Determination Of Residence Time Research Articles

Impact of the spindle number on the material transport and mixing during planetary roller melt granulation

In comparison to the established twin-screw machines, the application of a planetary roller granulator for continuous operation of melt granulation is a promising alternative based on the unique process concept. An initial study focused on the material transport during processing as a key driver for the overall performance. Hereby, the impact of direct process parameters on the residence time distribution was the main objective.These investigations are complemented in this study by considering the free processing volume, which is defined by the number of planetary spindles applied within a module. The impact on the processing conditions is evaluated with respect to the process setting in terms of feed rate and rotation speed.The results highlight the potential of altering the underlying transport function in planetary roller melt granulation (PRMG) via the investigated direct process and equipment parameters. The impact of the feed rate is lower in comparison, while a higher rotation speed as well as a higher free processing volume promote material mixing. Moreover, a normalization of the determined residence time distribution (RTD) model data was feasible with respect to the process settings and the number of applied planetary spindles in the processing zone. This demonstrates the key role of the free processing volume in the fundamental mechanisms of material transport and mixing during PRMG.

Numerical modelling of hydraulic efficiency and pollution transport in waste stabilization ponds

This paper investigates the hydraulic performance and solute transport processes in waste stabilization ponds (WSPs). A numerical model comprised of Reynolds-averaged Navier–Stokes (RANS) flow hydrodynamic model with the standard k − ε turbulence closure coupled with the advection-diffusion solute transport model, is developed in a three-dimensional Cartesian coordinate system. The proposed numerical model is successfully validated against laboratory-scale physical modelling measurements of flow hydrodynamics and solute characteristics across trapezoidal pond geometry. The developed numerical model is adopted to run series of scenario-based simulations to investigate the effects of WSP's geometrical features and implementation of an island retrofitting on the hydraulic performance and treatment efficiency of the WSPs. Fifteen pond configurations with varying side-walls slope and island configurations are simulated. Vertical and horizontal structures of flow hydrodynamics across the pond are investigated. Solute transport processes are studied through determining residence time distribution (RTDs) curves based on numerical tracer simulations. Two deflector island configurations (parallel and rotated) are simulated to investigate their influence on enhancing the hydraulic performance of the WSP. The analysis of the numerical results indicates an overall positive impact of deflector island retrofitting on the hydraulic performance of the WSP. The side-walls slope are shown to play a key role in determining the overall performance of the WSP. For the cases with side-walls slope of 1:1, 0.5:1 and 0:1, the hydraulic efficiency of the WSP was enhanced by adding both parallel and rotated islands. However, for the cases with side-walls slope of 2:1 and 1.5:1, addition of island deflector is shown to have negative impacts on the hydraulic performance of the waste stabilization pond.

Revealing subsurface processes in the Uhlířská catchment through combined modelling of unsaturated and saturated flow

AbstractA novel transferable modelling approach was applied to reveal subsurface flow processes and thus complement, verify, and enhance the conceptual knowledge of the small (1.78 km2) mountainous experimental catchment Uhlířská in the northern part of the Czech Republic. We used the S1D model to simulate flow and tracer movement in the vadose zone. MODFLOW‐2000, MODPATH and MT3DS models were used to determine residence time and flow trajectories in the saturated zone. The isotopic tracers 3H and 3H/3He were used to calibrate the groundwater model in the deeper aquifer layers. The modelling approach was established to enhance our understanding and quantification of interactions between the hillslope (82% of the area) and wetland (18% of the area), as well as the aquifer beneath the catchment. Numerical methods corroborated the estimated groundwater residence times and provided a catchment water balance in support of process knowledge. The combined modelling yielded the following water balance for the period 1961–2014: 1220 mm annual precipitation amount, 456 mm of percolation through the soil matrix domain on hillslopes, 534 mm of water through the hillslope preferential domain, and 22 mm of water through the matrix of the riparian wetland. This partitioning resulted in an area‐weighted average annual groundwater recharge of 430 mm. The water residence time on the hillslopes did not exceed 1 year, and was about 10 years for the saturated zone, with 20% of water older than 100 years in the deepest part of the aquifer. The conceptual knowledge of subsurface hydrological processes combined with numerical modelling, computation of water balance and isotope‐supported calibration is considered innovative, particularly the 3H/3He method to determine water residence times of young groundwater in the saturated zone. Lessons learned and recommendations are presented to apply the knowledge from the Uhlířská in the broad context of small research catchments.

Seasonal Differences in the Attenuation of Polar Trace Organics in the Hyporheic Zone of an Urban Stream

AbstractAttenuation of trace organic compounds (TrOCs) in a river occurs to a large extent in its hyporheic zone. A major part of the attenuation of polar TrOCs is of microbial origin. As microbial activity depends on temperature and redox conditions, seasonal differences in TrOC attenuation are likely. We investigated TrOC attenuation at a river influenced by treated wastewater during two sampling campaigns, one in summer and one in winter. In addition to redox conditions and temperature, we also determined residence times of porewater in sediment using three methods: (a) non‐parametric deconvolution of electrical conductivity time series, (b) the model VFLUX 2.0 based on temperature time series (only summer), and (c) applying Darcy's law to differences in hydraulic heads (only summer). Contrary to our expectations, we found higher attenuation for 12 out of 18 TrOCs in winter, while three TrOCs were better attenuated in summer. Sediment conditions varied between seasons as more of the top sandy layer with a higher hydraulic permeability accumulated on the river bed in summer. As a result, residence times in the sediment were shorter in summer. In winter, longer residence times, lower temperatures, and a steeper oxygen gradient in sediment coincided with higher TrOC attenuation. Further research is needed to understand our unexpected findings and underlying mechanisms.

Contact Map Fingerprints of Protein-Ligand Unbinding Trajectories Reveal Mechanisms Determining Residence Times Computed from Scaled Molecular Dynamics.

The binding kinetic properties of potential drugs may significantly influence their subsequent clinical efficacy. Predictions of these properties based on computer simulations provide a useful alternative to their expensive and time-consuming experimental counterparts, even at an early drug discovery stage. Herein, we perform scaled molecular dynamics (ScaledMD) simulations on a set of 27 ligands of HSP90 belonging to more than seven chemical series to estimate their relative residence times. We introduce two new techniques for the analysis and the classification of the simulated unbinding trajectories. The first technique, which helps in estimating the limits of the free energy well around the bound state, and the second one, based on a new contact map fingerprint, allow the description and the comparison of the paths that lead to unbinding. Using these analyses, we find that ScaledMD's relative residence time generally enables the identification of the slowest unbinders. We propose an explanation for the underestimation of the residence times of a subset of compounds, and we investigate how the biasing in ScaledMD can affect the mechanistic insights that can be gained from the simulations.

Simplified Method for the In Situ Collection and Laboratory Analysis of Cosmogenic Tracers (Sulfur-35 and Sodium-22) to Determine Residence Time Distributions and Water Ages

The use of cosmogenically produced sulfur-35 (T1/2 = 87 days) and sodium-22 (T1/2 = 2.6 years) as intrinsic tracers can provide valuable information on catchment hydrology, flow paths, and subsurface storage. A new and straightforward method was created to determine the activities of both 35S and 22Na in various water sources by pumping large volumes (up to 1000 L) of water through cation- and anion-exchange resin columns in the field to collect sodium and sulfate ions and simple chemistry in the lab. Samples are counted for 35S using liquid scintillation counting (LSC) and for 22Na via γ spectroscopy. Our novel in situ method provides faster sample throughput as well as better counting statistics and lower detection limits. Both methods were successfully applied at the Southern Sierra Critical Zone Observatory.

Biodistribution and Radiation Dosimetric Analysis of [68Ga]Ga-RM2: A Potent GRPR Antagonist in Prostate Carcinoma Patients

[68Ga]Ga-RM2 is a promising innovative positron emission tomography (PET) tracer for patients with primary or metastatic prostate carcinoma. This study aims to analyze the biodistribution and radiation dosimetry of [68Ga]Ga-RM2 in five prostate cancer patients. The percentages of injected activity in the source organs and blood samples were determined. Bone marrow residence time was calculated using an indirect blood-based method. OLINDA/EXM version 2.0 (Hermes Medical Solutions, Stockholm, Sweden) was used to determine residence times, organ absorbed and effective doses. Physiological uptake was seen in kidneys, urinary bladder, pancreas, stomach, spleen and liver. Blood clearance was fast and followed by rapid clearance of activity from kidneys resulting in high activity concentrations in the urinary bladder. The urinary bladder wall was the most irradiated organ with highest mean organ absorbed dose (0.470 mSv/MBq) followed by pancreas (0.124 mSv/MBq), stomach wall (0.063 mSv/MBq), kidneys (0.049 mSv/MBq) and red marrow (0.010 mSv/MBq). The effective dose was found to be 0.038 mSv/MBq. Organ absorbed doses were found to be comparable to other gallium-68 labelled GRPR antagonists and lower than [68Ga]Ga-PSMA with the exception of the urinary bladder, pancreas and stomach wall. Remarkable interindividual differences were observed for the organ absorbed doses. Therefore, [68Ga]Ga-RM2 is a safe diagnostic agent with a significantly lower kidney dose but higher pancreas and urinary bladder doses as compared to [68Ga]Ga-PSMA.

A New In‐line Optical System for Monitoring Residence Time during Polymer Processing Along a Twin‐Screw Extruder

AbstractResidence time (RT) is an important factor in the processing of molten materials, since it strongly influences the quality of the final product. In this study, a simple and low cost optical system is developed to determine residence time of polypropylene (PP) during its processing in a TeckTrill co‐rotational twin screw extruder. The temperature profile is 90/160/180/190/190/195/195/200/200/210 °C with a screw speed of 300 rpm and a feed rate of 2.3 kg h‐1, using a commercial tracer and different screw profiles. Through the capture of images of the processed material, obtained by a webcam at the matrix output, the developed program is able to calculate the average RGB (red‐green‐blue) color of the analysis area and convert it to the HSV (hue‐saturation‐value), generating a curve of color saturation as a function of time. The results suggest that the developed optical system is a potential suitable tool for in‐line RT measurements.

Optimization of residence time distribution in RCDG and an assessment of its applicability in continuous manufacturing

Knowledge of residence time is a critical aspect in developing control and material diversion strategies for continuous manufacturing processes in pharmaceutical manufacturing. Dry granulation is a promising continuous granulation technique as it is fast and economical. In this study, a step-change method to determine residence time in roll compaction/dry granulation is introduced. The factors roll speed and rotational speed of the impeller in the powder inlet unit of the compactor were evaluated using a central composite circumscribed statistical design of experiments in order to optimize the residence time. The fill volume in the compactor was varied exemplarily. It was found that high roll speed, low rotational speed of the impeller and low fill volume in the compactor are beneficial to generate fast transition through the compactor. The impact of roll speed increase was estimated. It can be concluded that despite fast residence time in the process, high roll speed and its subsequent high material throughput can generate a large amount of material that has to be discarded if material diversion is required.

LIF or dye: Comparison of different tracing methods for granular solids

Determination of residence time distribution is considered essential for continuous pharmaceutical unit operations, in order to enable process understanding and control. A common way for determining residence times are tracer based methods, yet at the moment most realizations are found in liquid systems whereas use of those methods on granular samples is rarely encountered.Here, we compare two different methods for applying and detecting tracers in granular material processed in a pharmaceutical capsule-filling unit. As first method, a simple colorimetric procedure, i.e. using a dye and a camera as photometer is used. As second method, light induced fluorescence, i.e. using a fluorescent tracer material, a stimulating source and the camera as photometer again, is used.Both methods are tested and compared for their performance and appeared to be sufficient for the use in residence time distribution determination, yet none of the two proved to be superior. Consequently, side issues rather than analytic performance determined the final preference for the colorimetric method.

Biodistribution and post-therapy dosimetric analysis of [177Lu]Lu-DOTAZOL in patients with osteoblastic metastases: first results

BackgroundPreclinical biodistribution and dosimetric analysis of [177Lu]Lu-DOTAZOL suggest the bisphosphonate zoledronate as a promising new radiopharmaceutical for therapy of bone metastases. We evaluated biodistribution and normal organ absorbed doses resulting from therapeutic doses of [177Lu]Lu-DOTAZOL in patients with metastatic skeletal disease.MethodFour patients with metastatic skeletal disease (age range, 64–83 years) secondary to metastatic castration-resistant prostate carcinoma or bronchial carcinoma were treated with a mean dose of 5968 ± 64 MBq (161.3 mCi) of [177Lu]Lu-DOTAZOL. Biodistribution was assessed with serial planar whole body scintigraphy at 20 min and 3, 24, and 167 h post injection (p.i.) and blood samples at 20 min and 3, 8, 24, and 167 h p.i. Percent of injected activity in the blood, kidneys, urinary bladder, skeleton, and whole body was determined. Bone marrow self-dose was determined by an indirect blood-based method. Urinary bladder wall residence time was calculated using Cloutier’s dynamic urinary bladder model with a 4-h voiding interval. OLINDA/EXM version 2.0 (Hermes Medical Solutions, Stockholm, Sweden) software was used to determine residence times in source organs by applying biexponential curve fitting and to calculate organ absorbed dose.ResultsQualitative biodistribution analysis revealed early and high uptake of [177Lu]Lu-DOTAZOL in the kidneys with fast clearance showing minimal activity by 24 h p.i. Activity in the skeleton increased gradually over time. Mean residence times were found to be highest in the skeleton followed by the kidneys. Highest mean organ absorbed dose was 3.33 mSv/MBq for osteogenic cells followed by kidneys (0.490 mSv/MBq), red marrow (0.461 mSv/MBq), and urinary bladder wall (0.322 mSv/MBq). The biodistribution and normal organ absorbed doses of [177Lu]Lu-DOTAZOL are consistent with preclinical data.Conclusion[177Lu]Lu-DOTAZOL shows maximum absorbed doses in bone and low kidney doses, making it a promising agent for radionuclide therapy of bone metastasis. Further studies are warranted to evaluate the efficacy and safety of radionuclide therapy with [177Lu]Lu-DOTAZOL in the clinical setting.

Partial residence times: determining residence time composition in different subregions

Residence time (RT) is a diagnosis widely used to quantify the water exchange rate and mass transport timescale in semi-enclosed systems. The RT focuses on only the total time a water parcel spends in a system (i.e., control region). However, for a system that consists of several subregions (e.g., sub-bays or functional zones), the RT will not include information about the time spent in different subregions. To determine the RT compositions in different subregions, partial residence times (PRTs) are proposed and defined as the amount of time a water parcel spends in different subregions until leaving the control region. The equations for PRTs are derived using the adjoint method, which can quickly determine the variation of PRTs in time and space. To validate the PRT diagnostic equation and numerical model, a test is conducted in an idealized 1D channel with idealized tidal currents. The numerical results are in excellent agreement with the analytical solution. Finally, the PRT method is applied to tide-dominated Jiaozhou Bay. The PRTs in six functional subregions of Jiaozhou Bay are derived, and the detailed RT compositions of the different functional subregions are presented. The application indicates that PRTs could provide detailed information and new insights into the water exchange process.

An experimental study on single drop rising in a low interfacial tension liquid–liquid system

Terminal velocity of liquid drops is one of the key parameters in liquid–liquid extraction column design. It is important in determining residence time, droplet lifetime, and mass transfer rate. In present paper, the rising behavior of a single drops were investigated in a low interfacial tension system by high speed camera. An n-butanol/water system was used as test system. Correlations for terminal velocity were evaluated and compared, both explicitly and implicitly. Moreover, the influence of salt addition in aqueous phase was also studied, including salt concentrations and types. A Weber–Reynolds correlation was derived on the basis of experimental data. Drag coefficient was then calculated and showed a good agreement compared to the correlations in literatures.

Ensemble-Based Steered Molecular Dynamics Predicts Relative Residence Time of A2A Receptor Binders.

Drug-target residence time, the length of time for which a small molecule stays bound to its receptor target, has increasingly become a key property for optimization in drug discovery programs. However, its in silico prediction has proven difficult. Here we describe a method, using atomistic ensemble-based steered molecular dynamics (SMD), to observe the dissociation of ligands from their target G protein-coupled receptor in a time scale suitable for drug discovery. These dissociation simulations accurately, precisely, and reproducibly identify ligand-residue interactions and quantify the change in ligand energy values for both protein and water. The method has been applied to 17 ligands of the A2A adenosine receptor, all with published experimental kinetic binding data. The residues that interact with the ligand as it dissociates are known experimentally to have an effect on binding affinities and residence times. There is a good correlation ( R2 = 0.79) between the computationally calculated change in water-ligand interaction energy and experimentally determined residence time. Our results indicate that ensemble-based SMD is a rapid, novel, and accurate semi-empirical method for the determination of drug-target relative residence time.

Heterogeneous Activation, Local Structure, and Softness in Supercooled Colloidal Liquids.

We experimentally characterize heterogeneous nonexponential relaxation in bidisperse supercooled colloidal liquids utilizing a recent concept called "softness" [Phys. Rev. Lett. 114, 108001 (2015)PRLTAO0031-900710.1103/PhysRevLett.114.108001]. Particle trajectory and structure data enable classification of particles into subgroups with different local environments and propensities to hop. We determine residence times t_{R} between particle hops and show that t_{R} derived from particles in the same softness subgroup are exponentially distributed. Using the mean residence time t[over ¯]_{R} for each softness subgroup, and a Kramers' reaction rate model, we estimate the activation energy barriers E_{b} for particle hops, and show that both t[over ¯]_{R} and E_{b} are monotonic functions of softness. Finally, we derive information about the combinations of large and small particle neighbors that determine particle softness, and we explicitly show that multiple exponential relaxation channels in the supercooled liquid give rise to its nonexponential behavior.

Structure and composition of rhodoliths from the Amazon River mouth, Brazil

Rhodolith beds are one of the main habitats of the Brazilian Equatorial Margin continental shelf due to their wide extent and provision of ecosystem services. Northern, Central and Southern zones of the Amazon River mouth were sampled between water-depths of 23 and 120 m, covering a continental shelf area of 9500 km2, to characterize the structure and composition of rhodoliths along depth gradients and related river plume influence. The deepest rhodoliths consist of a thin algal/bryozoan/encrusting foraminifer cover around relatively large nuclei that determine the nodule size and shape. At 120-m depth in the Northern zone the nuclei are made of fragments of invertebrate boundstone or oolite rudstone, whereas at 100-m depth in the Central zone the nuclei consist of sandstone clasts. In both cases, the nuclei are fragments of sedimentary rocks that accumulated on the outer shelf during significantly lower sea level. Low-light levels prevent substantial growth of the algal cover around the nuclei. Reduced illumination an d high nutrient levels led to the composition of rhodoliths at 95-m depth in the Northern zone, predominantly built by bryozoans with subordinate coralline algae around small bioclastic nuclei. In the Central zone at 50–55 m depths, coralline algae are the main components of mostly sub-spheroidal rhodoliths. They have relatively recent ages of hundreds of years or show two phases of growth with the older phase beginning 1300 years ago and then being interrupted from about 1000 years BP to 600 years BP. All this suggests relatively high burial rates due to sediment flux, changing in time to favor exhumation after burial in some instances. The rhodoliths from 23 m in the Southern zone are growing under a low influence of the river plume and have the highest diversity of coralline algae and other builders. The rhodolith structure in the different sampling zones and depths reflects plume influence on light penetration, nutrient and organic matter levels, and sedimentation on the shelf, determining residence times of rhodoliths on the seafloor before burial.

Comprehensive mucoadhesive study of anionic polymers and their derivate

AimThe purpose was to compare the mucoadhesive properties of well-known anionic polymers such as alginate (AL), carboxymethyl cellulose (CMC), polycarbophil (PC) and hyaluronic acid (HA) with regards to potential improvement in mucoadhesiveness based on chemical modification. MethodsAL, CMC, PC and HA, respectively, were modified with sulfhydryl groups of cysteine (CYS) on their polymeric backbone via amide bond formation. Viability and safety was evaluated on mucosal surface. Histology imaging was taken via H&E staining. Intense mucoadhesive studies were performed on mucosal tissue determining residence time, adhesion and total work of adhesion as well as maximum detachment force of unmodified and modified polymers, respectively. ResultsBoth polymers, unmodified anionic and modified ones, exhibit no toxicity at all. Histology imaging was in good agreement with the viability study on the mucosal surface. Unmodified anionic polymers reveal limited mucoadhesiveness whereas modified polymers showed up to 2.18-fold, 2.77-fold, 16.29-fold and 59.23-fold more pronounced total work of adhesion in case of CMCCYS, HACYS, PCCYS and ALCYS, respectively. ConclusionThis comprehensive study provides deep understanding for the appropriate choice of mucoadhesive excipient for the development of mucosal drug delivery systems.

Phosphate slurry RTD - Effect of the radiotracer choice

To determine residence time distribution (RTD) in the phosphate treatment reactor we apply radiotracer method. However this method becomes effective and profitable only if the radiotracer is the suitable one. The problem to resolve in our study is “which phase of the phosphate slurry our injected radiotracer is following?”. For that we add radiotracer to the phosphate slurry and we proceed to phase separation using a filtration system. We follow simultaneously -using appropriate detectors- the behavior and the quantity of the radiotracer in both phases during the separation stage. The same experiment is applied twice using successively 99mTc and 131I radiotracers. The comparative study proves that 131I is more suitable than 99mTc for solid phase labeling of phosphate slurry.

Numerical simulation of micromixing effect on the reactive flow in a co-rotating twin screw extruder

To control the multicomponent reactions in extrusion, reactive-mixing flow in a co-rotating twin screw extruder was numerically studied in the present paper. Effects of initial species distribution, rotating speed and flow rate on a competitive-parallel reaction were investigated and the relationship between mixing and reactions was discussed from the view of chemical reaction engineering. The simulation results show the studied operational parameters, which determine residence time distribution, earliness of mixing and segregation degree of reactive-mixing flows, affect the local species concentration and reaction time and hence have significant influences on the reaction extent. Orthogonal test was adopted to clarify the significance of operational parameters. The analysis shows that initial species distribution and flow rate are the most important factors in the control of reaction extent, and effect of rotating speed is conditional depending on the micro-mixing status of the fluid.

Human Radiation Dosimetry for the N-Methyl-D-Aspartate Receptor Radioligand 11C-CNS5161.

(11)C-CNS5161 (N-(2-chloro-5-methylthiophenyl)-N'-(3-methylthiophenyl)-N'-(11)C-methylguanidine) has been successfully used in PET imaging of N-methyl-d-aspartate (NMDA) receptors. However, no human dosimetry data have been published. We are planning to use this radiotracer for investigating NMDA receptor function in systemic lupus erythematosus, traumatic brain injury, and Parkinson disease. We have therefore undertaken (11)C-CNS5161 PET imaging to measure the whole-body distribution of this radionuclide and to estimate radiation dose to various organs. Dynamic PET studies of the whole body were performed on 5 healthy adults. Regions of interest were drawn over the visualized structures. Resultant time-activity curves were generated and used to determine residence times for dosimetry calculations. S factors were implemented within the OLINDA/EXM software for each structure or organ. For (11)C-CNS5161, organ doses ranged from 0.0002 to 0.0393 mGy/MBq (0.0006-0.1455 rad/mCi). The critical organ for radiation burden was the lungs, with a dose of 0.0393 mGy/MBq (0.1455 rad/mCi). Radiation doses to the reproductive and blood-forming organs were 0.0023, 0.0002, and 0.0020 mGy/MBq (0.0086, 0.0006, and 0.0074 rad/mCi) for the ovaries, testes, and red marrow, respectively. The effective dose equivalent was 0.0106 mSv/MBq (0.0392 rem/mCi). The radiation dosimetry for (11)C-CNS5161 for a standard single injection of 555 MBq (15 mCi) will result in an effective dose equivalent of 5.9 mSv (0.59 rem) and a lung dose of 21.8 mGy (2.18 rad) in young, healthy subjects.