Structure-based classification and ontology in chemistry

<p>Abstract</p> <p>Background</p> <p>Recent years have seen an explosion in the availability of data in the chemistry domain. With this information explosion, however, retrieving <it>relevant </it>results from the available information, and <it>organising </it>those results, become even harder problems. Computational processing is essential to filter and organise the available resources so as to better facilitate the work of scientists. Ontologies encode expert domain knowledge in a hierarchically organised machine-processable format. One such ontology for the chemical domain is ChEBI. ChEBI provides a classification of chemicals based on their structural features and a role or activity-based classification. An example of a structure-based class is 'pentacyclic compound' (compounds containing five-ring structures), while an example of a role-based class is 'analgesic', since many different chemicals can act as analgesics without sharing structural features. Structure-based classification in chemistry exploits elegant regularities and symmetries in the underlying chemical domain. As yet, there has been neither a systematic analysis of the types of structural classification in use in chemistry nor a comparison to the capabilities of available technologies.</p> <p>Results</p> <p>We analyze the different categories of structural classes in chemistry, presenting a list of patterns for features found in class definitions. We compare these patterns of class definition to tools which allow for automation of hierarchy construction within cheminformatics and within logic-based ontology technology, going into detail in the latter case with respect to the expressive capabilities of the Web Ontology Language and recent extensions for modelling structured objects. Finally we discuss the relationships and interactions between cheminformatics approaches and logic-based approaches.</p> <p>Conclusion</p> <p>Systems that perform intelligent reasoning tasks on chemistry data require a diverse set of underlying computational utilities including algorithmic, statistical and logic-based tools. For the task of automatic structure-based classification of chemical entities, essential to managing the vast swathes of chemical data being brought online, systems which are capable of hybrid reasoning combining several different approaches are crucial. We provide a thorough review of the available tools and methodologies, and identify areas of open research.</p

TLR9 expression in glioma tissues correlated to glioma progression and the prognosis of GBM patients

<p>Abstract</p> <p>Background</p> <p>Our study aims to evaluate the expression of TLR9 in glioma tissues, examine the association between TLR9 expression, clinicopathological variables, and glioma patient outcome, we further characterized the direct effects of TLR9 agonist CpG ODN upon the proliferation and invasion of glioma cells <it>in vitro</it>.</p> <p>Methods</p> <p>RT-PCR and immunofluorescence were used to determine the expression of TLR9 in glioma cell lines and clinical glioma samples. Tissue microarry and immunohistochemistry were applied to evaluated TLR9 expression in 292 newly diagnosed glioma and 13 non-neoplastic brain tissues. We further investigated the effect of CpG ODN on the proliferation and invasion of glioma cells <it>in vitro </it>with MTT assays and matrigel transwell assay respectively.</p> <p>Results</p> <p>RT-PCR showed that TLR9 expressed in all the glioma samples and glioma cell lines we examined. The tissue array analysis indicated that TLR9 expression is correlated with malignancy of glioma (p < 0.01). Multivariate Cox regression analysis revealed that TLR9 expression is an independent prognostic factor for PFS of GBM patients(P = 0.026). TLR9 agonist CpG ODN has no significant effect on glioma proliferation, but matrigel transwell analysis showed that TLR9 agonist CpG ODN can significantly enhance glioma invasion <it>in vitro</it>.</p> <p>Conclusions</p> <p>Our data indicated that TLR9 expression increases according to the histopathological grade of glioma, and the TLR9 expression level is related to the PFS of GBM patients. In addition, our findings warrant caution in the directly injection of TLR9 agonist CpG ODN into glioma tissues for the glioma immunotherapy.</p

Adjusting Phenotypes by Noise Control

Genetically identical cells can show phenotypic variability. This is often caused by stochastic events that originate from randomness in biochemical processes involving in gene expression and other extrinsic cellular processes. From an engineering perspective, there have been efforts focused on theory and experiments to control noise levels by perturbing and replacing gene network components. However, systematic methods for noise control are lacking mainly due to the intractable mathematical structure of noise propagation through reaction networks. Here, we provide a numerical analysis method by quantifying the parametric sensitivity of noise characteristics at the level of the linear noise approximation. Our analysis is readily applicable to various types of noise control and to different types of system; for example, we can orthogonally control the mean and noise levels and can control system dynamics such as noisy oscillations. As an illustration we applied our method to HIV and yeast gene expression systems and metabolic networks. The oscillatory signal control was applied to p53 oscillations from DNA damage. Furthermore, we showed that the efficiency of orthogonal control can be enhanced by applying extrinsic noise and feedback. Our noise control analysis can be applied to any stochastic model belonging to continuous time Markovian systems such as biological and chemical reaction systems, and even computer and social networks. We anticipate the proposed analysis to be a useful tool for designing and controlling synthetic gene networks

Vampires in the village Žrnovo on the island of Korčula: following an archival document from the 18th century

Središnja tema rada usmjerena je na raščlambu spisa pohranjenog u Državnom arhivu u Mlecima (fond: Capi del Consiglio de’ Dieci: Lettere di Rettori e di altre cariche) koji se odnosi na događaj iz 1748. godine u korčulanskom selu Žrnovo, kada su mještani – vjerujući da su se pojavili vampiri – oskvrnuli nekoliko mjesnih grobova. U radu se podrobno iznose osnovni podaci iz spisa te rečeni događaj analizira u širem društvenom kontekstu i prate se lokalna vjerovanja.The main interest of this essay is the analysis of the document from the State Archive in Venice (file: Capi del Consiglio de’ Dieci: Lettere di Rettori e di altre cariche) which is connected with the episode from 1748 when the inhabitants of the village Žrnove on the island of Korčula in Croatia opened tombs on the local cemetery in the fear of the vampires treating. This essay try to show some social circumstances connected with this event as well as a local vernacular tradition concerning superstitions

Impact of a Clonal Outbreak of Extended-Spectrum -Lactamase-Producing Klebsiella Pneumoniae in the Development and Evolution of Bloodstream Infections by K. Pneumoniae and Escherichia Coli: An 11 year experience in Oxfordshire, UK

OBJECTIVES: The objectives of this study were: (i) to describe an outbreak of multidrug-resistant Klebsiella pneumoniae in our population; (ii) to identify the potential source of this outbreak by examining antibiotic resistance trends in urocultures; (iii) to evaluate the contribution of this outbreak to resistance patterns over time in the two commonest Gram-negative blood culture isolates, namely K. pneumoniae and Escherichia coli; and (iv) to assess risk factors for multidrug resistance and the impact of this resistance on mortality and length of stay. METHODS: We searched Microbiology and Patient Administration Service databases retrospectively and describe resistance trends in E. coli and K. pneumoniae bloodstream infections (BSIs) in Oxfordshire, UK, over an 11 year period. RESULTS: An outbreak of a multidrug-resistant, CTX-M-15 extended-spectrum β-lactamase (ESBL)-producing K. pneumoniae clone was identified and shown by multilocus sequence typing to belong to a novel sequence type designated ST490. This was associated with a sporadic change in resistance rates in K. pneumoniae BSIs with rates of multidrug resistance (defined as resistance to three or more antibiotic classes) reaching 40%. A case-control study showed prior antibiotic exposure as a risk factor for infection with this organism. During the same time period, rates of ESBL-producing Klebsiella spp. isolated from urocultures increased from 0.5% to almost 6%. By contrast, the rate of multidrug resistance in E. coli rose more steadily from 0% in 2000 to 10% in 2010. CONCLUSIONS: Changes in resistance rates may be associated with outbreaks of resistant clones in K. pneumoniae. Changing resistance patterns may affect important health economic issues such as length of stay

Dam Methylation Participates in the Regulation of PmrA/PmrB and RcsC/RcsD/RcsB Two Component Regulatory Systems in Salmonella enterica Serovar Enteritidis

The absence of Dam in Salmonella enterica serovar Enteritidis causes a defect in lipopolysaccharide (LPS) pattern associated to a reduced expression of wzz gene. Wzz is the chain length regulator of the LPS O-antigen. Here we investigated whether Dam regulates wzz gene expression through its two known regulators, PmrA and RcsB. Thus, the expression of rcsB and pmrA was monitored by quantitative real-time RT-PCR and Western blotting using fusions with 36FLAG tag in wild type (wt) and dam strains of S. Enteritidis. Dam regulated the expression of both rcsB and pmrA genes; nevertheless, the defect in LPS pattern was only related to a diminished expression of RcsB. Interestingly, regulation of wzz in serovar Enteritidis differed from that reported earlier for serovar Typhimurium; RcsB induces wzz expression in both serovars, whereas PmrA induces wzz in S. Typhimurium but represses it in serovar Enteritidis. Moreover, we found that in S. Enteritidis there is an interaction between both wzz regulators: RcsB stimulates the expression of pmrA and PmrA represses the expression of rcsB. Our results would be an example of differential regulation of orthologous genes expression, providing differences in phenotypic traits between closely related bacterial serovars.Fil: Sarnacki, Sebastian Hernan. Consejo Nacional de Investigaciones Científicas y Técnicas . Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica; Argentina;Fil: Aya Castañeda, Maria del Rosario. Consejo Nacional de Investigaciones Científicas y Técnicas . Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica; Argentina;Fil: Noto Llana, Mariangeles. Consejo Nacional de Investigaciones Científicas y Técnicas . Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica; Argentina;Fil: Giacomodonato, Mónica Nancy. Consejo Nacional de Investigaciones Científicas y Técnicas . Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica; Argentina;Fil: Valvano, Miguel Angel. The Queens University Of Belfast;Fil: Cerquetti, Maria Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas . Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica; Argentina

Numerical Study of Mixing Thermal Conductivity Models for Nanofluid Heat Transfer Enhancement

Researchers have paid attention to nanofluid applications, since nanofluids have revealed their potentials as working fluids in many thermal systems. Numerical studies of convective heat transfer in nanofluids can be based on considering them as single- and two-phase fluids. This work is focused on improving the single-phase nanofluid model performance, since the employment of this model requires less calculation time and it is less complicated due to utilizing the mixing thermal conductivity model, which combines static and dynamic parts used in the simulation domain alternately. The in-house numerical program has been developed to analyze the effects of the grid nodes, effective viscosity model, boundary-layer thickness, and of the mixing thermal conductivity model on the nanofluid heat transfer enhancement. CuO–water, Al2O3–water, and Cu–water nanofluids are chosen, and their laminar fully developed flows through a rectangular channel are considered. The influence of the effective viscosity model on the nanofluid heat transfer enhancement is estimated through the average differences between the numerical and experimental results for the nanofluids mentioned. The nanofluid heat transfer enhancement results show that the mixing thermal conductivity model consisting of the Maxwell model as the static part and the Yu and Choi model as the dynamic part, being applied to all three nanofluids, brings the numerical results closer to the experimental ones. The average differences between those results for CuO–water, Al2O3–water, and CuO–water nanofluid flows are 3.25, 2.74, and 3.02%, respectively. The mixing thermal conductivity model has been proved to increase the accuracy of the single-phase nanofluid simulation and to reveal its potentials in the single-phase nanofluid numerical studies. © 2018, Springer Science+Business Media, LLC, part of Springer Nature