A Human-Curated Annotation of the Candida albicans Genome

Recent sequencing and assembly of the genome for the fungal pathogen Candida albicans used simple automated procedures for the identification of putative genes. We have reviewed the entire assembly, both by hand and with additional bioinformatic resources, to accurately map and describe 6,354 genes and to identify 246 genes whose original database entries contained sequencing errors (or possibly mutations) that affect their reading frame. Comparison with other fungal genomes permitted the identification of numerous fungus-specific genes that might be targeted for antifungal therapy. We also observed that, compared to other fungi, the protein-coding sequences in the C. albicans genome are especially rich in short sequence repeats. Finally, our improved annotation permitted a detailed analysis of several multigene families, and comparative genomic studies showed that C. albicans has a far greater catabolic range, encoding respiratory Complex 1, several novel oxidoreductases and ketone body degrading enzymes, malonyl-CoA and enoyl-CoA carriers, several novel amino acid degrading enzymes, a variety of secreted catabolic lipases and proteases, and numerous transporters to assimilate the resulting nutrients. The results of these efforts will ensure that the Candida research community has uniform and comprehensive genomic information for medical research as well as for future diagnostic and therapeutic applications

Distributed Spatial Data Sharing: a new era in sharing spatial data

The advancements in information and communications technology, including the widespread adoption of GPS-based sensors, improvements in computational data processing, and satellite imagery, have resulted in new data sources, stakeholders, and methods of producing, using, and sharing spatial data. Daily, vast amounts of data are produced by individuals interacting with digital content and through automated and semi-automated sensors deployed across the environment. A growing portion of this information contains geographic information directly or indirectly embedded within it. The widespread use of automated smart sensors and an increased variety of georeferenced media resulted in new individual data collectors. This raises a new set of social concerns around individual geopricacy and data ownership. These changes require new approaches to managing, sharing, and processing geographic data. With the appearance of distributed data-sharing technologies, some of these challenges may be addressed. This can be achieved by moving from centralized control and ownership of the data to a more distributed system. In such a system, the individuals are responsible for gathering and controlling access and storing data. Stepping into the new area of distributed spatial data sharing needs preparations, including developing tools and algorithms to work with spatial data in this new environment efficiently. Peer-to-peer (P2P) networks have become very popular for storing and sharing information in a decentralized approach. However, these networks lack the methods to process spatio-temporal queries. During the first chapter of this research, we propose a new spatio-temporal multi-level tree structure, Distributed Spatio-Temporal Tree (DSTree), which aims to address this problem. DSTree is capable of performing a range of spatio-temporal queries. We also propose a framework that uses blockchain to share a DSTree on the distributed network, and each user can replicate, query, or update it. Next, we proposed a dynamic k-anonymity algorithm to address geoprivacy concerns in distributed platforms. Individual dynamic control of geoprivacy is one of the primary purposes of the proposed framework introduced in this research. Sharing data within and between organizations can be enhanced by greater trust and transparency offered by distributed or decentralized technologies. Rather than depending on a central authority to manage geographic data, a decentralized framework would provide a fine-grained and transparent sharing capability. Users can also control the precision of shared spatial data with others. They are not limited to third-party algorithms to decide their privacy level and are also not limited to the binary levels of location sharing. As mentioned earlier, individuals and communities can benefit from distributed spatial data sharing. During the last chapter of this work, we develop an image-sharing platform, aka harvester safety application, for the Kakisa indigenous community in northern Canada. During this project, we investigate the potential of using a Distributed Spatial Data sharing (DSDS) infrastructure for small-scale data-sharing needs in indigenous communities. We explored the potential use case and challenges and proposed a DSDS architecture to allow users in small communities to share and query their data using DSDS. Looking at the current availability of distributed tools, the sustainable development of such applications needs accessible technology. We need easy-to-use tools to use distributed technologies on community-scale SDS. In conclusion, distributed technology is in its early stages and requires easy-to-use tools/methods and algorithms to handle, share and query geographic information. Once developed, it will be possible to contrast DSDS against other data systems and thereby evaluate the practical benefit of such systems. A distributed data-sharing platform needs a standard framework to share data between different entities. Just like the first decades of the appearance of the web, these tools need regulations and standards. Such can benefit individuals and small communities in the current chaotic spatial data-sharing environment controlled by the central bodies

Selected Papers from the 5th International Electronic Conference on Sensors and Applications

This Special Issue comprises selected papers from the proceedings of the 5th International Electronic Conference on Sensors and Applications, held on 15–30 November 2018, on sciforum.net, an online platform for hosting scholarly e-conferences and discussion groups. In this 5th edition of the electronic conference, contributors were invited to provide papers and presentations from the field of sensors and applications at large, resulting in a wide variety of excellent submissions and topic areas. Papers which attracted the most interest on the web or that provided a particularly innovative contribution were selected for publication in this collection. These peer-reviewed papers are published with the aim of rapid and wide dissemination of research results, developments, and applications. We hope this conference series will grow rapidly in the future and become recognized as a new way and venue by which to (electronically) present new developments related to the field of sensors and their applications

Current challenges and future perspectives

: The research group was funded by IPOLFG EPE and by iNOVA4Health (UID/Multi/04462/2019) a program financially supported by Fundação para a Ciência e Tecnologia (FCT)/Ministério da Educação e Ciência, through national funds. We also acknowledge funding from FCT-MCTES through Filipa Lopes-Coelho PhD (PD/BD/128337/2017).Anti-angiogenic therapy is an old method to fight cancer that aims to abolish the nutrient and oxygen supply to the tumor cells through the decrease of the vascular network and the avoidance of new blood vessels formation. Most of the anti-angiogenic agents approved for cancer treatment rely on targeting vascular endothelial growth factor (VEGF) actions, as VEGF signaling is considered the main angiogenesis promotor. In addition to the control of angiogenesis, these drugs can potentiate immune therapy as VEGF also exhibits immunosuppressive functions. Despite the mechanistic rational that strongly supports the benefit of drugs to stop cancer progression, they revealed to be insufficient in most cases. We hypothesize that the rehabilitation of old drugs that interfere with mechanisms of angiogenesis related to tumor microenvironment might represent a promising strategy. In this review, we deepened research on the molecular mechanisms underlying anti-angiogenic strategies and their failure and went further into the alternative mechanisms that impact angiogenesis. We concluded that the combinatory targeting of alternative effectors of angiogenic pathways might be a putative solution for anti-angiogenic therapies.publishersversionpublishe

Reversal of phenotype and plasticity of myofibroblasts to target peri-implantation fibrosis

Ph.DDOCTOR OF PHILOSOPH

Federal Register

Daily publication of the U.S. Office of the Federal Register contains rules and regulations, proposed legislation and rule changes, and other notices, including "Presidential proclamations and Executive Orders, Federal agency documents having general applicability and legal effect, documents required to be published by act of Congress, and other Federal agency documents of public interest" (p. ii). Table of Contents starts on page iii

Lipidomic profiling in patients with metastatic castration-resistant prostate cancer (mCRPC)

Background: A 3-lipid signature has been recently proposed to predict for prognosis in pts with mCRPC. This study aimed at assessing the lipidomic profiles of pts with mCRPC to identify new prognostic and predictive biomarkers. Methods: Plasma samples were collected from pts with mCRPC starting a 1st-line (1L) (n=29) and pretreated with >2 lines (>2L) (n=19). Lipids were extracted and analyzed with an untargeted lipidomic approach. T-test was applied to identify lipids differentially expressed. ROC curves and X-Tile were used to identify lipids’ threshold and to test association with overall survival (OS). Kaplan-Meier curves were constructed and Cox regression was used to adjust for prognostic variables. Results: We identified and quantified a total of 789 plasma lipids. 75 lipid specieswere significantly dysregulated in >2L compared to 1L samples. 63 species were upregulated, and 12 were downregulated. >2L pts showed higher levels of acylcar-nitine, diacylglycerols, phosphatidylethanolamine, triacylglycerols and ceramides (Cer). We tested the effect on OS of lipids included in the 3-lipid signature: Cer(d18:1/24:1), sphingomyelin (d18:2/16:0) and phosphatidylcholine (16:0/16:0). Only Cer (d18:1/24:1) was associated with OS, but without statistical significance in the multivariate model. Among upregulated lipids in >2L cohort, Cer (d18:1/18:0) (C18), Cer (d18:1/16:0), Cer (d18:2/18:0), Cer (d18:1/24:1) and Cer (d20:1/24:1) all showed proportional relative risk of death and significant association with OS in univariate models. However, only C18 retained significant association with OS after adjustmentfor basal PSA and line of treatment (HR: 3.26 [95% CI 1.37-7.76]). The association of C18 with OS was consistent in both subgroups 1L and >2L, separately analyzed. Biochemical response was only seen in 4/14 (28.6%) evaluable pts with high levels of C18. Conclusions: Using a quantitative mass spectrometry approach, we characterized the lipidomic profile of highly pretreated mCRPC pts. We found that C18 is increased in these pts compared to therapy-naïve men, and significantly associated with OS, paving the way for further investigations on its prognostic and predictive value

Federal Register

Daily publication of the U.S. Office of the Federal Register contains rules and regulations, proposed legislation and rule changes, and other notices, including "Presidential proclamations and Executive Orders, Federal agency documents having general applicability and legal effect, documents required to be published by act of Congress, and other Federal agency documents of public interest" (p. ii). Table of Contents starts on page iii