Bead Size Research Articles

Effects of stalk orientation and size of trapped bead on force-velocity relation of kinesin motor determined using single molecule optical trapping methods.

Conventional kinesin protein is a prototypical biological molecular motor that can step processively on microtubules towards the plus end by hydrolyzing ATP molecules, performing the biological function of intracellular transports. An important characteristic of the kinesin is the load dependence of its velocity, which is usually measured by using the single molecule optical trapping method with a large-sized bead attached to the motor stalk. Puzzlingly, even for the same kinesin, some experiments showed that the velocity is nearly independent of the forward load whereas others showed that the velocity decreases evidently with the increase in the magnitude of the forward load. Here, a theoretical explanation is provided of why different experiments give different dependencies of the velocity on the forward load. It is shown that both the stalk orientation and bead size play a critical role in the different dependencies. Additionally, the reason why the optical trapping experiments with the movable trap usually gave a sigmoid form of the velocity versus backward load whereas with the fixed trap gave a nearly linear form is also explained theoretically. The study is not only critical to the understanding of the response of the motor to the load but also provides strong insights into the coupling mechanism of the motor.

Sodium alginate/low methoxyl pectin composite hydrogel beads prepared via gas-shearing technology for enhancing the colon-targeted delivery of probiotics and modulating gut microbiota.

The probiotic encapsulation system has the potential to enhance the prebiotic effects of probiotics. However, challenges arise from the release behavior of this system in vivo and the large size of hydrogel beads. This study aims to address the issues related to the size of previous hydrogel beads and assess the colon-targeted delivery of probiotic polysaccharides composite hydrogel beads (PPHB). PPHB prepared by gas-shearing technique significantly reduced the average particle size and demonstrated a high protective capacity for probiotics (after simulating intestinal conditions for 4 h, the viability of encapsulated probiotics remained at 107 CFU/g). The use of indocyanine green along with near-infrared-II in vivo imaging technology demonstrated the colon-targeted delivery of PPHB in vivo, which also extended the retention time of probiotics in the cecum and colon. Additionally, the colon-targeted delivery of PPHB was also demonstrated by dietary supplementation in vivo. PPHB significantly enhanced the diversity and richness of intestinal microflora species, increased the levels of short-chain fatty acids, raised the relative abundance of beneficial bacteria, and significantly decreased the relative abundance of harmful bacteria. Alginate-based PPHB is more suitable for encapsulating functional ingredients for colon-targeted delivery and modulating gut microbiota.

Designing & optimisation of dual Ca2+ and SO4 2– ionic cross-linked sericin/pectin microbeads using response surface methodology for colon-specific delivery

Ulcerative colitis, a chronic inflammatory condition of the colon, requires precise and targeted treatment, and polysaccharides, with their pH responsiveness and biodegradability, offer an innovative approach for colon-specific drug delivery. This study aims to develop a highly precise drug delivery system with enhanced therapeutic and targeting efficiency for ulcerative colitis, focusing on the preparation, optimisation, and evaluation of dual cross-linked mesalamine-loaded sericin-pectin (DCLSPs) micro-beads. These beads utilise the pH-responsive and microflora biodegradability properties of polysaccharides for targeted colon delivery, employing the Response Surface Methodology. Formulated via the ionotropic gelation method with divalent cross-linking ions (Ca2+ and SO4 2–), the DCLSPs were optimised using a Box-Behnken design to assess the impact of the varying drug, pectin, and sericin polymer proportions. The DCLSPs were evaluated for entrapment efficiency, thermal behaviour, surface morphology, water uptake, swelling, and in-vitro drug release. Results indicated that spherical beads were successfully developed, with encapsulation efficiency ranging from 65.1% to 95.5%, drug loading between 32.5% and 49.9%, bead sizes of 0.75 mm to 0.92 mm, and degrees of swelling from 0.92 to 1.82. Drug release was controlled by both diffusion and swelling mechanisms, as supported by the Higuchi and Korsmeyer-Peppas models. The optimised formulation demonstrated high drug encapsulation efficiency, pH-responsive swelling, and strong adhesion to the colon, ensuring extended retention at the targeted site. Additionally, the incorporation of sericin enhanced the accuracy of Gaussian fitting for particle size distribution. Overall, the dual cross-linked sericin-pectin beads show potential as mucoadhesive carriers for delivering drugs specifically to the colon.

Controlled Release of Human Dental Pulp Stem Cell-Derived Exosomes from Hydrogels Attenuates Temporomandibular Joint Osteoarthritis.

Temporomandibular joint osteoarthritis (TMJOA) is a painful inflammatory condition that limits mouth opening. Cell-derived exosomes, which have anti-inflammatory effects, are emerging as a treatment for TMJOA. Injection of dental pulp stem cells (DPSCs), which secrete exosomes, can moderate tissue damage in a rat model of TMJOA. However, injected exosomes are quickly cleared, necessitating repeated injections for therapeutic efficacy. Here, vinyl sulfone-modified hyaluronic acid (HA-VS) hydrogels, suitable for encapsulating exosomes are formulated. HA-VS hydrogels degrade in the presence of hyaluronidase and allow for the release of beads of similar size to exosomes over 3 to 6 days. In a rat model of TMJOA, injection of exosomes or exosomes within HA-VS hydrogels significantly attenuated damage-mediated subchondral bone loss as determined by micro-computed tomography, and reduced inflammatory and tissue damage scores as assessed by histology. Overall, DPSCs-derived exosomes attenuated joint damage, but treatment with exosomes within HA-VS hydrogels shows additional protective effects on subchondral bone maintenance and integrity. These findings confirm the protective effects of DPSCs-derived exosomes in moderating tissue damage in TMJOA and suggest that combining exosomes with HA hydrogels can further promote their therapeutic effects.

Small-Scale Aqueous Suspension Preparation using Dual Centrifugation: The Effect of Process Parameters on the Sizes of Drug Particles

The dual centrifugation approach has in the recent years emerged as a powerful milling tool to prepare pharmaceutical suspensions in submicron range with a fast-milling capacity by milling 40 samples simultaneously in 2 mL vials. While there is some standardized milling conditions described in the literature when preparing aqueous suspensions with dual centrifugation, a more systematic and experimental understanding of the milling process to evaluate the impact of different process variables in the dual centrifuge on the final sizes of the suspended drug particles independent of the drug compound used. Overall, the present study demonstrated the applicability of the dual centrifuge for small-scale screening purposes and showed the impact of process parameters on the physical attributes of prepared suspensions. In the present work, the rate of size reduction on three different model compounds, i.e., cinnarizine, haloperidol, and indomethacin, was found to be mostly influenced by the milling speed, size of milling beads, and the bead loading during milling, whereas the rotor temperature did not affect the particle size profiles when stabilized with polysorbate 20 during milling with dual centrifugation. Smaller particle sizes were in general obtained at the highest milling intensity, i.e., 1500 rpm, smallest bead size, i.e., 0.2 mm, and higher bead loadings (42%, 56%, and 83%). The grinding limit of approximately 0.50 µm, 0.70 µm, and 0.35 µm for cinnarizine, haloperidol, and indomethacin, respectively, was achieved relatively fast, i.e., 30 minutes of milling at the specified conditions, compared to when suspensions were milled with larger bead sizes (i.e., 1.0 mm), lower milling intensities (e.g., 1000 rpm), and lower bead loadings (e.g., 14 or 28%). The study further confirmed that a higher milling intensity was necessary during milling of haloperidol suspensions probably due to the compounds predominantly plastic properties. Sizes of indomethacin particles increased with longer milling runs up to 240 minutes and also higher bead loadings of 56% and 83%. These observations were further supported by the color conversion from white to yellow of indomethacin suspensions which indicated generation of small quantities of amorphic material after milling with a high milling intensity. Upscale investigations showed comparable particle size profiles for all three model compounds while milling at 1500 rpm for five minutes.

Machine learning-based prediction of CoCrFeNiMo0.2 high-entropy alloy weld bead dimensions in wire arc additive manufacturing

Wire arc additive manufacturing (WAAM) is a promising method to fabricate large-sized components. By adjusting WAAM process parameters, dimensions of WAAM-produced weld beads can be optimized. To this end, the current study adopted the cold metal transition (CMT) process to produce different-sized beads of CoCrFeNiMo0.2 high-entropy alloy (HEA), varying WAAM parameters and linking them with the formed bead dimensions and bead-substrate contact angles. Three machine learning algorithms, namely back propagation neural network (BPNN), support vector regression (SVR), and random forest regression (RFR), were used to predict bead dimensions and contact angles under various WAAM parameters. The BPNN model has great prediction performance in the height of beads. The SVR model has the highest accuracy in predicting the width and cross-sectional area of beads. The RFR outperforms the other two models in contact angles prediction. This work not only provides a reference for the WAAM of high-entropy alloys, but also provides new ideas for predicting bead size in WAAM.

Mechanochemical Activation of Nickel Oxide Enabling Binder-Free Anodes for Alkaline Water Electrolysis

In recent decades, the imperative for clean energy generation has grown significantly. Water electrolysis stands out as a sustainable method for hydrogen production due to its zero carbon emissions. However, high energy requirements and costs hinder its widespread adoption for large-scale applications [1]. Non-noble metal-based materials have emerged as cost-effective and efficient anodes for the oxygen evolution reaction (OER). However, the stability and performance of these materials heavily rely on the integration of ionomers or binders into the electrode coatings. For example, Nafion, renowned for its high ionic conductivity and ability to stabilize coating structures [2], has been a preferred choice [3]. Yet, their high cost and impending regulations concerning per- and polyfluoro alkyl substances (PFAS) by European agencies necessitate the exploration of alternative approaches. Here, we propose a solution involving binder-free anode coatings, achieved through mechano-chemical activation via planetary ball milling of commercially available catalyst materials. This innovative method offers a promising avenue for developing environmentally sustainable anodes with effective performance, circumventing the limitations associated with conventional binder materials.In this study, nickel oxide (NiO, Merck group) was processed without binders through a modification of the powder material via planetary ball milling where parameters as bead size, rotation speed, and process time were varied. The initial visual contrast transformation from the green hue of the NiO feed to a dark grey or black shade appearance after ball milling which might indicate the presence of Ni2O3. Additionally, certain samples exhibited a needle-like morphology, with particle enlargement occurring selectively in instances involving larger beads during the milling process. These samples were discarded due to missing processability. Powder characterizations were conducted on both the as-purchased NiO feed (as reference) and the ball milled samples. Transmission electron microscopy (TEM) analysis confirmed reduced primary particle size across all ball milled samples as shown in the inset of Figure 1a-b. Energy dispersive X-ray (EDX) analysis indicated a decrease in the Ni metal content with a simultaneous increase in the oxygen content, while – in line with our expectations [4] – the reduced crystallinity of all NiO phases after ball milling was confirmed by X-ray diffraction (XRD) analysis. With regard to the surface species, Fourier-transform infrared (FTIR) spectroscopy evidenced a significant increase of hydroxide (OH) in the ball milled samples. At the same time X-ray photoelectron spectroscopy (XPS) data revealed an increase in the Ni3+ content, followed by a decrease in Ni2+ as analyzed from the Ni 2p spectrum. Combining both findings, we expect an improved anode performance due to the formation of Ni(OH)2 or NiOOH species [5]. Preliminary dispersion experiments were realized in different probe liquids [6] and subsequently the Hansen solubility parameters (HSP) were determined to achieve high-quality dispersions efficiently [7]. Because of the large particle size, all dispersions based on commercial NiO sedimented quickly, whereas the ball milled samples with significantly reduced primary particle size were stable in liquids like ethanol and isopropanol.This finding was quantified by transmittograms, where the sedimentation time, radial position and transmission are plotted together as shown in Figure 1a-b. Due to the inadequate dispersion stability of commercial NiO and thus missing processability, no electrodes were realized with this material. Finally, the ball milled samples were spray-coated onto Ni plate substrates without using binders. Scanning electron microscopy (SEM) images displayed diverse distributions of catalyst particles implying different coating structures and a range of morphologies. Electrochemical measurements at 100 mA cm-2 evidenced an improved activity of ~100 mV for the electrodes that were fabricated from the ball milled samples (Sample 1: 400 rpm, 4 h, Sample 2: 250 rpm, 2 h, constant bead size of 0.3 mm) during oxygen evolution compared to the bare Ni plate substrate as shown in Figure 1c. Within 2 h of testing, no delamination of the material was monitored evidencing its chemical and mechanical stability as a binder-free catalyst layer.In conclusion, this study presents a promising approach to achieve binder-free anodes enabled by mechanochemical activation. The versatility of this method offers opportunities to optimize non-noble metal-based materials for enhanced OER performance, thereby advancing the prospects of sustainable energy generation.

Enhanced therapeutic efficacy of granulocyte/monocyte adsorption in rats with drug-induced colitis : Insights from a downsized bead column and newly formed B cells.

Granulocyte/monocyte adsorption therapy can manage mild-to-moderate inflammatory bowel disease by removing activated granulocytes and monocytes. We evaluated granulocyte/monocyte adsorption using new columns with reduced bead size and theoretically enhanced adsorption. We assessed granulocyte/monocyte adsorption in rats with colitis by analyzing cell changes and cytokine production. Granulocyte/monocyte adsorption with the new columns improved histology in rats with colitis. Contrary to expectations, the adsorption rate of granulocytes/monocytes into the blood did not show a significant improvement. However, flow cytometry showed increased B cells in peripheral blood mononuclear cells and newly formed B cells in the bone marrow, which produced more interleukin-10 than peripheral blood B cells. Newly formed B cells adoptively transferred into colitis rats accumulated at the inflammation site and tended to inhibit intestinal shortening. Newly formed B cells with strong interleukin-10 production may alleviate inflammation. The new columns suggest potential for controlling colitis.

Machine learning strengthened formulation design of pharmaceutical suspensions

Many different formulation strategies have been investigated to oppose suboptimal treatment of long-term or chronic conditions, one of which are the nano- and microsuspensions prepared as long-acting injectables to prolong the release of an active pharmaceutical compound for a defined period of time by regulating the size of particles by milling. Typically, surfactant and/or polymers are added in the dispersion medium of the suspension during processing for stabilization purposes. However, current formulation investigations with milling are heavily based on prior expertise and trial-and-error approaches. Various interacting parameters such as the milling bead size, stabilizer type and concentration have confounded the investigation of milling process. The present study systematically exploited statistical and machine learning (ML) strategies to understand the relationship between suspension characteristics and formulation parameters under full-factorial milling experiments. Stabilizer concentration was identified as a significant factor (p < 0.001) for median suspension diameter (D50). A formulation stability classification ML model with high prediction accuracy (0.91) and F1-score (0.91) under 10-fold cross-validation was constructed based on 72 formulation datapoints. Model interpretation through Shapley additive explanations (SHAP) revealed the prominent impact of stabilizer concentration and milling bead size on formulation stability. The present work demonstrated the potential to achieve a deeper understanding of the design and optimization of nano- and microsuspensions through explainable ML modelling on formulation screening data.

Thymoquinone Pectin Beads Produced via Electrospray: Enhancing Oral Targeted Delivery for Colorectal Cancer Therapy.

Background/Objectives: Thymoquinone (TQ) exhibits diverse biological activities, but its poor solubility and bioavailability limit its cancer efficacy, requiring innovative solutions. This study explores the development of an oral delivery system targeting colon cancer based on TQ pectin beads (TQ-PBs) produced through an adjustable electrospray technique. This study hypothesised that adjusting bead diameter through the electrospray technique enables precise control over water absorption and erosion rates, thereby achieving a controlled release profile for encapsulated TQ, which enhances targeted delivery to the colon. Methods: TQ-PBs were synthesised and optimised using an electrospray technique based on the ionic gelation method. The prepared beads were characterised based on particle size, sphericity, encapsulation efficiency (EE), water uptake, erosion, surface morphology, molecular interactions, and texture. The cumulative TQ release studies, an accelerated stability test, and cytotoxicity evaluation against the colon cancer HT-29 cell line were also assessed. Results: The optimised TQ-PB formulation demonstrated an average bead size of 2.05 ± 0.14 mm, a sphericity of 0.96 ± 0.05, and an EE of 90.32 ± 1.04%. The water uptake was 287.55 ± 10.14% in simulated gastric fluid (SGF), 462.15 ± 12.73% in simulated intestinal fluid (SIF), and 772.41 ± 13.03% in simulated colonic fluid (SCF), with an erosion rate of 45.23 ± 5.22%. TQ release was minimal in SGF (8.13 ± 1.94% after 2 h), controlled in SIF (29.35 ± 3.65% after 4 h), and accelerated in SCF (94.43 ± 2.4% after 3 h). Stability studies over one month showed a size reduction of 17.50% and a 6.59% decrease in TQ content. Cytotoxicity assessments revealed significant anticancer activity of TQ-PB, with an IC50 of 80.59 ± 2.2 μg/mL. Conclusions: These findings underscore the potential of TQ-PB as an effective oral drug delivery system for targeted colorectal cancer therapy.

Separation of Lung Cancer Cells From Mixed Cell Samples Using Aptamer-Modified Magnetic Beads and Permalloy Micromagnets.

This study involved the design and fabrication of a microfluidic chip integrated with permalloy micromagnets. The device was used with aptamer-modified magnetic beads (MBs) of various sizes to successfully separate lung cancer cells from a mixture of other cells. The overall separation efficiency was evaluated based on the ratios of cells in the different outlets and inlets of the chip. The results showed efficiencies ranging from 43.4% to 50.2% for MB sizes between 1.36 and 4.50 µm. Interestingly, efficiency slightly decreased as the size of the MBs increased, contrary to predictions. Further examination revealed that larger MBs exerted gravitational force on the cell-bound MBs at low flow rates, causing the targets to settle before reaching the main microchannel region. This was attributed to fluidic resistance caused by a size mismatch between the inlet tube and the microfluidic conduit. An increase in cell accumulation at the inlet was observed with larger MB sizes due to gravity. Therefore, the definition of effective separation efficiency was revised to exclude the effect of cell accumulation at the inlet. Effective separation efficiencies were found to be 71.6%, 76.4%, and 79.4% for MB sizes of 1.36, 3.00, and 4.50µm, respectively. The study concluded that larger MBs interacted more with the magnetic force, resulting in better separation. However, cells with smaller MBs were more likely to evade the magnetic force. The investigation provides valuable insights into isolating lung cancer cells using this method, with the potential for clinical application in cancer diagnosis and treatment.

Effects of Glass Bead Size on Dissolution Profiles in Flow-through Dissolution Systems (USP 4).

The effects of glass bead size in the conical space of flow-through cells on the dissolution profiles were investigated in a USP apparatus 4. Dissolution tests of disintegrating and non-disintegrating tablets in flow-through dissolution systems were performed using semi-high precision glass beads with diameters ranging from 0.5mm to 1.5mm. Computational fluid dynamics (CFD) was used to evaluate the effect of shear stress from the dissolution media flow. The use of smaller glass beads in a larger cell resulted in a faster dissolution of the model formulations under certain test conditions. The effect on the dissolution was highly dependent on the size of the beads in the top layer, including those in contact with the tablets. The absence of a bead-size effect on the dissolution of an orodispersible tablet in a small cell can be explained by the floating fragments during the test. CFD analysis showed that smaller bead diameters led to greater shear stress on the tablet, which was correlated with the dissolution rate. Hence, fluid flow through the narrow gaps between the small beads generated strong local flows, causing shear stress. The size of the glass beads used in flow-through cells affects the dissolution rate of tablets by altering the shear stress on the tablets in certain cases (e.g., direct deposition of the formulation on glass beads, large cells, and very low flow rates). Thus, glass bead size must be considered for a robust dissolution test in a flow-through cell system.

Synthesis of Black Seed Oil-loaded-, Alginate-based, pH-sensitive Beads Using Electrospraying Technique.

Black seed oil (BSO), derived from the seeds of the Nigella sativa plant, has garnered attention for its potential anti-cancer properties, particularly in the context of colon cancer. Its active compound, thymoquinone, may help inhibit cancer cell growth and induce apoptosis in colon cancer cells. Additionally, black seed oil's anti-inflammatory and antioxidant effects could contribute to a healthier gut environment, potentially reducing cancer risk. Therefore, this study synthesized pH-sensitive alginate beads to deliver BSO into the colon in a controlled-release manner without releasing the drug at pH 1.2 (stomach), thus providing a well-defined release pattern at pH 6.8. The use of electrospray technology improves process performance by making it easier to formulate small, homogeneous beads with a higher rate of swelling and diffusion in the gastrointestinal medium. The formulated beads were characterized by an ex-vivo mucoadhesive strength test, bead size, sphericity factor (SF), encapsulation efficiency (EE), scanning electron microscope (SEM), in vitro swelling behavior (SB), and in vitro drug release in acidic and buffer media. All these manufactured beads demonstrated modest sizes of 0.58 ± 0.01 mm and spherical shape of 0.03 ± 0.00 mm in this testing. The formulation showed promising floating and releasing properties in vitro. With a very low cumulative percentage of beads, the oil EE of 90.13% ± 0.93% was high, and the release study demonstrated more than 90% in pH 6.8 with good floating nature in the stomach. Additionally, the beads were evenly spaced throughout the intestine. The electrospraying approach used in this protocol can be reproducible, yielding consistent outcomes. Therefore, this protocol can be used for large-scale production for commercialization purposes.

Assessment of inhaled cationic antibiotics in an in vitro model of Pseudomonas aeruginosa lung biofilm

ObjectivesThis study aimed to evaluate the efficacy of inhaled cationic antibiotics, including tobramycin (TOB) and colistin (CST), using an in vitro alginate bead model that simulates Pseudomonas aeruginosa lung biofilms. MethodsBioluminescent P. aeruginosa were encapsulated within alginate beads and dispersed in either Mueller-Hinton broth (MHB) or artificial sputum medium (ASM). The impact of bead size and culture medium on TOB and CST efficacy was assessed by monitoring bioluminescence kinetics, followed by colony-forming unit (CFU/mL) measurements. Antibiotic efficacy was quantified using a Hill inhibitory model to analyze variations in CFU/mL in response to TOB and CST concentrations. ResultsThe TOB EC50 was found to be 8-fold higher when P. aeruginosa was encapsulated in larger beads (1200 μm) compared to smaller beads (60 μm). TOB efficacy further decreased twofold when larger beads were dispersed in ASM. In contrast, CST demonstrated superior efficacy, being four times more potent than TOB, with corresponding EC50 values of 20.5 ± 2.8 times MIC and 78.4 ± 10.2 times MIC, respectively. No change in MICs was observed for either antibiotic, even after exposing bacteria to 200 times the MIC. ConclusionsThis P. aeruginosa biofilm model highlights how alginate and mucus modulated the efficacy of TOB and CST, and suggested the superior efficacy of CST in eradicating pulmonary biofilms.

Extraction, Characterization, and Encapsulation of Cinnamon Hydrosol Obtained via Microwave-Assisted Hydrodistillation: Analysis of Antioxidant and Antimicrobial Activities

Microwave-assisted hydrodistillation (MAHD) method was employed to extract cinnamon oil and hydrosol (a byproduct). The total polyphenol content (TPC) of the cinnamon hydrosol (CH) was determined using the Folin-Ciocalteu method, and its antioxidant power was assessed through the DPPH radical reduction method. Gas chromatography was utilized to quantify the main bioactive compound (cinnamaldehyde). The disc agar diffusion method was applied to evaluate the inhibition of pathogenic microorganisms. To protect the bioactive compound, an encapsulation method involving cross-linking with calcium alginate was utilized. The capsules were examined using environmental scanning electron microscopy (ESEM). The TPC content was found to be 15.63 ± 0.21 mg gallic acid/g dry matter, and the DPPH radical inhibition rate was 84.26 ± 1.35%. CH exhibited a significant inhibitory effect against Escherichia coli, and a moderate inhibition effect against Shigella flexneri, Salmonella spp., Salmonella typhimurium, and Escherichia coli EPEC. Finally, successful encapsulation of CH was achieved using sodium alginate, resulting in bead sizes ranging between 1.75 and 2.75 mm.

A Bronze Age Site on the Northern Coast of West Java

This study describes an early site on the northern coast of West Java, affected by the Austronesian culture—Subanglarang near Binong in the Subang Regency. Geologically, during the 2000–1000 BP interval, it was part of the coastline of the northern coast of West Java, situated more than 5 m asl. During the 2013 surveys and excavations in 2016 and 2018, five burials were revealed. On the basis of the fragments of red-slipped pottery, pickaxes, beads of various shape and size, and metal weapons, the site is dated to the Bronze Age. Artifacts similar to those of early Austronesians were discovered. The analysis of various beads from Subanglarang attests to trade relations with other areas. Further excavations on the northern coast of West Java will hopefully shed more light on the life of the Bronze Age people of that area.

Stirred media mills of fine and ultrafine grinding for subsequent beneficiation operations

This paper presents a brief review of the designs, characteristics, and operating parameters of Stirred media mills supplied by foreign manufacturers. An analysis of information on Stirred media mills , which are used to improve the efficiency of beneficiation and metallurgical operations, is carried out using available publications. The obtained results indicate the inexpediency of using conventional drum ball mills for flotation separation of ores and concentrates with a fine interpenetration of minerals. The application of conventional mills in extraction of ores and concentrates resistant to cyanidation, where gold is finely disseminated in sulfides, is limited by their high power consumption and the corresponding operating costs. In this work, different types of Stirred media mills are considered, including their vertical and horizontal types. The advantages of Stirred media mills over conventional ball mills, particularly in terms of energy efficiency, are noted. The designs and main characteristics of Stirred media mills , which have received wide application, are presented. According to the data presented in the reviewed publications, the main parameters determining the grinding process in such mills are outlined, including the ratio of bead size to mill feed size, density of grinding medium, density of pulp in the mill, volume loading of beads, stirring speed, etc. The conducted analysis of literature data indicated high efficiency of mills based on agitation of grinding media for fine and ultrafine grinding of ores and concentrates in comparison with conventional ball mills. Given that the volume of ores and concentrates resistant to processing by conventional methods is increasing, the application of Stirred media mills is expected become more widespread, thereby increasing the efficiency of subsequent beneficiation and metallurgical operations.

Ultrasensitive detection of cancer-associated nucleic acids and mutations by primer exchange reaction-based signal amplification and flow cytometry

The detection of cancer-associated nucleic acids and mutations through liquid biopsy has emerged as a highly promising non-invasive approach for early cancer detection and monitoring. In this study, we report the development of primer exchange reaction (PER) based signal amplification strategy that enables the rapid, sensitive and specific detection of nucleic acids bearing cancer specific single nucleotide mutations using flow cytometry. Using micrometer size beads as support for immobilizing oligonucleotides and programmable PER assembly for target oligonucleotide recognition and fluorescence signal amplification, we demonstrated the versatile detection of target nucleic acids including KRAS oligonucleotide, fragmented mRNAs, and miR-21. Moreover, our detection system can discriminate single base mutations frequently occurred in cancer-associated genes including KRAS, PIK3CA and P53 from cell extracts and circulating tumor DNAs (ctDNAs). The detection is highly sensitive, with a limit of detection down to 27 fM without pre-amplification. In view of a clinical application, we demonstrate the detection of single mutations after extraction and pre-amplification of ctDNAs from the plasma of breast cancer patients. Importantly, our detection strategy enabled the detection of single KRAS mutation even in the presence of 1000-fold excess of wild type (WT) DNA using multi-color flow cytometry detection approach. Overall, our strategy holds immense potential for clinical applications, offering significant improvements for early cancer detection and monitoring.

Making connections: ostrich eggshell beads as indicators of precolonial societal interaction in southeastern southern Africa

ABSTRACT Ostriches are peculiar birds and their strangeness has been recognised by southern African hunter-gatherers through multiple symbolic associations. Such qualities are likely to have been enhanced where people had access to beads made from their eggshell but did not have direct knowledge of the birds themselves. Southeastern southern Africa, encompassing the Maloti-Drakensberg Mountains, the eastern half of the Eastern Cape Province and much of KwaZulu-Natal is one such area. We review the unusual attributes and associations of ostriches and their eggshell before briefly summarising previous work that has used strontium isotope analysis to investigate past bead exchange networks in this region. Because bead size can be controlled and patently varies through time and space, we then employ it as another potential indicator of the existence and spatial extent of past social networks. Having critically considered previous efforts in this field, we report on our work to build the largest sample of such data yet obtained in southern Africa and compare our preliminary results with other signals of interaction between precolonial hunter-gatherer and (where applicable) agropastoralist communities.

Flow-on-repellent biofabrication of fibrous decellularized breast tumor-stroma models

On-the-fly biofabrication of reproducible 3D tumor models at a pre-clinical level is highly desirable to level-up their applicability and predictive potential. Incorporating ECM biomolecular cues and its complex 3D bioarchitecture in the design stages of such in vitro platforms is essential to better recapitulate the native tumor microenvironment. To materialize these needs, herein we describe an innovative flow-on-repellent (FLORE) 3D extrusion bioprinting technique that leverages expedited and automatized bioink deposition onto a customized superhydrophobic printing bed. We demonstrate that this approach enables the rapid generation of quasi-spherical breast cancer-stroma hybrid models in a mode governed by surface wettability rather than bioink rheological features. For this purpose, an ECM-mimetic bioink comprising breast tissue-specific decellularized matrix in the form of microfiber bundles (dECM-μF) and photocrosslinkable hyaluronan (HAMA), was formulated to generate triple negative breast tumor-stroma models. Leveraging on the FLORE bioprinting approach, a rapid, automated, and reproducible fabrication of physiomimetic breast cancer hydrogel beads was successfully demonstrated. Hydrogel beads size with and without dECM-μF was easily tailored by modelling droplet deposition time on the superhydrophobic bed. Interestingly, in heterotypic breast cancer-stroma beads a self-arrangement of different cellular populations was observed, independent of dECM-μF inclusion, with CAFs clustering overtime within the fabricated models. Drug screening assays showed that the inclusion of CAFs and dECM-μF also impacted the overall response of these living constructs when incubated with gemcitabine chemotherapeutics, with dECM-μF integration promoting a trend for higher resistance in ECM-enriched models. Overall, we developed a rapid fabrication approach leveraging on extrusion bioprinting and superhydrophobic surfaces to process photocrosslinkable dECM bioinks and to generate increasingly physiomimetic tumor-stroma-matrix platforms for drug screening.