Language Model Combination and Adaptation Using Weighted Finite State Transducers

In speech recognition systems language model (LMs) are often constructed by training and combining multiple n-gram models. They can be either used to represent different genres or tasks found in diverse text sources, or capture stochastic properties of different linguistic symbol sequences, for example, syllables and words. Unsupervised LM adaption may also be used to further improve robustness to varying styles or tasks. When using these techniques, extensive software changes are often required. In this paper an alternative and more general approach based on weighted finite state transducers (WFSTs) is investigated for LM combination and adaptation. As it is entirely based on well-defined WFST operations, minimum change to decoding tools is needed. A wide range of LM combination configurations can be flexibly supported. An efficient on-the-fly WFST decoding algorithm is also proposed. Significant error rate gains of 7.3% relative were obtained on a state-of-the-art broadcast audio recognition task using a history dependently adapted multi-level LM modelling both syllable and word sequence

Successive loadings of reactant in the hydrogen generation by hydrolysis of sodium borohydride in batch reactors

In this paper, for the first time, an experimental investigation is presented of five successive loadings of reactant alkaline solution of sodium borohydride (NaBH4) for hydrogen generation, using an improved nickel-based powder catalyst, under uncontrolled ambient conditions. The experiments were performed in two batch reactors with internal volumes of 0.646 l and of 0.369 l. The compressed hydrogen generated, at pressures below hydrogen critical pressure, gives emphasis on the importance of considering solubility effects during reaction, leading to storage of hydrogen in the liquid phase inside the reactor. The present work suggests that the sodium metaborate by-product formed by the alkaline hydrolysis of NaBH4, in a closed pressure vessel without temperature control, is NaBO2.xH2O, with x ≥ 2. The data obtained in this work lends credit to x ≈ 2, which was discussed based on the XRD results, and this call for increased caution in the definition of the hydrolysis reaction of NaBH4 up to temperatures of 333 K and up to pressures of 0.13 MP

Clinical and Genetic Analysis of Children with Kartagener Syndrome

Primary ciliary dyskinesia (PCD) is a rare autosomal recessive disorder characterized by dysfunction of motile cilia causing ineffective mucus clearance and organ laterality defects. In this study, two unrelated Portuguese children with strong PCD suspicion underwent extensive clinical and genetic assessments by whole-exome sequencing (WES), as well as ultrastructural analysis of cilia by transmission electron microscopy (TEM) to identify their genetic etiology. These analyses confirmed the diagnostic of Kartagener syndrome (KS) (PCD with situs inversus). Patient-1 showed a predominance of the absence of the inner dynein arms with two disease-causing variants in the CCDC40 gene. Patient-2 showed the absence of both dynein arms and WES disclosed two novel high impact variants in the DNAH5 gene and two missense variants in the DNAH7 gene, all possibly deleterious. Moreover, in Patient-2, functional data revealed a reduction of gene expression and protein mislocalization in both genes' products. Our work calls the researcher's attention to the complexity of the PCD and to the possibility of gene interactions modelling the PCD phenotype. Further, it is demonstrated that even for well-known PCD genes, novel pathogenic variants could have importance for a PCD/KS diagnosis, reinforcing the difficulty of providing genetic counselling and prenatal diagnosis to families.RP was funded by a PhD grant from the National Foundation for Science and Technology (FCT) (Ref.: PD/BD/105767/2014). This work was also supported by the Institutions of the authors and in part by FCT/UMIB (Pest-OE/SAU/UI0215/2014).info:eu-repo/semantics/publishedVersio

Tetracyclic thioxanthene derivatives: Studies on fluorescence and antitumor activity

Thioxanthones are bioisosteres of the naturally occurring xanthones. They have been described for multiple activities, including antitumor. As such, the synthesis of a library of thioxanthones was pursued, but unexpectedly, four tetracyclic thioxanthenes with a quinazoline– chromene scaffold were obtained. These compounds were studied for their human tumor cell growth inhibition activity, in the cell lines A375-C5, MCF-7 and NCI-H460. Photophysical studies were also performed. Two of the compounds displayed GI50 values below 10 µM for the three tested cell lines, and structure–activity relationship studies were established. Three compounds presented similar wavelengths of absorption and emission, characteristic of dyes with a push-pull character. The structures of two compounds were elucidated by X-ray crystallography. Two tetracyclic thioxanthenes emerged as hit compounds. One of the two compounds accumulated intracellularly as a bright fluorescent dye in the green channel, as analyzed by both fluorescence microscopy and flow cytometry, making it a promising theranostic cancer drug candidate.This research was partially supported by the Strategic Funding UIDB/04423/2020, UIDP/04423/2020 (Group of Natural Products and Medicinal Chemistry‐CIIMAR) and under the project PTDC/SAU‐PUB/28736/2017 (reference POCI‐01‐0145‐FEDER‐028736), co‐financed by COMPETE 2020, Portugal 2020 and the European Union through the ERDF and by FCT through national funds. Fernando Durães acknowledges his FCT grant (SFRH/BD/144681/2019). Hassan Bousbaa acknowledges funding from CESPU (IMPLDEBRIS‐PL‐3RL‐IINFACTS‐2019). This research was funded by Fundação para a Ciência e a Tecnologia (FCT) through research units UIDB/50006/2020, UID/CTM/50011/2019, UIDB/50011/2020 & UIDP/50011/2020 and by the European Union (FEDER program) through project CENTRO‐01‐0145‐FEDER‐000003

First Description of KPC-2-Producing Klebsiella oxytoca in Brazil

The present work reports the detection of the first case of nosocomial Klebsiella oxytoca producing class A carbapenemase KPC-2 in Brazil. the isolate KPN106 carried a 65-kb IncW-type plasmid that harbors the bla(KPC) gene and Tn4401b. Moreover, we detected the presence of a class 1 integron containing a new allele, arr-8, followed by a 5'-truncated dhfrIIIc gene. in view of the recent results, we emphasize the high variability of the bacterial and genetic hosts of this resistance determinant.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)FACEPEPFA/UPEUniv Pernambuco, Inst Ciencias Biol, Lab Resistencia Microbiana, Recife, PE, BrazilUniv Fed Pernambuco, Dept Genet, Lab Genet Microrganismos, Recife, PE, BrazilUniversidade Federal de São Paulo, Lab Alerta, São Paulo, BrazilCPqAM Fiocruz, Ctr Pesquisa Aggeu Magalhaes, Recife, PE, BrazilUniversidade Federal de São Paulo, Lab Alerta, São Paulo, BrazilWeb of Scienc

Linezolid Resistance in Brazilian Staphylococcus hominis Strains Is Associated with L3 and 23S rRNA Ribosomal Mutations

Univ São Paulo, Sch Pharm, Dept Clin Anal, BR-05508 São Paulo, BrazilHosp Beneficencia Portuguesa, Lab Clin Microbiol, São Paulo, SP, BrazilUniversidade Federal de São Paulo, Lab Alerta, São Paulo, SP, BrazilUniv São Paulo, Inst Biomed Sci, Dept Microbiol, BR-05508 São Paulo, BrazilUniversidade Federal de São Paulo, Lab Alerta, São Paulo, SP, BrazilWeb of Scienc

The role of the tyrosine kinase Wzc (Sll0923) and the phosphatase Wzb (Slr0328) in the production of extracellular polymeric substances (EPS) by Synechocystis PCC 6803

Many cyanobacteria produce extracellular polymeric substances (EPS) mainly composed of heteropolysaccharides with unique characteristics that make them suitable for biotechnological applications. However, manipulation/optimization of EPS biosynthesis/characteristics is hindered by a poor understanding of the production pathways and the differences between bacterial species. In this work, genes putatively related to different pathways of cyanobacterial EPS polymerization, assembly, and export were targeted for deletion or truncation in the unicellular Synechocystis sp. PCC 6803. No evident phenotypic changes were observed for some mutants in genes occurring in multiple copies in Synechocystis genome, namely ¿wzy (¿sll0737), ¿wzx (¿sll5049), ¿kpsM (¿slr2107), and ¿kpsM¿wzy (¿slr2107¿sll0737), strongly suggesting functional redundancy. In contrast, ¿wzc (¿sll0923) and ¿wzb (¿slr0328) influenced both the amount and composition of the EPS, establishing that Wzc participates in the production of capsular (CPS) and released (RPS) polysaccharides, and Wzb affects RPS production. The structure of Wzb was solved (2.28 Å), revealing structural differences relative to other phosphatases involved in EPS production and suggesting a different substrate recognition mechanism. In addition, Wzc showed the ATPase and autokinase activities typical of bacterial tyrosine kinases. Most importantly, Wzb was able to dephosphorylate Wzc in vitro, suggesting that tyrosine phosphorylation/dephosphorylation plays a role in cyanobacterial EPS production.Norte Portugal Regional Operational Programme (NORTE 2020), Grant/Award Number: NORTE‐01‐0145‐FE?ER‐000008 and NORTE‐01‐0145‐FE?ER‐000012; FCT ‐ Fundação para a Ciência e a Tecnologia/ Ministério da Ciência, Tecnologia e Ensino Superior, Grant/Award Number: PTDC/BIA‐ MIC/28779/2017, SFRH/BD /119920/2016, SFRH/B?/84914/2012 and SFRH/BD/99715/ 2014; FEDER ‐ Fundo Europeu de Desen‐ volvimento Regional funds through the COMPETE 2020 ‐ Operational Programme for Competitiveness and Internationalisation (POCI), Grant/Award Number: POCI‐01‐0145‐ FE?ER‐007274 ACKNOWLEDGMENTS: This work was financed by FEDER—Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020— Operational Programme for Competitiveness and Internationalisation (POCI); projects NORTE‐01‐0145‐FEDER‐000012—Structured Programme on Bioengineering Therapies for Infectious ?iseases and Tissue Regeneration and NORTE‐01‐0145‐FEDER‐000008— Porto Neurosciences and Neurologic Disease Research Initiative at i3S, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement; and by Portuguese funds through FCT—Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Ensino Superior in the framework of the project “Institute for Research and Innovation in Health Sciences” (POCI‐01‐0145‐FEDER‐007274 and PTDC/BIA‐ MIC/28779/2017) and grants SFRH/BD /119920/2016 (MS), SFRH/ BD /99715/2014 (CF), and SFRH/BD /129921/2017 (JPL). The au‐ thors thank F. Chauvat and the Commissariat à l’Energie Atomique (CEA), Direction des Sciences du Vivant, for providing the cas‐ sette for the deletion of the Synechocystis sll0923, the staff of the European Synchrotron Radiation Facility (Grenoble, France) and SOLEIL (Essonne, France) synchrotrons, Filipe Pinto, Frederico Silva, Hugo Osório, and Joana Furtado for their technical assistance

Antimicrobial activity of a library of thioxanthones and their potential as efflux pump inhibitors

The overexpression of efflux pumps is one of the causes of multidrug resistance, which leads to the inefficacy of drugs. This plays a pivotal role in antimicrobial resistance, and the most notable pumps are the AcrAB-TolC system (AcrB belongs to the resistance-nodulation-division family) and the NorA, from the major facilitator superfamily. In bacteria, these structures can also favor virulence and adaptation mechanisms, such as quorum-sensing and the formation of biofilm. In this study, the design and synthesis of a library of thioxanthones as potential efflux pump inhib-itors are described. The thioxanthone derivatives were investigated for their antibacterial activity and inhibition of efflux pumps, biofilm formation, and quorum-sensing. The compounds were also studied for their potential to interact with P-glycoprotein (P-gp, ABCB1), an efflux pump present in mammalian cells, and for their cytotoxicity in both mouse fibroblasts and human Caco-2 cells. The results concerning the real-time ethidium bromide accumulation may suggest a potential bacterial efflux pump inhibition, which has not yet been reported for thioxanthones. Moreover, in vitro studies in human cells demonstrated a lack of cytotoxicity for concentrations up to 20 µM in Caco-2 cells, with some derivatives also showing potential for P-gp modulation.This research was supported by national funds through FCT (Foundation for Science and Technology) within the scope of UIDB/04423/2020, UIDP/04423/2020 (Group of Natural Products and Medicinal Chemistry-CIIMAR), and under the project PTDC/SAU-PUB/28736/2017 (reference POCI-01–0145-FEDER-028736), co-financed by COMPETE 2020, Portugal 2020 and the European Union through the ERDF and by FCT through national funds and structured program of R&D&I ATLANTIDA (NORTE-01-0145-FEDER-000040), supported by NORTE2020, through ERDF, and CHIRALBIO ACTIVE-PI-3RL-IINFACTS-2019