BioCAT: PSSM-based algorithm to search biosynthetic gene clusters producing nonribosomal peptides with known structure

Motivation: Nonribosomal peptides (NRPs) are a class of secondary metabolites synthesized by multimodular enzymes named nonribosomal peptide synthetases (NRPSs) and mainly produced by bacteria and fungi. It has been shown that NRPs have a huge structural and functional diversity including antimicrobial activity, therefore, they are of increasing interest for modern biotechnology. Methods such as NMR and LC-MS/MS allow to determine NRP structure precisely, but it is often not a trivial task to find natural producers of them. Today, searches are usually performed manually, mostly with tools such as antiSMASH or Prism. However, there are cases when potential producers should be found among hundreds of strains, for instance, when analyzing metagenomes data. Thus, the development of automated approaches is a high-priority task for further NRP research. Results: We developed BioCAT, a two-side approach to find biosynthesys gene clusters (BGCs) which may produce a given NRP when the structure of interesting NRP has already been found. Formally, the BioCAT unites the antiSMASH software and the rBAN retrosynthesis tool but some improvements were added to both gene cluster and NRP chemical structure analyses. The main feature of the method is PSSM usage to store specificities of NRPS modules, which has increased the alignment quality in comparison with more strict approaches developed earlier. An ensemble model was implemented to calculate the final alignment score. We tested the method on a manually curated NRP producers database and compared it with a competing tool called GARLIC. Finally, we showed the method applicability on a several external examples.

Is It the Surgeon, the Patient, or the Device? A Comprehensive Clinical and Radiological Evaluation of Factors Influencing Patient Satisfaction in 648 Total Knee Arthroplasties

Total knee arthroplasty (TKA) is a successful and safe surgical procedure for treating osteoarthritic knees, but despite the overall good results, some patients remain dissatisfied. The aim of this study is to evaluate the influence of patient-related and surgery-related variables in a consecutive group of patients that underwent TKA. Individuals (n = 648) who had TKA performed between 01 January 2013 and 31 December 2017 were enrolled in the study. Postoperative Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, Knee Injury and Osteoarthritis Outcome Score (KOOS) and Forgotten Joint score (FJS-12) were collected at a mean follow-up of 4.79 years. Patient satisfaction was assessed with a questionnaire. Determinants of satisfaction (age, sex, smoking, presence of diabetes or cardiovascular disease, pain in other joints, preoperative arthritic stage) and components of satisfaction (slope variation, mechanical axis variation, outlier final alignment, surgeon experience) were examined to identify which variables correlated with positive outcome. Correlations with septic and mechanicals failures were also evaluated. Thirteen percent of patients were unsatisfied, despite good results in KOOS, WOMAC and FJS-12 tests. Female gender, low Kellgren–Lawrence grade and the presence of back pain and pain in other joints were factors associated with poor clinical results. Poorer clinical results were also reported in younger patients. Infection rate was correlated with active smoking and mechanical failure with an outlier final alignment. Comorbidities, smoking habits and high expectations have a big influence on TKA results and on final satisfaction after surgery.

Automatic extraction of digital elevation from IKONOS in-track stereo images

This Thesis addresses the topic of the extraction of Digital Elevation Models (DEMs) from the in-track stereo images acquired by IKONOS satellite. Research on this topic is mainly motivated by the need of DEMs in trasportation and the potential use of very high resolution satellite stereo images to replace the traditional aerial photography to generate the DEMs that may be used for preliminary planning and location issues, limiting expensive and time consuming photogrammetry work to the final alignment corridor. In this thesis, two methods for DEM extraction from IKONOS stereo images using a modified Rational Function Model (RFM) and the 3D physical model developed at the Canada Centre for Remote Sensing (CCRS) are used and the accuracy of the DEMs generated using these two models are evaluated. The nominal accuracy of ground points determined with the vendor-supplied RPCs is evaluated and systematic biases are found. A significant improvement in the DEM accuracy is made by removing the biases in both the image and ground domain with the information of ground control. DEMs are automatically generated bya chain of processes using the PCI Geomatica OrthoEngine software package with the refined RFM and 3D physical model, respectively. The DEMs from these two methods are then compared in a desktop ERDAS Imagine environment and the accuracy of the DEMs is evaluated by comparing the extracted DEMs with the DEM from airphotos. The DEMs generated using different mathematical models have a very good consistence and more than 97% of the difference between the generated DEMs and the DEM from airphotos is between -2 m to 2m.

Automatic extraction of digital elevation from IKONOS in-track stereo images

This Thesis addresses the topic of the extraction of Digital Elevation Models (DEMs) from the in-track stereo images acquired by IKONOS satellite. Research on this topic is mainly motivated by the need of DEMs in trasportation and the potential use of very high resolution satellite stereo images to replace the traditional aerial photography to generate the DEMs that may be used for preliminary planning and location issues, limiting expensive and time consuming photogrammetry work to the final alignment corridor. In this thesis, two methods for DEM extraction from IKONOS stereo images using a modified Rational Function Model (RFM) and the 3D physical model developed at the Canada Centre for Remote Sensing (CCRS) are used and the accuracy of the DEMs generated using these two models are evaluated. The nominal accuracy of ground points determined with the vendor-supplied RPCs is evaluated and systematic biases are found. A significant improvement in the DEM accuracy is made by removing the biases in both the image and ground domain with the information of ground control. DEMs are automatically generated bya chain of processes using the PCI Geomatica OrthoEngine software package with the refined RFM and 3D physical model, respectively. The DEMs from these two methods are then compared in a desktop ERDAS Imagine environment and the accuracy of the DEMs is evaluated by comparing the extracted DEMs with the DEM from airphotos. The DEMs generated using different mathematical models have a very good consistence and more than 97% of the difference between the generated DEMs and the DEM from airphotos is between -2 m to 2m.

Evolutionary history of Carnivora (Mammalia, Laurasiatheria) inferred from mitochondrial genomes

The order Carnivora, which currently includes 296 species classified into 16 families, is distributed across all continents. The phylogeny and the timing of diversification of members of the order are still a matter of debate. Here, complete mitochondrial genomes were analysed to reconstruct the phylogenetic relationships and to estimate divergence times among species of Carnivora. We assembled 51 new mitogenomes from 13 families, and aligned them with available mitogenomes by selecting only those showing more than 1% of nucleotide divergence and excluding those suspected to be of low-quality or from misidentified taxa. Our final alignment included 220 taxa representing 2,442 mitogenomes. Our analyses led to a robust resolution of suprafamilial and intrafamilial relationships. We identified 21 fossil calibration points to estimate a molecular timescale for carnivorans. According to our divergence time estimates, crown carnivorans appeared during or just after the Early Eocene Climatic Optimum; all major groups of Caniformia (Cynoidea/Arctoidea; Ursidae; Musteloidea/Pinnipedia) diverged from each other during the Eocene, while all major groups of Feliformia (Nandiniidae; Feloidea; Viverroidea) diversified more recently during the Oligocene, with a basal divergence of Nandinia at the Eocene/Oligocene transition; intrafamilial divergences occurred during the Miocene, except for the Procyonidae, as Potos separated from other genera during the Oligocene.

DAEOM: A Deep Attentional Embedding Approach for Biomedical Ontology Matching

Ontology Matching (OM) is performed to find semantic correspondences between the entity elements of different ontologies to enable semantic integration, reuse, and interoperability. Representation learning techniques have been introduced to the field of OM with the development of deep learning. However, there still exist two limitations. Firstly, these methods only focus on the terminological-based features to learn word vectors for discovering mappings, ignoring the network structure of ontology. Secondly, the final alignment threshold is usually determined manually within these methods. It is difficult for an expert to adjust the threshold value and even more so for a non-expert user. To address these issues, we propose an alternative ontology matching framework called Deep Attentional Embedded Ontology Matching (DAEOM), which models the matching process by embedding techniques with jointly encoding ontology terminological description and network structure. We propose a novel inter-intra negative sampling skill tailored for the structural relations asserted in ontologies, and further improve our iterative final alignment method by introducing an automatic adjustment of the final alignment threshold. The preliminary result on real-world biomedical ontologies indicates that DAEOM is competitive with several OAEI top-ranked systems in terms of F-measure.

Evolutionary history of Carnivora (Mammalia, Laurasiatheria) inferred from mitochondrial genomes

The order Carnivora, which currently includes 296 species classified into 16 families, is distributed across all continents. The phylogeny and the timing of diversifications are still a matter of debate.Here, complete mitochondrial genomes were analysed to reconstruct the phylogenetic relationships and to estimate divergence times among species of Carnivora. We assembled 51 new mitogenomes from 13 families, and aligned them with available mitogenomes by selecting only those showing more than 1% of nucleotide divergence and excluding those suspected to be of low-quality or from misidentified taxa. Our final alignment included 220 taxa representing 2,442 mitogenomes. Our analyses led to a robust resolution of suprafamilial and intrafamilial relationships. We identified 22 fossil calibration points to estimate a molecular timescale for carnivorans. According to our divergence time estimates, crown carnivorans appeared during or just after the Early Eocene Climatic Optimum; all major groups of Caniformia (Cynoidea/Arctoidea; Ursidae; Musteloidea/Pinnipedia) diverged from each other during the Eocene, while all major groups of Feliformia (Nandiniidae; Feloidea; Viverroidea) diversified more recently during the Oligocene, with a basal divergence of Nandinia at the Eocene/Oligocene transition; intrafamilial divergences occurred during the Miocene, except for the Procyonidae, as Potos separated from other genera during the Oligocene.

Clinical and Radiographic Comparisons of Distal Tibia Shaft Fractures Stabilized with an Intramedullary Nail: Blocking Pin Versus Blocking Screw

Background: Distal tibia shaft fractures have a high risk of mal-alignment when treated with intramedullary nailing (IMN). Permanent blocking screws (BSs) and temporary blocking pins (BPs) are often used as supplements to help IMN get good alignment. The purpose of this study was to compare the clinical and radiographic outcomes of temporary BPs and permanent BSs for distal tibia shaft fractures.Methods: From March 2014 to May 2019, a total of 89 patients with distal tibia shaft fractures were included in this retrospective study and divided into two groups. All fractures were located below the isthmus but 4 cm above the tibial plafond. The differences in operating time, intraoperative bleeding, fibula plate fixation, number of BP/BS, initial and final alignment, loss of reduction, fracture healing time, and postoperative complications were analyzed. Functional outcomes of the ankle were assessed with the American Orthopedic Foot and Ankle Society (AOFAS) score.Results: All patients underwent a minimum follow-up of 13 months. The operating time was (73.9±6.1) min and (80.2±8.6) min in the BP group and BS group, respectively (P < 0.05); intraoperative bleeding was (88.2±18.0) mL and (92.9±26.6) mL, respectively (P > 0.05); initial reduction deformity in coronal plane was (0.5±2.3) degrees and (0.9±2.3) degrees, respectively (P > 0.05); final alignment deformity in coronal plane was (1.2±2.7) degrees and (1.3±2.4) degrees, respectively (P > 0.05); initial reduction deformity in sagittal plane was (0.6±2.2) degrees and (0.6±2.4) degrees, respectively (P > 0.05); final alignment deformity in sagittal plane was (0.9±2.3) degrees and (1.0±2.2) degrees, respectively (P > 0.05); As for the loss of reduction, there was no significant difference in sagittal plane between the two groups(P > 0.05). Although the loss of reduction in the coronal plane of the BP group (0.8±0.7 degrees) is statistically higher than that of the BS group (0.5±0.5 degrees), the small difference was not clinically important (P < 0.05). No significant differences were found between the two groups in fracture healing time, AOFAS score and complications (P > 0.05).Conclusion: Both temporary BP and permanent BS can help achieve equivalent overall alignment. However, BP technique is simpler and takes less time.

Barcoding Analysis of Paraguayan Squamata

Paraguay is a key spot in the central region of South America where several ecoregions converge. Its fauna (and specifically its herpetofauna) is getting better studied than years before, but still there is a lack of information regarding molecular genetics, and barcoding analyses have proven to be an excellent tool in this matter. Here, we present results of a barcoding analysis based on 16S rRNA gene sequences, providing valuable data for the scientific community in the region. We based our fieldwork in several areas of Paraguay. We analyzed 249 samples (142 sequenced by us) with a final alignment of 615 bp length. We identified some taxonomic incongruences that can be addressed based on our results. Furthermore, we identify groups, where collecting efforts and research activities should be reinforced. Even though we have some blanks in the geographical coverage of our analysis—and there is still a lot to do towards a better understanding of the taxonomy of the Paraguayan herpetofauna—here, we present the largest genetic dataset for the mitochondrial DNA gene 16S of reptiles (particularly, Squamata) from Paraguay, which can be used to solve taxonomic problems in the region.

TERTIB DASAR PEMBENTUKAN PERATURAN DAERAH DI PROVINSI JAWA TIMUR

Regional autonomy has given authority to local governments to regulate and manage their own government households. The authority of the regional government in regulating this is realized through regional authority to make legal products called Regional Regulations. This regulation is an operational juridical instrument and controlling instrument for the implementation of regional autonomy. Law Number 12 of 2011 concerning the Establishment of Legislation Regulations mandates that there are stages that must be passed in forming legislation, namely through the stages of planning, drafting, discussion, ratification or stipulation, and promulgation. This study examines and answers the problems regarding the procedure for establishing Regional Regulations in East Java Province. From the normative aspect, how is the process of establishing a Regional Regulation in East Java Province, and whether its formation is in accordance with the orderly basis of the formation of the Laws and Regulations. This study is a normative juridical study using a statute approach and conceptual approach. The results of the study state that the Establishment of Regional Regulations in the Provinces in East Java is in accordance with the basic order of the establishment of Legislation. There are stages in the formation of the Regional Regulation, which refers to the East Java Provincial Regulation No. 1 of 2015 concerning the Establishment of Regional Legal Products. The stages of establishing a Regional Regulation include: Planning, drafting, discussion, final alignment, stipulation or ratification, enactment, clarification and evaluation; and dissemination.