A novel hanging spherical drop system for the generation of cellular spheroids and high throughput combinatorial drug screening

We propose a novel hanging spherical drop system for anchoring arrays of droplets of cell suspension based on the use of biomimetic superhydrophobic flat substrates, with controlled positional adhesion and minimum contact with a solid substrate. By facing down the platform, it was possible to generate independent spheroid bodies in a high throughput manner, in order to mimic in vivo tumour models on the lab-on-chip scale. To validate this system for drug screening purposes, the toxicity of the anti-cancer drug doxorubicin in cell spheroids was tested and compared to cells in 2D culture. The advantages presented by this platform, such as feasibility of the system and the ability to control the size uniformity of the spheroid, emphasize its potential to be used as a new low cost toolbox for high-throughput drug screening and in cell or tissue engineering.

Automatic generation of ETL physical systems from BPMN conceptual models

ETL conceptual modeling is a very important activity in any data warehousing system project implementation. Owning a high-level system representation allowing for a clear identification of the main parts of a data warehousing system is clearly a great advantage, especially in early stages of design and development. However, the effort to model conceptually an ETL system rarely is properly rewarded. Translating ETL conceptual models directly into something that saves work and time on the concrete implementation of the system process it would be, in fact, a great help. In this paper we present and discuss a hybrid approach to this problem, combining the simplicity of interpretation and power of expression of BPMN on ETL systems conceptualization with the use of ETL patterns to produce automatically an ETL skeleton, a first prototype system, which has the ability to be executed in a commercial ETL tool like Kettle.

A search for high-mass resonances decaying to τ+τ− in pp collisions at s√=8 TeV with the ATLAS detector

A search for high-mass resonances decaying into τ+τ− final states using proton-proton collisions at s√=8 TeV produced by the Large Hadron Collider is presented. The data were recorded with the ATLAS detector and correspond to an integrated luminosity of 19.5-20.3 fb−1. No statistically significant excess above the Standard Model expectation is observed; 95% credibility upper limits are set on the cross section times branching fraction of Z′ resonances decaying into τ+τ− pairs as a function of the resonance mass. As a result, Z′ bosons of the Sequential Standard Model with masses less than 2.02 TeV are excluded at 95% credibility. The impact of the fermionic couplings on the Z′ acceptance is investigated and limits are also placed on a Z′ model that exhibits enhanced couplings to third-generation fermions.

Carbon materials as new generation of new electron shuttles for the anaerobic degradation of environmental xenobiotics

Tese de Doutoramento em Engenharia Química e Biológica

High-level of viral genomic diversity in cervical cancers: a Brazilian study on human papillomavirus type 16

Invasive cervical cancer (ICC) is the third most frequent cancer among women worldwide and is associated with persistent infection by carcinogenic human papillomaviruses (HPVs). The combination of large populations of viral progeny and decades of sustained infection may allow for the generation of intra-patient diversity, in spite of the assumedly low mutation rates of PVs. While the natural history of chronic HPVs infections has been comprehensively described, within-host viral diversity remains largely unexplored. In this study we have applied next generation sequencing to the analysis of intra-host genetic diversity in ten ICC and one condyloma cases associated to single HPV16 infection. We retrieved from all cases near full-length genomic sequences. All samples analyzed contained polymorphic sites, ranging from 3 to 125 polymorphic positions per genome, and the median probability of a viral genome picked at random to be identical to the consensus sequence in the lesion was only 40%. We have also identified two independent putative duplication events in two samples, spanning the L2 and the L1 gene, respectively. Finally, we have identified with good support a chimera of human and viral DNA. We propose that viral diversity generated during HPVs chronic infection may be fueled by innate and adaptive immune pressures. Further research will be needed to understand the dynamics of viral DNA variability, differentially in benign and malignant lesions, as well as in tissues with differential intensity of immune surveillance. Finally, the impact of intralesion viral diversity on the long-term oncogenic potential may deserve closer attention.

Tapping the wealth of microbial data in high-throughput metabolic model reconstruction

Genome-scale metabolic models are valuable tools in the metabolic engineering process, based on the ability of these models to integrate diverse sources of data to produce global predictions of organism behavior. At the most basic level, these models require only a genome sequence to construct, and once built, they may be used to predict essential genes, culture conditions, pathway utilization, and the modifications required to enhance a desired organism behavior. In this chapter, we address two key challenges associated with the reconstruction of metabolic models: (a) leveraging existing knowledge of microbiology, biochemistry, and available omics data to produce the best possible model; and (b) applying available tools and data to automate the reconstruction process. We consider these challenges as we progress through the model reconstruction process, beginning with genome assembly, and culminating in the integration of constraints to capture the impact of transcriptional regulation. We divide the reconstruction process into ten distinct steps: (1) genome assembly from sequenced reads; (2) automated structural and functional annotation; (3) phylogenetic tree-based curation of genome annotations; (4) assembly and standardization of biochemistry database; (5) genome-scale metabolic reconstruction; (6) generation of core metabolic model; (7) generation of biomass composition reaction; (8) completion of draft metabolic model; (9) curation of metabolic model; and (10) integration of regulatory constraints. Each of these ten steps is documented in detail.