Semianalytical Solutions for Transport in Aquifer and Fractured Clay Matrix System

A three‐dimensional mathematical model that describes transport of contaminant in a horizontal aquifer with simultaneous diffusion into a fractured clay formation is proposed. A group of semianalytical solutions is derived based on specific initial and boundary conditions as well as various source functions. The analytical model solutions are evaluated by numerical Laplace inverse transformation and analytical Fourier inverse transformation. The model solutions can be used to study the fate and transport in a three‐dimensional spatial domain in which a nonaqueous phase liquid exists as a pool atop a fractured low‐permeability clay layer. The nonaqueous phase liquid gradually dissolves into the groundwater flowing past the pool, while simultaneously diffusing into the fractured clay formation below the aquifer. Mass transfer of the contaminant into the clay formation is demonstrated to be significantly enhanced by the existence of the fractures, even though the volume of fractures is relatively small compared to the volume of the clay matrix. The model solution is a useful tool in assessing contaminant attenuation processes in a confined aquifer underlain by a fractured clay formation.Abstract © AG

UNDERSTANDING ACTIN FUNCTION DURING CYTOKINESIS IN FISSION YEAST

Ph.DDOCTOR OF PHILOSOPH

Dynamic evolution of ceftazidime–avibactam resistance due to interchanges between blaKPC-2 and blaKPC-145 during treatment of Klebsiella pneumoniae infection

BackgroundThe emergence of ceftazidime–avibactam (CZA) resistance among carbapenem-resistant Klebsiella pneumoniae (CRKP) is of major concern due to limited therapeutic options.MethodsIn this study, 10 CRKP strains were isolated from different samples of a patient with CRKP infection receiving CZA treatment. Whole-genome sequencing (WGS) and conjugation experiments were performed to determine the transferability of the carbapenem resistance gene.ResultsThis infection began with a KPC-2-producing K. pneumoniae (CZA MIC = 2 μg/mL, imipenem MIC ≥ 16 μg/mL). After 20 days of CZA treatment, the strains switched to the amino acid substitution of T263A caused by a novel KPC-producing gene, blaKPC-145, which restored carbapenem susceptibility but showed CZA resistance (CZA MIC ≥ 256 μg/mL, imipenem MIC = 1 μg/mL). The blaKPC-145 gene was located on a 148,185-bp untransformable IncFII-type plasmid. The subsequent use of carbapenem against KPC-145-producing K. pneumoniae infection led to a reversion of KPC-2 production (CZA MIC = 2 μg/mL, imipenem MIC ≥ 16 μg/mL). WGS analysis showed that all isolates belonged to ST11-KL47, and the number of SNPs was 14. This implied that these blaKPC-positive K. pneumoniae isolates might originate from a single clone and have been colonized for a long time during the 120-day treatment period.ConclusionThis is the first report of CZA resistance caused by blaKPC-145, which emerged during the treatment with CZA against blaKPC-2-positive K. pneumoniae-associated infection in China. These findings indicated that routine testing for antibiotic susceptibility and carbapenemase genotype is essential during CZA treatment

Analytical Solutions for Efficient Interpretation of Single-well Push-pull Tracer Tests

Single-well push-pull tracer tests have been used to characterize the extent, fate, and transport of subsurface contamination. Analytical solutions provide one alternative for interpreting test results. In this work, an exact analytical solution to two-dimensional equations describing the governing processes acting on a dissolved compound during a modified push-pull test (advection, longitudinal and transverse dispersion, first-order decay, and rate-limited sorption/partitioning in steady, divergent, and convergent flow fields) is developed. The coupling of this solution with inverse modeling to estimate aquifer parameters provides an efficient methodology for subsurface characterization. Synthetic data for single-well push-pull tests are employed to demonstrate the utility of the solution for determining (1) estimates of aquifer longitudinal and transverse dispersivities, (2) sorption distribution coefficients and rate constants, and (3) non-aqueous phase liquid (NAPL) saturations. Employment of the solution to estimate NAPL saturations based on partitioning and non-partitioning tracers is designed to overcome limitations of previous efforts by including rate-limited mass transfer. This solution provides a new tool for use by practitioners when interpreting single-well push-pull test results

In vitro evaluation of bond strength and sealing ability of a new low-shrinkage, methacrylate resin-based root canal sealer

Background/PurposeThe aim of this study was to evaluate a new low-shrinkage, methacrylate resin-based root canal sealer (LSRCS) to determine its bond strength in radicular dentin and sealing ability.MethodsExtracted single-root teeth were randomly divided into three experimental groups (n=20) for obturation with Gutta-percha (GP)/AH Plus, Resilon/Epiphany, or Resilon/LSRCS. One-half of each experimental group was analyzed by the push-out test, using sections perpendicular to the long axis divided into 1mm serial slices and a universal testing machine to detect the loading force. The other half was analyzed by the dye penetration test using 2% methylene blue solution (pH=7) and measuring dye leakage under a stereomicroscope.ResultsThe push-out test revealed significant differences (p<0.05) in bond strength produced by the three sealers; the GP/AH Plus group showed the highest bond strength, followed by Resilon/LSRCS and Resilon/Epiphany. According to the microleakage data, GP/AH Plus showed the least dye penetration, which was significantly less than Resilon/Epiphany and Resilon/LSRCS. There was no difference in apical leakage between Resilon/Epiphany and Resilon/LSRCS.ConclusionThe newly developed LSRCS, although not superior to AH Plus in bond strength or sealing ability, possesses monoblock potential and application prospects

Modeling NAPL Dissolution from Pendular Rings in Idealized Porous Media

The dissolution rate of nonaqueous phase liquid (NAPL) often governs the remediation time frame at subsurface hazardous waste sites. Most formulations for estimating this rate are empirical and assume that the NAPL is the nonwetting fluid. However, field evidence suggests that some waste sites might be organic wet. Thus, formulations that assume the NAPL is nonwetting may be inappropriate for estimating the rates of NAPL dissolution. An exact solution to the Young‐Laplace equation, assuming NAPL resides as pendular rings around the contact points of porous media idealized as spherical particles in a hexagonal close packing arrangement, is presented in this work to provide a theoretical prediction for NAPL‐water interfacial area. This analytic expression for interfacial area is then coupled with an exact solution to the advection‐diffusion equation in a capillary tube assuming Hagen‐Poiseuille flow to provide a theoretical means of calculating the mass transfer rate coefficient for dissolution at the NAPL‐water interface in an organic‐wet system. A comparison of the predictions from this theoretical model with predictions from empirically derived formulations from the literature for water‐wet systems showed a consistent range of values for the mass transfer rate coefficient, despite the significant differences in model foundations (water wetting versus NAPL wetting, theoretical versus empirical). This finding implies that, under these system conditions, the important parameter is interfacial area, with a lesser role played by NAPL configuration. Abstract © AGU

Modeling NAPL dissolution from pendular rings in idealized porous media

The dissolution rate of nonaqueous phase liquid (NAPL) often governs the remediation time frame at subsurface hazardous waste sites. Most formulations for estimating this rate are empirical and assume that the NAPL is the nonwetting fluid. However, field evidence suggests that some waste sites might be organic wet. Thus, formulations that assume the NAPL is nonwetting may be inappropriate for estimating the rates of NAPL dissolution. An exact solution to the Young‐Laplace equation, assuming NAPL resides as pendular rings around the contact points of porous media idealized as spherical particles in a hexagonal close packing arrangement, is presented in this work to provide a theoretical prediction for NAPL‐water interfacial area. This analytic expression for interfacial area is then coupled with an exact solution to the advection‐diffusion equation in a capillary tube assuming Hagen‐Poiseuille flow to provide a theoretical means of calculating the mass transfer rate coefficient for dissolution at the NAPL‐water interface in an organic‐wet system. A comparison of the predictions from this theoretical model with predictions from empirically derived formulations from the literature for water‐wet systems showed a consistent range of values for the mass transfer rate coefficient, despite the significant differences in model foundations (water wetting versus NAPL wetting, theoretical versus empirical). This finding implies that, under these system conditions, the important parameter is interfacial area, with a lesser role played by NAPL configuration.Key Points:Exact solution to the Young‐Laplace equation for pendular ringsTheoretical determination of the mass transfer rate coefficient under hydrophobic conditionsPredicts similar NAPL dissolution rates for oil‐wet and water‐wet conditionsPeer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/145506/1/wrcr21729.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/145506/2/wrcr21729_am.pd

Blocking interaction between SHP2 and PD‐1 denotes a novel opportunity for developing PD‐1 inhibitors

Small molecular PD‐1 inhibitors are lacking in current immuno‐oncology clinic. PD‐1/PD‐L1 antibody inhibitors currently approved for clinical usage block interaction between PD‐L1 and PD‐1 to enhance cytotoxicity of CD8+ cytotoxic T lymphocyte (CTL). Whether other steps along the PD‐1 signaling pathway can be targeted remains to be determined. Here, we report that methylene blue (MB), an FDA‐approved chemical for treating methemoglobinemia, potently inhibits PD‐1 signaling. MB enhances the cytotoxicity, activation, cell proliferation, and cytokine‐secreting activity of CTL inhibited by PD‐1. Mechanistically, MB blocks interaction between Y248‐phosphorylated immunoreceptor tyrosine‐based switch motif (ITSM) of human PD‐1 and SHP2. MB enables activated CTL to shrink PD‐L1 expressing tumor allografts and autochthonous lung cancers in a transgenic mouse model. MB also effectively counteracts the PD‐1 signaling on human T cells isolated from peripheral blood of healthy donors. Thus, we identify an FDA‐approved chemical capable of potently inhibiting the function of PD‐1. Equally important, our work sheds light on a novel strategy to develop inhibitors targeting PD‐1 signaling axis

ArsR Family Regulator MSMEG_6762 Mediates the Programmed Cell Death by Regulating the Expression of HNH Nuclease in Mycobacteria

Programmed cell death (PCD) is the result of an intracellular program and is accomplished by a regulated process in both prokaryotic and eukaryotic organisms. Here, we report a programed cell death process in Mycobacterium smegmatis, an Actinobacteria species which involves a transcription factor and a DNase of the HNH family. We found that over-expression of an ArsR family member of the transcription factor, MSMEG_6762, leads to cell death. Transcriptome analysis revealed an increase in the genes’ transcripts involved in DNA repair and homologous recombination, and in three members of HNH family DNases. Knockout of one of the DNase genes, MSMEG_1275, alleviated cell death and its over-expression of programmed cell death. Purified MSMEG_1275 cleaved the M. smegmatis DNA at multiple sites. Overall, our results indicate that the MSMEG_6762 affects cell death and is mediated, at least partially, by activation of the HNH nuclease expression under a stress condition