Annals of Clinical Microbiology and Antimicrobials
Background A complex cascade of genes, enzymes, and transcription factors regulates AmpC β-lactam... more Background A complex cascade of genes, enzymes, and transcription factors regulates AmpC β-lactamase overexpression. We investigated the network of AmpC β-lactamase overexpression in Klebsiella aerogenes and identified the role of AmpG in resistance to β-lactam agents, including cephalosporins and carbapenems. Methods A transposon mutant library was created for carbapenem-resistant K. aerogenes YMC2008-M09-943034 (KE-Y1) to screen for candidates with increased susceptibility to carbapenems, which identified the susceptible mutant derivatives KE-Y3 and KE-Y6. All the strains were subjected to highly contiguous de novo assemblies using PacBio sequencing to investigate the loss of resistance due to transposon insertion. Complementation and knock-out experiments using lambda Red-mediated homologous recombinase and CRISPR–Cas9 were performed to confirm the role of gene of interest. Results In-depth analysis of KE-Y3 and KE-Y6 revealed the insertion of a transposon at six positions in eac...
Ferromagnetic low-temperature-phase (LTP) of MnBi has attracted much attention because it has a h... more Ferromagnetic low-temperature-phase (LTP) of MnBi has attracted much attention because it has a higher coercivity than that of Nd-Fe-B at high temperature (~ 200C) and it has been a desirable material as rare-earth-free permanent magnets that can be used in such high temperature. We present a change of magnetic properties of MnBi films by controlling the numbers of Bi/Mn bilayer. The thin films of LTP-MnBi were fabricated onto glass substrates by UHV sputtering, followed by in-situ annealing process at an optimized condition of 350C and 1.5 hours. The composition ratio of Bi/Mn in the films was adjusted with a variation of the thickness of Bi and Mn layers. The highest value of maximum energy product (BH)max was about 8.5 MGOe at room temperature, which was obtained in one Bi/Mn bilayer with the thickness ratio of 34 nm/16 nm. To investigate the effect of Bi/Mn multilayers on the magnetic properties, we increased the numbers of Bi/Mn bilayer ([Bi/Mn]N) up to five (N = 5). Here, the ...
We investigated the additional (secondary) cooling effect of casted strips on magnetic properties... more We investigated the additional (secondary) cooling effect of casted strips on magnetic properties of Nd-Fe-B sintered magnets. The Nd-Fe-B sintered magnets were fabricated with the casted strips prepared without and with additional cooling. The additional cooling was performed by blowing Ar gas with various pressures (0.1, 0.3, and 0.6 MPa) on the free-side surface of the strips during strip-casting process. The higher magnetic properties of Hc, Br, and (BH)max of the final Nd-Fe-B sintered magnets were obtained for 0.1 MPa rather than for 0.0 MPa. The best microstructure of columnar grains in the casted strips was produced with the aid of lower gas cooling at the free side. It was found that the microstructure of the strips affects the distribution of grains grown in the sintered magnets. This is the first report of demonstrating improved magnetic performance in Nd-Fe-B sintered magnets by additional gas cooling.
, ibid at 125. 35 Clarence Johnson was the founder of ‗Skunk Works', the classified Lockheed mili... more , ibid at 125. 35 Clarence Johnson was the founder of ‗Skunk Works', the classified Lockheed military aviation testing facility which designed and produced the SR-71 and U-2 which are the earliest stealth military aircrafts.
ZnO has been studied intensely for chemical sensors due to its high sensitivity and fast response... more ZnO has been studied intensely for chemical sensors due to its high sensitivity and fast response. Here, we present a simple approach to precisely control oxygen vacancy contents to provide significantly enhanced acetone sensing performance of commercial ZnO nanopowders. A combination of H2O2 treatment and thermal annealing produces optimal surface defects with oxygen vacancies on the ZnO nanoparticles (NPs). The highest response of ~27,562 was achieved for 10 ppm acetone in 0.125 M H2O2 treated/annealed ZnO NPs at the optimal working temperature of 400 ℃, which is significantly higher than that of reported so far in various acetone sensors based on metal-oxide-semiconductor (MOS). Furthermore, first-principles calculations indicate that pre-adsorbed O formed on the surface of H2O2-treated ZnO NPs can provide a favorable adsorption energy, especially for acetone detection, due to strong bidentate bonding between carbonyl C atom of acetone molecules and pre-adsorbed O on the ZnO surf...
The siderophore–antibiotic conjugate LCB10-0200 (a.k.a. GT-1) has been developed to combat multid... more The siderophore–antibiotic conjugate LCB10-0200 (a.k.a. GT-1) has been developed to combat multidrug-resistant Gram-negative bacteria. In this study, the in vitro activity of LCB10-0200 and LCB10-0200/avibactam (AVI) has been investigated against carbapenem-resistant Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa. Minimal inhibitory concentrations (MICs) of LCB10-0200, LCB10-0200/AVI, aztreonam, aztreonam/AVI, ceftazidime, ceftazidime/AVI, and meropenem were measured using the agar dilution method. Whole genome sequencing was performed using Illumina and the resistome was analyzed. LCB10-0200 displayed stronger activity than the comparator drugs in meropenem-resistant E. coli and K. pneumoniae, and the addition of AVI enhanced the LCB10-0200 activity to MIC ≤ 0.12 mg/L for 90.5% of isolates. In contrast, whereas LCB10-0200 alone showed potent activity against meropenem-resistant A. baumannii and P. aeruginosa at MIC ≤ 4 mg/L for 84.3% of...
With the recent reillumination of the hydrogen economy around the world, the demand for H2 sensor... more With the recent reillumination of the hydrogen economy around the world, the demand for H2 sensors is expected to increase rapidly. Due to safety issues caused by the highly flammable and explosive character of hydrogen gas (H2), it is imperative to develop the sensors that can quickly and sensitively detect H2 leaks. For the development of H2 sensors, Pd‐based materials have been extensively used due to the high affinity of Pd metal for H2. Among Pd‐based H2 sensors, Pd nanogap‐based sensors have been extensively investigated because these sensors can operate in an on–off manner, which enables them to have improved sensing capabilities, including high sensitivity, rapid response, short recovery time, and good reliability. Importantly, significant advances in H2‐sensing performance have been achieved by simply using an elastomeric substrate to form Pd nanogaps. Herein, the progress and advanced approaches achieved over the last decade for Pd nanogap‐based H2 sensors supported on elastomeric substrates are reviewed, with a focus on strategies to reduce detection limits and increase reliability, sensitivity, and stability.
We investigated the magnetic properties of large, compacted, sintered MnBi bulk magnets with dime... more We investigated the magnetic properties of large, compacted, sintered MnBi bulk magnets with dimensions of 20.3 Â 15.3 Â 10.3 mm 3. To obtain a high content of the low-temperature-phase (LTP) of MnBi in the precursor powders, a new process was implemented and produced about 98 wt% of LTP. To improve the coercive field of MnBi, particle sizes were controlled using different milling techniques. The dependence of magnetic properties of the bulk magnets on the particle size was analyzed. The highest maximum energy product, (BH) max , obtained among our samples was 7.3 MGOe. This is the first report of demonstrating high performance in large-sized MnBi bulk magnets.
Background: Colistin has become a last-resort antibiotic for the management of multidrugresistant... more Background: Colistin has become a last-resort antibiotic for the management of multidrugresistant gram-negative bacteria. The disk diffusion test is cheap and easy to perform but may be unreliable for colistin susceptibility testing due to poor diffusion of the large colistin molecule. An improved agar diffusion test would increase the reliability of colistin susceptibility testing. This study aimed to modify Muller-Hinton agar (MHA) to improve colistin diffusion in agar. Methods: MHA was modified by reducing the agar concentration from 100% to 30% and supplementing with protamine. We tested 60 gram-negative clinical isolates of Pseudomonas aeruginosa (N = 27) and Acinetobacter calcoaceticus-baumannii complex (N = 33). Disk diffusion test results were interpreted based on minimum inhibitory concentrations determined by broth microdilution. Results: The modified MHA yielded the best performance metrics, including 94.7% sensitivity, 100% specificity, and an area under the curve of 0.995 (95% confidence interval, 0.982-1.000), P < 0.001, at a cutoff point of 13 mm. Conclusions: A reduction of the agar concentration from 100% to 30% and the addition of protamine improved colistin diffusion in agar and allowed routine colistin susceptibility testing in a clinical microbiology laboratory, but should be handled with caution.
Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to the low density lipoprotein recept... more Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to the low density lipoprotein receptor (LDLR) and promotes degradation of the LDLR. Inhibition of PCSK9 either by reducing its expression or by blocking its activity results in the upregulation of the LDLR and subsequently lowers the plasma concentration of LDL-cholesterol. As a modality to inhibit PCSK9 action, we searched the chemical library for small molecules that block the binding of PCSK9 to the LDLR. Materials and Methods: We selected 100 chemicals that bind to PCSK9 where the EGF-AB fragment of the LDLR binds via in silico screening of the ChemBridge chemical library, using the computational GOLD algorithm analysis. Effects of chemicals were evaluated using the PCSK9-LDLR binding assay, immunoblot analysis, and the LDL-cholesterol uptake assay in vitro, as well as the fast performance liquid chromatography assay for plasma lipoproteins in vivo. Results: A set of chemicals were found that decreased the binding of PCSK9 to the EGF-AB fragment of the LDLR in a dose-dependent manner. They also increased the amount of the LDLR significantly and subsequently increased the uptake of fluorescencelabeled LDL in HepG2 cells. Additionally, one particular molecule lowered the plasma concentration of total cholesterol and LDL-cholesterol significantly in wild-type mice, while such an effect was not observed in Pcsk9 knockout mice. Conclusion: Our findings strongly suggest that in silico screening of small molecules that inhibit the protein-protein interaction between PCSK9 and the LDLR is a potential modality for developing hypercholesterolemia therapeutics.
Annals of Clinical Microbiology and Antimicrobials
Background A complex cascade of genes, enzymes, and transcription factors regulates AmpC β-lactam... more Background A complex cascade of genes, enzymes, and transcription factors regulates AmpC β-lactamase overexpression. We investigated the network of AmpC β-lactamase overexpression in Klebsiella aerogenes and identified the role of AmpG in resistance to β-lactam agents, including cephalosporins and carbapenems. Methods A transposon mutant library was created for carbapenem-resistant K. aerogenes YMC2008-M09-943034 (KE-Y1) to screen for candidates with increased susceptibility to carbapenems, which identified the susceptible mutant derivatives KE-Y3 and KE-Y6. All the strains were subjected to highly contiguous de novo assemblies using PacBio sequencing to investigate the loss of resistance due to transposon insertion. Complementation and knock-out experiments using lambda Red-mediated homologous recombinase and CRISPR–Cas9 were performed to confirm the role of gene of interest. Results In-depth analysis of KE-Y3 and KE-Y6 revealed the insertion of a transposon at six positions in eac...
Ferromagnetic low-temperature-phase (LTP) of MnBi has attracted much attention because it has a h... more Ferromagnetic low-temperature-phase (LTP) of MnBi has attracted much attention because it has a higher coercivity than that of Nd-Fe-B at high temperature (~ 200C) and it has been a desirable material as rare-earth-free permanent magnets that can be used in such high temperature. We present a change of magnetic properties of MnBi films by controlling the numbers of Bi/Mn bilayer. The thin films of LTP-MnBi were fabricated onto glass substrates by UHV sputtering, followed by in-situ annealing process at an optimized condition of 350C and 1.5 hours. The composition ratio of Bi/Mn in the films was adjusted with a variation of the thickness of Bi and Mn layers. The highest value of maximum energy product (BH)max was about 8.5 MGOe at room temperature, which was obtained in one Bi/Mn bilayer with the thickness ratio of 34 nm/16 nm. To investigate the effect of Bi/Mn multilayers on the magnetic properties, we increased the numbers of Bi/Mn bilayer ([Bi/Mn]N) up to five (N = 5). Here, the ...
We investigated the additional (secondary) cooling effect of casted strips on magnetic properties... more We investigated the additional (secondary) cooling effect of casted strips on magnetic properties of Nd-Fe-B sintered magnets. The Nd-Fe-B sintered magnets were fabricated with the casted strips prepared without and with additional cooling. The additional cooling was performed by blowing Ar gas with various pressures (0.1, 0.3, and 0.6 MPa) on the free-side surface of the strips during strip-casting process. The higher magnetic properties of Hc, Br, and (BH)max of the final Nd-Fe-B sintered magnets were obtained for 0.1 MPa rather than for 0.0 MPa. The best microstructure of columnar grains in the casted strips was produced with the aid of lower gas cooling at the free side. It was found that the microstructure of the strips affects the distribution of grains grown in the sintered magnets. This is the first report of demonstrating improved magnetic performance in Nd-Fe-B sintered magnets by additional gas cooling.
, ibid at 125. 35 Clarence Johnson was the founder of ‗Skunk Works', the classified Lockheed mili... more , ibid at 125. 35 Clarence Johnson was the founder of ‗Skunk Works', the classified Lockheed military aviation testing facility which designed and produced the SR-71 and U-2 which are the earliest stealth military aircrafts.
ZnO has been studied intensely for chemical sensors due to its high sensitivity and fast response... more ZnO has been studied intensely for chemical sensors due to its high sensitivity and fast response. Here, we present a simple approach to precisely control oxygen vacancy contents to provide significantly enhanced acetone sensing performance of commercial ZnO nanopowders. A combination of H2O2 treatment and thermal annealing produces optimal surface defects with oxygen vacancies on the ZnO nanoparticles (NPs). The highest response of ~27,562 was achieved for 10 ppm acetone in 0.125 M H2O2 treated/annealed ZnO NPs at the optimal working temperature of 400 ℃, which is significantly higher than that of reported so far in various acetone sensors based on metal-oxide-semiconductor (MOS). Furthermore, first-principles calculations indicate that pre-adsorbed O formed on the surface of H2O2-treated ZnO NPs can provide a favorable adsorption energy, especially for acetone detection, due to strong bidentate bonding between carbonyl C atom of acetone molecules and pre-adsorbed O on the ZnO surf...
The siderophore–antibiotic conjugate LCB10-0200 (a.k.a. GT-1) has been developed to combat multid... more The siderophore–antibiotic conjugate LCB10-0200 (a.k.a. GT-1) has been developed to combat multidrug-resistant Gram-negative bacteria. In this study, the in vitro activity of LCB10-0200 and LCB10-0200/avibactam (AVI) has been investigated against carbapenem-resistant Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa. Minimal inhibitory concentrations (MICs) of LCB10-0200, LCB10-0200/AVI, aztreonam, aztreonam/AVI, ceftazidime, ceftazidime/AVI, and meropenem were measured using the agar dilution method. Whole genome sequencing was performed using Illumina and the resistome was analyzed. LCB10-0200 displayed stronger activity than the comparator drugs in meropenem-resistant E. coli and K. pneumoniae, and the addition of AVI enhanced the LCB10-0200 activity to MIC ≤ 0.12 mg/L for 90.5% of isolates. In contrast, whereas LCB10-0200 alone showed potent activity against meropenem-resistant A. baumannii and P. aeruginosa at MIC ≤ 4 mg/L for 84.3% of...
With the recent reillumination of the hydrogen economy around the world, the demand for H2 sensor... more With the recent reillumination of the hydrogen economy around the world, the demand for H2 sensors is expected to increase rapidly. Due to safety issues caused by the highly flammable and explosive character of hydrogen gas (H2), it is imperative to develop the sensors that can quickly and sensitively detect H2 leaks. For the development of H2 sensors, Pd‐based materials have been extensively used due to the high affinity of Pd metal for H2. Among Pd‐based H2 sensors, Pd nanogap‐based sensors have been extensively investigated because these sensors can operate in an on–off manner, which enables them to have improved sensing capabilities, including high sensitivity, rapid response, short recovery time, and good reliability. Importantly, significant advances in H2‐sensing performance have been achieved by simply using an elastomeric substrate to form Pd nanogaps. Herein, the progress and advanced approaches achieved over the last decade for Pd nanogap‐based H2 sensors supported on elastomeric substrates are reviewed, with a focus on strategies to reduce detection limits and increase reliability, sensitivity, and stability.
We investigated the magnetic properties of large, compacted, sintered MnBi bulk magnets with dime... more We investigated the magnetic properties of large, compacted, sintered MnBi bulk magnets with dimensions of 20.3 Â 15.3 Â 10.3 mm 3. To obtain a high content of the low-temperature-phase (LTP) of MnBi in the precursor powders, a new process was implemented and produced about 98 wt% of LTP. To improve the coercive field of MnBi, particle sizes were controlled using different milling techniques. The dependence of magnetic properties of the bulk magnets on the particle size was analyzed. The highest maximum energy product, (BH) max , obtained among our samples was 7.3 MGOe. This is the first report of demonstrating high performance in large-sized MnBi bulk magnets.
Background: Colistin has become a last-resort antibiotic for the management of multidrugresistant... more Background: Colistin has become a last-resort antibiotic for the management of multidrugresistant gram-negative bacteria. The disk diffusion test is cheap and easy to perform but may be unreliable for colistin susceptibility testing due to poor diffusion of the large colistin molecule. An improved agar diffusion test would increase the reliability of colistin susceptibility testing. This study aimed to modify Muller-Hinton agar (MHA) to improve colistin diffusion in agar. Methods: MHA was modified by reducing the agar concentration from 100% to 30% and supplementing with protamine. We tested 60 gram-negative clinical isolates of Pseudomonas aeruginosa (N = 27) and Acinetobacter calcoaceticus-baumannii complex (N = 33). Disk diffusion test results were interpreted based on minimum inhibitory concentrations determined by broth microdilution. Results: The modified MHA yielded the best performance metrics, including 94.7% sensitivity, 100% specificity, and an area under the curve of 0.995 (95% confidence interval, 0.982-1.000), P < 0.001, at a cutoff point of 13 mm. Conclusions: A reduction of the agar concentration from 100% to 30% and the addition of protamine improved colistin diffusion in agar and allowed routine colistin susceptibility testing in a clinical microbiology laboratory, but should be handled with caution.
Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to the low density lipoprotein recept... more Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to the low density lipoprotein receptor (LDLR) and promotes degradation of the LDLR. Inhibition of PCSK9 either by reducing its expression or by blocking its activity results in the upregulation of the LDLR and subsequently lowers the plasma concentration of LDL-cholesterol. As a modality to inhibit PCSK9 action, we searched the chemical library for small molecules that block the binding of PCSK9 to the LDLR. Materials and Methods: We selected 100 chemicals that bind to PCSK9 where the EGF-AB fragment of the LDLR binds via in silico screening of the ChemBridge chemical library, using the computational GOLD algorithm analysis. Effects of chemicals were evaluated using the PCSK9-LDLR binding assay, immunoblot analysis, and the LDL-cholesterol uptake assay in vitro, as well as the fast performance liquid chromatography assay for plasma lipoproteins in vivo. Results: A set of chemicals were found that decreased the binding of PCSK9 to the EGF-AB fragment of the LDLR in a dose-dependent manner. They also increased the amount of the LDLR significantly and subsequently increased the uptake of fluorescencelabeled LDL in HepG2 cells. Additionally, one particular molecule lowered the plasma concentration of total cholesterol and LDL-cholesterol significantly in wild-type mice, while such an effect was not observed in Pcsk9 knockout mice. Conclusion: Our findings strongly suggest that in silico screening of small molecules that inhibit the protein-protein interaction between PCSK9 and the LDLR is a potential modality for developing hypercholesterolemia therapeutics.
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Papers by Brian kibet