Artículos de revistas: "Droplet disruption"

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Preiss, Felix Johannes, Teresa Dagenbach, Markus Fischer y Heike Petra Karbstein. "Development of a Pressure Stable Inline Droplet Generator with Live Droplet Size Measurement". ChemEngineering 4, n.º 4 (10 de noviembre de 2020): 60. http://dx.doi.org/10.3390/chemengineering4040060.

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For the research on droplet deformation and breakup in scaled high-pressure homogenizing units, a pressure stable inline droplet generator was developed. It consists of an optically accessible flow channel with a combination of stainless steel and glass capillaries and a 3D printed orifice. The droplet size is determined online by live image analysis. The influence of the orifice diameter, the mass flow of the continuous phase and the mass flow of the disperse phase on the droplet diameter were investigated. Furthermore, the droplet detachment mechanisms were identified. Droplet diameters with a small diameter fluctuation between 175 µm and 500 µm could be realized, which allows a precise adjustment of the capillary (Ca) and Weber (We) Number in the subsequent scaled high pressure homogenizer disruption unit. The determined influence of geometry and process parameters on the resulting droplet size and droplet detachment mechanism agreed well with the literature on microfluidics. Furthermore, droplet trajectories in an exemplary scaled high-pressure homogenizer disruption unit are presented which show that the droplets can be reinjected on a trajectory close to the center axis or close to the wall, which should result in different stresses on the droplets.

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Adeyo, Oludotun, Patrick J. Horn, SungKyung Lee, Derk D. Binns, Anita Chandrahas, Kent D. Chapman y Joel M. Goodman. "The yeast lipin orthologue Pah1p is important for biogenesis of lipid droplets". Journal of Cell Biology 192, n.º 6 (21 de marzo de 2011): 1043–55. http://dx.doi.org/10.1083/jcb.201010111.

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Lipins are phosphatidate phosphatases that generate diacylglycerol (DAG). In this study, we report that yeast lipin, Pah1p, controls the formation of cytosolic lipid droplets. Disruption of PAH1 resulted in a 63% decrease in droplet number, although total neutral lipid levels did not change. This was accompanied by an accumulation of neutral lipids in the endoplasmic reticulum (ER). The droplet biogenesis defect was not a result of alterations in neutral lipid ratios. No droplets were visible in the absence of both PAH1 and steryl acyltransferases when grown in glucose medium, even though the strain produces as much triacylglycerol as wild type. The requirement of PAH1 for normal droplet formation can be bypassed by a knockout of DGK1. Nem1p, the activator of Pah1p, localizes to a single punctum per cell on the ER that is usually next to a droplet, suggesting that it is a site of droplet assembly. Overall, this study provides strong evidence that DAG generated by Pah1p is important for droplet biogenesis.

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Kropotova, Svetlana y Pavel Strizhak. "Collisions of Liquid Droplets in a Gaseous Medium under Conditions of Intense Phase Transformations: Review". Energies 14, n.º 19 (27 de septiembre de 2021): 6150. http://dx.doi.org/10.3390/en14196150.

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The article presents the results of theoretical and experimental studies of coalescence, disruption, and fragmentation of liquid droplets in multiphase and multicomponent gas-vapor-droplet media. Highly promising approaches are considered to studying the interaction of liquid droplets in gaseous media with different compositions and parameters. A comparative analysis of promising technologies is carried out for the primary and secondary atomization of liquid droplets using schemes of their collision with each other. The influence of a range of factors and parameters on the collision processes of drops is analyzed, in particular, viscosity, density, surface, and interfacial tension of a liquid, trajectories of droplets in a gaseous medium, droplet velocities and sizes. The processes involved in the interaction of dissimilar droplets with a variable component composition and temperature are described. Fundamental differences are shown in the number and size of droplets formed due to binary collisions and collisions between droplets and particles at different Weber numbers. The conditions are analyzed for the several-fold increase in the number of droplets in the air flow due to their collisions in the disruption mode. A technique is described for generalizing and presenting the research findings on the interaction of drops in the form of theoretical collision regime maps using various approaches.

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Orme, M. "Experiments on droplet collisions, bounce, coalescence and disruption". Progress in Energy and Combustion Science 23, n.º 1 (1997): 65–79. http://dx.doi.org/10.1016/s0360-1285(97)00005-1.

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5

Gall, Vanessa y Heike P. Karbstein. "Influence of Cavitation and Mixing Conditions on Oil Droplet Size in Simultaneous Homogenization and Mixing (SHM)". ChemEngineering 4, n.º 4 (9 de diciembre de 2020): 64. http://dx.doi.org/10.3390/chemengineering4040064.

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High-pressure homogenizers (HPH) equipped with a Simultaneous Homogenization and Mixing (SHM) orifice allow for inducing a mixing stream directly into the disruption unit. Previous studies show that by doing so, synergies between the unit operations “emulsification” and “mixing” can be used to save energy, e.g., in homogenization of dairy products, or to extend the application range of HPH. Up to now, process design has mainly been based on the trial and error principle due to incomplete understanding of flow conditions and droplet break-up in the SHM unit. This study aims at a higher level of understanding of cavitation and mixing effects on emulsion droplet size. Experimental data were obtained using a model emulsion of low disperse phase concentration in order to avoid coalescence effects. The different flow conditions are created by varying the process and geometric parameters of an SHM unit. The results show that the oil droplet size only depends on mixing conditions when the emulsion droplets are added in the mixing stream. Furthermore, a smaller oil droplet size can be achieved by reducing cavitation, especially for droplets fed in the high-pressure stream.

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6

Yong, Ah Pis, Md Aminul Islam y Nurul Hasan. "The Effect of pH and High-Pressure Homogenization on Droplet Size". International Journal of Engineering Materials and Manufacture 2, n.º 4 (10 de diciembre de 2017): 110–22. http://dx.doi.org/10.26776/ijemm.02.04.2017.05.

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The aims of this study are to revisit the effect of high pressure on homogenization and the influence of pH on the emulsion droplet sizes. The high-pressure homogenization (HPH) involves two stages of processing, where the first stage involves in blending the coarse emulsion by a blender, and the second stage requires disruption of the coarse emulsion into smaller droplets by a high-pressure homogenizer. The pressure range in this review is in between 10-500 MPa. The homogenised droplet sizes can be reduced by increasing the homogenization recirculation, and there is a threshold point beyond that by applying pressure only, the size cannot be further reduced. Normally, homogenised emulsions are classified by their degree of kinetic stability. Dispersed phase present in the form of droplets while continuous phase also known as suspended droplets. With a proper homogenization recirculation and pressure, a more kinetically stable emulsion can be produced. The side effects of increasing homogenization pressure are that it can cause overprocessing of the emulsion droplets where the droplet sizes become larger rather than the expected smaller size. This can cause kinetic instability in the emulsion. The droplet size is usually measured by dynamic light scattering or by laser light scattering technique. The type of samples used in this reviews are such as chocolate and vanilla based powders; mean droplet sizes samples; basil oil; tomato; lupin protein; oil; skim milk, soymilk; coconut milk; tomato homogenate; corn; egg-yolk, rapeseed and sunflower; Poly(4-vinylpyridine)/silica; and Complex 1 until complex 4 approaches from author case study. A relationship is developed between emulsion size and pH. Results clearly show that lower pH offers smaller droplet of emulsion and the opposite occurs when the pH is increased.

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Demidovich, A. V., S. S. Kralinova, P. P. Tkachenko, N. E. Shlegel y R. S. Volkov. "Interaction of Liquid Droplets in Gas and Vapor Flows". Energies 12, n.º 22 (8 de noviembre de 2019): 4256. http://dx.doi.org/10.3390/en12224256.

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We investigated the conditions, characteristics, and outcomes of liquid droplet interaction in the gas medium using video frame processing. The frequency of different droplet collision outcomes and their characteristics were determined. Four interaction regimes were identified: bounce, separation, coalescence, and disruption. Collision regime maps were drawn up using the Weber, Reynolds, Ohnesorge, Laplace, and capillary numbers, as well as dimensionless linear and angular parameters of interaction. Significant differences were established between interaction maps under ideal conditions (two droplets colliding without a possible impact of the neighboring ones) and collision of droplets as aerosol elements. It was shown that the Weber number could not be the only criterion for changing the collision mode, and sizes and concentration of droplets in aerosols influence collision modes. It was established that collisions of droplets in a gaseous medium could lead to an increase in the liquid surface area by 1.5–5 times. Such a large-scale change in the surface area of the liquid significantly intensifies heat transfer and phase transformations in energy systems.

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8

Piskunov, Maxim, Nikita Shlegel, Svetlana Kralinova, Pavel Tkachenko y Olga Vysokomornaya. "Interaction times of homogeneous and heterogeneous droplets in gases". Thermal Science, n.º 00 (2021): 187. http://dx.doi.org/10.2298/tsci190928187p.

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In this research, we present the results of experiments measuring the interaction times of colliding liquid droplets in different modes (bounce, coalescence, separation, and disruption). The experiments involve water and typical water-based slurries, emulsions, and solutions. The main experimental parameters are close to those of high-potential gas-vapor-droplet technologies (heat and mass transfer power plants, thermal and flame water treatment systems, and fuel technologies): droplet size 0.1-5 mm; velocities 0.1-10 m/s; liquid temperature 20-80 ?C; impact angle 0-90?; relative volume and mass fractions of liquid and solid additives in water 0-10%. We explore how a set of parameters and effects influence the characteristics of the processes under study. The most important of these parameters are relative droplet velocity, impact angle, impact parameter, and temperature. Using dimensionless linear and angular interaction parameters as well as the Weber, Reynolds and Ohnesorge numbers, we produce interaction mode maps to consider the correlation of the main forces: inertia, surface tension, and viscosity. We determine the interaction times, number, size, and total surface area of the newly formed post-collision droplets and obtain approximations for the experimentally determined functions.

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9

Preiss, Felix Johannes, Benedikt Mutsch, Christian J. Kähler y Heike Petra Karbstein. "Scaling of Droplet Breakup in High-Pressure Homogenizer Orifices. Part I: Comparison of Velocity Profiles in Scaled Coaxial Orifices". ChemEngineering 5, n.º 1 (7 de febrero de 2021): 7. http://dx.doi.org/10.3390/chemengineering5010007.

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Properties of emulsions such as stability, viscosity or color can be influenced by the droplet size distribution. High-pressure homogenization (HPH) is the method of choice for emulsions with a low to medium viscosity with a target mean droplet diameter of less than 1 µm. During HPH, the droplets of the emulsion are exposed to shear and extensional stresses, which cause them to break up. Ongoing work is focused on better understanding the mechanisms of droplet breakup and relevant parameters. Since the gap dimensions of the disruption unit (e.g., flat valve or orifice) are small (usually below 500 µm) and the droplet breakup also takes place on small spatial and time scales, the resolution limit of current measuring systems is reached. In addition, the high velocities impede time resolved measurements. Therefore, a five-fold and fifty-fold magnified optically accessible coaxial orifice were used in this study while maintaining the dimensionless numbers characteristic for the droplet breakup (Reynolds and Weber number, viscosity and density ratio). Three matching material systems are presented. In order to verify their similarity, the local velocity profiles of the emerging free jet were measured using both a microparticle image velocimetry (µ-PIV) and a particle image velocimetry (PIV) system. Furthermore, the influence of the outlet geometry on the velocity profiles is investigated. Similar relationships were found on all investigated scales. The areas with the highest velocity fluctuations were identified where droplets are exposed to the highest turbulent forces. The Reynolds number had no influence on the normalized velocity fluctuation field. The confinement of the jet started to influence the velocity field if the outlet channel diameter is smaller than 10 times the diameter of the orifice. In conclusion, the scaling approach offers advantages to study very fast processes on very small spatial scales in detail. The presented scaling approach also offers chances in the optimization of the geometry of the disruption unit. However, the results also show challenges of each size scale, which can come from the respective production, measurement technology or experimental design. Depending on the problem to be investigated, we recommend conducting experimental studies at different scales.

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10

Lieber, J. G. y R. M. Evans. "Disruption of the vimentin intermediate filament system during adipose conversion of 3T3-L1 cells inhibits lipid droplet accumulation". Journal of Cell Science 109, n.º 13 (15 de diciembre de 1996): 3047–58. http://dx.doi.org/10.1242/jcs.109.13.3047.

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During the differentiation of 3T3-L1 pre-adipocytes, vimentin intermediate filaments are reorganized to form cage-like structures around the nascent lipid droplets. Initial studies with 3T3-L1 cells indicated that aggregation of vimentin filaments by nocodazole treatment during or shortly after induction of adipose conversion dramatically reduced the lipid droplet content of 3T3-L1 cells 96–120 hours after induction. Specific but transient disruption of vimentin following anti-IFA antibody injection also resulted in a decrease in lipid droplet formation in differentiating cells. To specifically and stably affect filament organization, 3T3-L1 cells lines were established by transfection with a glucocorticoid-regulatable, dominant negative mutant vimentin cDNA expression plasmid. Treatment of these cells (83 delta C) with dexamethasone resulted in expression of vimentin with a carboxyl-terminal deletion, which led to the disruption of the endogenous filament network. Induction of adipose conversion in 83 delta C cells lead to the formation of lipid droplets comparable to those seen in untransfected 3T3-L1 cells. Addition of dexamethasone during the adipose conversion of 83 delta C cells did not affect the induction of the marker enzyme glycerol-3-phosphate dehydrogenase or the incorporation of [14C]palmitate into triglycerides during a 10 minute pulse label. There was, however, a failure to form prominent lipid droplets and to accumulate [14C]palmitate-labeled triglycerides. Pulse-chase experiments indicated that the failure of these cells to accumulate triglyceride was associated with an increased rate of turnover. These studies indicate that vimentin filaments provide a function that influences lipid stability during adipose conversion of 3T3-L1 cells.

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11

Hommel, Angela, Deike Hesse, Wolfgang Völker, Alexander Jaschke, Markus Moser, Thomas Engel, Matthias Blüher et al. "The ARF-Like GTPase ARFRP1 Is Essential for Lipid Droplet Growth and Is Involved in the Regulation of Lipolysis". Molecular and Cellular Biology 30, n.º 5 (28 de diciembre de 2009): 1231–42. http://dx.doi.org/10.1128/mcb.01269-09.

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ABSTRACT ADP-ribosylation factor (ARF)-related protein 1 (ARFRP1) is a GTPase regulating protein trafficking between intracellular organelles. Here we show that mice lacking Arfrp1 in adipocytes (Arfrp1 ad−/−) are lipodystrophic due to a defective lipid droplet formation in adipose cells. Ratios of mono-, di-, and triacylglycerol, as well as the fatty acid composition of triglycerides, were unaltered. Lipid droplets of brown adipocytes of Arfrp1 ad−/− mice were considerably smaller and exhibited ultrastructural alterations, such as a disturbed interaction of small lipid-loaded particles with the larger droplets, suggesting that ARFRP1 mediates the transfer of newly formed small lipid particles to the large storage droplets. SNAP23 (synaptosomal-associated protein of 23 kDa) associated with small lipid droplets of control adipocytes but was located predominantly in the cytosol of Arfrp1 ad−/− adipocytes, suggesting that lipid droplet growth is defective in Arfrp1 ad−/− mice. In addition, levels of phosphorylated hormone-sensitive lipase (HSL) were elevated, and association of adipocyte triglyceride lipase (ATGL) with lipid droplets was enhanced in brown adipose tissue from Arfrp1 ad−/− mice. Accordingly, basal lipolysis was increased after knockdown of Arfrp1 in 3T3-L1 adipocytes. The data indicate that disruption of ARFRP1 prevents the normal enlargement of lipid droplets and produces an activation of lipolysis.

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12

Lin, Cherng-Yuan, Chein-Ming Lin y Che-Shiung Cheng. "An Experimental Investigation of Burning Droplets of Emulsified Marine Fuel Oils with Water". Journal of Ship Research 39, n.º 01 (1 de marzo de 1995): 95–101. http://dx.doi.org/10.5957/jsr.1995.39.1.95.

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An experimental investigation is presented of the influences of emulsification of marine fuel oils A and C with water on the micro-explosion phenomenon and combustion characteristics of a burning droplet. The amount of surfactant and water-to-oil ratio by volume in the emulsion are varied to observe the variations of ignition delay, flame length, time required to attain the maximum flame length, duration as well as intensity of micro-explosion, flame appearance, and overall burning time. The measurements show that the emulsification effects on the combustion of marine fuel oils A and C are different. A droplet of C-oil emulsion is shown to be influenced by the addition of water and surfactant more significantly. The micro-explosion phenomena of droplets of A-and C-oil emulsions are seen to occur after and before their ignition, respectively. In addition, separate combinations of water and surfactant content exist for these fuel oils to achieve better emulsification effects on combustion. Droplets of emulsions with W/O = 15/85, E% = 2% for fuel oil A and W/O = 25/75, E% = 1% for fuel oil C are found to have the most violent droplet-disruption phenomenon and the longest flame length.

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13

Ho, Yi-Ju, Yuan-Chih Chang y Chih-Kuang Yeh. "Improving Nanoparticle Penetration in Tumors by Vascular Disruption with Acoustic Droplet Vaporization". Theranostics 6, n.º 3 (2016): 392–403. http://dx.doi.org/10.7150/thno.13727.

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14

Weibel, Ginny L., Michelle R. Joshi, W. Gray Jerome, Sandra R. Bates, Kevin J. Yu, Michael C. Phillips y George H. Rothblat. "Cytoskeleton disruption in J774 macrophages: Consequences for lipid droplet formation and cholesterol flux". Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids 1821, n.º 3 (marzo de 2012): 464–72. http://dx.doi.org/10.1016/j.bbalip.2011.09.015.

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15

James, Christopher N., Patrick J. Horn, Charlene R. Case, Satinder K. Gidda, Daiyuan Zhang, Robert T. Mullen, John M. Dyer, Richard G. W. Anderson y Kent D. Chapman. "Disruption of theArabidopsisCGI-58 homologue produces Chanarin–Dorfman-like lipid droplet accumulation in plants". Proceedings of the National Academy of Sciences 107, n.º 41 (27 de septiembre de 2010): 17833–38. http://dx.doi.org/10.1073/pnas.0911359107.

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16

Vladisavljević, Goran T., Jeonghee Surh y Julian D. McClements. "Effect of Emulsifier Type on Droplet Disruption in Repeated Shirasu Porous Glass Membrane Homogenization". Langmuir 22, n.º 10 (mayo de 2006): 4526–33. http://dx.doi.org/10.1021/la053410f.

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17

Subitha, Mani, Antonisamy William James, Chinnarasu Sivaprakasam y Vasanthi Nachiappan. "Disruption in phosphate transport affects membrane lipid and lipid droplet homeostasis in Saccharomyces cerevisiae". Journal of Bioenergetics and Biomembranes 52, n.º 4 (27 de mayo de 2020): 215–27. http://dx.doi.org/10.1007/s10863-020-09837-5.

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18

Vysokomornaya, O. V., A. K. Rebrov, P. A. Strizhak y N. E. Shlegel. "A comparative analysis of the interaction regimes of two drops and their large population in an aerosol cloud". Доклады Академии наук 485, n.º 1 (22 de mayo de 2019): 38–43. http://dx.doi.org/10.31857/s0869-5652485138-43.

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A comparative analysis of experimental results obtained by different researchers using two different experimental approaches is presented: phenomenological (registration of conditions, characteristics and modes of interaction between a drop of a shell and a target drop) and statistical (analysis of collisions of tens and even hundreds of drops of liquids as part of an aerosol). The ranges of Weber criterion values (the basic parameter used for analyzing the effects of collisions of droplets in a gaseous medium) are established, corresponding to bounce, coalescence, reflexive and stretching separation, disruption, according to the results of all considered experimental research. The bounce of droplets upon collision can be observed under the conditions We = 0.35–0.5; the probability of droplet coalescence is maximum in the range We = 1–7.5; it is possible to reliably predict spreading at We = 15–50; splitting of droplets most often occurs at values We > 50. The probability of occurrence of other scenarios in the selected We ranges is not zero. The conclusion about the need to combine experimental techniques to obtain the most reliable data and their further use in the development of prognostic models is formulated.

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19

Shlegel, Nikita y Pavel Strizhak. "Collisions of water drops in a gas-vapor environment at high temperatures and vapor concentrations". Thermal Science, n.º 00 (2020): 200. http://dx.doi.org/10.2298/tsci191110200s.

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The study of the characteristics of secondary droplet atomization, leading to formation of an aerosol cloud of polydisperse child droplets appears to be promising. It is topical to assess the influence of properties of liquid and gas medium on the position of transition boundaries between the regimes of drop collisions and characteristics of the formed child droplets. This article presents the experimental results for the characteristics of drop collisions at various temperatures of the liquid and gas-vapor mixture and water vapor concentration in the latter with the aim of developing the prospective heat and mass transfer gas-vapor technologies. For this purpose, we have created the experimental setup that allows varying the relative humidity of gas-vapor mixture in the area of drop collisions from 20% to 100%, its temperature from 20?C to 100?C and the temperature of the liquid from 20?C to 90?C. The test fluid is water. The collisions are recorded by a high-speed video camera. The consequences of collision and the boundaries between them on the regime maps are determined in accordance using the approach, distinguishing: bounce, coalescence, separation, and disruption.

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20

Tesch, Sabine y Helmar Schubert. "Droplet Deformation and Disruption during the Emulsification in a High-Pressure Homogenizer with an Orifice Valve". Chemie Ingenieur Technik 73, n.º 6 (junio de 2001): 693. http://dx.doi.org/10.1002/1522-2640(200106)73:6<693::aid-cite6932222>3.0.co;2-4.

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21

Kelemen, Katharina, Anna C. Schuch y Heike P. Schuchmann. "Influence of Flow Conditions in High-Pressure Orifices on Droplet Disruption of Oil-in-Water Emulsions". Chemical Engineering & Technology 37, n.º 7 (6 de junio de 2014): 1227–34. http://dx.doi.org/10.1002/ceat.201400037.

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22

Schulze, Ryan J., Shaun G. Weller, Barbara Schroeder, Eugene W. Krueger, Susan Chi, Carol A. Casey y Mark A. McNiven. "Lipid droplet breakdown requires Dynamin 2 for vesiculation of autolysosomal tubules in hepatocytes". Journal of Cell Biology 203, n.º 2 (21 de octubre de 2013): 315–26. http://dx.doi.org/10.1083/jcb.201306140.

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Lipid droplets (LDs) are lipid storage organelles that in hepatocytes may be catabolized by autophagy for use as an energy source, but the membrane-trafficking machinery regulating such a process is poorly characterized. We hypothesized that the large GTPase Dynamin 2 (Dyn2), well known for its involvement in membrane deformation and cellular protein trafficking, could orchestrate autophagy-mediated LD breakdown. Accordingly, depletion or pharmacologic inhibition of Dyn2 led to a substantial accumulation of LDs in hepatocytes. Strikingly, the targeted disruption of Dyn2 induced a dramatic four- to fivefold increase in the size of autolysosomes. Chronic or acute Dyn2 inhibition combined with nutrient deprivation stimulated the excessive tubulation of these autolysosomal compartments. Importantly, Dyn2 associated with these tubules along their length, and the tubules vesiculated and fragmented in the presence of functional Dyn2. These findings provide new evidence for the participation of the autolysosome in LD metabolism and demonstrate a novel role for dynamin in the function and maturation of an autophagic compartment.

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23

Adu-Gyamfi, Nana y Dipak K. Sarker. "Interfacial Effects and the Nano-Scale Disruption in Adsorbed-Layer of Acrylate Polymer-Tween 80 Fabricated Steroid-Bearing Emulsions: A Rheological Study of Supramolecular Materials". Nanomaterials 11, n.º 6 (19 de junio de 2021): 1612. http://dx.doi.org/10.3390/nano11061612.

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The effect of polymer adsorption on the stability and viable shelf life of 55 μm diameter oil-in-water (O/W) emulsions containing the steroid, betamethasone 21-phosphate was investigated. Two acrylate polymers, Carbopol® 971P and 974P, were added in the role of emulsion stabilizers to a model system, representing a non-ionic low molecular weight surfactant-stabilized emulsion (topically applied medicinal cream). For the purposes of this study the dosage of the viscosifier was maintained below 1% w/v and consequently, the consistency of the emulsion was measured in the diluted form. One of the polymers was responsible for elevated degrees of droplet creaming and coalescence and this was closely linked to its surface tension lowering capacity. This lowering was seen at 62 mN/m compared to the routine values at equivalent concentrations of 68 mN/m and 35 mN/m for the betamethasone drug and non-ionic surfactant-Tween 80, respectively. The same polymer also demonstrated a predisposition to form low-micron and greater sized aggregates of nanoparticles that led to extensive flocculation and the formation of a sedimentary precipitate, formed from an amalgam of the components found in the creamed droplet layer.

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24

Morozov, Andrej V., Anna V. Pityk, Sergej V. Ragulin, Azamat R. Sahipgareev, Aleksandra S. Soshkina y Aleksandr S. Shlyopkin. "Estimation influence of boric acid drop entrainment to its accumulation in the VVER reactor in the case of accident". Nuclear Energy and Technology 4, n.º 1 (18 de octubre de 2018): 65–71. http://dx.doi.org/10.3897/nucet.4.29844.

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Process of boric acid mass transfer during accidents accompanied with rupture of circulation pipelines in VVER reactors of new generation equipped with passive safety systems are examined. Results of calculation of variation of boric acid concentration in VVER-TOI reactor in case of accident development process are presented. Positive effects of boric acid droplet entrainment on the processes of acid accumulation and crystallization in the reactor core are demonstrated. The obtained results allow formulating the conclusion on the possibility of these processes in the reactor core which may lead to the disruption of heat removal from fuel pins. Review of available published reference data on physical properties of boric acid solutions (density, viscosity, thermal conductivity) is given. It is established that available information is of too general nature and fails to cover the whole range of parameters (acid temperature, pressure and concentration) typical for potential emergency situation on NPP equipped with VVER reactor. Necessity of experimental study of processes of droplet entrainment under parameters typical for VVER emergency operation conditions, as well as investigation of thermal physics properties of boric acid within wide range of acid concentration values is required.

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Venkatesh, S. y Z. A. Memish. "SARS: the new challenge to international health and travel medicine". Eastern Mediterranean Health Journal 10, n.º 4-5 (13 de septiembre de 2004): 655–62. http://dx.doi.org/10.26719/2004.10.4-5.655.

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Severe acute respiratory syndrome [SARS], the first severe new infectious disease of this millennium, caused widespread public disruption. By July 2003, 8427 probable SARS cases had been reported from 29 countries with a case fatality rate of 9.6%. The new febrile respiratory illness spread around the world along the routes of international air travel, with outbreaks concentrated in transportation hubs or densely populated areas. The etiologic agent was identified as a novel coronavirus, SARS-CoV. The disease is transmissible person-to-person through direct contact, large droplet contact and indirect contact from fomites and unwashed h and s. Saudi Arabia successfully prevented the entry of the disease by imposing travel restrictions, special entry requirements, screening procedures at airports, including temperature checks, and quarantine. Ongoing efforts are aimed at developing case investigation, case management and surveillance protocols for SARS

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Costa, H. S., N. C. Toscano, D. L. Hendrix y T. J. Henneberry. "Patterns of Honeydew Droplet Production by Nymphal Stages of Bemisia argentifolii (Homoptera: Aleyrodidae) and Relative Composition of Honeydew Sugars". Journal of Entomological Science 34, n.º 3 (1 de julio de 1999): 305–13. http://dx.doi.org/10.18474/0749-8004-34.3.305.

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Honeydew droplets were collected from nymphal and adult Bemisia argentifolii Bellows and Perring. Nymphs produced a regular pattern of honeydew droplets consisting of periods of production followed by periods where no droplets were produced. The mean length of individual production periods increased from the second (40 ± 1 min) to the fourth (162 ±11 min) stadium, until the late fourth stadium when honeydew production by most nymphs became continuous. In contrast, the periods of no production decreased in length as nymphs developed from the second (35 ± 1 min) to the fourth (23 ± 1 min) stadium. The frequency of droplets during the production periods decreased from the first (80 ± 1 drops per h) to the fourth (22 ± 1 drops per h) stadium. This periodic pattern is consistent with previous reports for Trialeurodes vaporariorum (Westwood), however, the functional significance of this pattern remains unknown. If this cyclic pattern should prove critical to the successful feeding and development of whiteflies, its disruption may decrease survival and provide a novel target for pest control strategies. Second and third instars had higher percentages of di- and trisaccharides (sucrose, trehalulose, and melezitose) and lower percentages of monosaccharides (fructose and glucose) compared to first and fourth instars. This could indicate a change in metabolic needs of nymphs during periods of rapid growth, or indicate that trehalulose synthase producing endosymbiotic bacteria are more abundant, or more actively producing enzyme during the second and third stadia.

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Boulant, Steeve, Paul Targett-Adams y John McLauchlan. "Disrupting the association of hepatitis C virus core protein with lipid droplets correlates with a loss in production of infectious virus". Journal of General Virology 88, n.º 8 (1 de agosto de 2007): 2204–13. http://dx.doi.org/10.1099/vir.0.82898-0.

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In infected cells, hepatitis C virus (HCV) core protein is targeted to lipid droplets, which serve as intracellular storage organelles. Using a tissue culture system to generate infectious HCV, we have shown that the coating of lipid droplets by the core protein occurs in a time-dependent manner and coincides with higher rates of virus production. At earlier times, the protein was located at punctate sites in close proximity to the edge of lipid droplets. Investigations by using Z-stack analysis have shown that many lipid droplets contained a single punctate site that could represent positions where core transfers from the endoplasmic reticulum membrane to droplets. The effects of lipid droplet association on virus production were studied by introducing mutations into the domain D2, the C-terminal region of the core protein necessary for droplet attachment. Alteration of a phenylalanine residue that was crucial for lipid droplet association generated an unstable form of the protein that could only be detected in the presence of a proteasome inhibitor. Moreover, converting two proline residues in D2 to alanines blocked coating of lipid droplets by core, although the protein was directed to punctate sites that were indistinguishable from those observed at early times for wild-type core protein. Neither of these virus mutants gave rise to virus progeny. By contrast, mutation at a cysteine residue positioned 2 aa upstream of the phenylalanine residue did not affect lipid droplet localization and produced wild-type levels of infectious progeny. Taken together, our findings indicate that lipid droplet association by core is connected to virus production.

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28

Friedl, Julian David, Christian Steinbring, Sergey Zaichik, Nguyet-Minh Nguyen Le y Andreas Bernkop-Schnürch. "Cellular uptake of self-emulsifying drug-delivery systems: polyethylene glycol versus polyglycerol surface". Nanomedicine 15, n.º 19 (agosto de 2020): 1829–41. http://dx.doi.org/10.2217/nnm-2020-0127.

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Aim: Comparison of the impact of polyethylene glycol (PEG) and polyglycerol (PG) surface decoration on self-emulsifying drug delivery system (SEDDS)-membrane interaction and cellular uptake. Materials & methods: PEG-, PEG/PG- and PG-SEDDS were assessed regarding their self-emulsifying properties, surface charge, bile salt fusibility, cellular uptake and interaction with endosome-mimicking membranes. Results: SEDDS exhibited droplet sizes between 150 and 175 nm, a narrow size distribution and self-emulsified within 7 min. Higher PEG-surfactant amounts in SEDDS resulted in charge-shielding and thus in a decrease of ζ potential up to Δ11 mV. The inert PEG-surface hampered bile salt fusion and interfered SEDDS–cell interaction. By reducing the PEG-surfactant amount to 10%, cellular uptake increased twofold compared with PEG-SEDDS containing 40% PEG-surfactant. PG-SEDDS containing no PEG-surfactants showed a threefold increased cellular uptake. Furthermore, complete replacement of PEG-surfactants by PG-surfactants led to enhanced cellular interaction and improved disruption endosome-like membranes. Conclusion: PG-surfactants demonstrated high potential to address PEG-surface associated drawbacks in SEDDS.

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29

Lee, Seon-Jin, Jinglan Zhang, Augustine M. K. Choi y Hong Pyo Kim. "Mitochondrial Dysfunction Induces Formation of Lipid Droplets as a Generalized Response to Stress". Oxidative Medicine and Cellular Longevity 2013 (2013): 1–10. http://dx.doi.org/10.1155/2013/327167.

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Lipid droplet (LD) formation is a hallmark of cellular stress. Cells attempt to combat noxious stimuli by switching their metabolism from oxidative phosphorylation to glycolysis, sparing resources in LDs for generating cellular reducing power and for anabolic biosynthesis. Membrane phospholipids are also a source of LDs. To elucidate the formation of LDs, we exposed mice to hyperoxia, hypoxia, myocardial ischemia, and sepsis induced by cecal ligation and puncture (CLP). All the above-mentioned stressors enhanced the formation of LDs, as assessed by transmission electron microscopy, with severe mitochondrial swelling. Disruption of mitochondria by depleting mitochondrial DNA (ρ0 cells) significantly augmented the formation of LDs, causing transcriptional activation of fatty acid biosynthesis and metabolic reprogramming to glycolysis. Heme oxygenase (HO)-1 counteracts CLP-mediated septic shock in mouse models. In HO-1-deficient mice, LD formation was not observed upon CLP, but a concomitant decrease in “LD-decorating proteins” was observed, implying a link between LDs and cytoprotective activity. Collectively, LD biogenesis during stress can trigger adaptive LD formation, which is dependent on mitochondrial integrity and HO-1 activity; this may be a cellular survival strategy, apportioning energy-generating substrates to cellular defense.

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30

Meyer, Christopher J., Jason K. Norsworthy, Greg R. Kruger y Tom Barber. "Effects of Nozzle Selection and Ground Speed on Efficacy of Liberty and Engenia Applications and Their Implication on Commercial Field Applications". Weed Technology 30, n.º 2 (junio de 2016): 401–14. http://dx.doi.org/10.1614/wt-d-15-00145.1.

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Sprayer applicator–controlled variables, such as nozzle selection and ground speed, will become increasingly important for making labeled POST applications of dicamba in next-generation cropping systems. Typically, nozzle orifice sizes and ground speeds differ greatly between small-plot research applications, from which efficacy recommendations are made, and commercial field applications. However, little research has been conducted to compare applications made with backpack sprayers and tractor sprayers. Thus, a field experiment was conducted in 2013 and 2014 at the Northeast Research and Extension Center in Keiser, AR. Tank mixtures of Engenia™ (N, N-Bis-(aminopropyl) methylamine form of dicamba), Liberty (glufosinate-ammonium), and Liberty + Engenia were applied with TeeJet XR, TT, AIXR, AI, and TTI nozzles at 5 km h−1and 20 km h−1. Two nozzle sizes (110015 and 11006 rated at 0.58 L min−1and 2.27 L min−1at 276 kPa, respectively) were used to keep spray volume constant at 141 L ha−1, whereas ground speed was varied. Weed control ratings were typically lower at 5 km h−1than at 20 km h−1. For example, Palmer amaranth control 4 WAT in 2013 with glufosinate and the TTI nozzle was 89% at 5 km h−1and 96% at 20 km h−1. More differences between speeds were observed for the coarser nozzles, such as the TTI and AI, as opposed to finer nozzles, such as the XR and TT. Results from this research suggest increasing orifice size increases droplet size and that other factors related to applications at faster speeds (e.g., higher droplet velocity, disruption of the crop canopy) may influence the efficacy of herbicide applications. However, increasing ground speed is not a recommended means for increasing efficacy of herbicide applications.

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31

Dutra, Lara, Ole Franz, Veli-Mikko Puupponen y Marja Tiirola. "DNA recovery from Droplet Digital™ PCR emulsions using liquid nitrogen". BioTechniques 69, n.º 6 (diciembre de 2020): 450–54. http://dx.doi.org/10.2144/btn-2020-0076.

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Droplet microfluidics is a technology that enables the production and manipulation of small volumes. In biosciences, the most popular application of this technology is Droplet Digital™ PCR (ddPCR™), where parallel nanoliter-scale PCR assays are used to provide a high sensitivity and specificity for DNA detection. However, the recovery of PCR products for downstream applications such as sequencing can be challenging due to the droplets' stability. Here we compared five methods for disrupting the droplets to recover DNA. We found that rapid freezing in liquid nitrogen results in a clear phase separation and recovery of up to 70% of the DNA content. Liquid nitrogen freezing can thus offer a simple and environmentally friendly protocol for recovering DNA from ddPCR.

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32

Asimakopoulou, Anastasia, Kathrin M. Engel, Nikolaus Gassler, Thilo Bracht, Barbara Sitek, Eva M. Buhl, Stavroula Kalampoka et al. "Deletion of Perilipin 5 Protects against Hepatic Injury in Nonalcoholic Fatty Liver Disease via Missing Inflammasome Activation". Cells 9, n.º 6 (28 de mayo de 2020): 1346. http://dx.doi.org/10.3390/cells9061346.

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Nonalcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver diseases with an increasing prevalence due to rising rates of obesity, metabolic syndrome and type II diabetes. Untreated NAFLD may progress to steatohepatitis (NASH) and ultimately liver cirrhosis. NAFLD is characterized by lipid accumulation, and when sufficient excess lipids are obtained, irreversible liver injury may follow. Perilipin 5 (PLIN5), a known lipid droplet coating protein and triglyceride metabolism regulator, is highly expressed in oxidatively modified tissues but it is still unclear how it affects NAFLD/NASH progress. We here studied how PLIN5 affects NAFLD development induced by a 30-week high-fat diet (HFD) administration in wild type and PLIN5 knock out (Plin5−/−) mice. The disruption of PLIN5 induced differences in lipid metabolism during HFD feeding and was associated with reduced hepatic fat accumulation. Surprisingly, Plin5−/− mice showed mitigated activation of the NLR family pyrin domain-containing 3 (NLRP3) inflammasome, leading to minor hepatic damage. We conclude that PLIN5 is a pleiotropic regulator of hepatic homeostasis in NASH development. Targeting the PLIN5 expression appears critical for protecting the liver from inflammatory activation during chronic NAFLD.

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33

Bai, Xiaofei, Leng-Jie Huang, Sheng-Wen Chen, Benjamin Nebenfuehr, Brian Wysolmerski, Jui-Ching Wu, Sara K. Olson, Andy Golden y Chao-Wen Wang. "Loss of the seipin gene perturbs eggshell formation in Caenorhabditiselegans". Development 147, n.º 20 (20 de agosto de 2020): dev192997. http://dx.doi.org/10.1242/dev.192997.

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ABSTRACTSeipin, an evolutionary conserved protein, plays pivotal roles during lipid droplet (LD) biogenesis and is associated with various human diseases with unclear mechanisms. Here, we analyzed Caenorhabditis elegans mutants deleted of the sole SEIPIN gene, seip-1. Homozygous seip-1 mutants displayed penetrant embryonic lethality, which is caused by the disruption of the lipid-rich permeability barrier, the innermost layer of the C. elegans embryonic eggshell. In C. elegans oocytes and embryos, SEIP-1 is associated with LDs and is crucial for controlling LD size and lipid homeostasis. The seip-1 deletion mutants reduced the ratio of polyunsaturated fatty acids (PUFAs) in their embryonic fatty acid pool. Interestingly, dietary supplementation of selected n-6 PUFAs rescued the embryonic lethality and defective permeability barrier. Accordingly, we propose that SEIP-1 may maternally regulate LD biogenesis and lipid homeostasis to orchestrate the formation of the permeability barrier for eggshell synthesis during embryogenesis. A lipodystrophy allele of seip-1 resulted in embryonic lethality as well and could be rescued by PUFA supplementation. These experiments support a great potential for using C. elegans to model SEIPIN-associated human diseases.

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Maciak, Sebastian, Katarzyna Michalak, Shiv D. Kale y Pawel Michalak. "Nucleolar Dominance and Repression of 45S Ribosomal RNA Genes in Hybrids between Xenopus borealis and X. muelleri (2n = 36)". Cytogenetic and Genome Research 149, n.º 4 (2016): 290–96. http://dx.doi.org/10.1159/000450665.

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Nucleolar dominance is a dramatic disruption in the formation of nucleoli and the expression of ribosomal RNA (rRNA) genes, characteristic of some plant and animal hybrids. Here, we report that F1 hybrids produced from reciprocal crosses between 2 sister species of Xenopus clawed frogs, X. muelleri and X. borealis, undergo nucleolar dominance somewhat distinct from a pattern previously reported in hybrids between phylogenetically more distant Xenopus species. Patterns of nucleolar development, 45S rRNA expression, and gene copy inheritance were investigated using a combination of immunostaining, pyrosequencing, droplet digital PCR, flow cytometry, and epigenetic inhibition. In X. muelleri × X. borealis hybrids, typically only 1 nucleolus is formed, and 45S rRNA genes are predominantly expressed from 1 progenitor's alleles, X. muelleri, regardless of the cross-direction. These changes are accompanied by an extensive (∼80%) loss of rRNA gene copies in the hybrids relative to their parents, with the transcriptionally underdominant variant (X. borealis) being preferentially lost. Chemical treatment of hybrid larvae with a histone deacetylase inhibitor resulted in a partial derepression of the underdominant variant. Together, these observations shed light on the genetic and epigenetic basis of nucleolar dominance as an underappreciated manifestation of genetic conflicts within a hybrid genome.

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35

van Staden, Daniélle, Jeanetta du Plessis y Joe Viljoen. "Development of a Self-Emulsifying Drug Delivery System for Optimized Topical Delivery of Clofazimine". Pharmaceutics 12, n.º 6 (8 de junio de 2020): 523. http://dx.doi.org/10.3390/pharmaceutics12060523.

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A quality-by-design and characterization approach was followed to ensure development of self-emulsifying drug delivery systems (SEDDSs) destined for topical delivery of the highly lipophilic clofazimine. Solubility and water-titration experiments identified spontaneous emulsification capacity of different excipient combinations and clofazimine. After identifying self-emulsification regions, check-point formulations were selected within the self-emulsification region by considering characteristics required to achieve optimized topical drug delivery. Check-point formulations, able to withstand phase separation after 24 h at an ambient temperature, were subjected to characterization studies. Experiments involved droplet size evaluation; size distribution; zeta-potential; self-emulsification time and efficacy; viscosity and pH measurement; cloud point assessment; and thermodynamic stability studies. SEDDSs with favorable properties, i.e., topical drug delivery, were subjected to dermal diffusion studies. Successful in vitro topical clofazimine delivery was observed. Olive oil facilitated the highest topical delivery of clofazimine probably due to increased oleic acid levels that enhanced stratum corneum lipid disruption, followed by improved dermal clofazimine delivery. Finally, isothermal microcalometric experiments studied the compatibility of excipients. Potential interactions were depicted between argan oil and clofazimine as well as between Span®60 and argan-, macadamia- and olive oil, respectively. However, despite some mundane incompatibilities, successful development of topical SEDDSs achieved enhanced topical clofazimine delivery.

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36

Sun, Hong, Yang Yuan y Zi-Lin Sun. "Cholesterol Contributes to Diabetic Nephropathy through SCAP-SREBP-2 Pathway". International Journal of Endocrinology 2013 (2013): 1–8. http://dx.doi.org/10.1155/2013/592576.

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Diabetic nephropathy (DN) has been associated with the presence of lipid deposition. We hypothesized that the disruption of intracellular cholesterol feedback may contribute to DN. Diabetes was induced by high fat/sucrose diet and low-dose intraperitoneal injection of streptozocin (STZ) in male Sprague-Dawley rats. Then diabetic rats were randomly divided into two groups: untreated diabetic group (DM) and atorvastatin-treated group (DM + AT). We found that the levels of serum blood urea nitrogen and creatinine, as well as 24-hour urine protein and urinary neutrophil gelatinase-associated lipocalin, were significantly increased in diabetic rats. This result indicated that the diabetic rats suffered from functional renal damage. We also observed lipid droplet accumulation and increase in 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoAR), low density lipoprotein receptor (LDLr), sterol regulatory element binding protein-2 (SREBP-2), and SREBP-cleavage activating protein (SCAP) in the kidneys of diabetic rats. However, atorvastatin ameliorated renal lipid accumulation and improved the renal function of diabetic rats despite an increase in mRNA and protein expressions of HMG-CoAR, LDLr, and SREBP-2. These results demonstrated that intracellular cholesterol feedback regulation is disrupted in rats with type 2 diabetes, thereby causing renal cholesterol accumulation. Atorvastatin ameliorated renal cholesterol accumulation by reducing renal cholesterol synthesis.

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37

Sun, Zhaoyu, Sain Shushanov, Derek LeRoith y Teresa L. Wood. "Decreased IGF Type 1 Receptor Signaling in Mammary Epithelium during Pregnancy Leads to Reduced Proliferation, Alveolar Differentiation, and Expression of Insulin Receptor Substrate (IRS)-1 and IRS-2". Endocrinology 152, n.º 8 (31 de mayo de 2011): 3233–45. http://dx.doi.org/10.1210/en.2010-1296.

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The IGFs and the IGF type 1 receptor (IGF-1R) are essential mediators of normal mammary gland development in mice. IGF-I and the IGF-1R have demonstrated functions in formation and proliferation of terminal end buds and in ductal outgrowth and branching during puberty. To study the functions of IGF-1R during pregnancy and lactation, we established transgenic mouse lines expressing a human dominant-negative kinase dead IGF-1R (dnhIGF-1R) under the control of the whey acidic protein promoter. We provide evidence that the IGF-1R pathway is necessary for normal epithelial proliferation and alveolar formation during pregnancy. Furthermore, we demonstrate that the whey acidic protein-dnhIGF-1R transgene causes a delay in alveolar differentiation including lipid droplet formation, lumen expansion, and β-casein protein expression. Analysis of IGF-1R signaling pathways showed a decrease in P-IGF-1R and P-Akt resulting from expression of the dnhIGF-1R. We further demonstrate that disruption of the IGF-1R decreases mammary epithelial cell expression of the signaling intermediates insulin receptor substrate (IRS)-1 and IRS-2. No alterations were observed in downstream signaling targets of prolactin and progesterone, suggesting that activation of the IGF-1R may directly regulate expression of IRS-1/2 during alveolar development and differentiation. These data show that IGF-1R signaling is necessary for normal alveolar proliferation and differentiation, in part, through induction of signaling intermediates that mediate alveolar development.

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38

Rahdar, Abbas, Saman Sargazi, Mahmood Barani, Sheida Shahraki, Fakhara Sabir y M. Aboudzadeh. "Lignin-Stabilized Doxorubicin Microemulsions: Synthesis, Physical Characterization, and In Vitro Assessments". Polymers 13, n.º 4 (21 de febrero de 2021): 641. http://dx.doi.org/10.3390/polym13040641.

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Encapsulation of the chemotherapy agents within colloidal systems usually improves drug efficiency and decreases its toxicity. In this study, lignin (LGN) (the second most abundant biopolymer next to cellulose on earth) was employed to prepare novel doxorubicin (DOX)-loaded oil-in-water (O/W) microemulsions with the aim of enhancing the bioavailability of DOX. The droplet size of DOX-loaded microemulsion was obtained as ≈ 7.5 nm by dynamic light scattering (DLS) analysis. The entrapment efficiency (EE) % of LGN/DOX microemulsions was calculated to be about 82%. In addition, a slow and sustainable release rate of DOX (68%) was observed after 24 h for these microemulsions. The cytotoxic effects of standard DOX and LGN/DOX microemulsions on non-malignant (HUVEC) and malignant (MCF7 and C152) cell lines were assessed by application of a tetrazolium (MTT) colorimetric assay. Disruption of cell membrane integrity was investigated by measuring intracellular lactate dehydrogenase (LDH) leakage. In vitro experiments showed that LGN/DOX microemulsions induced noticeable morphological alterations and a greater cell-killing effect than standard DOX. Moreover, LGN/DOX microemulsions significantly disrupted the membrane integrity of C152 cells. These results demonstrate that encapsulation and slow release of DOX improved the cytotoxic efficacy of this anthracycline agent against cancer cells but did not improve its safety towards normal human cells. Overall, this study provides a scientific basis for future studies on the encapsulation efficiency of microemulsions as a promising drug carrier for overcoming pharmacokinetic limitations.

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39

Khurshed, Mohammed, Remco J. Molenaar, Myra E. van Linde, Ron A. Mathôt, Eduard A. Struys, Tom van Wezel, Cornelis J. F. van Noorden, Heinz-Josef Klümpen, Judith V. M. G. Bovée y Johanna W. Wilmink. "A Phase Ib Clinical Trial of Metformin and Chloroquine in Patients with IDH1-Mutated Solid Tumors". Cancers 13, n.º 10 (19 de mayo de 2021): 2474. http://dx.doi.org/10.3390/cancers13102474.

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Background: Mutations in isocitrate dehydrogenase 1 (IDH1) occur in 60% of chondrosarcoma, 80% of WHO grade II-IV glioma and 20% of intrahepatic cholangiocarcinoma. These solid IDH1-mutated tumors produce the oncometabolite D-2-hydroxyglutarate (D-2HG) and are more vulnerable to disruption of their metabolism. Methods: Patients with IDH1-mutated chondrosarcoma, glioma and intrahepatic cholangiocarcinoma received oral combinational treatment with the antidiabetic drug metformin and the antimalarial drug chloroquine. The primary objective was to determine the occurrence of dose-limiting toxicities (DLTs) and the maximum tolerated dose (MTD). Radiological and biochemical tumor responses to metformin and chloroquine were investigated using CT/MRI scans and magnetic resonance spectroscopy (MRS) measurements of D-2HG levels in serum. Results: Seventeen patients received study treatment for a median duration of 43 days (range: 7–74 days). Of twelve evaluable patients, 10 patients discontinued study medication because of progressive disease and two patients due to toxicity. None of the patients experienced a DLT. The MTD was determined to be 1500 mg of metformin two times a day and 200 mg of chloroquine once a day. A serum D/L-2HG ratio of ≥4.5 predicted the presence of an IDH1 mutation with a sensitivity of 90% and a specificity of 100%. By utilization of digital droplet PCR on plasma samples, we were able to detect tumor-specific IDH1 hotspot mutations in circulating tumor DNA (ctDNA) in investigated patients. Conclusion: Treatment of advanced IDH1-mutated solid tumors with metformin and chloroquine was well tolerated but did not induce a clinical response in this phase Ib clinical trial.

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40

Mosquera, Jose Verdezoto, Meghan C. Bacher y James R. Priess. "Nuclear lipid droplets and nuclear damage in Caenorhabditis elegans". PLOS Genetics 17, n.º 6 (16 de junio de 2021): e1009602. http://dx.doi.org/10.1371/journal.pgen.1009602.

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Fat stored in the form of lipid droplets has long been considered a defining characteristic of cytoplasm. However, recent studies have shown that nuclear lipid droplets occur in multiple cells and tissues, including in human patients with fatty liver disease. The function(s) of stored fat in the nucleus has not been determined, and it is possible that nuclear fat is beneficial in some situations. Conversely, nuclear lipid droplets might instead be deleterious by disrupting nuclear organization or triggering aggregation of hydrophobic proteins. We show here that nuclear lipid droplets occur normally in C. elegans intestinal cells and germ cells, but appear to be associated with damage only in the intestine. Lipid droplets in intestinal nuclei can be associated with novel bundles of microfilaments (nuclear actin) and membrane tubules that might have roles in damage repair. To increase the normal, low frequency of nuclear lipid droplets in wild-type animals, we used a forward genetic screen to isolate mutants with abnormally large or abundant nuclear lipid droplets. Genetic analysis and cloning of three such mutants showed that the genes encode the lipid regulator SEIP-1/seipin, the inner nuclear membrane protein NEMP-1/Nemp1/TMEM194A, and a component of COPI vesicles called COPA-1/α-COP. We present several lines of evidence that the nuclear lipid droplet phenotype of copa-1 mutants results from a defect in retrieving mislocalized membrane proteins that normally reside in the endoplasmic reticulum. The seip-1 mutant causes most germ cells to have nuclear lipid droplets, the largest of which occupy more than a third of the nuclear volume. Nevertheless, the nuclear lipid droplets do not trigger apoptosis, and the germ cells differentiate into gametes that produce viable, healthy progeny. Thus, our results suggest that nuclear lipid droplets are detrimental to intestinal nuclei, but have no obvious deleterious effect on germ nuclei.

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41

Georgiadis, Christos, Jane Rasaiyaah, Soragia Athina Gkazi, Roland Preece, Annie Etuk, Abraham Christi y Waseem Qasim. "Universal' Fratricide-Resistant CAR T Cells Against T Cell Leukemia Generated By Coupled & Uncoupled Deamination Mediated Base Editing". Blood 134, Supplement_1 (13 de noviembre de 2019): 3219. http://dx.doi.org/10.1182/blood-2019-130057.

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Chimeric antigen receptor (CAR) T cell approaches to target T cell malignancies have been hampered by the fundamental issue of 'T v T' fratricide when T lineage antigens such as CD3 or CD7 are targeted. Genome-editing can be employed to efficiently eliminate expression of shared target antigens, and multiplexed approaches can deliver simultaneous removal of additional molecules relevant to generating 'universal' T cells, such as the αβ T cell receptor, β2m and CD52, the target antigen for Alemtuzumab. However, these strategies have generally relied on nuclease mediated double stranded DNA cleavage and repair by non homologous end joining (NHEJ), and this can trigger apoptosis and generate predictable and unpredictable chromosomal translocations. Base editing using CRISPR guided chemical deamination offers the possibility of highly precise, seamless, cytidine to uridine deamination (resulting in C→T or G→A substitutions) which can be directed to create stop codons or to disrupt splice donor/acceptor sites. This enables simultaneous genetic disruption of critical antigens or receptors required for the generation of 'off the shelf' cell banks that can be infused in combination without fratricidal effects. A CRISPR-CAR coupled lentiviral configuration with a single guide RNA (sgRNA) specific for the constant region of TCR β chain (TRBC) was incorporated into the 3'ΔU3LTR of the vector under the control of a minimal U6 pol III polymerase promoter. The configuration supported high level base conversion and efficiently disrupted TCRαβ expression. When followed by stringent magnetic bead mediated depletion of residual TCRαβ T cells, highly homogenous CAR+TCR- populations with <1% residual TCRαβ T cells were obtained, an important consideration in the application of mismatched allogeneic T cells. Combinational delivery during electroporation of additional, uncoupled sgRNAs against additional molecules relevant to overcoming HLA barriers supported up to 92% triple knockout of TCR/CD52/β2M in CAR expressing cells. CRISPR guide RNAs targeting CD7 and/or TRBC (for TCR/CD3 disruption) were delivered by electroporation to primary T cells in combination with codon-optimized (co) base editor 3 (BE3) or coCas9 mRNA, ahead of transduction with sin-lentiviral vectors expressing CARs against CD3 or CD7. Simultaneous disruption of TCR/CD3 and CD7 was confirmed by flow cytometry and verified by direct sequencing of the target loci. Efficient multiplexed editing enabled co-culture of T cell populations expressing anti-CD3 and anti-CD7 specific CARs, with fratricidal elimination of residual non-edited populations. Chromium release and flow based cytotoxic functional responses were similar between cells generated using coCas9 and coBE3. However, digital droplet PCR of coCas9 edited cells detected low frequency (1-3%) predicted translocation events, while these were barely detectable in base edited cells. In vivo anti-leukemic functionality of base edited CAR T cells was verified by serial imaging of NOD/SCID/γc mice engrafted with luciferase labelled Jurkat T cells modified to express CD3, or CD7, alone or in combination. Effector inoculation with T cells expressing anti-CD3 and anti-CD7 CARs inhibited leukemic expansion and luciferase signal. Additional characterisation of T cells following multiple deamination mediated editing is underway to investigate wider RNA and DNA effects of chemical deamination. The strategies are readily scalable through the adaption of existing semi-automated manufacturing processes. A time limited therapeutic application of 'universal' anti-T CAR T cells is planned to deliver leukemic clearance and deep molecular remissions ahead of conditioning and programmed allogeneic stem cell transplantation for donor derived multilineage immune reconstitution. Disclosures Qasim: UCLB: Other: revenue share eligibility; Autolus: Equity Ownership; Orchard Therapeutics: Equity Ownership; Servier: Research Funding; Bellicum: Research Funding; CellMedica: Research Funding.

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Ojha, Pawan Kumar, Raktim Maji y Srinibas Karmakar. "Effect of crystallinity on droplet regression and disruptive burning characteristics of nanofuel droplets containing amorphous and crystalline boron nanoparticles". Combustion and Flame 188 (febrero de 2018): 412–27. http://dx.doi.org/10.1016/j.combustflame.2017.10.005.

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43

Belyaev, Dmitry, Julian Schütt, Bergoi Ibarlucea, Taiuk Rim, Larysa Baraban y Gianaurelio Cuniberti. "Nanosensors-Assisted Quantitative Analysis of Biochemical Processes in Droplets". Micromachines 11, n.º 2 (26 de enero de 2020): 138. http://dx.doi.org/10.3390/mi11020138.

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Here, we present a miniaturized lab-on-a-chip detecting system for an all-electric and label-free analysis of the emulsion droplets incorporating the nanoscopic silicon nanowires-based field-effect transistors (FETs). We specifically focus on the analysis of β-galactosidase e.g., activity, which is an important enzyme of the glycolysis metabolic pathway. Furthermore, the efficiency of the synthesis and action of β-galactosidase can be one of the markers for several diseases, e.g., cancer, hyper/hypoglycemia, cell senescence, or other disruptions in cell functioning. We measure the reaction and reaction kinetics-associated shift of the source-to-drain current Isd in the system, which is caused by the change of the ionic strength of the microenvironment. With these results, we demonstrate that the ion-sensitive FETs are able to sense the interior of the aqueous reactors; thus, the conjunction of miniature nanosensors and droplet-based microfluidic systems conceptually opens a new route toward a sensitive, optics-less analysis of biochemical processes.

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44

Muhammad, Aadil, Rajashekhar Pendyala y Nejat Rahmanian. "CFD Simulation of Droplet Formation under Various Parameters in Prilling Process". Applied Mechanics and Materials 625 (septiembre de 2014): 394–97. http://dx.doi.org/10.4028/www.scientific.net/amm.625.394.

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A computational fluid dynamics (CFD) model is used to investigate the droplet formation and deformation under the influence of different parameters. Droplet breakup phenomenon depends on several factors such as viscosity, velocity, pressure difference, and geometry. The most important parameter for droplet breakup is the Weber number (We) which is the ratio of disrupting aerodynamics forces to the surface tension forces. Volume of fluid (VOF) model is used in present work to simulate the droplet breakup. This work presents the effect of liquid velocity, viscosity, and orifice diameters on droplet formation and breakup.

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Piskunov, M. V., N. E. Shlegel y P. A. Strizhak. "Disruption of colliding liquid droplets with different surface geometries". Powder Technology 355 (octubre de 2019): 526–34. http://dx.doi.org/10.1016/j.powtec.2019.07.060.

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46

Zhu, Jialong, Zhong Wang, Ruina Li y Shuai Liu. "Experimental Research on the Disruptive Evaporation and the Motion Characteristics of Secondary Droplets for Emulsified Biodiesel with a Suspended Droplet Configuration". ACS Omega 6, n.º 28 (9 de julio de 2021): 17848–60. http://dx.doi.org/10.1021/acsomega.1c01091.

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47

Takahashi, F., I. J. Heilweil y F. L. Dryer. "Disruptive Burning Mechanism of Free Slurry Droplets". Combustion Science and Technology 65, n.º 1 (1 de mayo de 1989): 151–65. http://dx.doi.org/10.1080/00102208908924046.

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48

Wong, S. c. y S. R. Turns. "Disruptive Burning of Aluminum/arbon Slurry Droplets". Combustion Science and Technology 66, n.º 1-3 (julio de 1989): 75–92. http://dx.doi.org/10.1080/00102208908947140.

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Kim, YoungJun y James C. Hermanson. "Disruption of Volatile and Nonvolatile Droplets Under Locally Supersonic Conditions". AIAA Journal 50, n.º 8 (agosto de 2012): 1754–65. http://dx.doi.org/10.2514/1.j051582.

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Kosif, Irem, Mengmeng Cui, Thomas P. Russell y Todd Emrick. "Triggered In situ Disruption and Inversion of Nanoparticle-Stabilized Droplets". Angewandte Chemie International Edition 52, n.º 26 (13 de mayo de 2013): 6620–23. http://dx.doi.org/10.1002/anie.201302112.

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