form for sets is extended with further restrictions, in order to accommodate the nested bag model, allow the Pig Latin nest and unnest operators revert each other, and create a suitable environment to the incremental computations. Subsequently, the extended operators – extended union and extended difference – are defined for the nested bag data model with the partitioned normal form for bags (PNF Bag) restriction, and semantics for the extended operators are given. Finally, incremental data propagation expressions are proposed for the nest and unnest operators on the data model proposed with the PNF Bag restriction, and the proof of correctness is given.

Analisador de qualidade de energia eléctrica embebido na instalação eléctrica

A monitorização da qualidade da energia eléctrica tem revelado importância crescente na gestão e caracterização da rede eléctrica. Estudos revelam que os custos directos relacionados com perda de qualidade da energia eléctrica podem representar cerca de 1,5 % do PIB nacional. Para além destes, tem-se adicionalmente os custos indirectos o que se traduz num problema que necessita de minimização. No contexto da minimização dos danos causados pela degradação de energia, são utilizados equipamentos com capacidade de caracterizar a energia eléctrica através da sua monitorização. A utilização destes equipamentos têm subjacente normas de qualidade de energia, que impõem requisitos mínimos de modo a enquadrar e classificar eventos ocorridos na rede eléctrica. Deste modo obtêm-se dados coerentes provenientes de diferentes equipamentos. A monitorização dos parâmetros associados à energia eléctrica é frequentemente realizada através da instalação temporária dos esquipamentos na rede eléctrica, o que resulta numa observação de distúrbios a posteriori da sua ocasião. Esta metodologia não permite detectar o evento eléctrico original mas, quando muito, outros que se espera que sejam semelhantes ao ocorrido. Repare-se, no entanto, que existe um conjunto alargado de eventos que não são repetitivos, constituindo assim uma limitação aquela metodologia. Este trabalho descreve uma alternativa à metodologia de utilização tradicional dos equipamentos. A solução consiste em realizar um analisador de energia que faça parte integrante da instalação e permita a monitorização contínua da rede eléctrica. Este equipamento deve ter um custo suficientemente baixo para que seja justificável nesta utilização alternativa. O analisador de qualidade de energia a desenvolver tem por base o circuito integrado ADE7880, que permite obter um conjunto de parâmetros da qualidade de energia eléctrica de acordo com as normas de energia IEC 61000-4-30 e IEC 61000-4-7. Este analisador permite a recolha contínua de dados específicos da rede eléctrica, e que posteriormente serão armazenados e colocados à disposição do utilizador. Deste modo os dados recolhidos serão apresentados ao utilizador para consulta, de maneira a verificar, de modo continuo a eventual ocorrência das anomalias na rede. Os valores adquiridos podem ainda ser reutilizados vantajosamente para muitas outras finalidades tais como efectuar estudos sobre a optimização energética. O trabalho presentemente desenvolvido decorre de uma utilização alternativa do dispositivo WeSense Energy1 desenvolvido pela equipa da Evoleo Technologies. A presente vertente permite obter parâmetros determinados pelo ADE7880 tais como por exemplo harmónicos, eventos transitórios de tensão e corrente e o desfasamento entre fases, realizando assim uma nova versão do dispositivo, o WeSense Energy2. Adicionalmente este trabalho inclui a visualização remota dos através de uma página web.

Combining open and closed world reasoning for the semantic web

Dissertação para obtenção do Grau de Doutor em Informática

Brokerage Platform for Media Content Recommendation

Near real time media content personalisation is nowadays a major challenge involving media content sources, distributors and viewers. This paper describes an approach to seamless recommendation, negotiation and transaction of personalised media content. It adopts an integrated view of the problem by proposing, on the business-to-business (B2B) side, a brokerage platform to negotiate the media items on behalf of the media content distributors and sources, providing viewers, on the business-to-consumer (B2C) side, with a personalised electronic programme guide (EPG) containing the set of recommended items after negotiation. In this setup, when a viewer connects, the distributor looks up and invites sources to negotiate the contents of the viewer personal EPG. The proposed multi-agent brokerage platform is structured in four layers, modelling the registration, service agreement, partner lookup, invitation as well as item recommendation, negotiation and transaction stages of the B2B processes. The recommendation service is a rule-based switch hybrid filter, including six collaborative and two content-based filters. The rule-based system selects, at runtime, the filter(s) to apply as well as the final set of recommendations to present. The filter selection is based on the data available, ranging from the history of items watched to the ratings and/or tags assigned to the items by the viewer. Additionally, this module implements (i) a novel item stereotype to represent newly arrived items, (ii) a standard user stereotype for new users, (iii) a novel passive user tag cloud stereotype for socially passive users, and (iv) a new content-based filter named the collinearity and proximity similarity (CPS). At the end of the paper, we present off-line results and a case study describing how the recommendation service works. The proposed system provides, to our knowledge, an excellent holistic solution to the problem of recommending multimedia contents.

Phenotypic and molecular characterization of Salmonella Enteritidis strains isolated in São Paulo, Brazil

In São Paulo State, Brazil, the epidemic increase in isolation of Salmonella Enteritidis has been observed since 1994. A total of 105 S. Enteritidis strains (72 from human and 33 from non-human sources) isolated during the period 1975-1995, previously characterized by phage typing, was analyzed by antimicrobial susceptibility, plasmid profile, and ribotyping. Over 70% of the strains were susceptible to all antimicrobial agents tested, however, multiple resistance to antimicrobials was observed among the studied strains, mainly those from hospitalized patients. Phage type 8 (PT-8) was predominant among the strains isolated during the period of 1975-1992, but in the following years, PT-4 was the most frequent phage type identified. Seven different plasmid profiles were detected and 96% of the isolates harbored a plasmid of approximately 36 MDa. Ribotyping discriminated fourteen ribotypes (R1 to R14) among the strains examined. By analysis of dendrogram the strains were included in three groups with similarity level of 60%. The obtained results indicate that, a single ribotype (R11), determined for PT-4 strains isolated from 1993, characterizes the epidemic clone of S. Enteritidis in our region.

Electrophoretic protein patterns and numerical analysis of Candida albicans from the oral cavities of healthy children

The aim of this research was to evaluate the protein polymorphism degree among seventy-five C. albicans strains from healthy children oral cavities of five socioeconomic categories from eight schools (private and public) in Piracicaba city, São Paulo State, in order to identify C. albicans subspecies and their similarities in infantile population groups and to establish their possible dissemination route. Cell cultures were grown in YEPD medium, collected by centrifugation, and washed with cold saline solution. The whole-cell proteins were extracted by cell disruption, using glass beads and submitted to SDS-PAGE technique. After electrophoresis, the protein bands were stained with Coomassie-blue and analyzed by statistics package NTSYS-pc version 1.70 software. Similarity matrix and dendrogram were generated by using the Dice similarity coefficient and UPGMA algorithm, respectively, which made it possible to evaluate the similarity or intra-specific polymorphism degrees, based on whole-cell protein fingerprinting of C. albicans oral isolates. A total of 13 major phenons (clusters) were analyzed, according to their homogeneous (socioeconomic category and/or same school) and heterogeneous (distinct socioeconomic categories and/or schools) characteristics. Regarding to the social epidemiological aspect, the cluster composition showed higher similarities (0.788 < S D < 1.0) among C. albicans strains isolated from healthy children independent of their socioeconomic bases (high, medium, or low). Isolates of high similarity were not found in oral cavities from healthy children of social stratum A and D, B and D, or C and E. This may be explained by an absence of a dissemination route among these children. Geographically, some healthy children among identical and different schools (private and public) also are carriers of similar strains but such similarity was not found among other isolates from children from certain schools. These data may reflect a restricted dissemination route of these microorganisms in some groups of healthy scholars, which may be dependent of either socioeconomic categories or geographic site of each child. In contrast to the higher similarity, the lower similarity or higher polymorphism degree (0.499 < S D < 0.788) of protein profiles was shown in 23 (30.6%) C. albicans oral isolates. Considering the social epidemiological aspect, 42.1%, 41.7%, 26.6%, 23.5%, and 16.7% were isolates from children concerning to socioeconomic categories A, D, C, B, and E, respectively, and geographically, 63.6%, 50%, 33.3%, 33.3%, 30%, 25%, and 14.3% were isolates from children from schools LAE (Liceu Colégio Albert Einstein), MA (E.E.P.S.G. "Prof. Elias de Melo Ayres"), CS (E.E.P.G. "Prof. Carlos Sodero"), AV (Alphaville), HF (E.E.P.S.G. "Honorato Faustino), FMC (E.E.P.G. "Prof. Francisco Mariano da Costa"), and MEP (E.E.P.S.G. "Prof. Manasses Ephraim Pereira), respectively. Such results suggest a higher protein polymorphism degree among some strains isolated from healthy children independent of their socioeconomic strata or geographic sites. Complementary studies, involving healthy students and their families, teachers, servants, hygiene and nutritional habits must be done in order to establish the sources of such colonization patterns in population groups of healthy children. The whole-cell protein profile obtained by SDS-PAGE associated with computer-assisted numerical analysis may provide additional criteria for the taxonomic and epidemiological studies of C. albicans.

Pseudo Phase Plane and Fractional Calculus Modelling of Western Global Economic Downturn

This paper applies Pseudo Phase Plane (PPP) and Fractional Calculus (FC) mathematical tools for modeling world economies. A challenging global rivalry among the largest international economies began in the early 1970s, when the post-war prosperity declined. It went on, up to now. If some worrying threatens may exist actually in terms of possible ambitious military aggression, invasion, or hegemony, countries’ PPP relative positions can tell something on the current global peaceful equilibrium. A global political downturn of the USA on global hegemony in favor of Asian partners is possible, but can still be not accomplished in the next decades. If the 1973 oil chock has represented the beginning of a long-run recession, the PPP analysis of the last four decades (1972–2012) does not conclude for other partners’ global dominance (Russian, Brazil, Japan, and Germany) in reaching high degrees of similarity with the most developed world countries. The synergies of the proposed mathematical tools lead to a better understanding of the dynamics underlying world economies and point towards the estimation of future states based on the memory of each time series.

Tifo Murino em Portugal

Murine typhus or endemic typhus is a wide spread infectious disease, with a low prevalence in developed countries, but surely underdiagnosed. Its relative benignity, the similarity to other infectious diseases and the discretion of its epidemiologic chain, as well as the usual unexpectedness of its existence, makes its diagnosis more difficult. The clinical presentation and evolution of this case illustrate the necessity of being aware of this nosological entity.

Human vaccinia-like virus outbreaks in São Paulo and Goiás States, Brazil: virus detection, isolation and identification

Since October 2001, the Adolfo Lutz Institute has been receiving vesicular fluids and scab specimens of patients from Paraíba Valley region in the São Paulo and Minas Gerais States and from São Patricio Valley, in the Goiás State. Epidemiological data suggested that the outbreaks were caused by Cowpox virus or Vaccinia virus. Most of the patients are dairy milkers that had vesiculo-pustular lesions on the hands, arms, forearms, and some of them, on the face. Virus particles with orthopoxvirus morphology were detected by direct electron microscopy (DEM) in samples of 49 (66.21%) patients of a total of 74 analyzed. Viruses were isolated in Vero cell culture and on chorioallantoic membrane (CAM) of embryonated chicken eggs. Among 21 samples submitted to PCR using primers for hemagglutinin (HA) gene, 19 were positive. Restriction digestion with TaqI resulted in four characteristic Vaccinia virus fragments. HA nucleotide sequences showed 99.9% similarity with Cantagalo virus, described as a strain of Vaccinia virus. The only difference observed was the substitution of one nucleotide in the position 616 leading to change in one amino acid of the protein in the position 206. The phylogenetic analysis showed that the isolates clustered together with Cantagalo virus, other Vaccinia strains and Rabbitpox virus.