Motile bacteria are able to penetrate in the distal areas of blood vessel, which makes bacteria attractive to researchers as a drug delivery vehicle carrying anti-cancer drugs to tumors. Not only ...therapeutic bacteria show wide anti-tumor effect but also the combination of therapeutic bacteria and conventional chemotherapy leads to dramatically large synergetic effect. We provide a mechanistic understanding of enhanced drug delivery in tumors by co-administration of chemotherapeutic agents and therapeutic bacteria. In this work, simultaneous delivery of C. novyi-NT and chemotherapeutic agents in tumors is mathematically modeled. Simulated doxorubicin concentration in tumors after Doxil administration with or without bacteria agreed reasonably well with experimental literature. Simulated doxorubicin concentration in tumors by the combination of Doxil and C. novyi-NT is over twice higher than that of Doxil alone. This enhanced doxorubicin concentration in tumors is due to the degradation of extracellular matrix of collagen by bacterial proteolytic activity, which increases hydraulic conductivity of interstitium, reduces interstitial fluid pressure, and thus increases convection through vessel walls. Additionally, it alleviates solid stress, which decompresses blood vessels, and thus increases vessel density. On the other hand, simulated doxorubicin concentration in tumors for non-liposomal free-doxorubicin is not enhanced by C. novyi-NT because vascular permeability of free-doxorubicin is larger than Doxil, and thus increased but relatively small convection across vessel walls is offset by the efflux due to increased interstitial flow. A strategy to further enhance this combination therapy is discussed along with sensitivity analysis.
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•Delivery of anti-cancer agents and therapeutic bacteria in tumors is mathematically modeled.•Predicetd drug concentraiton in tumors for both Doxil and doxorubicin compared well•Degradation of ECM of collagen by bacterial proteolysis reduces interstitial fluid pressure.•Reduced interstitial fluid pressure increases convection through vessel walls
As oral or intestinal bacteria have been found in pancreatic cystic fluid and tumors, understanding bacterial migration from the duodenum into the pancreas via hepato-pancreatic duct is critical. ...Mathematical models of migration of aerobic bacteria from the duodenum to the pancreas with tumors were developed. Additionally, the bacterial distributions under the pH gradient and those under flow were measured in double-layer flow based microfluidic device and T-shaped cylinders. Migration of aerobic bacteria from the duodenum into pancreas is counteracted by bile and pancreatic juice flow but facilitated by pH-taxis from acidic duodenum fluid toward more favorable slightly alkaline pH in pancreatic juice. Additionally, the reduced flow velocity in cancer patients, due to compressed pancreatic duct by solid tumor, facilitates migration. Moreover, measured distribution of GFP E. coli under the pH gradient in a microfluidic device validated pH-tactic behaviors. Furthermore, Pseudomonas fluorescens in hydrochloride solution, but not in bicarbonate solution, migrated upstream against bicarbonate flow of > 20 μm/s, with an advancement at approximately 50 μm/s.
•Fluorescence signal was separated by two-dimensional Savitzky–Golay second-order differentiation of EEMs.•Florescence peak from ATP was detected at Ex=286nm and Em=386 and 412nm from second ...derivatives of EEMs.•The second derivative of fluorescence intensity from ATP decreased with ATP content.•Good correlation was observed between ATP content and plate count on pork meat surface (R2=0.94).•ATP content and plate count were quantitatively evaluated based on second derivative of EEMs by PLSR.
We investigated the potential application of excitation–emission matrix (EEM) spectroscopy in the rapid, non-destructive evaluation of cleanliness in meat processing plants. ATP can be an indicator of microbial contamination. Thus, the fluorescent signal of ATP was detected at Ex=286nm and Em=386 and 412nm by applying two-dimensional Savitzky–Golay second-order differentiation of EEM obtained from the pork meat surface. The second derivative of the fluorescence intensity at Ex=284nm and Em=412nm, i.e., the wavelengths assigned to ATP, decreased with the ATP content. The ATP content and plate count were quantified using the second derivatives of EEMs by partial least squares regression in good agreement coefficient correlation, 0.87; RMSEP, log10 (0.70, molcm−2) for the predicted ATP content. The model directly reflected the ATP fluorescent signal changes.
Hafnium oxyphosphate was prepared as a novel photocatalyst for hydrogen production from water. Here, Hf4+ with d0 electronic configuration was selected as the constituent cation, because efficient ...photocatalysts generally contain d0 or d10 metal cations. In addition, most phosphates are reported to have high photoreduction ability of water due to their wide bandgap compared to oxides. By using Hf2O(PO4)2, hydrogen gas was generated from water under the ultraviolet light irradiation, while a simple hafnium oxide, HfO2, did not show a hydrogen evolution ability. The hydrogen production rate of Hf2O(PO4)2 was estimated to be 800 µmol·h−1. Also, oxygen gas evolution was observed for Hf2O(PO4)2.
Tiny amount of bacteria are found in the pancreas in pancreatitis and cancer, which seemed involved in inflammation and carcinogenesis. However, bacterial infiltration from the duodenum is inhibited ...by the physical defense mechanisms such as bile flow and the sphincter of Oddi. To understand how the bacteria possibly infiltrate the pancreas through a deformable pancreatic duct, influenced by the periodic contractions of the sphincter of Oddi, a mathematical model of bacterial infiltration is developed that considered large deformation, fluid flow, and bacterial transport in a deformable pancreatic duct. In addition, the sphincter's contraction wave is modeled by including its propagation from the pancreas toward the duodenum. Simulated structure of the deformed duct with the relaxed sphincter and simulated bile distribution agreed reasonably well with the literature, validating the model. Bacterial infiltration from the duodenum in a deformable pancreatic duct, following the sphincter's contraction, is counteracted by a gradual peristalsis-like deformation of the pancreatic duct, due to an antegrade contraction wave propagation from the pancreas to the duodenum, Parametric sensitivity analysis demonstrated that bacterial infiltration is increased with lower bile and pancreatic juice flow rate, greater contraction amplitude and frequency, thinner wall thickness, and retrograde contraction wave propagation. Since contraction waves following retrograde propagation are increased in patients with common bile duct stones and pancreatitis, they may possibly be factors for continuum inflammation of pancreas. (224 words).
Platinum (Pt) is widely applied for electrochemical catalysis, thus creating porosity in Pt-based materials would enhance their catalytic efficacy. This study demonstrates a new route to synthesize a ...Pt material with macropores and spherical morphology by the combination of evaporation induced self-assembly of a hard template (i.e., silica nanoparticles) and infiltration/reduction of Pt species in micro-emulsion systems. The synthesized macroporous Pt microballs (denoted as MPtM) are characterized with scanning electron microscopy (SEM), transmission electron microscopy (TEM), and it is found that MPtM exhibits uniform macropores (diameter of 300nm) and Pt crystalline framework, which would be potential for enhanced catalytic reactions.
•Macroporous platinum microballs with pore size of 200nm were successfully synthesized.•The first report using silica colloidals as the hard template.•The structural properties of the samples were characterized with SEM and TEM.
Novel environmentally friendly blue pigments, (Li1−xNax)2Cu5(PO4)4 (0 ≤ x ≤ 0.20), were synthesized and their color properties were investigated. By doping larger Na+ ions into Li+ ion sites, the ...crystal lattice was distorted, which strongly affected the d–d transition absorption nature of Cu2+. In the series of (Li1−xNax)2Cu5(PO4)4, (Li0.90Na0.10)2Cu5(PO4)4 showed a vivid blue hue with a blueness value (−b*) of 39.4 in the CIE L*a*b* system; this value is higher than that of the commercial FeIII4FeII(CN)63 pigment (dark blue, −b* = 19.3).
We established the Research Center for Business Simulation in Yokohama National University in 2011. We believe Business Game is a powerful method for education and research of business ...administration. Yokohama Business Game (YBG) system is a useful tool to develop and operate business games. Using YBG, we have been developing and evaluating various business models.
Understanding bacterial penetration into meat is critical to make it safe for consumption. A mathematical model for transport of aerobic bacteria into meat was developed that includes bacterial ...motility, chemotaxis driven by oxygen concentration, and growth. The effect of proteolysis was also included in the model and the proteolytic kinetic parameters of Pseudomonas spp. on sarcoplasmic protein from poultry were measured. Deeper penetration into the meat due to motility is counteracted by chemotaxis toward the surface where oxygen concentration is higher and by a reduction in motility at deeper locations due to oxygen starvation. More rapid bacterial penetration during proteolysis is due to both high motility and increased oxygen diffusion (reduced starvation and chemotaxis) in a reduced viscosity fluid caused by the degradation of the sarcoplasmic protein. Penetration rates in both proteolytic and non-proteolytic bacteria are affected more by oxygen starvation than by chemotaxis toward oxygen.
•Bacterial migration into meat was modeled using a diffusion-reaction transport.•Bacterial transport includes motility, chemotaxis toward oxygen, and growth.•Proteolysis kinetics parameters were obtained by our experiment.•Predicted penetration rates compared reasonably well.•Faster penetration rate of proteolytic bacteria was observed with proteolysis.
Chapter 1 examines the long-term economic impact of levee systems, which mitigate flood damage, on the local economy and optimal policy targeting for levee systems. First, I estimate the causal ...effects of levee systems using a standard difference-in-differences approach. Second, I develop a framework for computing ex-post optimal treatment assignments using a changes-in-changes approach and a statistical treatment rule. I find that the levee systems decreased the flood risks in counties with more enormous flood risks. From the optimal targeting exercise, I show that while there could be a better treatment allocation, the externality of levee construction makes it challenging to achieve the optimal allocation. Moreover, I show that an additional 20% over the current total investment in U.S. levee systems is necessary to reduce the number of disasters by at least one per decade. Chapter 2 examines the causal impact of the levee investment projects under the American Recovery and Reinvestment Act (ARRA) of 2009 on employment at the county level. To address endogeneity, I use a new instrument: the length of levees. As the length of levees is a persistent stock variable and is unrelated to the magnitude of the recession, it constitutes an ideal instrument to measure the effect of levee projects. I find that a county's receipt of a marginal $100,000 investment in levees resulted in an additional 4.2 job-years, 1.8 of which were in the construction sector. I also find that the projects showed short implementation lags and seasonal cycles in employment gains. Chapter 3 examines the impact of Hurricanes Katrina and Rita on firms' bidding behavior using data on highway procurement auctions in Louisiana. Using a high-dimensional sparse regression technique to account for auction-specific observable heterogeneity and a difference-in-differences approach, I find that parishes affected by the two hurricanes faced higher costs and a less competitive environment than those not affected. I use a standard first-price auction model with endogenous entry to analyze the mechanism and simulate the counterfactual scenarios. I show that (i) the government would save 10% on procurement if the hurricanes did not occur, and (ii) subsidizing firms’ bids may not be an optimal post-hurricane strategy.
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