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Scientific Reports Jun 2024The combustion of hydrogen and carbon-monoxide mixtures, so-called syngas, plays an increasingly important role in the safety context of non-fossil energy generation,...
The combustion of hydrogen and carbon-monoxide mixtures, so-called syngas, plays an increasingly important role in the safety context of non-fossil energy generation, more specifically in the risk management of incidents in process engineering plants for ammonia synthesis and in nuclear power plants. In order to characterize and simulate syngas/air combustion on industrially relevant scales, subgrid modelling is required, which is often based on a reaction progress variable. To understand the influence of different fuel compositions, turbulence intensities and flame topologies on different possible definitions of reaction progress variable, detailed chemistry direct numerical simulations data of premixed, lean hydrogen/air and syngas/air flames has been considered. A reaction progress variable based on normalized molecular oxygen mass fraction has been found not to capture the augmentation of the normalized burning rate per unit flame surface area in comparison to the corresponding 1D unstretched premixed flame due to preferential diffusion effects. By contrast, reaction progress variables based on other individual species, such as hydrogen, can capture the augmentation of the rate of burning well, but exhibit a pronounced sensitivity to preferential diffusion effects, especially in response to flame curvatures. However, a reaction progress variable based on the linear combination of the main products can accurately represent the temperature evolution of the flame for different mixtures, turbulence intensities and varying local flame topology, while effectively capturing the augmentation of burning rate due to preferential diffusion effects. However, its tendency to assume values larger than 1.0 in the regions of super-adiabatic temperatures poses challenges for future modeling approaches, whereas the reaction progress variable based on hydrogen mass fraction remains bound between 0.0 and 1.0 despite showing deviations in comparison to corresponding variations obtained from the unstretched laminar flame depending on flame curvature variations.
PubMed: 38937515
DOI: 10.1038/s41598-024-64552-0 -
Nature Communications Jun 2024The Stöber method is a widely-used sol-gel route for synthesizing amorphous SiO colloids and conformal coatings. However, the material systems compatible with this...
The Stöber method is a widely-used sol-gel route for synthesizing amorphous SiO colloids and conformal coatings. However, the material systems compatible with this method are still limited. Herein, we have extended the approach to metal-organic frameworks (MOFs) and coordination polymers (CPs) by mimicking the Stöber method. We introduce a general synthesis route to amorphous MOFs or CPs by making use of a base-vapor diffusion method, which allows to precisely control the growth kinetics. Twenty-four different amorphous CPs colloids were successfully synthesized by selecting 12 metal ions and 17 organic ligands. Moreover, by introducing functional nanoparticles (NPs), a conformal amorphous MOFs coating with controllable thickness can be grown on NPs to form core-shell colloids. The versatility of this amorphous coating technology was demonstrated by synthesizing over 100 core-shell composites from 20 amorphous CPs shells and over 30 different NPs. Besides, various multifunctional nanostructures, such as conformal yolk-amorphous MOF shell, core@metal oxides, and core@carbon, can be obtained through one-step transformation of the core@amorphous MOFs. This work significantly enriches the Stöber method and introduces a platform, enabling the systematic design of colloids exhibiting different level of functionality and complexity.
PubMed: 38937499
DOI: 10.1038/s41467-024-49772-2 -
Scientific Reports Jun 2024Nasally colonized staphylococci carry antibiotic resistance genes and may lead to serious opportunistic infections. We are investigating nasal carriage of Staphylococcus...
Nasally colonized staphylococci carry antibiotic resistance genes and may lead to serious opportunistic infections. We are investigating nasal carriage of Staphylococcus aureus and Staphylococci other than S. aureus (SOSA) among young volunteers in Egypt to determine their risk potential. Nasal swabs collected over 1 week in June 2019 from 196 volunteers were cultured for staphylococcus isolation. The participants were interviewed to assess sex, age, general health, hospitalization and personal hygiene habits. Identification was carried out using biochemical tests and VITEK 2 automated system. Disc diffusion and minimum inhibitory concentration tests were performed to determine antibiotic susceptibility. Screening for macrolide resistance genes (ermA, ermB, ermC, ermT and msrA) was performed using polymerase chain reaction. Thirty four S. aureus and 69 SOSA were obtained. Multi-drug resistance (MDR) was detected among most staphylococcal species, ranging from 30.77% among S. hominis to 50% among S. epidermidis. Phenotypic resistance to all tested antibiotics, except for linezolid, was observed. Susceptibility to rifampicin, vancomycin and teicoplanin was highest. ermB showed the highest prevalence among all species (79.41% and 94.2% among S. aureus and SOSA, respectively), and constitutive macrolide-lincosamide-streptogramin B (MLS) resistance was equally observed in S. aureus and SOSA (11.11% and 16.22%, respectively), whereas inducible MLS resistance was more often found in S. aureus (77.78% and 43.24%, respectively). The species or resistance level of the carried isolates were not significantly associated with previous hospitalization or underlying diseases. Although over all colonization and carriage of resistance genes are within normal ranges, the increased carriage of MDR S. aureus is alarming. Also, the fact that many macrolide resitance genes were detected should be a warning sign, particularly in case of MLS inducible phenotype. More in depth analysis using whole genome sequencing would give a better insight into the MDR staphylococci in the community in Egypt.
Topics: Humans; Egypt; Female; Male; Staphylococcus; Microbial Sensitivity Tests; Staphylococcal Infections; Anti-Bacterial Agents; Adult; Phenotype; Young Adult; Genotype; Staphylococcus aureus; Drug Resistance, Multiple, Bacterial; Adolescent
PubMed: 38937465
DOI: 10.1038/s41598-024-60924-8 -
ENeuro Jun 2024Ghrelin is a stomach-derived hormone that increases feeding and is elevated in response to chronic psychosocial stressors. The effects of ghrelin on feeding are mediated...
Ghrelin is a stomach-derived hormone that increases feeding and is elevated in response to chronic psychosocial stressors. The effects of ghrelin on feeding are mediated by the binding of ghrelin to the growth hormone secretagogue receptor (GHSR), a receptor located in hypothalamic and extra-hypothalamic regions important for regulating food intake and metabolic rate. The ability of ghrelin to enter the brain, however, seems to be restricted to circumventricular organs like the median eminence and the brain stem area postrema (AP), whereas ghrelin does not readily enter other GHSR expressing regions like the ventral tegmental area (VTA). Interestingly, social stressors result in increased blood brain barrier permeability, and this could therefore facilitate the entry of ghrelin into the brain. To investigate this, we exposed mice to social defeat stress for 21 days, then peripherally injected a Cy5-labelled biologically active ghrelin analogue. Results demonstrate that chronically stressed mice exhibit higher Cy5-ghrelin fluorescence in several hypothalamic regions in addition to the ARC, including the hippocampus and midbrain. Furthermore, Cy5-ghrelin injections resulted in increased FOS expression in regions associated with the reward system in the chronically stressed mice. Further histologic analyses identified a reduction in branching of hypothalamic astrocytes in the ARC-median eminence junction, suggesting increased blood-brain barrier permeability. These data support the hypothesis that during metabolically challenging conditions like chronic stress, ghrelin may be more able to cross the blood brain barrier and diffuse throughout the brain to target GHSR expressing brain regions away from circumventricular organs. Ghrelin is secreted in response to negative energy balance states including stress and is associated with changes in food intake and energy balance. The receptors for ghrelin are found throughout the brain but ghrelin seems to only reach circumventricular regions where the blood brain barrier is more porous. In this paper we demonstrate that chronic social defeat stress increases brain permeability to ghrelin to allow for entry and activation of target sites in the mesolimbic dopaminergic system that are not accessible to ghrelin under non-stress conditions. Overall, these results provide for an explanation as to how ghrelin can access the mesolimbic dopaminergic system in a state dependent manner.
PubMed: 38937108
DOI: 10.1523/ENEURO.0093-24.2024 -
Journal of Cardiovascular Magnetic... Jun 2024In-vivo diffusion tensor CMR (DT-CMR) is an emerging technique for microstructural tissue characterisation in the myocardium. Most studies are performed at 3T, where...
BACKGROUND
In-vivo diffusion tensor CMR (DT-CMR) is an emerging technique for microstructural tissue characterisation in the myocardium. Most studies are performed at 3T, where higher signal to noise ratio (SNR) should benefit this signal starved method. However, a few studies have suggested that DT-CMR is possible at 1.5T, where EPI artefacts may be less severe and 1.5T hardware is more widely available.
METHODS
We recruited 20 healthy volunteers and performed mid-ventricular short axis DT-CMR at 1.5 T and 3 T. Acquisitions were performed at peak systole and end-diastole using both stimulated echo acquisition mode (STEAM) and motion compensated spin-echo (MCSE) sequences at matched spatial resolutions. DT-CMR parameters were averaged over the LV and compared between 1.5 T and 3 T sequences using both datasets with and without the blow reference data included.
RESULTS
Eleven (1.5T) and 12 (3T) diastolic MCSE acquisitions were rejected as the helix angle (HA) demonstrated <50% normal appearance circumferentially or the acquisition was abandoned due to poor image quality; a maximum of one acquisition was rejected for other datasets. Subjective HA map quality was significantly better at 3T than 1.5T for STEAM (p<0.05), but not for MCSE and other DT-CMR quality measures were consistent with improvements in STEAM at 3T over 1.5T. When b data was excluded, no significant differences in mean diffusivity were observed between field strengths, but fractional anisotropy was significantly higher at 1.5T than 3T for STEAM systole (p<0.05). Absolute second eigenvector orientation (E2A, sheetlet angle) was significantly higher at 1.5T than 3T for MCSE systole and STEAM diastole, but significantly lower for STEAM systole (all p<0.05). Transmural HA distribution was less steep at 1.5T than 3T for STEAM diastole data (p<0.05). SNR in the b images was higher at 3T than 1.5T for all acquisitions (p<0.05).
CONCLUSION
While 3T provides benefits in terms of SNR, both STEAM and MCSE can be performed at 1.5T. However, MCSE is unreliable in diastole at both field strengths and STEAM benefits from the improved SNR at 3T over 1.5T. Future clinical research studies may be able to leverage the wider availability of 1.5T CMR hardware where MCSE acquisitions are desirable.
PubMed: 38936803
DOI: 10.1016/j.jocmr.2024.101052 -
Journal of Global Antimicrobial... Jun 2024Novel beta-lactams/beta-lactamase inhibitors (BIBLI) combinations are commercially available and they have been used for treating carbapenem-resistant Klebsiella...
Susceptibility evaluation of novel beta-lactam/beta-lactamase inhibitor combinations against carbapenem-resistant Klebsiella pneumoniae from bloodstream infections in hospitalized patients in Brazil.
Novel beta-lactams/beta-lactamase inhibitors (BIBLI) combinations are commercially available and they have been used for treating carbapenem-resistant Klebsiella pneumoniae (CRKP) infections. Continuous surveillance of susceptibility profile and resistance mechanisms identification are necessary to monitor the evolution of resistance as these agents are used. The purpose of this study was to evaluate susceptibility rates to ceftazidime/avibactam, imipenem/relebactam and meropenem/vaborbactam in CRKP isolates from patients with bloodstream infection screened for a randomized clinical trial in Brazil. Minimum inhibitory concentration (MIC) was determined by gradient diffusion strip method for meropenem, ceftazidime/avibactam, imipenem/relebactam and meropenem/vaborbactam. Carbapenemase genes were detected by multiplex qPCR. KPC-producing isolates showing resistance to any BLBLI and NDM-producing isolates showing susceptibility to any BLBLI were further submitted to whole genome sequencing. From a total of 69 CRKP isolates, 39 were positive for bla, 19 for bla and 11 for bla and bla. KPC-producing isolates demonstrated susceptibility rates above 94% for all BLBLI. Two isolates with resistance to meropenem/vaborbactam showed a Gly and Asp duplication at OmpK36 protein and truncated ompK35 genes. All NDM-producing isolates, including KPC and NDM coproducers, demonstrated susceptibility rates for ceftazidime/avibactam, imipenem/relebactam and meropenem/vaborbactam of 0%, 9.1 to 21.1% and 9.1 to 26.3%, respectively. Five NDM-producing isolates that presented susceptibility to BLBLI also demonstrated alterations in porins. This study demonstrated that, although high susceptibility rates to the BLBLI were found, KPC-2 isolates can also demonstrate resistance due to porin mutations. Additionally, NDM-1 isolates can demonstrate susceptibility in vitro to the BLBLI.
PubMed: 38936472
DOI: 10.1016/j.jgar.2024.06.007 -
Behavioural Brain Research Jun 2024The tendency to show the renewal effect of extinction appears as an intra-individually stable, reproducible processing strategy associated with differential patterns of...
The tendency to show the renewal effect of extinction appears as an intra-individually stable, reproducible processing strategy associated with differential patterns of BOLD activation in hippocampus, iFG and vmPFC, as well as differential resting-state functional connectivity between prefrontal regions and the dorsal attention network. Also, pharmacological modulations of the noradrenergic system that influence attentional processing have partially different effects upon individuals with (REN) and without (NoREN) a propensity for renewal. However, it is as yet unknown whether REN and NoREN individuals differ regarding microstructural properties in attention-related white matter (WM) regions, and whether such differences are related to noradrenergic processing. In this diffusion tensor imaging (DTI) analysis we investigated the relation between microstructural properties of attention-related WM tracts and ABA renewal propensity, under conditions of noradrenergic stimulation by means of the noradrenergic reuptake inhibitor atomoxetine, compared to placebo. Fractional anisotropy (FA) was higher in participants with noradrenergic stimulation (ATO) compared to placebo (PLAC), the effect was predominantly left-lateralized and based on the comparison of ATO REN and PLAC REN participants. In REN participants of both treatment groups, FA in several WM tracts showed a positive correlation with the ABA renewal level, suggesting higher renewal levels were associated with higher microstructural integrity. These findings point towards a relation between microstructural properties of attention-related WM tracts and the propensity for renewal that is not specifically dependent on noradrenergic processing.
PubMed: 38936425
DOI: 10.1016/j.bbr.2024.115125 -
Advances in Colloid and Interface... Jun 2024Surfactant mass transport towards an interface plays a critical role during formation of emulsions, foams and in industrial processes where two immiscible phases... (Review)
Review
Surfactant mass transport towards an interface plays a critical role during formation of emulsions, foams and in industrial processes where two immiscible phases coexist. The understanding of these mechanisms as experimentally observed by dynamic interfacial tension measurements, is crucial. In this review, theoretical models describing both equilibrated systems and surfactant kinetics are covered. Experimental results from the literature are analysed based on the nature of surfactants and the tensiometry methods used. The innovative microfluidic techniques that have become available to study both diffusion and adsorption mechanisms during surfactant mass transport are discussed and compared with classical methods. This review focuses on surfactant transport during formation of droplets or bubbles; stabilisation of dispersed systems is not discussed here.
PubMed: 38936181
DOI: 10.1016/j.cis.2024.103239 -
European Journal of Cancer (Oxford,... Jun 2024Phosphatidylinositol 3-kinase (PI3-K) signalling pathway is a crucial path in cancer for cell survival and thus represents an intriguing target for new paediatric... (Review)
Review
Phosphatidylinositol 3-kinase (PI3-K) signalling pathway is a crucial path in cancer for cell survival and thus represents an intriguing target for new paediatric anti-cancer drugs. However, the unique clinical toxicities of targeting this pathway (resulting in hyperglycaemia) difficulties combining with chemotherapy, rarity of mutations in childhood tumours and concomitant mutations have resulted in major barriers to clinical translation of these inhibitors in treating both adults and children. Mutations in PIK3CA predict response to PI3-K inhibitors in adult cancers. The same mutations occur in children as in adults, but they are significantly less frequent in paediatrics. In children, high-grade gliomas, especially diffuse midline gliomas (DMG), have the highest incidence of PIK3CA mutations. New mutation-specific PI3-K inhibitors reduce toxicity from on-target PI3-Kα wild-type activity. The mTOR inhibitor everolimus is approved for subependymal giant cell astrocytomas. In paediatric cancers, mTOR inhibitors have been predominantly evaluated by academia, without an overall strategy, in empiric, mutation-agnostic clinical trials with very low response rates to monotherapy. Therefore, future trials of single agent or combination strategies of mTOR inhibitors in childhood cancer should be supported by very strong biological rationale and preclinical data. Further preclinical evaluation of glycogen synthase kinase-3 beta inhibitors is required. Similarly, even where there is an AKT mutation (∼0.1 %), the role of AKT inhibitors in paediatric cancers remains unclear. Patient advocates strongly urged analysing and conserving data from every child participating in a clinical trial. A priority is to evaluate mutation-specific, central nervous system-penetrant PI3-K inhibitors in children with DMG in a rational biological combination. The choice of combination, should be based on the genomic landscape e.g. PTEN loss and resistance mechanisms supported by preclinical data. However, in view of the very rare populations involved, innovative regulatory approaches are needed to generate data for an indication.
PubMed: 38936103
DOI: 10.1016/j.ejca.2024.114145 -
PLoS Computational Biology Jun 2024Therapeutic interventions are designed to perturb the function of a biological system. However, there are many types of proteins that cannot be targeted with...
Therapeutic interventions are designed to perturb the function of a biological system. However, there are many types of proteins that cannot be targeted with conventional small molecule drugs. Accordingly, many identified gene-regulatory drivers and downstream effectors are currently undruggable. Drivers and effectors are often connected by druggable signaling and regulatory intermediates. Methods to identify druggable intermediates therefore have general value in expanding the set of targets available for hypothesis-driven validation. Here we identify and prioritize potential druggable intermediates by developing a network perturbation theory, termed NetPert, for response functions of biological networks. Dynamics are defined by a network structure in which vertices represent genes and proteins, and edges represent gene-regulatory interactions and protein-protein interactions. Perturbation theory for network dynamics prioritizes targets that interfere with signaling from driver to response genes. Applications to organoid models for metastatic breast cancer demonstrate the ability of this mathematical framework to identify and prioritize druggable intermediates. While the short-time limit of the perturbation theory resembles betweenness centrality, NetPert is superior in generating target rankings that correlate with previous wet-lab assays and are more robust to incomplete or noisy network data. NetPert also performs better than a related graph diffusion approach. Wet-lab assays demonstrate that drugs for targets identified by NetPert, including targets that are not themselves differentially expressed, are active in suppressing additional metastatic phenotypes.
PubMed: 38935814
DOI: 10.1371/journal.pcbi.1012195