Fixed Concentration Ratio Research Articles

A Theoretical Study of the Energy‐Harvesting Properties of Nontracking Semicircular Concentrating Troughs

The objective of this paper is to give a theoretical appraisal of the light harvesting attributes of nontracking concentrating troughs of a simple semicircular cross section. Emphasis is placed on the importance of the geometry of the caustic exhibited by reflection from a semicircular surface. The efficacy of various placings of the absorber tube is assessed using the method of ray tracing calculations. Utilization of the caustic geometry leads to troughs of optimized width which can capture 100% of the incident radiation normal to the fixed trough aperture. Troughs of different optimized widths (in units of the diameter of planar or cylindrical absorbers) are examined. The major results are to show that these troughs, with fixed concentration ratios, have universal properties which scale with the absorber size and that a favorable comparison is made with the ubiquitous compound parabolic concentrator of the same order of magnitude in size. This work suggests that there is further scope for the optimized design and testing of semicircular troughs.

RENAL3: Hybrid Concentration Method of Ascites Filtration and Concentration Equipment for Cell-free and Concentrated Ascites Reinfusion Therapy

Study: As a safe and effective treatment for refractory ascites, more than 30,000 cases of Cell-free and concentrated ascites reinfusion therapy (CART) are performed annually in Japan. In ascites processing, concentration has been performed at a fixed concentration ratio (constant ratio concentration) with a standard value of 10-fold concentration. However, as the main target disease for CART has shifted from cirrhosis to cancerous peritonitis, it has become necessary to deal with the clogging of the concentration filter when processing large amounts of cancerous ascites with high protein concentrations. Our technology for self-regulation function of the concentration ratio has been introduced into M-CART and other CART specialized equipment, enabling safe automatic concentration within set pressure range (constant pressure concentration). However, when treating ascites with low protein concentration, constant pressure concentration at a high concentration ratio may enhance protein leakage into the waste fluid and reduce protein recovery rate. Therefore, we devised a hybrid concentration method that combines constant pressure and constant ratio concentration, and investigated its usefulness in improving protein recovery by using simulated ascites and analyzing multicenter clinical evaluations. Methods: In the experiment, simulated ascites using substitute plasma agent (hydroxyethylated starch, HSE) was used to simulate cancerous ascites. In the clinical evaluation, 129 sessions of CART performed using M-CART were examined. Results: In the experiment, as the control pressure was increased, the waste fluid volume and HSE concentration in the waste fluid increased and the recovery rate decreased. In the analysis of clinical cases, protein recovery rate was lower in cases where constant pressure concentration was performed. These results indicate that constant-pressure concentration at a high concentration ratio in ascites with a low protein concentration risks decreasing the protein recovery rate, and that the hybrid concentration method enables concentration with a high recovery rate according to the condition of the ascites fluid.

Identification and quantification of the combined phytotoxicity of one element with various valences: Cr(III) and Cr(VI) for barley root elongation as an example

There is uncertainty in quantifying the toxic effects of total chromium (Cr) in the environment by modeling the toxicity of individual Cr(III) or Cr(VI). In the present study, the effects of Cr(III) and Cr(VI) on barley root elongation were investigated in a hydroponic system where Cr(III) and Cr(VI) combination dose-response experiments under monotoxicity concentration, single-dose addition, and fixed concentration ratios were designed to identify and quantify their combined phytotoxicity of one element with various valences. The results show that the calculated mixed toxicity unit values for 50% inhibition (TUmix50) ranged from 1.06 to 1.45, indicating the weak antagonism effects of Cr(III) and Cr(VI) on barley root toxicity. Also, the single-dose group experiment has proved that the EC50 of Cr(VI) was increased from 71.2 μM to 119.9 μM with Cr(III) addition, which suggested that Cr(III) has antagonism on the toxicity of Cr(VI). While EC50 of Cr(III) was not affected by Cr(VI) addition. After introducing the expansion coefficient of Cr(III) on Cr(VI) toxicity, both the extended concentration addition model (e-CA) based on the log-logistic and Weibull equations and the extended independent action model (e-IA) could more accurately predict the barley root elongation under Cr(III) and Cr(VI) interaction. The e-CA model based on the Weibull equation had almost the best correlation coefficient (R2) and lowest root mean square error (RMSE) between the measured and predicted values. Finally, the combined toxicity and antagonism of the same element with co-existing different valences simultaneously were successfully and firstly identified and quantified in the present study.

Interactive Metal Mixture Toxicity to Daphnia magna Populations as an Emergent Property in a Dynamic Energy Budget Individual-Based Model.

Environmental risk assessment of metal mixtures is challenging due to the large number of possible mixtures and interactions. Mixture toxicity data cannot realistically be generated for all relevant scenarios. Therefore, methods for prediction of mixture toxicity from single-metal toxicity data are needed. We tested how well toxicity of Cu-Ni-Zn mixtures to Daphnia magna populations can be predicted based on the Dynamic Energy Budget theory with an individual-based model (DEB-IBM), assuming non-interactivity of metals on the physiological level. We exposed D. magna populations to Cu, Ni, and Zn and their mixture at a fixed concentration ratio. We calibrated the DEB-IBM with single-metal data and generated blind predictions of mixture toxicity (population size over time), with account for uncertainty. We compared the predictive performance of the DEB-IBM with respect to mixture effects on population density and population growth rates with that of two reference models applied on the population level, independent action and concentration addition. Our inferred physiological modes of action (pMoA) differed from literature-reported pMoAs, raising the question of whether this is a result of different model selection approaches, intraspecific variability, or whether different pMoAs might actually drive toxicity in a population context. Observed mixture effects were concentration- and endpoint-dependent. The independent action was overall more accurate than the concentration addition but concentration addition-predicted effects on population growth rate were slightly better. The DEB-IBM most accurately predicted effects on 6-week density, including antagonistic effects at high concentrations, which emerged from non-interactivity at the physiological level. Mixture effects on initial population growth rate appear to be more difficult to predict. To explain why model accuracy is endpoint-dependent, relationships between individual-level and population-level endpoints should be illuminated. Environ Toxicol Chem 2021;40:3034-3048. © 2021 SETAC.

Synergistic antibacterial effect of inhaled aztreonam and tobramycin fixed dose combination to combat multidrug-resistant Gram-negative bacteria.

The limited therapeutic option for respiratory infections caused by multi-drug resistant microbial pathogens is a major global health threat. Topical delivery of antibacterial combinations to the lung could dramatically enhance antibacterial activities and provide a means to overcome bacterial resistance development. The aim of the study was to investigate the potential of new inhalable dry powder combinations consisting of a fixed dose of aztreonam (Azt) and tobramycin (Tob) using a spray drying process, against antibiotic resistant Gram-negative respiratory pathogens. The interactions of Azt with Tob on resistant Pseudomonas aeruginosa, Klebsiella pneumoniae and Acinetobacter baumannii were determined by calculating factional inhibitory concentration indices (FICI). A fixed concentration ratio of Azt and Tob that exhibited a synergistic antimicrobial effect was selected and formulated into inhalable dry powders by co-spray drying with and without L-leucine. The obtained dry powders were characterized with respect to the morphology, particle size distribution, solid state, moisture sorption behaviour, and in vitro dissolution. Storage stability, aerosol performance, and in vitro antibacterial activity were also evaluated. Inhalable dry powders consisting of Azt, Tob and L-leucine could be readily obtained via the spray drying process with a fine particle fraction of above 40% as determined using a next generation impactor. The co-spray drying process resulted in amorphous Azt/Tob dry powders with or without the addition of L-leucine as indicated by X-ray powder diffraction. The dissolution rates of the co-spray dried Azt/Tob dry powders were decreased, and the storage stability was improved with an increase in the proportion of L-leucine in the formulations. The inclusion of L-leucine did not affect the minimum inhibitory concentration and the co-spray dried powders reserved the synergistic antibacterial effects and exhibited enhanced antibacterial activities as compared to the individual antibiotic used alone on multidrug-resistant (Azt and Tob resistant) P. aeruginosa 25756 and A. baumannii K31. This study demonstrates that inhalable Azt/Tob dry powders using L-leucine as a moisture protector as well as a dispersing agent can be readily prepared by the spray drying process. This new inhalable fixed dose combinational dry powders may represent an alternative treatment against multidrug-resistant Gram-negative respiratory pathogens.

Performance Evaluation of a Modified Compound Parabolic Concentrating Collector with Varying Concentration Ratio

Thermosyphon based evacuated tube solar collectors have seen exponential growth in the last few decades for domestic hot water applications. The output temperatures of such collectors can be increased by integrating evacuated tube receivers with compound parabolic concentrators (CPCs) to meet many industrial heat loads. This paper presents a new concept of increasing concentration of solar radiation along the length of an evacuated tube receiver coupled with a modified CPC with 52.5° and 38.5° acceptance half-angles at the inlet and outlet sides respectively. The effect of varying concentration ratio in the longitudinal direction is analyzed in terms of increasing heat flux and temperature gradient between the inlet and outlet of the receiver. Monte Carlo ray-tracing analysis confirmed a gradual increase of power density along the length of the receiver paired with the modified CPC. The daily average energy collection by the modified CPC was comparable with that of equal aperture area CPC with a fixed concentration ratio along its length. The experimental results demonstrated about a 15% higher temperature gradient in the case of CPC with a varying concentration ratio as compared to equal aperture area CPC with a fixed concentration ratio single-phase thermosyphon flow.

CO2 and N2 adsorption and separation using aminated UiO-66 and Cu3(BTC)2: A comparative study

UiO-66 and Cu3(BTC)2, two well-known metal organic frameworks (MOFs), were aminated through insitu modification approach to improve CO2/N2 separation. UiO-66 was synthesized by solvothermal method, while Cu3(BTC)2 was synthesized with two electrochemical and solvothermal approaches for the sake of comparison. NH2-UiO-66 structure was optimized by evaluating the effect of key parameters, such as synthesis temperature, ligand to metal salt molar ratio, and modulator to metal salt molar ratio, on CO2/N2 selectivity. The effect of different weight percentage of 2-aminoterephthalic acid (NH2-BDC) on electrochemical synthesis of NH2-Cu3(BTC)2 was also investigated. Products were characterized by FTIR, BET, FESEM, XRD, and TGA analyses. Single CO2 adsorption experiment for NH2-UiO-66 showed higher capacity compared to UiO-66. However, for NH2-Cu3(BTC)2, an opposite trend was observed. The CO2 adsorption capacity for NH2-UiO-66 and NH2-Cu3(BTC)2 at 1 bar and 25 °C was 3.32 and 3.86 mmol/g, respectively. CO2/N2 selectivity with fixed concentration ratio (15/85 vol%) was also studied for aminated samples, and the values of 120 and 53 were determined for NH2-UiO-66 and NH2-Cu3(BTC)2, respectively. NH2-Cu3(BTC)2 showed the highest isosteric heat of adsorption among all samples (43 kJ/mol).

The prediction of combined toxicity of Cu–Ni for barley using an extended concentration addition model

Environment pollution often occurs as an obvious combined effect involving two (or more) elements, and this effect changes with the concentrations of the different elements. The effects on barley root elongation were studied in hydroponic systems to investigate the toxicity of Cu–Ni combined at low doses and at a fixed concentration ratio. For low doses of Cu–Ni, the addition of Ni (<0.5 μM) to Cu significantly decreased Cu toxicity for barley, but the addition of Cu (<0.25 μM) had no significant effect on Ni toxicity. At a fixed concentration ratio, according to the single effective concentration (EC) (barley root elongation inhibitory concentration) values of Cu and Ni, five sets of Cu–Ni fixed ratios were used: ECn(Cu)+ECm(Ni) (n + m = 100) (ECn and ECm indicate toxicity unit value for n% and m% inhibition of barley root length, respectively). The calculated toxicity unit value for 50% inhibition of root length ranged from 0.44 to 0.98 (i.e., <1), indicating a synergistic effect. To consider the interactions between the metal ions, the extended concentration addition model (e-CA) was established by integrating the Cu–Ni interaction into the concentration addition model (CA), and the data of two groups (the low doses of Cu–Ni and at a fixed concentration ratio) were respectively fitted. The e-CA accurately predicted the root length of barley under the Cu–Ni combined action. The correlation coefficient (r) and the root-mean-square error (RMSE) between predicted and observed values were 0.97 and 6.6 (low-dose group) and 0.96 and 8.12 (fixed-ratio group), respectively, and e-CA significantly improved the prediction accuracy compared to the traditional CA model without consideration of the Cu–Ni competition (r = 0.89, RMSE = 14.16). The results provided a theoretical basis for evaluation and remediation of soil contaminated with heavy metal composites.

Abstract 1090: Preclinical evaluation of combination therapy with dasatinib and sorafenib for the treatment of brain metastases

Abstract Brain metastases, the most common type of intracranial tumors in adults, carry a dismal prognosis with a median survival of less than 18 months regardless of primary status or treatment given. As part of an ongoing project, this study is concerned with the preclinical evaluation of targeted combination therapy for the treatment of brain metastases. The cell line used in this study was the H1915 (ATCC® CRL-5904TM) human lung cancer cell line, which was originally derived from a brain metastasis from primary lung adenocarcinoma. The cell line was stably transfected with a plasmid that allows expression of firefly luciferase (i.e., H1915-luc) so that the tumor growth in a mouse orthotopic model of brain metastases can be assessed in real time using the Xenogen in vivo bioluminescence imaging (BLI). Our previous study has demonstrated that the synergistic effect of combined dasatinib and sorafenib treatment was cell-line dependent. In this study, the cytotoxicity of dasatinib and sorafenib, when used alone or in combination at the fixed molar ratios of 3:1, 1:1 and 1:3 (dasatinib:sorafenib), was further examined in H1915-luc cells using the MTT assay. The results demonstrated that simultaneous and continuous exposure of H1915-luc cells to dasatinib and sorafenib at the fixed concentration ratio of 1:1 and 1:3 for 72 h showed synergism (the combination index value between 0.7 and 0.8) at effect levels of 40 and 80% inhibition of cell viability. For the in vivo study, an orthotopic mouse model of brain metastases was established by injecting H1915-luc cells into the right general carotid artery of individual athymic nude mice followed by permanent ligation. The preliminary study showed that following the intracarotid injection of H1915-luc cells, brain metastases were formed and readily to be detected by BLI. The obtained whole brain samples were fixed in OCT and stored at -80oC. The brain sections are to be subjected to the immunofluorescence double staining of CD31 and firefly luciferase to assess the potential effect of the dasatinib-sorafenib combination on microscopic brain metastasis formation and progression and vessel co-option. Given the fact that brain metastases usually have a poor response to chemotherapeutic agents in part due to the presence of blood-brain barrier, a pharmacokinetic study is underway to characterize the distribution of sorafenib and dasatinib in normal brain tissues and brain metastases using the serial blood sampling and brain microdialysis technique. Overall, results from the in vitro cytotoxicity study demonstrated the synergistic effect of dasatinib and sorafenib on H1915-luc human lung cancer cells, providing a rationale for the in vivo evaluation the potential of this combination for the treatment of brain metastases from lung carcinomas. Citation Format: Qingyu Stephanie Zhou, Xiaofang Guo. Preclinical evaluation of combination therapy with dasatinib and sorafenib for the treatment of brain metastases [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1090. doi:10.1158/1538-7445.AM2017-1090

Two-Stage Prediction on Effects of Mixtures Containing Phenolic Compounds and Heavy Metals on Vibrio qinghaiensis sp. Q67.

Two-stage prediction (TSP) model had been developed to predict toxicities of mixtures containing complex components, but its prediction power need to be further validated. Six phenolic compounds and six heavy metals were selected as mixture components. One mixture (M1) was built with equivalent-effect concentration ratio and four mixtures (M2-M5) were designed with fixed concentration ratio. In M1-M5, the toxicities were well predicted by TSP model, while CA overestimated and IA underestimated the toxicities. In M1-M5, compared with the actual mixture EC50 value, the prediction errors of TSP model (13.9%, 17.9%, 19.2%, and 17.3% and 15.8%, respectively) were significantly lower than those in the CA (higher than 30%) and IA models (20.9%, 33.0%, 20.6%, 21.8% and 12.5%, respectively). Thus, the TSP model performed better than the CA and IA model.

Mechanism-Based Drug Combinations with the DNA Strand-Breaking Nucleoside Analog CNDAC.

CNDAC (2'-C-cyano-2'-deoxy-1-β-d-arabino-pentofuranosyl-cytosine, DFP10917) and its orally bioavailable prodrug, sapacitabine, are undergoing clinical trials for hematologic malignancies and solid tumors. The unique action mechanism of inducing DNA strand breaks distinguishes CNDAC from other deoxycytidine analogs. To optimize the clinical potentials of CNDAC, we explored multiple strategies combining CNDAC with chemotherapeutic agents targeting distinct DNA damage repair pathways that are currently in clinical use. The ability of each agent to decrease proliferative potential, determined by clonogenic assays, was determined in paired cell lines proficient and deficient in certain DNA repair proteins. Subsequently, each agent was used in combination with CNDAC at fixed concentration ratios. The clonogenicity was quantitated by median effect analysis, and a combination index was calculated. The c-Abl kinase inhibitor imatinib had synergy with CNDAC in HCT116 cells, regardless of p53 status. Inhibitors of PARP1 that interfere with homologous recombination (HR) repair or base excision repair (BER) and agents such as temozolomide that cause DNA damage repaired by the BER pathway were also synergistic with CNDAC. The toxicity of the nitrogen mustards bendamustine and cytoxan, or of platinum compounds, which generate DNA adducts repaired by nucleotide excision repair and HR, was additive with CNDAC. An additive cell killing was also achieved by the combination of CNDAC with taxane mitotic inhibitors (paclitaxel and docetaxel). At concentrations that allow survival of the majority of wild-type cells, the synergistic or additive combination effects were selective in HR-deficient cells. This study provides mechanistic rationales for combining CNDAC with other active drugs. Mol Cancer Ther; 15(10); 2302-13. ©2016 AACR.

Effects of multi-component mixtures of polyaromatic hydrocarbons and heavy metal/loid(s) on Nrf2-antioxidant response element (ARE) pathway in ARE reporter-HepG2 cells.

Exposure to polyaromatic hydrocarbons (PAHs) and heavy metal/loid(s) has been demonstrated to induce an oxidative stress response in mammalian cells. The combined effect of PAHs and heavy metal/loid(s) on the oxidative stress response has not been reported extensively. The Nrf2 antioxidant response pathway plays an important role in cellular antioxidant defense against oxidative stress-induced cell damage. In this study, we have determined the combined effect of four PAHs (benzo[a]pyrene (B[a]P), naphthalene (Nap), phenanthrene (Phe) and pyrene (Pyr)) and three heavy metal/loid(s) (arsenic (As), cadmium (Cd) and lead (Pb)) on the Nrf2 antioxidant pathway using the ARE reporter-HepG2 cell line. The mixture study was carried out for binary, ternary, quaternary and seven-component combinations of PAHs and heavy metal/loid(s). Initially, individual dose responses for the PAHs (B[a]P, Nap, Phe and Pyr) and heavy metal/loid(s) (As, Cd and Pb), as well as their respective concentrations that induced an induction ratio of 1.5 (ECIR1.5), were determined. The luciferase assay system was used to quantify the induction of the Nrf2 antioxidant pathway. The individual dose response study showed that both PAHs and heavy metal/loid(s) activated the Nrf2 antioxidant pathway in ARE reporter-HepG2 cells. Among these chemicals, Cd was the most potent inducer, followed by B[a]P and As. Based on the individual dose response findings, PAHs and heavy metal/loid(s) were mixed at equipotent ratios using a fixed concentration ratio, and the effects of the mixtures of PAHs and heavy metal/loid(s) (binary to seven-component) on the Nrf2 antioxidant pathway were determined. The mixture effects were predicted by using the concentration addition (CA) model. Overall, the results showed that the multi-component mixtures of PAHs and heavy metal/loid(s) induced an oxidative stress response in ARE reporter-HepG2 cells, and that the CA model is an appropriate model to predict the interaction effect of these selected mixtures. A human cell line-based reporter gene assay system was successfully used to determine the mixture effects of two groups of common contaminants on oxidative stress response pathway.

Synthesis and characterization of manganese-rich transition metal carbonate precursor in the presence of ethanol

Manganese-rich transition metal carbonate precursors (Ni0.15Co0.15Mn0.7CO3) have been synthesized by the carbonate precipitation in the presence of ethanol. The physical properties of the precursors with different concentration of ethanol have been examined by XRD and SEM. The XRD results show that the precursors prepared by this method are typical hexagonal structure. The SEM results show that the particles of the precursors with the presence of ethanol display more spherical and dispersed than those prepared without using ethanol. Galvanostatic charge–discharge experiments demonstrate that the initial discharge capacity of the cathode material (Li1.2Ni0.12Co0.12Mn0.56O2) is improved by the addition of ethanol. In addition, the effects of reaction temperature, the molar ratio of precipitant/total-cations on the morphology of the resultant precursors and the electrochemical properties of the prepared powders are also investigated. Among the synthesized materials, the sample prepared with 10vol% ethanol and a fixed concentration ratio ([CO32−]/[M2+]=10) at 65°C exhibits not only a relatively high discharge capacity of 272.1mAhg−1, but also excellent rate performance and good cycling performance.

Mixture toxicity effects of sea louse control agents in Daphnia magna

Caligid sea lice are ectoparasites causing major disease problems in industrial salmon farming. Sea louse control currently relies widely on parasiticides. Among non-target species, crustaceans are particularly susceptible to salmon delousing agents. Drug combinations have recently been suggested for sea louse control; however, no information is available on the non-target effects of such mixtures. To obtain first insights into combination effects of salmon parasiticides, acute toxicity tests with the crustacean model species Daphnia magna were conducted. Four compounds, including two organophosphates and two pyrethroids, were tested individually and in all pair-wise combinations at one fixed concentration ratio. For most combinations, observed toxicities were close to predictions assuming concentration additivity. However, deltamethrin and cypermethrin showed greater than predicted combination effects, while the inverse was observed for deltamethrin and malathion. The results demonstrate combination effects of anti-sea louse agents and suggest that predictions based on concentration additivity are in most cases protective.

Mixture effects of benzene, toluene, ethylbenzene, and xylenes (BTEX) on lung carcinoma cells via a hanging drop air exposure system.

A recently developed hanging drop air exposure system for toxicity studies of volatile chemicals was applied to evaluate the cell viability of lung carcinoma A549 cells after 1 and 24 h of exposure to benzene, toluene, ethylbenzene, and xylenes (BTEX) as individual compounds and as mixtures of four or six components. The cellular chemical concentrations causing 50% reduction of cell viability (EC50) were calculated using a mass balance model and came to 17, 12, 11, 9, 4, and 4 mmol/kg cell dry weight for benzene, toluene, ethylbenzene, m-xylene, o-xylene, and p-xylene, respectively, after 1 h of exposure. The EC50 decreased by a factor of 4 after 24 h of exposure. All mixture effects were best described by the mixture toxicity model of concentration addition, which is valid for chemicals with the same mode of action. Good agreement with the model predictions was found for benzene, toluene, ethylbenzene, and m-xylene at four different representative fixed concentration ratios after 1 h of exposure, but lower agreement with mixture prediction was obtained after 24 h of exposure. A recreated car exhaust mixture, which involved the contribution of the more toxic p-xylene and o-xylene, yielded an acceptable, but lower quality, prediction as well.

Evaluating Stability of Aqueous Multiwalled Carbon Nanotube Nanofluids by Using Different Stabilizers

The 0.5 wt.% multiwalled carbon nanotubes/water nanofluids (MWNFs) were produced by using a two‐step synthetic method with different types and concentrations of stabilizers. The static position method, centrifugal sedimentation method, zeta potential measurements, and rheological experiments were used to assess the stability of the MWNFs and to determine the optimal type and fixed MWCNTs‐stabilizer concentration of stabilizer. Finally, MWNFs with different concentrations of MWCNTs were produced using the optimal type and fixed concentration ratio of stabilizer, and their stability, thermal conductivity, and pH were measured to assess the feasibility of using them in heat transfer applications. MWNFs containing SDS and SDBS with MWCNTs‐stabilizer concentration ratio were 5 : 2 and 5 : 4, respectively, showed excellent stability when they were evaluated by static position, centrifugal sedimentation, zeta potential, and rheological experiments at the same time. The thermal conductivity of the MWNFs indicated that the most suitable dispersing MWNF contained SDBS. MWNFs with MWCNTs concentrations of 0.25, 0.5, and 1.0 wt.% were fabricated using an aqueous SDBS solution. In addition, the thermal conductivity of the MWNFs was found to have increased, and the thermal conductivity values were greater than that of water at 25°C by 3.20%, 8.46%, and 12.49%.

Amphotericin B- and Voriconazole-Echinocandin Combinations against Aspergillus spp.: Effect of Serum on Inhibitory and Fungicidal Interactions

Antifungal combination therapy with voriconazole or amphotericin B and an echinocandin is often employed as primary or salvage therapy for management particularly of refractory aspergillosis. The pharmacodynamic interactions of amphotericin B- and voriconazole-based combinations with the three echinocandins caspofungin, micafungin, and anidulafungin in the presence of serum were tested against 15 Aspergillus fumigatus complex, A. flavus complex, and A. terreus complex isolates to assess both their growth-inhibitory and fungicidal activities. The in vitro activity of each drug alone and in combination at a 1:1 fixed concentration ratio was tested with a broth microdilution colorimetric method, and interactions were assessed by isobolographic analysis. Synergy was found for all amphotericin B- and voriconazole-based combinations, with amphotericin B-based combinations showing strong inhibitory synergistic interactions (interaction indices of 0.20 to 0.52) and with voriconazole-based combinations demonstrating strong fungicidal synergistic interactions (interaction indices of 0.10 to 0.29) (P < 0.001). Drug- and species-specific differences were found, with caspofungin and the A. fumigatus complex exhibiting the weakest synergistic interactions. In the presence of serum, the synergistic interactions were reduced in the order (from largest to smallest decrease) micafungin > anidulafungin > caspofungin, and A. flavus complex > A. fumigatus complex > A. terreus complex, resulting in additive interactions, particularly for inhibitory activities of amphotericin B-echinocandin combinations and fungicidal activities of voriconazole-echinocandin combinations. Drug- and species-specific differences were found in the presence of serum for inhibitory activities of antifungal drugs, with the lowest interaction indices being observed for amphotericin B-caspofungin (median, 0.77) and for the A. terreus complex (median, 0.56). The present in vitro data showed that serum had a major impact on synergistic interactions of amphotericin B-echinocandin and voriconazole-echinocandin combinations, resulting in additive interactions and explaining the indifferent outcomes usually observed in vivo.

Mixture effects of organic micropollutants present in water: Towards the development of effect-based water quality trigger values for baseline toxicity

In this study we propose for the first time an approach for the tentative derivation of effect-based water quality trigger values for an apical endpoint, the cytotoxicity measured by the bioluminescence inhibition in Vibrio fischeri. The trigger values were derived for the Australian Drinking Water Guideline and the Australian Guideline for Water Recycling as examples, but the algorithm can be adapted to any other set of guideline values. In the first step, a Quantitative Structure–Activity Relationship (QSAR) describing the 50% effect concentrations, EC50, was established using chemicals known to act according to the nonspecific mode of action of baseline toxicity. This QSAR described the effect of most of the chemicals in these guidelines satisfactorily, with the exception of antibiotics, which were more potent than predicted by the baseline toxicity QSAR. The mixture effect of 10–56 guideline chemicals mixed at various fixed concentration ratios (equipotent mixture ratios and ratios of the guideline values) was adequately described by concentration addition model of mixture toxicity. Ten water samples were then analysed and 5–64 regulated chemicals were detected (from a target list of over 200 chemicals). These detected chemicals were mixed in the ratios of concentrations detected and their mixture effect was predicted by concentration addition. Comparing the effect of these designed mixtures with the effect of the water samples, it became evident that less than 1% of effect could be explained by known chemicals, making it imperative to derive effect-based trigger values. The effect-based water quality trigger value, EBT-EC50, was calculated from the mixture effect concentration predicted for concentration-additive mixture effects of all chemicals in a given guideline divided by the sum of the guideline concentrations for individual components, and dividing by an extrapolation factor that accounts for the number of chemicals contained in the guidelines and for model uncertainties. While this concept was established using the example of Australian recycled water, it can be easily adapted to any other set of water quality guidelines for organic micropollutants. The cytotoxicity based trigger value cannot be used in isolation, it must be applied in conjunction with effect-based trigger values targeting critical specific modes of action such as estrogenicity or photosynthesis inhibition.

Broadband near-infrared photoluminescence and energy transfer in Tm3+/Er3+-codoped low phonon energy gallate bismuth lead glasses

Tm3+/Er3+-codoped gallate bismuth lead (GBL) glasses are prepared and characterized optically. Broadband near-infrared fluorescence spectra composed of Er3+ 1.53 µm emission from the 4I13/2 → 4I15/2 transition and Tm3+ 1.47 µm emission from the 3H4 → 3F4 transition are recorded under 793 nm excitation wavelength. The full-width at half-maximum of the broad emission band depends on the Tm3+–Er3+ concentration ratio ([Tm]/[Er]), and a maximum bandwidth of 165 nm is achieved when the concentration ratio reaches 4, and the lineshape characteristic of the broadband emission remains the same for a fixed concentration ratio. The energy transfer processes involved are proposed and discussed, and the primary processes responsible for the flat broadband emission can be ascribed to the [Tm3+(3H4) + Tm3+(3H6)] → [Tm3+(3F4) + Tm3+(3F4)] and [Tm3+(3H4) + Er3+(4I15/2)] → [Tm3+(3F4) + Er3+(4I13/2)] processes. An investigation on energy transfer with assistance of matrix phonons shows that the matrix phonons play an important role in bridging the energy gap in the energy transfer processes.

State-space methods for calculating concentration dynamics in multizone buildings

This work explores analytic solutions to contaminant transport in multizone systems as a means of solving concentration dynamics more rapidly and providing insight into system behaviour. A general formulation is developed that is consistent with state-space theory. This is used to provide general and specific solutions for the concentration time series. In particular, an analytical expression is presented for the case of constant system parameters and constant input conditions using the eigenvalues and eigenvectors for the case of a diagonalisable state matrix for the multizone system. A method for using this expression to solve concentrations over a series of varying building and input states is developed, with potential for use as a rapid means of calculating concentrations at any time. In principle, this method could be used as a complementary method for solving concentration dynamics within multizone software. Analytical expressions for cumulative exposure for the same case are also presented. The characteristic behaviour of the solutions and their dependence on the eigenvalues and eigenvectors of the state matrix are explored for the steady state case and the decay solution. In particular, the behaviour in the late decay phase is shown to be characterised by a single decay rate, given by the smallest magnitude eigenvalue, and a fixed concentration ratio, given by the associated eigenvector. The independence of the concentration ratio in this phase to the initial conditions is also demonstrated. Two example cases are used to illustrate these and additional features.