Linear Kinetics Research Articles

Study on In Vitro Metabolism and In Vivo Pharmacokinetics of Beauvericin.

Beauvericin (BEA) is a well-known mycotoxin produced by many fungi, including Beaveria bassiana. The purpose of this study was to evaluate the in vitro distribution and metabolism characteristics as well as the in vivo pharmacokinetic (PK) profile of BEA. The in vitro metabolism studies of BEA were performed using rat, dog, mouse, monkey and human liver microsomes, cryopreserved hepatocytes and plasma under conditions of linear kinetics to estimate the respective elimination rates. Additionally, LC-UV-MSn (n = 1~2) was used to identify metabolites in human, rat, mouse, dog and monkey liver microsomes. Furthermore, cytochrome P450 (CYP) reaction phenotyping was carried out. Finally, the absolute bioavailability of BEA was evaluated by intravenous and oral administration in rats. BEA was metabolically stable in the liver microsomes and hepatocytes of humans and rats; however, it was a strong inhibitor of midazolam 1′-hydroxylase (CYP3A4) and mephenytoin 4′-hydroxylase (CYP2C19) activities in human liver microsomes. The protein binding fraction values of BEA were >90% and the half-life (T1/2) values of BEA were approximately 5 h in the plasma of the five species. The absolute bioavailability was calculated to be 29.5%. Altogether, these data indicate that BEA has great potential for further development as a drug candidate. Metabolic studies of different species can provide important reference values for further safety evaluation.

Impact of multiple hurdles on Listeria monocytogenes dispersion of survivors

Pathogen exposure to multiple hurdles could result in variation in the number of survivors, which needs to be carefully considered using appropriate regression models for dealing with survivor dispersion. The aim of this study was to evaluate the impact of the hurdles on the random component of the measured variation and on its unexplained part (over or under-dispersion) representing the departure from randomness, i.e. non-randomness, in survivors of a multi-strain mixture of L. monocytogenes. The pathogen inactivation curves were fitted to the Weibull model within the Conway-Maxwell-Poisson process. In all the 20 hurdle combinations, the surviving cells, whether they showed an upward curvature or linear kinetics, displayed the randomness revealed by the degree of dispersion of the inactivation parameters (-b and p). In 15 combinations, a significant dispersion coefficient (c0), which reflected the non–random component of variation was evident, denoting either over–dispersion (c0 > 0 in 13 combinations) or under-dispersion (c0 < 0 in 2 combinations). The observed dependence of the under- and over-dispersion conditions on the inactivation rate was confirmed by a Monte Carlo simulation based on the inactivation parameter -b. Including both randomness and non-randomness provides a more accurate estimation of survivors, which certainly impacts on intervention practices.

Initial High-Temperature Oxidation Behavior of Fe–Mn Binaries in Air: The Kinetics and Mechanism of Oxidation

High-temperature oxidation of steels can be relatively fast when exposed to air. Consequently, elucidating the effect of different parameters on the oxidation mechanism and kinetics is challenging. In this study, short-time oxidation was investigated to determine the oxidation mechanism, the affecting parameters, and the linear-to-parabolic growth transition of different Fe–Mn alloys in various oxygen partial pressures (10–30 kPa) and gas flow rates (26.6 and 53.3 sccm) in a temperature range of 950–1150 °C. Oxidation kinetics was investigated using a thermogravimetric analyzer (TGA) under controlled atmosphere. Linear oxide growth was observed within the first 20 minutes of oxidation. The linear rate constant was significantly increased by increasing the oxygen partial pressure or the flow rate of the oxidizing gas. The morphology of the oxide layer was determined by scanning electron microscopy (SEM). The crystal structure of the oxides formed was followed by in-situ X-ray diffraction (XRD), confirming that the growing layer consists of wustite mainly, which upon slow cooling to room temperature, transformed into magnetite. Energy-dispersive X-ray spectroscopy (EDS) showed that the atomic ratio of Fe+Mn to O was ~ 1.03:1 in the oxide scale, corresponding to Fe(Mn)O formation. Based on the characterization and a model for linear growth kinetics, it is concluded that the oxidation rate is controlled by the diffusion of oxidizing molecules through the gas layer to the sample’s surface. The findings led to a better understanding of initial oxidation behavior and provided a pathway for improved insight into the high-temperature oxidation behavior for more complex alloys.

Preclinical Pharmacokinetics and Bioavailability of Oxypeucedanin in Rats after Single Intravenous and Oral Administration.

Oxypeucedanin, a furanocoumarin extracted from many traditional Chinese herbal medicines, has a variety of pharmacological effects. However, the independent pharmacokinetic characteristics and bioavailability of this compound remains elusive. In this study, a rapid, sensitive, and selective method using ultra-high performance liquid chromatography–tandem mass spectrometry (UPLC/MS/MS) was developed for evaluating the intravenous and oral pharmacokinetics of oxypeucedanin. After intravenous administration of oxypeucedanin (2.5, 5, and 10 mg/kg), and intragastric administration of oxypeucedanin (20 mg/kg), blood samples were collected periodically from the tail vein. The plasma concentration-time curves were plotted, and the pharmacokinetic parameters were calculated using a non-compartmental model analysis. After intravenous administration of oxypeucedanin (single dosing at 2.5, 5, and 10 mg/kg) to rats, the pharmacokinetics fit the linear kinetics characteristics, which showed that some parameters including average elimination half-life (T1/2Z of 0.61~0.66 h), mean residence time (MRT of 0.62~0.80 h), apparent volume of distribution (VZ of 4.98~7.50 L/kg), and systemic clearance (CLZ of 5.64~8.55 L/kg/h) are dose-independent and the area under concentration-time curve (AUC) increased in a dose-proportional manner. Single oral administration of oxypeucedanin (20 mg/kg) showed poor and slow absorption with the mean time to reach the peak concentration (Tmax) of 3.38 h, MRT of 5.86 h, T1/2Z of 2.94 h, and a mean absolute bioavailability of 10.26% in rats. These results provide critical information for a better understanding of the pharmacological effect of oxypeucedanin, which will facilitate its research and development.

Cu(0)-mediated RDRP as new alternative for controlled synthesis of poly(pentafluorophenyl methacrylate)

The present work addresses for the first time the controlled synthesis of poly(pentafluorophenyl methacrylate) (PPFPMA) using Cu(0)-mediated reversible deactivation radical polymerization (Cu(0)-mediated RDRP). The influences of several components like ligand, initiator, and solvent are examined and discussed in details to deduce the best-found condition to synthesize PPFPMA with low dispersity (1.05–1.33) in a wide range of molecular weight (6000 g mol−1 to 129 000 g mol−1). The polymerization under the best-found condition shows controlled polymerization features with no induction period, linear first-order kinetics, and linear correlation in monomer conversion. In addition, the chain-end fidelity of polymer obtained by found-optimized conditions is also investigated by various techniques including 1H NMR, MALDI-ToF, and chain extension experiments.

Nano-silica from kaolinitic clay used as adsorbent for anionic and cationic dyes removal: linear and non-linear regression isotherms and kinetics studies

The increasing occurrence of wastewaters associated with industrial development has begotten a permanent search for new and more efficient techniques for the removal of hazardous substances such as heavy metals and dyes. The use of natural and available resources to develop improved and sustainable commodities for this purpose remains crucial and is among promising emerging green technologies for water treatment. It offers the gradual shifting of hazardous industrial chemicals precursors to the abundant non-metallic mineral resources that receive an added value. This work investigated the uptake capacity by the adsorption process of methylene blue (MB) and azocarmine G (AG) onto nano-silica synthesized from kaolinite clay. The effects of contact time (0-30 min), the adsorbent dosage (5-100 mg), the initial pH of the solution (1-11 for MB and 1-7 for AG), and the initial dye concentration (5-50 mg/L) were studied. The selected conditions to carry out kinetic and isotherm adsorption experiments were: 15 mins, 20 mg, 11 for MB, 1.01 for AG, and 50 mg/L. Four adsorption isotherms and three kinetic models were used to model the adsorption data thanks to linear and non-linear regression methods. From the obtained results, the Freundlich isotherm model fitted well the adsorption phenomenon while the pseudo-second-order kinetic model described well the adsorption mechanism. Furthermore, the free energy of adsorption was similar for the two absorbents, 0.71 kJ, pointing physisorption as the dominant adsorption mechanism. The optimum MB and AG uptake were respectively 13.8 and 36.1 mg/g. Conclusively, the nano-silica represents a potentially viable and powerful adsorbent whose use could lead to a plausible improvement in environmental preservation.

Oxidation resistance of WB and W2B-W neutron shields

Tungsten borides are candidate radiation shielding materials for compact fusion reactors. However little is known about their performance when oxidised at high temperatures in the case of an accident combining loss of coolant and vacuum. Candidate materials containing 0, 16, 30, and 50 at.% B were exposed to air at 600–1100 °C in a thermogravimeter and the kinetic rate constants were evaluated. The corresponding oxide scales were characterised by X-ray diffraction and electron microscopy. The boron containing materials showed parabolic kinetics, more protective behaviour than tungsten, and an improvement in oxidation resistance with increasing boron content. For example, the rate constant was a factor of 600 lower for 50 at.% B vs. pure W at 1000 °C. In 16 and 30 at.% B materials the scale formed a microstructure of interpenetrating B2O3 and WO3. In the 50 at.% B material, two distinct layers formed, with a B2O3-rich layer on the surface, and fine WO3-based layer beneath. The protective scale was disrupted in all materials at 1000–1100 °C, depending on boron content. The disruption resulted in a transition to linear kinetics and can be explained by the B2O3 evaporation rate exceeding its formation rate. Encouragingly, all tungsten borides have superior oxidation resistance compared to pure tungsten, suggesting favourable accident tolerance.

Linear and nonlinear kinetics analysis and adsorption characteristics of packed bed column for phenol removal using rice husk-activated carbon

The linear and nonlinear kinetics analysis and adsorption characteristics of phenol adsorption onto activated carbon synthesized from rice husk biomass were investigated in a packed bed column. Several analyses such as physical properties, BET surface area, pore size distribution, FTIR, and SEM were used to investigate the adsorption properties of the rice husk-activated carbon (RHAC). The column adsorption studies indicated that the adsorption of phenol onto RHAC is favored by an increase in bed height and a decrease in solution flow rate, influent phenol concentration, and particle size. Various dynamic adsorption parameters depicting the adsorption characteristics of phenol onto RHAC were estimated from the breakthrough analysis of the experimental data. The fitting of the experimental data to the Thomas, Adams–Bohart, Yoon–Nelson, and Wolborska models using linear and nonlinear regression techniques showed that the four models gave good fits to the experimental data. The R2 values for the regressed lines ranged from 0.6827 to 0.9918, and 0.9958 to 1.0000 for the linear and nonlinear regression techniques, respectively. Experimentally, a maximum adsorption capacity value of 14.57 mg/g was obtained; at the same experimental conditions, 14.88 mg/g was predicted by the nonlinear regression, while 9.78 mg/g was predicted by the linear regression of the Thomas model. The results affirmed the potency of RHAC for the treatment of phenol-contaminated wastewater. It provided comprehensive data needed for the design of phenol adsorption columns using RHAC. It equally revealed that a better model analysis would be achieved with the application of nonlinear regression.

Reaction-diffusion in a packed-bed reactors: Enzymatic isomerization with Michaelis-Menten Kinetics

A theoretical model for the enzyme catalysed isomerisation reaction in a packed-bed reactors made up of microporous particles is discussed. The system is described in terms of finite-range Fickian diffusion and non linear Michaelis-Menten reaction kinetics to produce a non linear reaction/diffusion equation which is solved both numerically by MATLAB and analytically by hyperbolic function methods (HFM). Approximate analytical expressions of the substrate concentration within the microparticle, the related flux and the effectiveness factor for a wide range of values of pore-level Thiele modulus and kinetic parameters are reported using these simple, and robust methods. A satisfactory agreement is obtained between the estimated analytical solution and the numerical simulation.

Effect of Zr and Ti on isothermal oxidation behavior of Nb–Si based alloys

The isothermal oxidation behavior of 56Nb-16Si-(20-x)Ti–3Cr–3Al-2Hf-xZr (x ​= ​0, 2, 5, 10 ​at. %) alloys was investigated at 800 ​°C and 1250 ​°C, respectively. The results show that increasing the Zr content evidently increased the oxidation rates at 800 ​°C, accompanied by the obvious occurrence of pesting oxidation. The alloys showed alike linear oxidation kinetics at 1250 ​°C. With the increase of Zr content, the adherence and integrity of oxide scales were improved, but the overall oxidation resistance was slightly deteriorated. The observed oxidation behavior may be attributed to the composition variation of Zr and Ti in the alloys. The oxidation mechanism associated with the composition variation is discussed in this study.

Cockle (Anadara granosa) shells-based hydroxyapatite and its potential for defluoridation of drinking water

The present study describes the synthesis and characterization of a hydroxyapatite (HAp)-based adsorbent derived from biogenic cockle (Anadara granosa) shells for the defluoridation of drinking water. The raw cockle shells and synthesized HAp were characterized by X-ray fluorescence spectroscopy (XRF), attenuated total reflection-Fourier transform infrared (ATR-FTIR), X-ray diffraction (XRD), Field emission scanning electron microscopes-energy dispersive X-ray (FESEM-EDX) and Brunauer-Emmett-Teller (BET) surface area analysis. As demonstrated by FTIR, cockle shells were found to be composed of calcium carbonate (97.4%), an aragonite polymorphous type of carbonate mineral. XRD and SEM analysis supported the formation of a nanocrystalline HAp with an average crystal size of 19.08 nm and 57.1 nm, respectively, with a surface area of 105.8 m2/g and a pore size of 5.6 nm, as depicted by BET. Batch adsorption experiments were conducted using the Box-Behnken design (BBD) with five input parameters: adsorbent dose (2–10 g/L), initial fluoride concentration (10–80 mg/L), contact time (0.5–24 h), reaction temperature (303–333 K), and pH. (3–11). BBD revealed the following optimum conditions: adsorbent dose (6 g/L), initial fluoride concentration (45 mg/L), contact period 12.25 h, reaction temperature (303 K), and pH 3. Experimentally, the adsorption of fluoride on HAp fitted well with the non-linear Langmuir isotherm and linear pseudo-second order kinetics, signifying the chemisorption process. A maximum adsorption capacity (qm) of 15.374 mg/g, which is closer to the experimental value of 14.053 mg/g, was presented by the Langmuir isotherm. Thermodynamically, the adsorption process was spontaneous, endothermic, and stable in nature. The defluoridation mechanism was through electrostatic attraction, ion exchange, hydrogen bonding, and precipitation. Furthermore, the synthesized HAp and bone char were used to examine their efficacy in defluoridating field water: HAp performed better at natural pH, where the treated water met WHO and TBS standards, whereas bone char had insufficient fluoride removal, especially at high fluoride levels. As a result, this study suggests that HAp derived from Anadara granosa shells could be a viable adsorbent for the defluoridation of drinking water.

Abstract P2-13-09: An investigational next generation ADC (DAN-311) is highly effective in HER2-low breast cancer models

Abstract Background: Nanoparticles (NPs) have been developed to enhance the pharmacokinetic (PK) and biodistribution characteristics of molecules. Many early NPs, including liposomes, dendrimers, and polymeric micelles, were limited in their ability to access target tissue and lacked uniform release rates. A promising nanoparticle therapeutic has been developed utilizing biocompatible polymer chemistry. By covalently attaching chemotherapy to the polymer through linker strategies that allow for modulation of release and PK, polymeric nanoparticles provide advantages over encapsulation nanoparticle strategies. Additionally, a targeting moiety can be added to make a next-generation ADC with the drug-to-antibody-ratio (DAR) well controlled and significantly greater (e.g. DAR=60) compared to traditional ADCs. DAN-311 is a Next-Generation Antibody Drug Conjugate (NG-ADC) with a HER2-targeting agent (trastuzumab) conjugated to a therapeutic nanoparticle with camptothecin (CPT), a topoisomerase I inhibitor. The advantages that DAN-311 offers to the 50% of patients with breast cancer have tumors with low HER2 expression is two-fold: 1) the larger DAR can lead to an enhanced bystander effect where the chemotherapy is effective against the targeted cells and also the neighboring cells, and 2) the nanoparticle is also active against HER2 non-expressing cells through the enhanced permeability and retention (EPR) effect. Here, we present the control and consistency of key DAN-311 NP characteristics that allow for efficient and large scale-manufacture, including particle size, chemotherapy load (DAR), and payload release rate. We also report the enhanced efficacy of DAN-311 in a HER2-low breast cancer (JIMT-1) xenograft mouse model. Methods: Release of CPT from nanoparticles across range of combined properties was evaluated by HPLC in pH 5.5 PBS (endosomal pH), pH 7.4 PBS (physiologic pH), mouse plasma, and human plasma. HER2-low breast cancer tumor cells (JIMT-1) were implanted into female CB.17 SCID mice. Mice were randomized to vehicle or treatment arms until tumors reached 2000 mm3 or day 46. The groups evaluated included trastuzumab, the non-targeted core nanoparticle of DAN-311, and DAN-311. Results: NPs across a wide range in polymer molecular weight and drug loading demonstrate striking consistency in particle size (ca. 30-45 nm), DAR (ca. 60-70 CPT molecules), and demonstrate linear release kinetics in various physiologically-relevant media. DAN-311 exhibited significantly greater tumor growth inhibition compared to vehicle, core particle, and trastuzumab. The non-targeted core particle also demonstrated significant tumor growth inhibition compared to vehicle and trastuzumab, which was sustained for at least 3 weeks after the final dose. Core particle = same DAN-311 nanoparticle without HER2 targeting. Conclusions: DAN-311, a Next-Generation ADC with a HER2-targeting agent (trastuzumab) on a polymeric nanoparticle conjugated with CPT demonstrated a significant ability to inhibit tumor growth in a HER2-low xenograft mouse model. Importantly, the nanoparticle targeted delivery of CPT for cells with low expression of receptors is highly efficient in cell killing and the large DAR provides greater bystander cell killing capability; and non-HER2-expressing lesions or regions of tumors will additionally be treated by the nanoparticle through EPR. DAN-311 is advancing to clinical study to treat HER2-low metastatic breast cancer patients. TreatmentDose (mg/kg)Day 22 TGI (%)Day 46 TGI (%)Trastuzumab10 mg/kg Tras629Core particle1 mg/kg CPT3955DAN-31110 mg/kg Tras/1 mg/kg CPT8777 Citation Format: Ashley P Wright, Emily A Wyatt, Robert J Lamm, Carl M Blumenfeld, Jodi D Bradley, Gayatri Shrikhande, Timothy Hagerty. An investigational next generation ADC (DAN-311) is highly effective in HER2-low breast cancer models [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-13-09.

Abstract P5-16-16: A novel investigational nanoparticle therapeutic (DAN-222) for breast cancer and other solid tumors

Abstract Background: Here we introduce a novel nanoparticle therapeutic, DAN-222, which offers a variety of potential clinical benefits in delivery of chemotherapy versus native drug, including a broader therapeutic index. DAN-222 is a polymeric nanoparticle covalently conjugated with camptothecin (CPT), a topoisomerase I inhibitor, that demonstrates enhanced efficacy over native CPT at the same dose and has significantly reduced bone marrow exposure (limiting potential safety concerns), thus widening the therapeutic index with respect to both efficacy and safety. The nanoparticle therapeutic provides sustained drug exposure through conjugation of the chemotherapy payload to the novel biocompatible polymer scaffold that can be modulated by choice of linker, allowing for optimization of the release rate for a given payload and target. To illustrate the flexibility and capabilities of modulating payload release kinetics, we present a series of CPT-containing nanoparticles with different linkers encompassing a wide range of in vitro release rates. We also demonstrate the vastly enhanced efficacy of DAN-222 in multiple breast cancer xenograft mouse models. Methods: In vitro release: Release of CPT from nanoparticles formed with various linkers was evaluated by HPLC in pH 5.5 PBS (endosomal pH), pH 7.4 PBS (physiologic pH), mouse plasma, and human plasma. Efficacy: Breast cancer xenograft tumor models with human BT-474 and MDA-MB-231 were propagated in CB.17 SCID and NCr nu/nu mice respectively, with 10 animals per group. Results: All linkers demonstrate linear kinetics and release slowly at reduced pH, consistent with the mechanism of release. At physiologic pH, a diversity of in vitro release rates is achieved by modulating the sensitivity of the linker. Importantly, all linkers have similar release in mouse and human plasma, indicating strong cross-species translation. Results in the mouse xenograft models showed that DAN-222 had a superior and sustained efficacy compared to CPT and irinotecan (an approved topoisomerase-1 inhibitor) as demonstrated by tumor growth inhibition. Conclusions: We demonstrate the ability to modulate the payload release kinetics from the nanoparticle therapeutic by the choice of linker, with species-independent release rates. With an optimal linker selected, DAN-222 shows enhanced and sustained efficacy over native CPT. Since DAN-222 has previously been shown to have reduced bone marrow exposure of chemotherapy, it may provide a significant therapeutic advancement with a wider therapeutic index based on both enhanced efficacy and improved safety. DAN-222 is advancing to a clinical trial in HER2-negative metastatic breast cancer. In vitro release half-lives (t1/2) (hours)Linker 1Linker 2Linker 3Linker 4Linker 5PBS, pH 5.5&amp;gt;50&amp;gt;50&amp;gt;50&amp;gt;50&amp;gt;50PBS, pH 7.47.120.5&amp;gt;50&amp;gt;50&amp;gt;50Mouse Plasma1.74.817.237.7&amp;gt;50Human Plasma1.64.817.137.8&amp;gt;50 TreatmentBT-474MDA-MB-231Day 25 TGI(%)Day 36 TGI*(%)Day 25 TGI (%)Day 32 TGI* (%)Camptothecin (3 mg/kg)64404756Irinotecan (100 mg/kg)71594751DAN-222 (3 mg/kg CPT)93967475*Day the vehicle control group reached the study endpoint. Citation Format: Emily A Wyatt, Ashley P Wright, Carl M Blumenfeld, Robert J Lamm, Timothy Hagerty. A novel investigational nanoparticle therapeutic (DAN-222) for breast cancer and other solid tumors [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-16-16.

Post-Stroke Hemiplegic Rodent Evaluation: A Framework for Assessing Forelimb Movement Quality Using Kinematics.

Kinematics is the gold-standard method for measuring detailed joint motions. Recent research demonstrates that post-stroke kinematic analysis in rats reveals reaching abnormalities similar to those seen in humans after stroke. Nonetheless, behavioral neuroscientists have failed to incorporate kinematic methods for assessing movement quality in stroke models. The availability of a user-friendly method to assess multi-segment forelimb kinematics models should greatly increase uptake of this approach. Here, we present a framework for multi-segment forelimb analysis in rodents after stroke. This method greatly enhances the understanding of post-stroke forelimb motor recovery by including several movement quality metrics often used in human clinical work, such as upper-limb linear and angular kinematics, movement smoothness and kinetics, abnormal synergies, and compensations. These metrics may constitute a preclinical surrogate for the Fugl-Meyer assessment of hemiplegic patients. The data obtained using this method are 83 outputs of linear and angular kinematics and kinetics. The outputs also include 24 time series of continuous data, which afford a graphical representation of the kinematics and kinetics of the reaching cycle. We show that post-stroke rodents displayed many features resembling those seen in humans after stroke that are evident only when multi-segment kinematics models are considered. This method expands the knowledge derived from methods constrained to paw movements to a multi-segment forelimb movement quality framework. Moreover, it highlights the need for preclinical work to consider more sensitive measures of sensorimotor impairment and recovery as a means to enhance the interpretation of true recovery and compensation. © 2022 Wiley Periodicals LLC. Basic Protocol: Recording and data analysis of rodents performing the Montoya staircase task.

RETRACTED: Investigating the solid-state diffusion at the interface of Ni/Ti laminated composite

The fabrication of Ni/Ti laminated composite via cross accumulative roll bonding (CARB) and subsequent annealing treatment has been studied. The relationships between annealing conditions and microstructure at interfaces of Ni/Ti have been investigated by SEM, XRD, and EDS analyses. The results show that the layers were well-bonded by the CARB process, and by increasing the temperature and time of annealing treatment, the interfacial layers grew as a result of the interdiffusion of Ni and Ti atoms. The main intermetallic phases were NiTi and NiTi 2 , both of which obeyed linear kinetics of growth. However, the calculated activation energy of NiTi was lower than that of NiTi 2 , indicating the comparable growth of NiTi. Further, based upon the results of tensile tests, the ultimate strength of samples decreased as the intermetallic layers grew; the detachment of layers and the intergranular fraction of intermetallic compounds were the main fracture mechanisms. • Ni/Ti laminated composite was produced by using the CARB process and post-annealing. • The following sequence of phases was detected: Ti/NiTi 2 /NiTi/Ni 3 Ti/Ni • The thickness of NiTi 2 and NiTi layers rose as the temperature and time of annealing treatment increased. • As the intermetallic layers grew, the values of ultimate tensile strength and elongation decreased and fluctuated, respectively.

Diverse classes of constraints enable broader applicability of a linear programming-based dynamic metabolic modeling framework

Current metabolic modeling tools suffer from a variety of limitations, from scalability to simplifying assumptions, that preclude their use in many applications. We recently created a modeling framework, Linear Kinetics-Dynamic Flux Balance Analysis (LK-DFBA), that addresses a key gap: capturing metabolite dynamics and regulation while retaining a potentially scalable linear programming structure. Key to this framework’s success are the linear kinetics and regulatory constraints imposed on the system. However, while the linearity of these constraints reduces computational complexity, it may not accurately capture the behavior of many biochemical systems. Here, we developed three new classes of LK-DFBA constraints to better model interactions between metabolites and the reactions they regulate. We tested these new approaches on several synthetic and biological systems, and also performed the first-ever comparison of LK-DFBA predictions to experimental data. We found that no single constraint approach was optimal across all systems examined, and systems with the same topological structure but different parameters were often best modeled by different types of constraints. However, we did find that when genetic perturbations were implemented in the systems, the optimal constraint approach typically remained the same as for the wild-type regardless of the model topology or parameterization, indicating that just a single wild-type dataset could allow identification of the ideal constraint to enable model predictivity for a given system. These results suggest that the availability of multiple constraint approaches will allow LK-DFBA to model a wider range of metabolic systems.

Sorptive riddance of enrofloxacin from wastewater: linear and non-linear isotherm and kinetics, safe disposal, and cost analysis

Sorptive riddance of enrofloxacin from wastewater: linear and non-linear isotherm and kinetics, safe disposal, and cost analysis

Enhanced electrocatalytic activity of N-doped nano-onion/gold nanorod nanocomposites for the oxygen reduction reaction

The development of improved electrocatalysts for the oxygen reduction reaction (ORR) is a key to achieving green energy conversion and storage. In this study, heterogeneous amorphous nanoonions were derived from nanodiamonds by thermal annealing and subsequently doped with nitrogen by hydrothermal and pyrolytic methods as potential catalytic supports. Electrocatalytic activity and capacity of the nanocomposites with gold nanorods were significantly modulated for the ORR, depending on heteroatom N configuration into the nanoonions. AuNR/ N-doped nanoonion composite having chemical composition of rich pyridinic and low amine N exhibited mainly first-order linear kinetics, indicating four-electron transfer toward the ORR. AuNR/hydrothermally N-doped nanoonions composite having high pyrrolic and lower pyridinic N affected the pseudocapacitance. The interfacial interaction between gold and amorphous nanoonion provided facilitated electronic transfer on the heterojunction and thus, electrocatalytic activity were critically affected by N configuration-dependent nanoonoin for ORR. The N-doped nanoonions reported herein are a potential platform to develop diverse metal composites with electrocatalytic functions by providing excellent conductivity and resistance to gold decomposition.

Study on Central Composite Design Method to Optimize the Preparation Process of Chrysophanol‐Pluronic F127 Nanomicelles and Pharmacokinetics

Objective. In order to find the best process for the preparation of Chrysophanol‐Pluronic F127 nanomicelles in the laboratory, the preparation of Chrysophanol‐Pluronic F127 nanomicelles was optimized using the central composite design method. In order to investigate the properties of the prepared Chrysophanol‐Pluronic F127 nanomicelles, physicochemical properties were examined and in vitro dissolution experiments were performed, and the pharmacokinetics of Chrysophanol and Chrysophanol‐Pluronic F127 nanomicelles were investigated in rabbits. Methods. In the preexperimental study, the best physical solubilization method and organic solvent for Chrysophanol were selected. The ratio of drug dosage to excipient dosage and the amount of organic solvents were evaluated by single‐factor test. Based on the single‐factor test, the optimal prescription was obtained by screening the formulation and optimizing the preparation process using the central composite design method with the encapsulation efficiency as the index. Chrysophanol‐Pluronic F127 nanomicelles were prepared according to the optimal prescription, and their particle size, potential, appearance, and in vitro release experiments were carried out. Chrysophanol and Chrysophanol‐Pluronic F127 nanomicelles were injected intravenously through the ear margins to rabbits, and the drug concentrations in the blood were measured at different time points by HPLC. The obtained blood concentration data were fitted with PK Solver 2.0 program to obtain pharmacokinetic parameters. Results. In the preexperimental study, ultrasonic method was selected as the physical solubilization method, and acetone was selected as the organic solvent. In single‐factor test, the highest encapsulation efficiency was achieved when the ratio of drug dosage to excipient dosage was 1 : 15; the highest encapsulation efficiency was achieved when the amount of organic solvent (acetone) was 8 mL. The equation fitted to the model for the optimized prescription by the central composite design method is as follows: R1 = −166.93629 + 16.86478A + 32.55582B − 0.169750AB − 0.4826752 − 2.25797B2(R2 = 0.9457). The best prescription for the preparation of Chrysophanol‐Pluronic F127 nanomicelles was obtained in the ratio of drug dosage to excipient dosage of 1 : 16.309 and the dosage of organic solvent was 6.595 mL. The prepared nanomicelles have a particle size of 152.8 nm and a potential of ‐23.9 mV. It was observed by transmission electron microscope that the prepared nanomicelles are uniform and spherical in appearance. The drug metabolism of Chrysophanol and nanomicelles in rabbits conforms to the two‐compartment open model, and both of them show linear kinetics in the drug dose range. T(1/2α) was 0.31 ± 0.21 h and 0.47 ± 0.35 h, and T(1/2β) was 2.06 ± 1.14 h and 7.72 ± 2.04 h for Chrysophanol and Chrysophanol‐Pluronic F127 nanomicelles, respectively. Conclusions. The adopted central composite design method can well optimize the prescription process of Chrysophanol‐Pluronic F127 nanomicelles prepared by dialysis, and the method is simple and easy to be prepared in the laboratory. The prepared nanomicelles have uniform particle size and good zeta potential and appear as uniform black spherical shape under transmission electron microscopy. In vitro release studies showed that the Chrysophanol‐Pluronic F127 nanomicelles released significantly better than Chrysophanol. The results of pharmacokinetics of Chrysophanol and Chrysophanol‐Pluronic F127 nanomicelles in rabbits showed that the Chrysophanol‐Pluronic F127 nanomicelles did not change the metabolic process of the drug in vivo but could stay in vivo for a longer period of time and exert longer effects. It is hoped that this study can provide a laboratory basis for the preparation of Chrysophanol‐Pluronic F127 nanomicelles and a reference for further in vivo studies of Chrysophanol.

Reaction kinetics of an Mg/CO2 power system for Mars exploration

This study investigates the heterogeneous and homogeneous reaction characteristics of the Mg/CO2 and coexisting Mg/CO systems using thermal analysis kinetics and quantum chemical calculation methods, respectively. The corresponding kinetic parameters are subsequently obtained using detailed theoretical calculations. The Mg/CO2 power system is a very promising propulsion mode for future Mars exploration due to the abundant carbon dioxide resources in the atmosphere of Mars. At present, much of the research on Mg combustion in CO2 has focused on the ignition and combustion characteristics at the macro level and few databases exist for microreaction characteristics. Three sets of thermal analysis experiments at different temperature rise rates are carried out in CO2 and CO atmospheres to extract the kinetic parameters. The results show that the heterogeneous reactions between Mg and CO2/CO are controlled by the first-order reaction model (F1), that is, by linear kinetics. There are two intermediate transition states in the homogeneous reaction between Mg and CO2. However, a suitable transition state structure is not observed in the homogeneous reaction between Mg and CO. The total energy barrier of this reaction is significantly higher than that of the Mg/CO2 reaction system. In addition, the rate constant of the Mg/CO2 homogeneous reaction is 10–17 orders of magnitude higher than that of the Mg/CO homogeneous reaction in the temperature range between the boiling point of Mg and 2000 K. The conclusions of this study are valuable for the combustion models of Mg/CO2 systems, which are expected to contribute to the structural design and optimisation of Mg/CO2 rocket engines or burners for Mars exploration.