Absence Of Aggregation Research Articles

Impact of pneumatic tube transportation on the aggregation of monoclonal antibodies in clinical practice

Postproduction handling and in-hospital transportation of antibody drugs cause mechanical stress, including interfacial and shear stress, that can induce antibody unfolding and aggregation. The handling practices differ significantly between hospitals and the impact on protein stability is unknown. For example, the mechanical stress caused by transport via pneumatic tube systems (PTS) on therapeutic antibody aggregation is a potential safety and quality gap.The aim of this study was to investigate whether mechanical stress and PTS transportation in a hospital cause aggregation of five commonly used antibody drugs diluted in infusion bags.Orthogonal analytical methods showed that the handling and PTS transportation in this hospital did not cause aggregation of the investigated mAbs. The absence of aggregation could be explained by the reduction of interfacial stress due to headspace removal from the infusion bags and a mechanical sensor indicated that there was also only a moderate amount of mechanical stress caused by transportation with this particular PTS.Although this case study focuses on five antibody drugs and the practices in one hospital, the work demonstrates how to evaluate whether other handling and transportation practices cause significant mechanical stress that could compromise the quality and safety of antibody drugs.

Simulation of radioactive plume transport in the atmosphere including dynamics of particle aggregation and breakup

Accurate prediction of the atmospheric transport of debris particles relies heavily on our knowledge of the size distribution of the particles within a debris cloud. Assuming a fixed particle size during simulations is not always viable since the size distribution of the debris can change during transport. Various microphysical processes, such as aggregation and breakup, influence debris particles and dictate any changes to the size distribution. To track those changes that can occur, a population balance model can be adopted and instituted within a model framework. Nonetheless, many of the models that simulate the transport of radioactive debris following a device-driven fission incident have historically neglected to consider these processes. As such, this work describes our effort to develop a modeling framework capable of simulating the transport and deposition of a radioactive plume generated from a fission incident with a dynamic population balance including particle aggregation and breakup. The impact of aggregation and breakup, individually and collectively, on the particle size distribution is explored using the developed framework. When simulating aggregation, for example, six mechanisms, including Brownian coagulation, the convective enhancement to Brownian coagulation, van der Waals-viscous force correction for Brownian coagulation, gravitational collection, turbulent inertial motion, and turbulent shear, are considered. Brownian coagulation and its corrections have, as one would expect, a large impact on relatively small aggregates. Aggregates with a diameter that is less than or equal to 1.0 μm, for instance, comprise 50.6 vol % of all aggregates in the absence of aggregation and 31.2 vol % when Brownian coagulation and its corrections are considered. Gravitational collection and, to a much lesser extent, turbulent shear and turbulent inertial motion are, conversely, of great importance to relatively large aggregates (i.e., diameter greater than 3.0 μm). Additionally, the individual effects of atmospheric and particle parameters, such as wind speed and particle density, are examined. Of the parameters examined, turbulent energy dissipation and aggregate fractal dimension (i.e., aggregate shape with lower values representing more irregular particles) were of substantial importance since both terms directly impact aggregate stability and, by extension, the breakup rate. Large-scale transport and deposition simulations in a dry atmosphere are also presented and discussed as a proof of concept.

Hybrid Nanoparticles of Citrate-Coated Manganese Ferrite and Gold Nanorods in Magneto-Optical Imaging and Thermal Therapy.

The development of nanomaterials has drawn considerable attention in nanomedicine to advance cancer diagnosis and treatment over the last decades. Gold nanorods (GNRs) and magnetic nanoparticles (MNPs) have been known as commonly used nanostructures in biomedical applications due to their attractive optical properties and superparamagnetic (SP) behaviors, respectively. In this study, we proposed a simple combination of plasmonic and SP properties into hybrid NPs of citrate-coated manganese ferrite (Ci-MnFe2O4) and cetyltrimethylammonium bromide-coated GNRs (CTAB-GNRs). In this regard, two different samples were prepared: the first was composed of Ci-MnFe2O4 (0.4 wt%), and the second contained hybrid NPs of Ci-MnFe2O4 (0.4 wt%) and CTAB-GNRs (0.04 wt%). Characterization measurements such as UV-Visible spectroscopy and transmission electron microscopy (TEM) revealed electrostatic interactions caused by the opposing surface charges of hybrid NPs, which resulted in the formation of small nanoclusters. The performance of the two samples was investigated using magneto-motive ultrasound imaging (MMUS). The sample containing Ci-MnFe2O4_CTAB-GNRs demonstrated a displacement nearly two-fold greater than just using Ci-MnFe2O4; therefore, enhancing MMUS image contrast. Furthermore, the preliminary potential of these hybrid NPs was also examined in magnetic hyperthermia (MH) and photoacoustic imaging (PAI) modalities. Lastly, these hybrid NPs demonstrated high stability and an absence of aggregation in water and phosphate buffer solution (PBS) medium. Thus, Ci-MnFe2O4_CTAB-GNRs hybrid NPs can be considered as a potential contrast agent in MMUS and PAI and a heat generator in MH.

Dexamethasone-Loaded biodegradable magnetic microparticles for treatment of CFA-induced chronic pain in rats

ABSTRACT Traditional drug solutions or suspensions, have been shown to treat pain in complete Freund’s adjuvant (CFA)-induced chronic inflammatory pain in rats, with or without combination with magnetic therapy. In this study, we aimed to prepare, characterize, and evaluate the therapeutic effects of microparticles containing dexamethasone for local administration and treatment of chronic inflammatory pain. The results showed the following; a) Preparation and characterization: two ratios of poly(lactic-co-glycolic acid) (PLGA)/poly(lactic acid) (PLA) were used. The prepared batches were similar in size and magnetic responsiveness. The microparticle size distribution assessed via electron microscopy suggested a homogeneous distribution and absence of aggregates. Dexamethasone release profiles (microparticles synthesized with a feed ratio of 1:4) showed a sustained release in vitro and good biocompatibility with tissues. b) Therapeutic effect: the treatment effect of dexamethasone-PLGA magnetic microspheres + magnetic therapy was substantially better than that observed for other groups on day 4, as monitored by appearance, mechanical pain threshold, and histological analysis. This type of carrier could be a suitable magnetically retainable local drug delivery system for treating chronic pain.

Wound Healing Efficacy of Rosuvastatin Transethosomal Gel, I Optimal Optimization, Histological and In Vivo Evaluation.

This study aimed to make a formulation and statistical optimization of transethosomal formulations of rosuvastatin (ROS) to enhance its topical wound healing efficiency. Design-Expert® software was used to employ I optimal design. The formulation variables in the study were surfactant concentration (%w/v), ethanol concentration (%w/v) and surfactant type (span 60 or tween 80), while the dependent responses were entrapment efficiency percent (EE%), vesicle size (VS) and zeta potential (ZP). The numerical optimization process employed by the design expert software resulted in an optimum formula composed of 0.819439 (%w/v) span 60, 40 (%w/v) ethanol and 100 mg lecithin with a desirability of 0.745. It showed a predicted EE% value of 66.5517 vs. 277.703 nm and a ZP of -33. When it was prepared and validated, it showed less than a 5% deviation from the predicted values. The optimum formula was subjected to further characterizations, such as DSC, XRD, TEM, in vitro release, the effect of aging and wound healing efficiency. The DSC thermogram made a confirmation of the compatibility of ROS with the ingredients used in the formulation. XRD showed the encapsulation of ROS in the transethosomal vesicles. The TEM image pointed out the spherical nature of the nanovesicles with the absence of aggregation. Additionally, the optimum formula revealed an enhancement of drug release in comparison with the drug suspension. It also showed good stability for one month. Furthermore, it revealed good wound healing efficiency when compared with the standard silver sulphadiazine (1% w/w) ointment or the drug-loaded gel, which could be related to the enhanced penetration of the nanosized vesicles of TESMs into the skin, which enhances the wound healing process. So, it could be regarded as a promising carrier of ROS for the treatment of chronic wounds.

Uniform size PEGylated iron oxide nanoparticles as a potential theranostic agent synthesized by a simple optimized coprecipitation route

Iron oxide nanoparticles, due to their unique intrinsic magnetic properties, have attracted significant interest in biomedical applications. Therefore, the optimization of Magnetic Nanoparticles (MNPs) properties has always been the center of attention. For example, controlling the size of MNPs and enhancing their stability are the two most important parameters for biomedical applications that must be considered using an appropriate synthesis method. In this study, we synthesized bare magnetite NPs via an optimized coprecipitation route, followed by a post-synthesis procedure to coat them with polyethylene glycol (PEG). The synthesized MNPs presented optimized physiochemical properties, such as high stability, uniform size, relatively high saturation magnetization, and the absence of aggregation. The X-ray diffraction results revealed the high crystallinity of MNPs. Fourier-transform infrared studies confirmed the surface modification of particles with PEG. Moreover, an in vitro biological assay on the bacterial strain of Escherichia coli (E. coli) Rosetta (DE3) demonstrated low cytotoxicity and no evident cytotoxicity for bare MNPs and PEG-MNPs, respectively at a high concentration (0.5 mg/mL). Lastly, the potential of these MNPs was investigated as theranostic agents in magnetomotive ultrasound imaging (MMUS) and magnetic hyperthermia (MH). Based on the obtained results, both MNPs demonstrated the same performance in MMUS; however, PEG-coated MNPs showed a higher heating efficiency. These results show the great potential of the particles to be used as theranostic agents or other biomedical applications owing to their high saturation magnetization.

SMC complexes can traverse physical roadblocks bigger than their ring size.

Ring-shaped structural maintenance of chromosomes (SMC) complexes like condensin and cohesin extrude loops of DNA. It remains, however, unclear how they can extrude DNA loops in chromatin that is bound with proteins. Here, we use invitro single-molecule visualization to show that nucleosomes, RNA polymerase, and dCas9 pose virtually no barrier to loop extrusion by yeast condensin. We find that even DNA-bound nanoparticles as large as 200nm, much bigger than the SMC ring size, also translocate into DNA loops during extrusion by condensin and cohesin. This even occurs for a single-chain version of cohesin in which the ring-forming subunits are covalently linked and cannot open to entrap DNA. The data show that SMC-driven loop extrusion has surprisingly little difficulty in accommodating large roadblocks into the loop. The findings also show that the extruded DNA does not pass through the SMC ring (pseudo)topologically, hence pointing to a nontopological mechanism for DNA loop extrusion.

A new species of the spider genus Tekellina Levi, 1957 from Chile, with a broadened definition of the family Synotaxidae (Arachnida, Araneae)

A new species, Tekellina araucana sp. n., is described from Chile and Argentina. Detailed morphological data from the spinnerets and male palp of T. araucana sp. n. and Tekellina sadamotoiYoshida & Ogata, 2016 is provided. A new diagnostic character of TekellinaLevi, 1957, a row of bottle-like modified setae between the anal tubercle and the spinnerets was found. The absence of aggregate and cylindrical gland spigots may be a further diagnostic character for the genus. New molecular sequence data of T. araucana sp. n., Tekellina archboldiLevi, 1957 (generotype) and Nescina kohiLin, Ballarin & Li, 2016, is provided and analyzed together with legacy genetic and transcriptomic data from a wide sampling of species representing all areaneoid families. Both molecular and morphological data suggest that Tekellina is closely related to Synotaxus Simon, 1895 together with three genera formerly placed in Nesticidae. From those results we broaden the limits of Synotaxidae to include the genera Synotaxus, HamusBallarin & Li, 2015, NescinaBallarin & Li, 2015, Gaucelmus Keyserling, 1884, and Tekellina. The morphological data, especially of the male palps, is consistent with that re-limitation.

Dispersion of Hydrophilic "Hedgehog" Microparticles in Liquid CO2 Mixtures.

Liquid and supercritical CO2 are nontoxic and nonflammable reaction media with pressure-variable physical properties. These states of CO2 also have high solubility limits for gas and liquid hydrocarbons, making them good candidates for "green" hydrophobic solvents in sustainable chemical technologies. However, the dispersion of hydrophilic colloidal nanoscale and microscale particles in CO2 is challenging due to the tendency of polar particles to aggregate in nonpolar media, limiting their available surface area and catalytic efficiencies. Here we show that native hydrophilic semiconductor particles can be effectively dispersed in a liquid CO2 mixture with acetonitrile (ACN) without additional chemical or mechanical dispersion techniques. Using surface corrugation as a method to prevent aggregation, we find that geometrically complex particles with a halo of stiff nanoscale spikes disperse and remain suspended longer in liquid CO2 than those without or with less prominent nanoscale corrugation. For the particles of this size and liquid CO2 mixtures, individual particle mass remains a prominent factor determining particle sedimentation rate even in the absence of aggregation. Particle dispersion and structural stability are confirmed using a combination of UV-vis spectroscopy, finite-difference time-domain modeling, and electron microscopy. The necessity of the cosolvent (ACN) indicates that particle behavior in liquid CO2 is vastly different than in traditional liquid-phase solvents and highlights the need for future studies to understand the wetting behavior of hydrophilic particles in high-pressure nonpolar environments.

Quantitative Interpretation of Protein Diffusion Coefficients in Mixed Protiated-Deuteriated Aqueous Solvents.

Diffusion-ordered nuclear magnetic resonance (NMR) spectroscopy is widely used for the analysis of mixtures, dispersing the signals of different species in a two-dimensional spectrum according to their diffusion coefficients. However, interpretation of these diffusion coefficients is typically purely qualitative, for example, to deduce which species are bigger or smaller. In studies of proteins in solution, important questions concern the molecular weight of the proteins, the presence or absence of aggregation, and the degree of folding. The Stokes–Einstein Gierer–Wirtz estimation (SEGWE) method has been previously developed to simplify the complex relationship between diffusion coefficient and molecular mass, allowing the prediction of a species’ diffusion coefficient in a pure solvent based on its molecular weight. Here, we show that SEGWE can be extended to successfully predict both peptide and protein diffusion coefficients in mixed protiated–deuteriated water samples and, hence, distinguish effectively between globular and disordered proteins.

Investigation of Immune Responses to Oxidation, Deamidation, And Isomerization in Therapeutic Antibodies using Preclinical Immunogenicity Risk Assessment Assays

Product- and process- related critical quality attributes have the potential to impact pharmacokinetics, immunogenicity, potency, and safety of biotherapeutics. Among these critical quality attributes are chemical degradations, specifically oxidation, deamidation, and isomerization. These degradations can be induced by stressors such as light, pH, or temperature; they can also occur naturally under normal conditions. The immunogenicity risk of chemical degradations, particularly in the absence of aggregation, has not been thoroughly understood. In this study, model antibodies with known labile residues were stressed to induce each of the three chemical degradation classes. Aggregate-free and chemically modified antibody species were fractionalized and characterized, followed by testing in standardized and qualified preclinical immunogenicity risk assessment assays for dendritic cell internalization and presentation, monocyte activation, and pre-existing reactivity. Preclinical immunogenicity risk was assessed holistically in vitro based on changes in innate activation risk, CD4 T cell risk, and B cell risk compared to corresponding native antibody. The results of this study suggest an overall moderate increase in immune activation potential for the antibody with isomerization, with only slight increases observed in oxidized and deamidated antibodies. These findings could lend understanding to the immunogenicity risk of chemical degradations in therapeutic antibodies and therefore inform optimization engineering at particular labile residues and risk assessment under the Quality by Design framework.

DEVELOPMENT OF TECHNOLOGICAL PARAMETERS FOR THE FORMATION OF FASTS BY THE SLIDING CASTING METHOD

The materials of the article consider the effectiveness of additives for stabilization and dilution of clay-free slippers. For theproduction of radio-transparent ceramic materials of Celsius-Willemite composition, the most efficient and energy-saving methodof production is the method of slip casting. According to the charge composition, this technology is complicated by the lack of claycomponents, which shows the need to use impurities to improve the rheology of such a slip. The main characteristics of aqueousceramic slippers are density, humidity, fluidity, viscosity, density factor, rate of mass accumulation. The slip must meet thefollowing requirements: be free from foam and gas inclusions, have satisfactory fluidity under low viscosity; be aggregativelystable (characterized by the absence of aggregation, coagulation and sedimentation of solid phase particles); have a high filteringcapacity to ensure fast and defect-free weight gain; to be chemically inert, to provide sufficient strength and low shrinkage of semifinished products, as well as the possibility of their easy release from the mold.

A machine learning model of microscopic agglutination test for diagnosis of leptospirosis.

Leptospirosis is a zoonosis caused by the pathogenic bacterium Leptospira. The Microscopic Agglutination Test (MAT) is widely used as the gold standard for diagnosis of leptospirosis. In this method, diluted patient serum is mixed with serotype-determined Leptospires, and the presence or absence of aggregation is determined under a dark-field microscope to calculate the antibody titer. Problems of the current MAT method are 1) a requirement of examining many specimens per sample, and 2) a need of distinguishing contaminants from true aggregates to accurately identify positivity. Therefore, increasing efficiency and accuracy are the key to refine MAT. It is possible to achieve efficiency and standardize accuracy at the same time by automating the decision-making process. In this study, we built an automatic identification algorithm of MAT using a machine learning method to determine agglutination within microscopic images. The machine learned the features from 316 positive and 230 negative MAT images created with sera of Leptospira-infected (positive) and non-infected (negative) hamsters, respectively. In addition to the acquired original images, wavelet-transformed images were also considered as features. We utilized a support vector machine (SVM) as a proposed decision method. We validated the trained SVMs with 210 positive and 154 negative images. When the features were obtained from original or wavelet-transformed images, all negative images were misjudged as positive, and the classification performance was very low with sensitivity of 1 and specificity of 0. In contrast, when the histograms of wavelet coefficients were used as features, the performance was greatly improved with sensitivity of 0.99 and specificity of 0.99. We confirmed that the current algorithm judges the positive or negative of agglutinations in MAT images and gives the further possibility of automatizing MAT procedure.

Enrichment of aqueous solubility and dissolution profile of mesalamine: In vitro evaluation of solid dispersion

The aim of the present study was to formulate solid dispersion (SD) of Mesalamine to enrich the aqueous solubility and dissolution rate. Mesalamine is used in the management of acute ulcerative colitis and for the prevention of relapse of active ulcerative colitis. In the present study, Solid dispersion of Mesalamine was prepared by Fusion and Solvent evaporation method with different polymers. SD’s were characterized by % practical yield, drug content, Solubility, FT-IR, PXRD (Powder X- ray diffractometry), SEM (Scanning electron microscopy), in vitro dissolution studies and Stability studies. The percent drug release of prepared solid dispersion of Mesalamine by fusion and solid dispersion method (FM47, FM67, SE47 and SE67) in 1:7 ratio was found 81.36±0.41, 86.29±0.64, 82.45±0.57and 87.25±1.14 respectively. The aqueous solubility and percent drug release of solid dispersion of Mesalamine by both methods was significantly increased. The PXRD demonstrated that there was a significant decrease in crystallinity of pure drug present in the solid dispersions, which resulted in an increased aqueous solubility and dissolution rate of Mesalamine.The significant increase in aqueous solubility and dissolution rate of Mesalamine was observed in solid dispersion as the crystallinity of the drug decreased, absence of aggregation and agglomeration, increased wetability and good dispersibility after addition of PEG 4000 and PEG 6000.

Mathematical model for strength of alkali-activated materials

In this work, geopolymers are assessed both qualitatively and quantitatively, with an emphasis on strength. Produced by mixing binders with an alkaline solution, geopolymers have been quite often suffered from the absence of aggregate. Even when aggregate is included, inadequate attention has been paid to the control of the geopolymer paste volume (GPV) which plays a vital role in lowering materials cost and enhancing dimensional stability. To better understand the properties of geopolymer and facilitate its wider application, this paper examined geopolymer from the perspective of two phases: alkaline paste and aggregate. Utilizing abundant data of 159 mixtures extracted from the literature, the key factors affecting the strength of geopolymer mixtures were identified. Furthermore, a robust model for predicting the strength of geopolymer is established with high accuracy by correlating the key factors quantitatively to the strength. This study shall advance the development of geopolymer by providing practical guidelines for economic, sustainable and durable mix design.

The nickel-chelator dimethylglyoxime inhibits human amyloid beta peptide in vitro aggregation

One of the hallmarks of the most common neurodegenerative disease, Alzheimer’s disease (AD), is the extracellular deposition and aggregation of Amyloid Beta (Aβ)-peptides in the brain. Previous studies have shown that select metal ions, most specifically copper (Cu) and zinc (Zn) ions, have a synergistic effect on the aggregation of Aβ-peptides. In the present study, inductively coupled plasma mass spectrometry (ICP-MS) was used to determine the metal content of a commercial recombinant human Aβ40 peptide. Cu and Zn were among the metals detected; unexpectedly, nickel (Ni) was one of the most abundant elements. Using a fluorescence-based assay, we found that Aβ40 peptide in vitro aggregation was enhanced by addition of Zn2+ and Ni2+, and Ni2+-induced aggregation was facilitated by acidic conditions. Nickel binding to Aβ40 peptide was confirmed by isothermal titration calorimetry. Addition of the Ni-specific chelator dimethylglyoxime (DMG) inhibited Aβ40 aggregation in absence of added metal, as well as in presence of Cu2+ and Ni2+, but not in presence of Zn2+. Finally, mass spectrometry analysis revealed that DMG can coordinate Cu or Ni, but not Fe, Se or Zn. Taken together, our results indicate that Ni2+ ions enhance, whereas nickel chelation inhibits, Aβ peptide in vitro aggregation. Hence, DMG-mediated Ni-chelation constitutes a promising approach towards inhibiting or slowing down Aβ40 aggregation.

Platelets Independently Recruit into Asthmatic Lungs and Models of Allergic Inflammation via CCR3.

Platelet activation and pulmonary recruitment occur in patients with asthma and in animal models of allergic asthma, in which leukocyte infiltration, airway remodeling, and hyperresponsiveness are suppressed by experimental platelet depletion. These observations suggest the importance of platelets to various characteristics of allergic disease, but the mechanisms of platelet migration and location are not understood. The aim of this study was to assess the mechanism of platelet recruitment to extravascular compartments of lungs from patients with asthma and after allergen challenge in mice sensitized to house dust mite (HDM) extract (contains the DerP1 [Dermatophagoides pteronyssinus extract peptidase 1] allergen); in addition, we assessed the role of chemokines in this process. Lung sections were immunohistochemically stained for CD42b+ platelets. Intravital microscopy in allergic mice was used to visualize platelets tagged with an anti–mouse CD49b-PE (phycoerythrin) antibody. Platelet–endothelial interactions were measured in response to HDM (DerP1) exposure in the presence of antagonists to CCR3, CCR4, and CXCR4. Extravascular CD42b+ platelets were detected in the epithelium and submucosa in bronchial biopsy specimens taken from subjects with steroid-naive mild asthma. Platelets were significantly raised in the lung parenchyma from patients with fatal asthma compared with postmortem control-lung tissue. Furthermore, in DerP1-sensitized mice, subsequent HDM exposure induced endothelial rolling, endothelial adhesion, and recruitment of platelets into airway walls, compared with sham-sensitized mice, via a CCR3-dependent mechanism in the absence of aggregation or interactions with leukocytes. Localization of singular, nonaggregated platelets occurs in lungs of patients with asthma. In allergic mice, platelet recruitment occurs via recognized vascular adhesive and migratory events, independently of leukocytes via a CCR3-dependent mechanism.

Calorimetric observation of lysozyme degradation at elevated temperature in water and DMSO-water mixtures

The reversibility of protein denaturation is an essential factor for biotechnology. Previous differential scanning calorimetry (DSC) studies demonstrated the development of the low-temperature shoulder on the calorimetric denaturation peak of lysozyme in successive heating-cooling cycles, which implies irreversible denaturation. However, this effect was not thoroughly investigated. In the present work, we have quantitatively studied the effect of incubation at the elevated temperature on the state of lysozyme in water and mixtures of water with dimethyl sulfoxide (DMSO) using DSC. The changes to the state of the lysozyme molecule indicated by DSC thermograms were also evaluated by circular dichroism (CD), Fourier transform infrared spectroscopy (FTIR) and dynamic light scattering (DLS) techniques. It is noted that with the increase of duration or temperature of incubation, the low-temperature peak on DSC thermograms grows, while the height of the unfolding peak of native structure decreases. The increase in the height of the low-temperature peak in DSC scans correlates with the development of the sideband associated with the absorption of the carboxyl group in the infrared spectra. This result suggests that the low-temperature endothermic peak corresponds to the unfolding of the deamidated protein. At the same time, DLS measurements indicate absence of aggregation, while FTIR and CD data demonstrate that deamidated protein maintains a native-like structure. The evaluation of the DSC thermograms allowed to determine the rates and activation energy of the degradation of protein molecules at the elevated temperatures. The addition of DMSO slows down the protein degradation but has little effect on the apparent activation energy of the process.

Compaction behaviour of lime-treated metakaolin

Metakaolin has been widely used as pozzolanic additive to improve the pozzolanic activity of lime-based products. In this study, the normal standard Proctor compaction test was performed on metakaolin with (5% lime) and without (0% lime) lime addition. The changes in stiffness, suction, and microstructure with remoulding water content were investigated on statically compacted samples. Results show that lime-treated metakaolin exhibits a 1.5-peak compaction curve, while untreated metakaolin exhibits common one-peak compaction curve. The uncommon shape of the compaction curve of the treated metakaolin can be explained by the non-fully developed soil suction when water is not continuous. Treated and untreated samples compacted at both dry and wet of optimum show uni-modal pore-size distribution characteristics, indicating the absence of aggregates. This is related to the specific thermal treatment, forming separate metakaolin platelets and leading to a modified uniform structure with diffuse platelets. The soil stiffness is rather dominated by the number of particle contacts or soil dry density, the effect of suction being insignificant. For the suction changes, on the dry side, the effect of pore-size distribution prevails facing the effect of water content, while on the wet side it is the effect of water content that becomes dominating.

Bio-synthesized iron oxide nanoparticles for cancer treatment.

Various living organisms, such as bacteria, plants, and animals can synthesize iron oxide nanoparticles (IONP). The mechanism of nanoparticle (NP) formation is usually described as relying on the reduction of ferric/ferrous iron ions into crystallized nanoparticulate iron that is surrounded by an organic stabilizing layer. The properties of these NP are characterized by a composition made of different types of iron oxide whose most stable and purest one appears to be maghemite, by a size predominantly comprised between 5 and 380nm, by a crystalline core, by a surface charge which depends on the nature of the material coating the iron oxide, and by certain other properties such as a sterility, stability, production in mass, absence of aggregation, that have apparently only been studied in details for IONP synthesized by magnetotactic bacteria, called magnetosomes. In the majority of studies, bio-synthesized IONP are described as being biocompatible and as not inducing cytotoxicity towards healthy cells. Anti-tumor activity of bio-synthesized IONP has mainly been demonstrated in vitro, where this type of NP displayed cytotoxicity towards certain tumor cells, e.g. through the anti-tumor activity of IONP coating or through IONP anti-oxidizing property. Concerning in vivo anti-tumor activity, it was essentially highlighted for magnetosomes administered in different types of glioblastoma tumors (U87-Luc and GL-261), which were exposed to a series of alternating magnetic field applications, resulting in mild hyperthermia treatments at typical temperatures of 41-45°C, leading to the full disappearance of these tumors without any observable side effects.