Journal of Atmospheric and Oceanic Technology, 2011
Ocean wave energy is used to drive a buoyant instrument platform down a wire suspended from a sur... more Ocean wave energy is used to drive a buoyant instrument platform down a wire suspended from a surface float. At the lower terminus of the profiling range, the cam that rectifies wave vertical motion is released and the package, termed the Wirewalker, free ascends. No electronic components are used in the profiler, and only a few moving parts are involved. The Wirewalker is tolerant of a broad range of payloads: the ballast is adjusted by adding discrete foam blocks. The Wirewalker profiles 1000–3000 km month−1, vertically, with typical missions lasting from days to months. A description of the profiler is presented along with a discussion of basic profiling dynamics.
Journal of Atmospheric and Oceanic Technology, 2012
A wirewalker exploits the difference in vertical motion between a wire attached to a surface buoy... more A wirewalker exploits the difference in vertical motion between a wire attached to a surface buoy and the water at the depth of a profiling body to provide the power to execute deep profiles: when the wire’s relative motion is upward, the profiler lets go; when it is downward, the profiler clamps on, and the weight attached at depth pulls the wire down, dragging the profiler downward against its buoyancy. The difference between the upward wire and profiler motion has to exceed the buoyancy-driven upward acceleration of the profiler body for this to work. Because the relative motion of the wire and water decreases as the surface is approached, the profiler might get stuck near the surface, especially when it is calm. However, two things mitigate this: 1) the system has a damped resonant response (~1.3 Hz), which induces relative motion between the buoy and water even at the surface; and 2) for waves too gentle to directly exceed the required acceleration, drag on the profiler can pul...
The majority of cancer therapeutics induces DNA damage to kill cells. Normal proliferating cells ... more The majority of cancer therapeutics induces DNA damage to kill cells. Normal proliferating cells undergo cell cycle arrest in response to DNA damage, thus allowing DNA repair to protect the genome. DNA damage induced cell cycle arrest depends on an evolutionarily conserved signal transduction network in which the Chk1 kinase plays a critical role. In mammalian cells, the p53 and RB pathways further augment the cell cycle arrest response to prevent catastrophic cell death. Given the fact that most tumor cells suffer defects in the p53 and RB pathways, it is likely that tumor cells would depend more on the Chk1 kinase to maintain cell cycle arrest than would normal cells. Therefore Chk1 inhibition could be used to specifically sensitize tumor cells to DNA‐damaging agents. We have previously shown that siRNA‐mediated Chk1 knockdown abrogates DNA damage‐induced checkpoints and potentiates the cytotoxicity of several DNA‐damaging agents in p53‐deficient cell lines. In this study, we have...
International Journal for Vitamin and Nutrition Research, 1999
A microbiological method for the determination of thiamine in biological fluids and food using 96... more A microbiological method for the determination of thiamine in biological fluids and food using 96-well microtitre plates and automatic plate reader, suitable for using in routine clinical diagnosis is described. Thiamine was extracted from samples by acid digestion (acetate buffer, pH 4.5) at 110 degrees C for 20 minutes. Assay recovery and reproducibility were optimally evaluated. Results obtained from this method were compared with those obtained using traditional microbiological and HPLC methods. The values resulting from this method were more or less the same as those of the traditional microbiological method, but much higher than those of HPLC assay. However, the new assay presents many advantages: it reduces the use of serum volume, which is a main benefit for clinical analysis. It lowers also the reagent costs and increases the number of analyses as well as it is easy to perform for routine clinical laboratory.
Diagnostic Microbiology and Infectious Disease, 2002
Community-acquired methicillin-resistant Staphylococcus aureus (MRSA) infections are increasing. ... more Community-acquired methicillin-resistant Staphylococcus aureus (MRSA) infections are increasing. Since most published data are on nosocomial MRSA, our goal was to identify the antimicrobial susceptibility profile and resistance mechanisms of pretreatment MRSA isolates obtained from adult subjects participating in recent clinical treatment trials of community respiratory infections. Out of 465 S. aureus isolates, 43 were identified as MRSA. Antimicrobial susceptibility testing indicated susceptibility rates to: vancomycin (100%), gentamicin (86%), clindamycin (39%), quinolones (49%), and erythromycin (12%). Among our MRSA isolates, the MLS constitutive phenotype and ermA were more prevalent than the MLS inducible phenotype and ermC. No isolates had ermB or msrA. All ciprofloxacin resistant isolates had an amino acid change in GyrA and GrlA. The relatedness of our MRSA strains was assessed by ribotyping. Our results indicate that MRSA from adult subjects with community respiratory infections have similar antimicrobial susceptibility profiles and resistance mechanisms as nosocomial MRSA, and represent a genetically diverse group.
ABSTRACT The drive for efficiency improvements in post-combustion CO2 capture (PCC) technologies ... more ABSTRACT The drive for efficiency improvements in post-combustion CO2 capture (PCC) technologies continues to grow, with recent attention being directed towards flexible operation of PCC plants. However, there is a lack of research into the effect of process disturbances when operating flexibly, justifying a need for validated dynamic models of the PCC process. This review critically examines the dynamic PCC process models developed to date and analyses the different approaches used, as well as the model complexity and their limitations. Dynamic process models coupled with economic analysis will play a crucial role in process control and optimisation. Also discussed are key areas that need to be addressed in future dynamic models, including the lack of reliable dynamic experimental data for their validation, development of feasible flexible operation and process control strategies, as well as process optimisation by integrating accurate process models with established economic analysis tools.
As part of a fully integrated and comprehensive strategy to discover novel antibacterial agents, ... more As part of a fully integrated and comprehensive strategy to discover novel antibacterial agents, NMR‐ and mass spectrometry‐based affinity selection screens were performed to identify compounds that bind to protein targets uniquely found in bacteria and encoded by genes essential for microbial viability. A biphenyl acid lead series emerged from an NMR‐based screen with the Haemophilus influenzae protein HI0065, a member of a family of probable ATP‐binding proteins found exclusively in eubacteria. The structure–activity relationships developed around the NMR‐derived biphenyl acid lead were consistent with on‐target antibacterial activity as the Staphylococcus aureus antibacterial activity of the series correlated extremely well with binding affinity to HI0065, while the correlation of binding affinity with B‐cell cytotoxicity was relatively poor. Although further studies are needed to conclusively establish the mode of action of the biphenyl series, these compounds represent novel le...
For biofuel applications, synthetic endoglucanase E1 and xylanase (Xyn10A) derived from Acidother... more For biofuel applications, synthetic endoglucanase E1 and xylanase (Xyn10A) derived from Acidothermus cellulolyticus were transiently expressed in detached whole sunflower (Helianthus annuus L.) leaves using vacuum infiltration. Three different expression systems were tested, including the constitutive CaMV 35S-driven, CMVar (Cucumber mosaic virus advanced replicating), and TRBO (Tobacco mosaic virus RNA-Based Overexpression Vector) systems. For 6-day leaf incubations, codon-optimized E1 and xylanase driven by the CaMV 35S promoter were successfully expressed in sunflower leaves. The two viral expression vectors, CMVar and TRBO, were not successful although we found high expression in Nicotiana benthamiana leaves previously for other recombinant proteins. To further enhance transient expression, we demonstrated two novel methods: using the plant hormone methyl jasmonic acid in the agroinfiltration buffer and two-phase optimization of the leaf incubation temperature. When methyl jasmonic acid was added to Agrobacterium tumefaciens cell suspensions and infiltrated into plant leaves, the functional enzyme production increased 4.6-fold. Production also increased up to 4.2-fold when the leaf incubation temperature was elevated above the typical temperature, 20C, to 30C in the late incubation phase, presumably due to enhanced rate of protein synthesis in plant cells. Finally, we demonstrated co-expression of E1 and xylanase in detached sunflower leaves. To our knowledge, this is the first report of (co)expression of heterologous plant cell wall-degrading enzymes in sunflower.
Bioorganic & Medicinal Chemistry Letters, 2004
A series of novel 6-O-arylpropargyl-9-oxime-ketolides was synthesized and evaluated against vario... more A series of novel 6-O-arylpropargyl-9-oxime-ketolides was synthesized and evaluated against various pathogens. These new compounds show promising in vitro antibacterial potency and in vivo efficacy against macrolide resistant strains.
Chk1 is the major mediator of cell-cycle checkpoints in response to various forms of genotoxic st... more Chk1 is the major mediator of cell-cycle checkpoints in response to various forms of genotoxic stress. Although it was previously speculated that checkpoint abrogation due to Chk1 inhibition may potentiate the efficacy of DNA-damaging agents through induction of mitotic catastrophe, there has not been direct evidence proving this process. Here, through both molecular marker and morphological analysis, we directly demonstrate that specific downregulation of Chk1 expression by Chk1 siRNA potentiates the cytotoxicities of topoisomerase inhibitors through the induction of premature chromosomal condensation and mitotic catastrophe. More importantly, we discovered that the cellular cyclin B1 level is the major determinant of the potentiation. We show that downregulation of cyclin B1 leads to impairment of the induction of mitotic catastrophe and correspondingly a reduction of the potentiation ability of either Chk1 siRNA or a small molecule Chk1 inhibitor. More significantly, we have extended the study by examining a panel of 10 cancer cell-lines with different tissue origens for their endogenous levels of cyclin B1 and the ability of a Chk1 inhibitor to sensitize the cells to DNA-damaging agents. The cellular levels of cyclin B1 positively correlate with the degrees of potentiation achieved. Of additional interest, we observed that the various colon cancer cell lines in general appear to express higher levels of cyclin B1 and also display higher sensitivity to Chk1 inhibitors, implying that Chk1 inhibitor may be more efficacious in treating colon cancers. In summary, we propose that cyclin B1 is a biomarker predictive of the efficacy of Chk1 inhibitors across different types of cancers. Unlike previously established efficacy-predictive biomarkers that are usually the direct targets of the therapeutic agents, cyclin B1 represents a non-drug-target biomarker that is based on the mechanism of action of the target inhibitor. This finding may be potentially very useful for the stratification of patients for Chk1 inhibitor clinical trials and hence, maximize its chance of success.
Journal of Atmospheric and Oceanic Technology, 2011
Ocean wave energy is used to drive a buoyant instrument platform down a wire suspended from a sur... more Ocean wave energy is used to drive a buoyant instrument platform down a wire suspended from a surface float. At the lower terminus of the profiling range, the cam that rectifies wave vertical motion is released and the package, termed the Wirewalker, free ascends. No electronic components are used in the profiler, and only a few moving parts are involved. The Wirewalker is tolerant of a broad range of payloads: the ballast is adjusted by adding discrete foam blocks. The Wirewalker profiles 1000–3000 km month−1, vertically, with typical missions lasting from days to months. A description of the profiler is presented along with a discussion of basic profiling dynamics.
Journal of Atmospheric and Oceanic Technology, 2012
A wirewalker exploits the difference in vertical motion between a wire attached to a surface buoy... more A wirewalker exploits the difference in vertical motion between a wire attached to a surface buoy and the water at the depth of a profiling body to provide the power to execute deep profiles: when the wire’s relative motion is upward, the profiler lets go; when it is downward, the profiler clamps on, and the weight attached at depth pulls the wire down, dragging the profiler downward against its buoyancy. The difference between the upward wire and profiler motion has to exceed the buoyancy-driven upward acceleration of the profiler body for this to work. Because the relative motion of the wire and water decreases as the surface is approached, the profiler might get stuck near the surface, especially when it is calm. However, two things mitigate this: 1) the system has a damped resonant response (~1.3 Hz), which induces relative motion between the buoy and water even at the surface; and 2) for waves too gentle to directly exceed the required acceleration, drag on the profiler can pul...
The majority of cancer therapeutics induces DNA damage to kill cells. Normal proliferating cells ... more The majority of cancer therapeutics induces DNA damage to kill cells. Normal proliferating cells undergo cell cycle arrest in response to DNA damage, thus allowing DNA repair to protect the genome. DNA damage induced cell cycle arrest depends on an evolutionarily conserved signal transduction network in which the Chk1 kinase plays a critical role. In mammalian cells, the p53 and RB pathways further augment the cell cycle arrest response to prevent catastrophic cell death. Given the fact that most tumor cells suffer defects in the p53 and RB pathways, it is likely that tumor cells would depend more on the Chk1 kinase to maintain cell cycle arrest than would normal cells. Therefore Chk1 inhibition could be used to specifically sensitize tumor cells to DNA‐damaging agents. We have previously shown that siRNA‐mediated Chk1 knockdown abrogates DNA damage‐induced checkpoints and potentiates the cytotoxicity of several DNA‐damaging agents in p53‐deficient cell lines. In this study, we have...
International Journal for Vitamin and Nutrition Research, 1999
A microbiological method for the determination of thiamine in biological fluids and food using 96... more A microbiological method for the determination of thiamine in biological fluids and food using 96-well microtitre plates and automatic plate reader, suitable for using in routine clinical diagnosis is described. Thiamine was extracted from samples by acid digestion (acetate buffer, pH 4.5) at 110 degrees C for 20 minutes. Assay recovery and reproducibility were optimally evaluated. Results obtained from this method were compared with those obtained using traditional microbiological and HPLC methods. The values resulting from this method were more or less the same as those of the traditional microbiological method, but much higher than those of HPLC assay. However, the new assay presents many advantages: it reduces the use of serum volume, which is a main benefit for clinical analysis. It lowers also the reagent costs and increases the number of analyses as well as it is easy to perform for routine clinical laboratory.
Diagnostic Microbiology and Infectious Disease, 2002
Community-acquired methicillin-resistant Staphylococcus aureus (MRSA) infections are increasing. ... more Community-acquired methicillin-resistant Staphylococcus aureus (MRSA) infections are increasing. Since most published data are on nosocomial MRSA, our goal was to identify the antimicrobial susceptibility profile and resistance mechanisms of pretreatment MRSA isolates obtained from adult subjects participating in recent clinical treatment trials of community respiratory infections. Out of 465 S. aureus isolates, 43 were identified as MRSA. Antimicrobial susceptibility testing indicated susceptibility rates to: vancomycin (100%), gentamicin (86%), clindamycin (39%), quinolones (49%), and erythromycin (12%). Among our MRSA isolates, the MLS constitutive phenotype and ermA were more prevalent than the MLS inducible phenotype and ermC. No isolates had ermB or msrA. All ciprofloxacin resistant isolates had an amino acid change in GyrA and GrlA. The relatedness of our MRSA strains was assessed by ribotyping. Our results indicate that MRSA from adult subjects with community respiratory infections have similar antimicrobial susceptibility profiles and resistance mechanisms as nosocomial MRSA, and represent a genetically diverse group.
ABSTRACT The drive for efficiency improvements in post-combustion CO2 capture (PCC) technologies ... more ABSTRACT The drive for efficiency improvements in post-combustion CO2 capture (PCC) technologies continues to grow, with recent attention being directed towards flexible operation of PCC plants. However, there is a lack of research into the effect of process disturbances when operating flexibly, justifying a need for validated dynamic models of the PCC process. This review critically examines the dynamic PCC process models developed to date and analyses the different approaches used, as well as the model complexity and their limitations. Dynamic process models coupled with economic analysis will play a crucial role in process control and optimisation. Also discussed are key areas that need to be addressed in future dynamic models, including the lack of reliable dynamic experimental data for their validation, development of feasible flexible operation and process control strategies, as well as process optimisation by integrating accurate process models with established economic analysis tools.
As part of a fully integrated and comprehensive strategy to discover novel antibacterial agents, ... more As part of a fully integrated and comprehensive strategy to discover novel antibacterial agents, NMR‐ and mass spectrometry‐based affinity selection screens were performed to identify compounds that bind to protein targets uniquely found in bacteria and encoded by genes essential for microbial viability. A biphenyl acid lead series emerged from an NMR‐based screen with the Haemophilus influenzae protein HI0065, a member of a family of probable ATP‐binding proteins found exclusively in eubacteria. The structure–activity relationships developed around the NMR‐derived biphenyl acid lead were consistent with on‐target antibacterial activity as the Staphylococcus aureus antibacterial activity of the series correlated extremely well with binding affinity to HI0065, while the correlation of binding affinity with B‐cell cytotoxicity was relatively poor. Although further studies are needed to conclusively establish the mode of action of the biphenyl series, these compounds represent novel le...
For biofuel applications, synthetic endoglucanase E1 and xylanase (Xyn10A) derived from Acidother... more For biofuel applications, synthetic endoglucanase E1 and xylanase (Xyn10A) derived from Acidothermus cellulolyticus were transiently expressed in detached whole sunflower (Helianthus annuus L.) leaves using vacuum infiltration. Three different expression systems were tested, including the constitutive CaMV 35S-driven, CMVar (Cucumber mosaic virus advanced replicating), and TRBO (Tobacco mosaic virus RNA-Based Overexpression Vector) systems. For 6-day leaf incubations, codon-optimized E1 and xylanase driven by the CaMV 35S promoter were successfully expressed in sunflower leaves. The two viral expression vectors, CMVar and TRBO, were not successful although we found high expression in Nicotiana benthamiana leaves previously for other recombinant proteins. To further enhance transient expression, we demonstrated two novel methods: using the plant hormone methyl jasmonic acid in the agroinfiltration buffer and two-phase optimization of the leaf incubation temperature. When methyl jasmonic acid was added to Agrobacterium tumefaciens cell suspensions and infiltrated into plant leaves, the functional enzyme production increased 4.6-fold. Production also increased up to 4.2-fold when the leaf incubation temperature was elevated above the typical temperature, 20C, to 30C in the late incubation phase, presumably due to enhanced rate of protein synthesis in plant cells. Finally, we demonstrated co-expression of E1 and xylanase in detached sunflower leaves. To our knowledge, this is the first report of (co)expression of heterologous plant cell wall-degrading enzymes in sunflower.
Bioorganic & Medicinal Chemistry Letters, 2004
A series of novel 6-O-arylpropargyl-9-oxime-ketolides was synthesized and evaluated against vario... more A series of novel 6-O-arylpropargyl-9-oxime-ketolides was synthesized and evaluated against various pathogens. These new compounds show promising in vitro antibacterial potency and in vivo efficacy against macrolide resistant strains.
Chk1 is the major mediator of cell-cycle checkpoints in response to various forms of genotoxic st... more Chk1 is the major mediator of cell-cycle checkpoints in response to various forms of genotoxic stress. Although it was previously speculated that checkpoint abrogation due to Chk1 inhibition may potentiate the efficacy of DNA-damaging agents through induction of mitotic catastrophe, there has not been direct evidence proving this process. Here, through both molecular marker and morphological analysis, we directly demonstrate that specific downregulation of Chk1 expression by Chk1 siRNA potentiates the cytotoxicities of topoisomerase inhibitors through the induction of premature chromosomal condensation and mitotic catastrophe. More importantly, we discovered that the cellular cyclin B1 level is the major determinant of the potentiation. We show that downregulation of cyclin B1 leads to impairment of the induction of mitotic catastrophe and correspondingly a reduction of the potentiation ability of either Chk1 siRNA or a small molecule Chk1 inhibitor. More significantly, we have extended the study by examining a panel of 10 cancer cell-lines with different tissue origens for their endogenous levels of cyclin B1 and the ability of a Chk1 inhibitor to sensitize the cells to DNA-damaging agents. The cellular levels of cyclin B1 positively correlate with the degrees of potentiation achieved. Of additional interest, we observed that the various colon cancer cell lines in general appear to express higher levels of cyclin B1 and also display higher sensitivity to Chk1 inhibitors, implying that Chk1 inhibitor may be more efficacious in treating colon cancers. In summary, we propose that cyclin B1 is a biomarker predictive of the efficacy of Chk1 inhibitors across different types of cancers. Unlike previously established efficacy-predictive biomarkers that are usually the direct targets of the therapeutic agents, cyclin B1 represents a non-drug-target biomarker that is based on the mechanism of action of the target inhibitor. This finding may be potentially very useful for the stratification of patients for Chk1 inhibitor clinical trials and hence, maximize its chance of success.
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