Generally the number of software and hardware components that need to communicate seamlessly with each other is fast increasing in the digital lab environment. Many of these systems are customized ...for a specific task or application, practically involving software development. Such software can range from simple pump controls to management systems, over SiLA 2 drivers for laboratory instruments. Once developed, this software needs to be installed and maintained on the desired hardware. In addition, managing the configuration of the software is equally important for successful use in the laboratory. In case of hardware problems or failure, reinstalling the software may become difficult if the information is lost. With this article, it is explained how this problem can be solved with an automated workflow and developed software, mkbox - a tool for creating reliable application-specific Linux images. The goal of mkbox is to create Linux images using simple description files. Images can be distributed to target devices in the laboratory by using the integrated update and deployment mechanism. Using the mkbox tool has simplified the development workflow in the lab environment and reduced the time required to maintain software on target devices.
Grain-size control on sediment composition is investigated in modern proximal sediment from the Sila Massif, where basic to felsic intrusive rocks are exposed in a Mediterranean humid–temperate ...upland climate. Samples were taken from small creeks and weathering profiles from three areas reflecting different bed rock compositions. Samples were separated into eleven grain size fractions from very coarse sand to clay and analyzed by (i) X-ray fluorescence for chemical composition and (ii) X-ray diffraction and Mineral Liberation Analysis for mineralogical composition. The chemical composition vs. grain size relations were modeled by compositional linear regression. Mineralogical composition of selected samples is used to substantiate the interpretations based on geochemistry.
reveal a high degree of chemical weathering with chemical index of alteration (CIA) up to 92. High CIA values are restricted to the fine-grained fractions, while sand-sized sediment average at low to moderate CIA values (~60). Although strongly weathered, the three sample suites reflecting basic to felsic plutonic bed rock can be effectively discriminated across all grain-size classes using trace elements such as V, Rb, and Sr. Linear trend modeling and mineralogical data reflect similar patterns for all sample suites implying similar processes independent of source rock composition. This includes overall decrease of quartz and K-feldspar over the full grain-size range from very coarse sand to clay, which is contrasted by overall increase of sheet silicates from coarse to fine. Among the latter, increase of clay minerals strongly outpaces the increase of micas in silt to clay fractions. A more complex behavior is shown by plagioclase, which is most abundant in intermediate grain-size fractions for all sample suites. This is likely caused by initial hydrolysis along cleavage and twinning planes and subsequent breakage of plagioclase crystals into smaller fragments. Towards finer grain size, intense hydrolysis has destroyed most feldspars.
Research on plant–animal interactions has been focused on direct consumer interactions (i.e. plants as resources), but non-trophic interactions including providing shelter or interference with ...movement can also affect the fine-scale distribution of animals. In particular, non-trophic interactions that are positive could support threatened animal populations. Positive interactions have been used in the restoration of plant communities, but have not yet been extended to the management of animal habitat. In this study, we tested the hypothesis that non-trophic interactions influence the occurrence of an endangered lizard species in an arid shrub-annual system. At a location known to have a population of blunt-nosed leopard lizards (Gambelia sila), we geotagged 700 shrubs, measured shrub morphometric traits, collected biomass samples, and surveyed for lizard presence using scat detection dogs over two years. Relative to 2014, in 2013 plant productivity was high and lizard scats were found more frequently in areas with low invasive grass cover (i.e. residual dry matter, RDM). In 2014, plant productivity was low because of an extreme drought year, and lizard scats were more frequently observed under shrub canopies, particularly those with relatively dense cover. These findings support the novel theory that positive non-trophic interactions are a critical form of plant–animal interactions in addition to consumption. Dominant shrubs can act as a foundation species by functioning as a basal node in structuring both plant and animal communities through a network of interactions. Managing dominant plants, in addition to habitat, is therefore important for conserving animal species in arid ecosystems.
The structural similarity between an MmpL3 inhibitor BM212, and a cannabinoid receptor modulator rimonabant, prompted us to investigate the anti-tubercular activity of rimonabant and its analogues. ...Further optimization, particularly through incorporation of silicon into the scaffold, resulted in new compounds with significant improvement in anti-tubercular activity against Mycobacterium tuberculosis (H37Rv). The sila analogue 18a was found to be the most potent antimycobacterial compound (MIC, 31 ng/mL) from this series with an excellent selectivity index.
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•The antitubercular activity of diaryl pyrazoles (rimonabant analogues) was investigated as part of drug scaffold repurposing.•From SAR analysis, silicon incorporation increased the anti-TB potential of the series.•The sila analogue 18a was the most potent compound (MIC 31 ng/mL, H37Rv).•Compound 18e (MIC 390 ng/mL) was the best in terms of in vitro pharmacokinetics.
Loperamide (1a), an opioid receptor agonist, is in clinical use as an antidiarrheal agent. Carbon/silicon exchange (sila‐substitution) at the 4‐position of the piperidine ring of 1a (R3COH→R3SiOH) ...leads to sila‐loperamide (1b). Sila‐loperamide was synthesized in a multistep procedure, starting from triethoxyvinylsilane and taking advantage of the 4‐methoxyphenyl (MOP) unit as a protecting group for silicon. The in vitro and in vivo pharmacokinetic (PK) and pharmacodynamic (PD) properties of the C/Si analogues 1a and 1b were determined and compared. Despite significant differences in the in vitro PK properties of loperamide and sila‐loperamide regarding clearance, permeability, and efflux, both compounds exhibited nearly identical in vivo PK profiles. The increase in metabolic stability of the silicon compound 1b observed in vitro seems to be counterbalanced by an increase in efflux and diminished permeability compared to the parent carbon compound 1a. Overall, sila‐loperamide exhibits high unbound clearance (CLu), leading to a significant decrease in unbound concentration (Cu) and unbound area under the curve (AUCu) after oral exposure, compared to loperamide. In vitro and in vivo metabolic studies showed an altered profile of biotransformation for the silicon compound 1b, leading to the formation of a more polar and quickly cleared metabolite and preventing the formation of the silicon analogue of the neurotoxic metabolite observed for the parent carbon compound 1a. These differences can be correlated with the different chemical properties of the C/Si analogues 1a and 1b. This study provides some of the most detailed insights into the effects of a carbon/silicon switch and how this carbon/silicon exchange affects overall drug properties.
Carbon/silicon switch: Sila‐loperamide (1b), a silicon analogue of the opioid receptor agonist loperamide (1a), was synthesized. A head‐to‐head comparison of the in vitro pharmacodynamics and pharmacokinetics and the in vivo pharmacokinetics of 1a and 1b revealed that the C/Si switch strategy is a smart choice to modulate potency, efficacy, stability, and metabolic fate.
Fluoroquinolones (FQs) are the most commonly used antimicrobial drugs and regardless of their advantages in the healthcare sector, the pollution of these antimicrobial drugs in the environment has ...big concerns about human and environmental health. The presence of these antibiotic drugs even at the lowest concentrations in the environment has resulted in the emergence and spread of antibiotic resistance. Hence, it is necessary to remediate these pollutants from the environment. Previously alkaline laccase (SilA) from Streptomyces ipomoeae has been demonstrated to show degrading potentials against two of the FQs, Ciprofloxacin (CIP) and Norfloxacin (NOR); however, the molecular mechanism was not elucidated in detail. In this study, we have analyzed the possible molecular catalytic mechanism of FQ degrading SilA-laccase for the degradation of the FQs, CIP, NOR and Ofloxacin (OFL) using three-dimensional protein structure modeling, molecular docking and molecular dynamic (MD) studies. The comparative protein sequence analysis revealed the presence of tetrapeptide conserved catalytic motif, His
102
-X-His
104
-Gly
105
. After evaluating the active site of the enzyme in depth using CDD, COACH and S-site tools, we have identified the catalytic triad composed of three conserved amino acid residues, His
102
, Val
103
and Tyr
108
with which ligands interacted during the catalysis process. By analyzing the MD trajectories, it is revealed that the highest degradation potential of SilA is for CIP followed by NOR and OFL. Ultimately, this study provides the possible comparative catalytic mechanism for the degradation of CIP, NOR and OFL by the SilA enzyme.
Communicated by Ramaswamy H. Sarma
A series of silicon‐containing derivatives of the polycyclic musk odorant galaxolide (4 a) was synthesized, that is, disila‐galaxolide ((4RS,7SR)‐4 b/(4RS,7RS)‐4 b), its methylene derivative rac‐9, ...and its nor analogue rac‐10. The tricyclic title compounds with their 7,8‐dihydro‐6,8‐disila‐6 H‐cyclopentagisochromane skeleton were prepared in multistep syntheses by using a cobalt‐catalyzed 2+2+2 cycloaddition of the mono‐ yne H2CCHCH2OCH2CCB(pin) (B(pin)=4,4,5,5‐tetramethyl‐1,3,2‐di‐ oxaborolan‐2‐yl) with the diynes H2CCSi(CH3)2CCH2 or H2C‐ Si(CH3)2CCH2 as the key step. Employing Cr(CO)3(MeCN)3 as an auxiliary, the disila‐galaxolide diastereomers (4RS,7SR)‐4 b and (4RS,7RS)‐4 b could be chromatographically separated through their tricarbonylchromium(0) complexes, followed by oxidative decomplexation. The identity of the title compounds and their precursors was established by elemental analyses and multinuclear NMR spectroscopic studies and in some cases additionally by crystal structure analyses. Compounds (4RS,7SR)‐4 b, (4RS,7RS)‐4 b, rac‐9, and rac‐10 were characterized for their olfactory properties, including GC‐olfactory studies of the racemic compounds on a chiral stationary phase. As for the parent galaxolide stereoisomers 4 a, only one enantiomer of the silicon compounds (4RS,7SR)‐4 b, (4RS,7RS)‐4 b, rac‐9, and rac‐10, smelt upon enantioselective GC‐olfactometry, which according to the elution sequence is assumed to be also (4S)‐configured as in the case of the galaxolide stereoisomers. The disila‐analogues (4S,7R)‐4 b and (4S,7S)‐4 b were, however, about one order of magnitude less intense in terms of their odor threshold than their parent carbon compounds (4S,7R)‐4 a and (4S,7S)‐4 a. The introduction of a 7‐methylene group in disila‐galaxolide (4 b→rac‐9) improved the odor threshold by a factor of two. With the novel silicon‐containing galaxolide derivatives, the presumed hydrophobic bulk binding pocket of the corresponding musk receptor(s) could be characterized in more detail, which could be useful for the design of novel musk odorants with an improved environmental profile.
Fragrant sila‐musks: Silicon‐containing derivatives of the polycyclic musk odorant galaxolide (see scheme) were synthesized and characterized for their olfactory properties. The disila‐galaxolide diastereomers (4RS,7SR) and (4RS,7RS) were obtained by chromatographic separation of their corresponding chromium complexes, followed by oxidative decomplexation. The relatively rigid structures of these polycycles, in combination with the carbon/silicon switch strategy, makes the single stereoisomers of these C/Si analogues ideal candidates for structure–odor correlations in the musk domain.
Therapeutic options for brain infections caused by pathogens with a reduced sensitivity to drugs are limited. Recent reports on the potential use of linezolid in treating brain infections prompted us ...to design novel compounds around this scaffold. Herein, we describe the design and synthesis of various oxazolidinone antibiotics with the incorporation of silicon. Our findings in preclinical species suggest that silicon incorporation is highly useful in improving brain exposures. Interestingly, three compounds from this series demonstrated up to a 30-fold higher brain/plasma ratio when compared to linezolid thereby indicating their therapeutic potential in brain associated disorders.
The construction industry of all countries in the world is facing the issue of sustainable development. How to make effective and accurate decision-making on the three pillars (Environment; Economy; ...Social influence) is the key factor. This manuscript is based on an accurate evaluation framework and theoretical modelling. Through a comprehensive evaluation of six cable-stayed highway bridges in the entire life cycle of five provinces in China (from cradle to grave), the research shows that life cycle impact assessment (LCIA), life cycle cost assessment (LCCA), and social impact life assessment (SILA) are under the influence of multi-factor change decisions. The manuscript focused on the analysis of the natural environment over 100 years, material replacement, waste recycling, traffic density, casualty costs, community benefits and other key factors. Based on the analysis data, the close connection between high pollution levels and high cost in the maintenance stage was deeply promoted, an innovative comprehensive evaluation discrete mathematical decision-making model was established, and a reasonable interval between gross domestic product (GDP) and sustainable development was determined.
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