Pure Volume Research Articles

Origin of the metamagnetic transitions in Y1−xErxFe2(H,D)4.2 compounds

The structural and magnetic properties of Y1−xErxFe2 intermetallic compounds and their hydrides and deuterides Y1−xErxFe2H(D)4.2 have been investigated using X-ray diffraction and magnetic measurements under static and pulsed magnetic field up to 60 T. The intermetallics crystallize in the C15 cubic structure (Fd-3m space group), whereas corresponding hydrides and deuterides crystallize in a monoclinic structure (Pc space group). All compounds display a linear decrease of the unit cell volume versus Er concentration; the hydrides have a 0.8% larger cell volume compared to the deuterides with same Er content. They are ferrimagnetic at low field and temperature with a compensation point at x = 0.33 for the intermetallics and x = 0.57 for the hydrides and deuterides. A sharp first order ferromagnetic-antiferromagnetic (FM-AFM) transition is observed upon heating at TFM−AFM for both hydrides and deuterides. These compounds show two different types of field induced transitions, which have different physical origin. At low temperature (T < 50 K), a forced ferri-ferromagnetic metamagnetic transition with Btrans1 ≈ 8 T, related to the change of the Er moments orientation from antiparallel to parallel Fe moment, is observed. Btrans1 is not sensitive to Er concentration, temperature and isotope effect. A second metamagnetic transition resulting from antiferromagnetic to ferrimagnetic state is also observed. The transition field Btrans2 increases linearly versus temperature and relates to the itinerant electron metamagnetic behavior of the Fe sublattice. An onset temperature TM0 is obtained by extrapolating TFM−AFM (B) at zero field. TM0 decreases linearly versus the Er content and is 45 ± 5 K higher for the hydrides compared to the corresponding deuteride. The evolution of TM0 versus cell volume shows that it cannot be attributed exclusively to a pure volume effect and that electronic effects should also be considered.

Gas hydrates porosity and effective volume under multiphase flow conditions

Gas hydrate is a severe flow assurance problem in oil and gas production. Hydrate formation is a phase transition of systems containing small guest molecules and water molecules. Traditionally the industry handles hydrate challenges by keeping the systems out of the hydrate forming region. Due to the high costs, the industry is turning to hydrate slurry management, which does not prevent hydrate formation but focus on dispersing hydrate as solid particles and generating a transportable slurry. The hydrate slurry management requires a good prediction of the hydrate slurry transportability to manage the risks associated with the presence of solids, including its potential accumulation along the flowline. Hydrate slurry is a multiphase flow system with solids. On the macroscale, the porosity and effective volume of hydrate matrix are important variables to predict the overall system transportability. Despite their importance, they have not been widely discussed in the open literature. In this article, we report the hydrate formation results of different multiphase flow systems to highlight the importance of hydrate porosity and effective volume. Our results show that water, oil, and gas can all be trapped into the hydrate matrix, resulting a highly porous structure without and with additives, such as anti-agglomerants. The effective solid volume in our study was 3–10 times as large as the calculated pure hydrate volume. Our results suggest that the porosity is necessary in the multiphase models to better capture the physical characteristics and characterize the flow assurance risks.

Efficiency of activated carbon prepared from scrap tires magnetized by Fe3O4 nanoparticles: characterisation and its application for removal of reactive blue19 from aquatic solutions

ABSTRACT Huge quantities of different dyes are generated by various industries such as cosmetic, leather, printing and textile and food. This study aimed to generate and apply tire-derived activated carbon magnetised with the Fe3O4 nanoparticles (MAC) for the removal of reactive blue 19 (RB19) dye from aquatic solutions. FE-SEM, VSM, XRD, FTIR and BET analyses were used to determine MAC properties. Under optimal conditions of pH 3, the initial concentration of dye 100 mg/L, the composite dose 1 g/L and the reaction time of 45 min, the removal efficiency for RB19 was 93.22%. Isotherm findings illustrated that RB19 adsorption onto the MAC followed the Langmuir model. Moreover, the absorption kinetics is well interpreted by the pseudo-second-order model in low scrutinised concentrations. The SBET and total pure volume for the MAC were 421.11 m2 g−1 and 0.467 cm3 g−1. Under the optimum conditions, maximum adsorption capacity of the MAC in Langmuir model enhanced to the amount of 119.05 mg/g. Also, the reusability (with NaOH) of the MAC revealed about 21% decreases in the removal efficiency within five consecutive runs. It is concluded that the application of the magnetised activated carbon due to its high efficiency in removing RB19 from laboratory and actual samples can be evaluated in future studies to be utilised in real scales.

Investigations on the Influence of Chemical Compounds on Fog Microphysical Parameters

Lab experiments related to artificial fog studies are limited due to instrument sensitivity to small fog and aerosol particles; therefore, the goal of this work is to evaluate aerosol solute effects on fog physical properties in a lab environment. To reach the goal, an automated fog-generating system was designed and that includes controlled chemical compounds dissolved in pure water. In the analysis, the impact of changing the mass concentration of potassium dihydrogen phosphate—KH2PO4, urea-CO(NH2)2, and potassium hexacyanoferrate trihydrate-K3(Fe(CN)6) on fog droplet size spectra is studied, because visibility is directly related to fog droplet spectra and aerosol composition. In the experiment, various microphysical conditions, including fog droplet size and volume concentration, were analyzed as a function of changing aerosol composition/spectra and fixed thermodynamic conditions. The results showed that fog droplet size spectra vary with the addition of chemical impurities to the pure water volume. For example, increasing KH2PO4 concentration compared to distilled water volume resulted in a higher mean particle size, which led to faster droplet settlement, and that resulted in cleaning air more efficiently compared to pure water fog. Overall, both issues and challenges of the experimental fog generating system with respect to water and aerosol solutions resembling CRBN (chemical, radiological, biological, and nuclear agents) characteristics are provided and evaluated.

Application of low-cost material for adsorption of dye from aqueous solution

ABSTRACT Cationic dyes are one of the aromatic compounds that cause major environmental problems. The adsorption process has attracted a lot of attention in recent years. In this study, the seeds were used as a low-cost adsorbent for the removal of cationic Blue 41 dye from aquatic environments. The studied parameters included the effect of adsorbent dosage, pH of the solution, contact time, and the initial concentration of Cationic Blue 41 dye. The removal efficiency in optimal conditions for Cationic Blue 41 with Salvia seeds (concentration = 50 mg/L, dose = 2 g/L, reaction time = 120 min and pH = 9) was obtained 70%. The data were evaluated using Freundlich and Langmuir methods. The structure and characteristics of the seeds were determined by Field Emission Scanning Electron Microscopy (FESEM), Fourier Transform Infrared Spectroscopy (FT-IR) and Brunauer-Emmett-Teller (BET) techniques. The SBET and total pure volume for the Salvia seeds were 3.053 m2/g and 0.684 cm3/g. The results showed that the adsorption process follows Langmuir model with an adsorption capacity of 19.16 mg/g. According to the result of the pseudo-first and pseudo-second kinetic study, it was found that the process of dye adsorption on the low-cost seeds best described by pseudo-second kinetic. The findings showed that the Salvia seeds can be used as a natural absorbent, environmentally friendly and affordable treatment for water and wastewater, especially those containing cationic dyes.

Beam and installation improvements of the NIO1 ion source.

The NIO1 (Negative Ion Optimization phase 1) source can provide continuous beam operation, which is convenient for systematic parameter and equipment studies. Even in the pure volume production regime, the source yield was found to depend on conditioning procedures. Magnetic configuration tests continued adding magnets to the existing setup; the filter field component Bx has been progressively extended to span the -12 to 5 mT range, and as a trend, source performances improved with |Bx|. The progress of camera beam diagnostics and of the quality of the volume-produced H- beam is also shown. The status, off-line results, and reliability of a first NIO1 cesium oven are discussed; other upgrades in preparation (cavity ring down spectrometer, the end calorimeter, and conceptual tests of the energy recovery system) are also listed.

Density Functional Study of the Electronic, Elastic and Optical Properties of Bi2O2Te

Abstract Layered crystal Bi2O2Te has recently been found to have high electron mobility and excellent thermoelectric properties for technical applications; however, its other properties are not well studied yet. In this work, the electronic, elastic and optical properties of Bi2O2Te are systematically studied using the density functional method. The results indicate that Bi2O2Te is a narrow band gap semiconductor. The gap is formed by the Te 5p orbital at the top of the valence band and the Bi 6p orbital at the bottom of the conduction band. There are both ionic and covalent interactions within the Bi–O layers, and these layers are linked by the ionic Bi–Te bonds forming the crystal. Bi2O2Te is mechanically stable but anisotropic. It is easy to fracture along the c axis under shear stress. Its shear modulus is far smaller than its bulk modulus, so shape deformation is easier to occur than pure volume change. Its melting point is predicted to be 1284.0 K based on an empirical formula. The calculated refractive index at zero frequency reveals that Bi2O2Te is a negative uniaxial crystal with a birefringence of 0.51, making it a potential tuning material for optical application. The characteristics and origins of other optical properties are also discussed.

Permeability improvements of an outburst‐prone coal seam by means of presplitting and blasting with multiple deep boreholes

AbstractCoalbed methane, which is a significant potential unconventional source of energy, exhibits considerable challenges in the implementation of the exploration and production process, especially the degasification in low permeability of coal seams with high gas concentrations. Due to the difficulties in gas extraction, long mining period and low extraction concentration in soft and outburst coal seams, the permeability improvement method using presplitting and blasting technology with multiple boreholes has been proposed and applied to improve the permeability of soft coal seam, which is achieved by optimizing the inseam distribution of generated fractures through multiple control boreholes. Research results showed that the permeability improved by presplitting and blasting with deep boreholes is 2.5 times higher than that of the original coal seam. Within 6 days of extraction, the average extraction concentration and pure volume of the extraction borehole were 40.13% and 0.113 m3/min, respectively, which are 2.9 times and 4.1 times higher than the original data, respectively. Likewise, the average extraction concentration and purity of the extraction hole were 21.75% and 0.063 m3/min after being extracted within 14 days, which is twice and three times higher than that of the original average extraction concentration and purity volume, respectively. Besides, proposed technology has a little influence on the methane concentration of the coal seam 70 m ahead of the heading face. The research results promote the prevention and control of coal‐gas outburst in low permeability and high gas concentration coal seams.

Forest Height Estimation Using PolInSAR Optimal Normal Matrix Constraint and Cross-Iteration Method

A novel method based on the optimal normal matrix constraint and cross-iteration algorithm is proposed in this letter to estimate the forest height using the polarimetric interferometry synthetic aperture radar (PolInSAR) data. First, to avoid the null ground-to-volume ratio assumption of the three-stage method, we use the PolInSAR optimal normal matrix constraint method to find out the pure volume coherence. This method can also provide a more accurate initial value for the least-squares iteration. Second, the cross-iteration is used for the forest height inversion, which provides better selection of the best polarization channel and solves the ill-conditioned matrix in the traditional least-squares iteration algorithm. This new method is validated using the BioSAR 2008 P-band data. The results show that the proposed method achieves an average accuracy of 2.6 m, which is better than that of the three-stage inversion method [root-mean-square error (RMSE) = 5.89 m] and the 6-D nonlinear iteration method (RMSE = 4.42 m).

Polymer Brushes Immersed in Two-Component Solvents with Pure Volume Exclusion: Effect of Solvent Molecular Shape

Polymer brushes have wide application in surface modification. We study dense, short polymer brushes immersed in a mixing solvent under athermal conditions using the classical density functional theory. The brush polymer is short so that the equilibrium behavior of the brush deviates far from the scaling laws for infinite brush chains. The excluded volume interaction is the only interaction in the system. We compare the excluded volume effect of solvent molecules of different shapes. Two types of mixing solvents are considered: solvent composed of linear oligomers and monomers, or that of spherical particles and monomers. The effects of grafting density, solvent molecular size, and solvent number density on the brush height, the density profiles, the relative excess adsorption, and the brush–solvent interface width are systematically analyzed. In the adsorption aspect, the spherical particles have stronger ability than the linear oligomers do to penetrate through the brush layer and gather at the substrate. In the screening aspect, the oligomers are more capable of screening the excluded volume interaction between the brush chains than the spherical particles. The brush–solvent interface width decreases monotonically with increasing oligomer length, but it has a minimum with the increasing spherical particle size. Our research differentiates the attractive-interaction-induced phenomenon and the volume-exclusion-induced phenomenon in dense brush systems and exhibits the difference in the antifouling properties of the brushes contacting solvent molecules of different shapes.

The effect of mineral fractions on physical and phosphorus-related chemical properties of peat-based substrates for pot plants

Physicochemical traits of peat-based pot substrates prepared from mixing of 20 or 40 vol.% of some different mineral fractions (sub. 1 to 7, subjected to decreasing amount of clay content of 66.1, 61.2, 49.7, 38.5, 26.0, 23.7 and 19.4%, respectively) with black peat were evaluated and then phosphorus uptake of poinsettia (Euphorbia pulcherima) simulated mechanistically as a case study pot plant. For preparation of substrate number 8, pure peat was mixed with 40 vol.% of the same mineral component as substrate number 6 (with 23.7% clay). Result revealed that adding different mineral fractions up to 40 vol.% to pure peat, water-holding capacity and total pore volume were reduced only by 11 and 15 vol.%, respectively. It was found that keeping the moisture content of peat-based substrates with 20 vol.% of mineral soils around 60%–70%, the optimum ventilation and enough free space of about 15%–25% will be provided around the root system. In addition, simulated P uptake did not change significantly with addition of 20 vol.% of different mineral components in peat-based substrates. As a result, P uptake mainly was dependent on the amount of plant available P level than different mineral fractions.

Application of Blood Oxygenation Level-Dependent Magnetic Resonance Imaging and Intravoxel Incoherent Motion to Assess Bilateral Renal Pathophysiological Processes Induced by Iodixanol Renal Artery First-Pass in Rabbit Model.

Noninvasive blood oxygen level-dependent imaging and intravoxel incoherent motion sequences were used to assess bilateral renal oxygenation, hemodynamics, and proton diffusion in iodixanol renal artery first-pass in rabbit model. Forty-two rabbits were divided into 2 groups. Saline and iodixanol (1 g iodine/kg, left renal artery) were administered. Magnetic resonance imaging scans were acquired longitudinally at 24 hours prior to and 1, 24, 48, and 72 hours after administration to assess apparent diffusion coefficient, pure molecular diffusion (D), perfusion-related diffusion (D*), volume fraction (f), and relative spin-spin relaxation rate (R2*) values, respectively. The experiment evaluated serum creatinine, histological, and hypoxia-inducible factor 1α immunoexpression. During 1 to 48 hours, the values of D, f, and D* significantly decreased (P < 0.05), but R2* values significantly increased (P < 0.05) in cortex, outer medulla, and inner medulla after administration of iodixanol through left renal artery, which showed in the 72 hours. The change of the left kidney is noteworthy. Significant negative correlations were observed between apparent diffusion coefficient, D, f, and R2* in cortex, outer medulla, and inner medulla (all P < 0.001, r = -0.635-0.697). The first-pass effect of the contrast agent significantly reduces ipsilateral renal perfusion and renal oxygenation, and noninvasive monitoring can be performed by using blood oxygen level-dependent magnetic resonance imaging and intravoxel incoherent motion.

Limits on Transformation Strains for Non-Negative Dissipation

Abstract We consider the maximum value of the magnitude of transformation strain for an Eshelby inclusion set by the requirement of non-negative dissipation. The general formulation for a linear elastic solid shows that the dissipation associated with a strain transformation can be calculated as an integral over the transformed inclusion. Closed-form expressions are given for the maximum transformation strain magnitude in an isotropic linear elastic solid for both cylindrical and spherical inclusions that have undergone transformations corresponding to either a pure volume (or area) change or a pure shear. Most results presented are for transformations in an infinite solid and presume uniform material properties. Examples of the effect of a finite boundary and of differing material properties inside and outside the transformed inclusion are also given. The analytical results indicate that non-negative dissipation typically limits the transformation strain to being a constant of order unity times the critical stress at transformation divided by a relevant elastic modulus.

Transcranial Doppler and Hematoma Expansion in Acute Spontaneous Primary Intracerebral Hemorrhage.

Context:The data on the role of Transcranial Doppler (TCD) in the management of acute primary intracerebral hemorrhage (ICH) is meager.Aims:To study TCD variables associated with hematoma expansion in acute primary ICH.Settings and Design:The study was carried out in the neurosciences department of Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh from July 2010 to September 2011 employing a prospective, double blinded non randomized study design.Materials and Methods:Acute ICH patients within 24 h of symptom onset were recruited. Baseline neuroimaging study (Computerized tomography, CT scan of brain) was performed to assess the pure hematoma volume by AXBXC/2 method. Baseline TCD parameters were obtained from both the middle cerebral arteries (MCAs; affected and unaffected hemisphere): Peak Systolic velocity, End Diastolic velocity, Mean Flow velocity, Resistance Index, and Pulsatility Index. Follow up (24 h) assessment of hematoma volume and TCD were carried out. Each of the TCD variables were compared in hematoma expansion (>33% increase in hematoma volume on the follow-up CT) and non-expansion group.Statistical analysis:On univariate analysis, the Student's t-test and contingency tables with the X2 test were used. A forward stepwise multivariate logistic regression analysis with hematoma expansion at 24 h as the dependent variable and ROC analysis was carried out, using SPSS software version 16 (Chicago, IL). P value < 0.05 was considered significant.Results:Twenty-five patients completed the study. Ten patients (40%) had hematoma expansion. Multivariate analysis revealed unaffected hemisphere MCA Pulsatility Index ratio [unaffected hemisphere MCA Follow up Pulsatility Index/baseline Pulsatility Index] of > 1.055 as the lone correlate of hematoma expansion (sensitivity of 90% and specificity of 60%).Conclusion:Frequent assessment with TCD could aid in prediction of hematoma expansion by measuring unaffected hemisphere Pulsatility Index ratios.

Synthesis of mesoporous Fe-Mn bimetal oxide nanocomposite by aeration co-precipitation method: Physicochemical, structural, and optical properties

Abstract Fe-Mn bimetal oxide nanocomposite was synthesized by a new aeration co-precipitation method. For this purpose, the Fe3+ and Mn3+ in a molar ratio of 2:1 were simultaneously precipitated in the presence of excess oxygen. The physicochemical, structural and optical properties of the synthesized nanocomposite were investigated by Field Emission Scanning Electron Microscope (FESEM), Energy Dispersive X-ray analysis (EDX), X-Ray Diffraction (XRD), X-Ray Fluorescence (XRF), Brunauer–Emmet–Teller (BET), and UV–Visible analysis. The FESEM images showed that the synthesized nanocomposite had a dominant spheroid-like shape and homogeneous morphological structure with many aggregated nanocomposite and rough surfaces. The average size of synthesized nanocomposite was 13.75 nm with a range of 10.33–17.48 nm. The EDX analysis confirmed the presence of Fe (25.23 wt%) and Mn (21.55 wt%) in the nanocomposite. The XRF analysis showed that the Fe-Mn nanocomposite contained 49.83% Fe2O3 and 29.36% Mn2O3. The XRD analysis confirmed that the nanocomposite had two peaks at 32.9° and 36.5°, which were respectively related to Mn2O3 and Fe2O3. UV–Vis absorption peaks of Fe-Mn nanocomposite was between 358 and 369 nm and the band gap energy was 2.06 eV. The BET specific surface area and pore volume of the nonocomposite were 244.79 m2/g and 0.6633 cm3/g, respectively. So, considering the spherical, uniform, and mesoporous structure with large surface area and pure volume, the aeration-co-precipitation, as an appropriate synthesis method, is suitable to synthesize Fe-Mn bimetal nanocomposite that can be widely used as a catalyst in photocatalytic oxidation or can be applied as a nano-adsorbent to remove pollutants from the contaminated water.

A bordo do Guaspari

This article presents part of the process of the modernity of the city of Porto Alegre in the mid-1930s through the analysis of the Guaspari building, designed by Fernando Corona in 1936, and the overlapping of times throughout the existence of this building. The great event of the Farroupilha Revolution’s Centennial Exhibition in 1935 and the construction of buildings with pure volumes and facades devoid of ornamentation are some of the indications of the arrival of the new times in the capital of Rio Grande do Sul. The Guaspari building has a light of its own that condenses the spirit of the thirties, as one of the reminiscences of the Exhibition’s ephemeral pavilions, remaining in the imaginary of the city. The reference of the ship was present both in the architecture of Le Corbusier and in expressionism, particularly in the works of Mendelsohn. With more or less intensity, the Guaspari building resembles naval engineering, with the intention of translating the laws of motion architecturally, as if they were floating in the sea of the flow of people and cars or accompanying their movement. The history of the Guaspari building has three phases: the first consists in the elaboration, articulation of references, approval and construction of the architectural project – anchored; the second registers the building submerged in luxalon for a long period, totally unrecognizable – covered; and the third registers the resurgence of the Guaspari building in center of Porto Alegre – in sight. Keywords: Fernando Corona, Guaspari Building, modern architecture in Porto Alegre.

Numerical investigation of indirect freeze desalination using an ice maker machine

To overcome the water shortage problem, sea water desalination is a prospective answer in order to cater for the escalating demand for fresh water. Freeze desalination is where the freezing of sea water permits the separation of salts from the water in order to produce potable water. The ice formed is of pure water as the ice crystal lattice prevents the inclusion of any salts. The lower energy usage of freeze desalination in comparison to other desalination processes is the key advantage; as the latent heat of fusion (333.5 kJ/kg) is about 1/7th that of the latent heat of vaporisation (2256.7 kJ/kg). CFD ANSYS fluent software has been used to simulate the freeze desalination process; results were compared with experimental tests showing a maximum deviation of 0.93% for the temperature change during the ice forming process and the percentage errors obtained for the salinities of ice and brine were 15% and 10.5% respectively. From parametric analysis study, results showed that, as the freezing temperature reduces, the volume of the generated ice block increases, where at 225 K freeze temperature, 5 times more ice was produced compared to that at 257.15 K, but with a high salinity level of 3.02%. Results also showed that the lowest average salinity achieved was 0.5% at an ice layer thickness of around 4 mm using a freezing temperature of 245 K. This is higher than the 0.1% salinity level recommended by the World Health Organization (WHO) standards as safe to drink water. Therefore, a second stage freezing process was applied to this 0.5% saline water to produce the required salinity level. Results showed that the achieved average ice salinity in the second stage of freezing process was below 0.05% which is regarded as good quality drinking water; also freezing at 225 K temperature produced the largest pure ice volume. These results highlight the potential of using freeze desalination to produce drinking water.

From Bedside to Bench: The Effect of Muscular Denervation on Fat Grafting to the Breast by Comparing Take Rate, Quality, and Longevity.

Autologous fat grafting (AFG) to the breast is a frequent procedure in aesthetic and reconstructive surgery. Despite pure volume gain, questions remain regarding the engraftment rate, quality, and longevity. Little is known about the role of recipient tissue or innervation of the grafted area. The goal of this study was to determine the optimal recipient layer and muscular pretreatment of AFG. Fat was grafted to the breast, pectoralis muscle, or adjacent subcutaneous tissue of 42 rats. Nerve treatment included excision of a nerve segment, botulinum toxin (BTX) injection, or no treatment. Magnetic resonance imaging (MRI) and histological workup were carried out after 2 and 6 weeks. Six weeks after AFG, the proportion of viable fat cells within the grafted fat stayed high (median, [IQR]: 81% [72% to 85%]). The signs of inflammation decreased over time. Intramuscular grafting with intact nerves had a decreasing effect on the viability of the grafted cells compared with subcutaneous treatment (-10.21%; 95% confidence interval [-21.1 to 0.68]). If utilized on an intact nerve, intramuscular injection may lead to inferior results. If the nerve was cut or treated with BTX; however, intramuscular injection tends to be superior. These findings may prove interesting for future studies and eventual clinical application.

Some Insights About the Small Ball Probability Factorization for Hilbert Random Elements

Asymptotic factorizations for the small-ball probability (SmBP) of a Hilbert valued random element $X$ are rigorously established and discussed. In particular, given the first $d$ principal components (PCs) and as the radius $\varepsilon$ of the ball tends to zero, the SmBP is asymptotically proportional to (a) the joint density of the first $d$ PCs, (b) the volume of the $d$-dimensional ball with radius $\varepsilon$, and (c) a correction factor weighting the use of a truncated version of the process expansion. Moreover, under suitable assumptions on the spectrum of the covariance operator of $X$ and as $d$ diverges to infinity when $\varepsilon$ vanishes, some simplifications occur. In particular, the SmBP factorizes asymptotically as the product of the joint density of the first $d$ PCs and a pure volume parameter. All the provided factorizations allow to define a surrogate intensity of the SmBP that, in some cases, leads to a genuine intensity. To operationalize the stated results, a non-parametric estimator for the surrogate intensity is introduced and it is proved that the use of estimated PCs, instead of the true ones, does not affect the rate of convergence. Finally, as an illustration, simulations in controlled frameworks are provided.

Bendamustine–PAMAM Conjugates for Improved Apoptosis, Efficacy, and in Vivo Pharmacokinetics: A Sustainable Delivery Tactic

Successful delivery of a chemotherapeutic agent like bendamustine still remains a challenge in clinical conditions like chronic lymphatic leukemia (CLL), non-Hodgkin lymphoma (NHL), and multiple myeloma. We have conjugated bendamustine to polyamidoamine (PAMAM) dendrimers after conjugating with N-(hydroxyethyl)maleimide (spacer) via an ester bond. The particle size of PAMAM-bendamustine conjugate was 49.8 ± 2.5 nm. In vitro drug release resulted in sustained release with improved solution stability of drug up to 72 h. In a 24 h cytotoxicity study by MTT assay against human monoblastic leukemia cells (THP-1), the IC50 value for PAMAM-bendamustine was 32.1 ± 4.8 μM compared to 50.42 ± 3.4 μM and 2303 ± 106.5 μM for bendamustine and PAMAM dendrimer, respectively. Significantly higher cell uptake and apoptosis were observed in THP-1 cells by PAMAM-bendamustine conjugate which was confirmed by flow cytometry and confocal laser scanning microscopy. Preliminary in vivo studies undertaken included pharmacokinetics studies, organ distribution studies, and tumor inhibition studies. In healthy Wistar rat model (1CBM IV push model), the pharmacokinetic studies revealed that bioavailability and t1/2 increased significantly, i.e., almost 8.5-fold (193.8 ± 1.116 vs 22.8 ± 0.158 μg mL-1/h) and 5.1-fold (0.75 ± 0.005 vs 3.85 ± 0.015 h), respectively, for PAMAM-bendamustine conjugate compared to pure bendamustine ( p < 0.05), however, clearance and volume of distribution were found to be decreased compared to those of free drug. The study suggests that PAMAM-bendamustine conjugate was not only stable for the longer period but also least toxic and highly taken up by THP-1 cells to exert an anticancer effect at the reduced dose. Tumor inhibition and biodistribution studies in tumor-bearing BALB/c mice revealed that PAMAM-bendamustine conjugate was more effective than the pure drug and showed higher accumulation in the tumor.