Cell based carriers are increasingly recognized as a good system for cargo delivery to cells. One of the reasons is their biocompatibility and low toxicity compared to artificial systems. Giant plasma membrane vesicles (GPMV) derive from the cell plasma membrane. Thus they offer the closest approximation to it, which makes them good candidates for potential drug delivery systems. To evaluate the applicability of GPMVs as carriers, we analyzed their basic biophysical properties to test their robustness in the face of changeable physiological conditions, as well as their ability to translocate across the membrane into cells. GPMVs formed from human umbilical vein endothelial cells (HUVEC) sustain a drastic osmotic challenge (50–500 mOsmoL/kg) unlike giant unilamelar vesicles (GUVs). In hyper-osmotic solutions the average volume decreases and membrane invaginations form, while in the hypo-osmolar buffer the volume of GPMVs increases and these changes were not reversible. The membranes of flaccid GPMVs started to wrinkle unevenly giving rise to buds after exposure to lipopolysaccharide (LPS). The shape changes in GUVs are reversible in contrast to GPMVs after LPS removal. GPMVs exposed to fluorescent LPS exhibited a signal that remained visible in some GPMVs even after LPS removal, which was never the case with GUVs. Calcein penetrated both into GUVs and GPMVs, however after the removal from the bulk solution some of the GPMVs still exhibited very bright signal, while in GUVs only a weak fluorescent signal was detected. We could also see that practically all GPMVs incorporated dextran initially, but after the dextran solution was changed with the initial non-fluorescent solution it remained only in 20% of them. The majority of HUVEC cells displayed a fluorescent signal after the incubation with GPMVs that contained fluorescently labeled dextran. Our findings indicate that GPMVs behave quite differently from artificially made giant phospholipid vesicles and the changes induced by the different treatments we subjected them to are not reversible. We also demonstrate that different substances can be both loaded into them and delivered into cells, so GPMVs may be of potential use as cargo/therapy delivery systems.

The objective of the study is to improve understanding of the practical role of niobium (Nb) in the case of industrial inconsistent rolling processes such as the rolling of heavy gauge plates where a lower stored energy rolling practice will result in a less stable and less repeatable static recrystallization (SRX) activation that prevents complete recrystallization. In the current study, these variabilities are validated by comparing the mean flow stress (MFS) indirectly determined from the rolling force measured on a reverse four-high rolling mill stand. The material resistance to deformation and grain size evolution of a C-Mn steel during hot rolling was observed and validated with and without Nb addition. The pre-defined rolling schedule was predicted to exhibit incomplete recrystallization in the roughing phase due to the limited stored energy of deformation that resulted from low rolling loads and a higher number of rolling passes. The prior austenite grain size (PAGS) distribution was predicted and compared to the measured effective ferrite grain (FG) size distribution after the completion of hot rolling and phase transformation achieved using natural air plate cooling. Both the predicted PAG and measured FG distributions revealed the presence of multimodality, and both distributions were used for grain size reduction factor determination for γ → α transformation for the current study with 1.96 for 0 Nb and 1.70 for 240 Nb. The results presented in this paper are not only limited to the rolling schedule used in this paper because instabilities resulting in incomplete austenite conditioning are also observed when evaluating the cross-sections of other heavy plates and various steel grades utilizing different processing routes with comparable compositions such as modern lean abrasion-resistant steels, regular line pipe steels, and other similar grades.

When regarding as-cast microstructures of highly alloyed metals, microsegregation of alloying elements is a common feature resulting from non-equilibrium conditions during solidification. The aim of this work is to predict the occurrence and severity of microsegregation in highly alloyed, centrifugally cast high speed steel used for rolls. The prediction was performed using thermodynamic Scheil-Gulliver modelling with Thermo-Calc software. The modelled predictions were then compared with differential scanning calorimetry, X-ray diffraction, light and electron microscopy with energy dispersive spectroscopy, all performed on an as-cast roll shell. Results show that chromium, molybdenum and vanadium have the highest tendency to microsegregation. Vanadium tends to form negative microsegregation, while molybdenum and chromium form positive microsegregation. Scanning electron microscopy revealed the presence of complex eutectic carbides, confirming the Scheil-Gulliver non-equilibrium solidification path via two main successive eutectic reactions.

A study was undertaken to investigate the effects of small boron additions on the solidification and microstructure of hypo-eutectic alloyed grey cast iron. The characteristic temperatures upon crystallisation of the treated metal melt were recorded, specifically those concerning small boron addition by using thermal analysis with the ATAS system. Additionally, a standardised wedge test was set to observe any changes in chill performance. The microstructures of thermal analysis samples were analysed using a light optical microscope (LOM) and field emission scanning electron microscopy (FE-SEM) equipped with energy dispersive spectroscopy (EDS), which reveal variations in graphite count number with the addition of boron within observed random and undercooled flake graphite. The effect of boron was estimated by the classical analytical and statistical approach. The solidification behaviour under equilibrium conditions was predicted by a thermodynamic approach using Thermo-Calc. Based on all gathered data, a response model was set with boron for given melt quality and melt treatment using the experimentally determined data. The study reveals that boron as a ferrite and carbide-promoting element under the experimental set shows weak nucleation potential in synergy with other heterogenic nuclei at increased solidification rates, but no considerable changes were observed by the TA samples solidified at slower cooling rates, indicating the loss of the overall inoculation effect. The potential presence of boron nitride as an inoculator for graphite precipitation for a given melt composition and melt treatment was not confirmed in this study. It seems that boron at increased solidification rates can contribute to overall inoculation, but at slower cooling rates these effects are gradually lost. In the last solidification range, an increased boron content could have a carbide forming nature, as is usually expected. The study suggests that boron in traces could affect the microstructure and properties of hypo-eutectic alloyed grey cast iron.

Protein particles in biological drugs can significantly impact drug efficacy and carry the risk of adverse effects. Despite advancements, the understanding and control of particle formation in biopharmaceutical manufacturing remain incomplete. Therefore, further investigation into protein particles is warranted, especially considering that novel formats of biological drugs may be more susceptible to aggregation and particle formation than conventional monoclonal antibodies. In this study, we introduce a microfluidic approach for the real-time analysis of individual sub-visible protein particles during buffer exchange. We find that the modulation of intermolecular forces, achieved by changing the buffer pH or urea concentration, leads to the reversible swelling and shrinkage of particles by up to 50%, which is a consequence of altered intermolecular distances. Additionally, we identify a discrepancy in the biophysical behavior of protein particles compared to monomeric protein. This finding highlights the limited predictive power of commonly applied biophysical characterization methods for particle formation in early formulation development. Moreover, the observed particle swelling may be associated with manufacturing deviations, such as filter clogging. These results highlight the importance of studying individual particles to gain a comprehensive insight into particle behavior and the impact of formulation variations in the biopharmaceutical industry.