There is growing interest in the development of new vaccines based on live‐attenuated viruses (LAVs) and virus‐like particles. The large size of these vaccines, typically 100–400 nm, significantly ...complicates the use of sterile filtration. The objectives of this study are to examine the performance of several commercial sterile filters for filtration of a cytomegalovirus vaccine candidate (referred to as the LAV) and to develop and evaluate the use of a model nanoparticle suspension to perform a more quantitative assessment. Data obtained with a mixture of 200‐ and 300‐nm fluorescent particles provided yield and pressure profiles that captured the behavior of the viral vaccine. This included the excellent performance of the Sartorius Sartobran P filter, which provided greater than 80% yield of both the vaccine and model particles even though the average particle size was more than 250 nm. The particle yield for the Sartobran P was independent of filtrate flux above 200 L/m2/h, but increased with increasing particle concentration, varying from less than 10% at concentrations around 107 particles/ml to more than 80% at concentrations above 1010 particles/ml due to saturation of particle capture/binding sites within the filter. These results provide important insights into the factors controlling transmission and fouling during sterile filtration of large vaccine products.
The authors developed a model nanoparticle suspension that mimics the filtration behavior of a live attenuated virus (LAV) vaccine during sterile filtration. Data were obtained for the effect of key process parameters on yield and capacity. The low yield observed at low feed concentrations was due to saturation of binding sites within the Sartobran P membrane.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
This work addresses the functional properties of the core‐shell resins Capto Core 400 and 700 for a broad range of proteins spanning 66.5 to 660 kDa in molecular mass, including bovine serum albumin ...(BSA) in monomer and dimer form, fibronectin, thyroglobulin, and BSA conjugates with 10 and 30 kDa poly(ethylene glycol) chains. Negatively charged latex nanoparticles (NPs) with nominal diameters of 20, 40, and 100 nm are also studied as surrogates for bioparticles. Protein binding and its trends with respect to salt concentration depend on the protein size and are different for the two agarose‐based multimodal resins. For the smaller proteins, the amount of protein bound over practical time scales is limited by the resin surface area and is larger for Capto Core 400 compared with Capto Core 700. For the larger proteins, diffusion is severely restricted in Capto Core 400, resulting in lower binding capacities than those observed for Capto Core 700 despite the larger surface area. Adding 500 mM NaCl reduces the local bound protein concentration and diffusional hindrance resulting in higher binding capacities for the large proteins in Capto Core 400 compared with low ionic strength conditions. The NPs are essentially completely excluded from the Capto Core 400 pores. However, 20 and 40 nm NPs bind significantly to Capto Core 700, further hindering protein diffusion. A model is provided to predict the dynamic binding capacities as a function of residence time.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
A systematic method is employed for the design and analysis of a small size eddy current (EC) displacement sensor. Simulations are first performed to determine the optimal winding structure and ...dimensions of the sensor. A linear-fitting approach is then developed for converting the AC displacement signal of the sensor to a DC signal. Finally, a compensation method is proposed for mitigating the temperature drift of the EC sensor under different working temperatures. The experimental results show that the proposed sensor has a sensitivity of approximately 3 μm, a working temperature range of 25–55 °C, and a linearity of ±1.025%.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Live virus vaccine (LVV) purification, employing chromatography, can be challenged by low binding capacities and elution yields. Alternatively, processes relying solely on enzymatic digestion steps ...and size‐based membrane separations can be limited by suboptimal reduction of process related impurities and poorly scalable unit operations. Here, we demonstrate that the combination of flowthrough mode chromatography and an ultrafiltration/diafiltration (UF/DF) unit operation delivers a purification process for two different LVV candidates, V590 and Measles, expressed in adherent Vero cells. For V590, chromatography with mixed mode cation exchange resins returned final product yields of ∼50% and logarithmic reduction values (LRVs) of 1.7–>3.4 and 2.5–3.0 for host cell DNA (hcDNA) and host cell proteins (HCPs), respectively. For Measles, chromatography with mixed mode anion exchange resins returned final product yields of ∼50% and LRVs of 1.6 and 2.2 for hcDNA and HCPs, respectively. For both V590 and Measles processing, the employed resins cleared a key HCP, fibronectin, which could foul the UF/DF unit operation, and thusly enabling it to further reduce HCPs and to formulate the final LVV products. This integrated purification process utilizes the complementary action of the two unit operations and its applicability across LVVs supports its consideration for their processing.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Over the past few years, with the prevalence of smart mobile devices, several well-known museums and researchers have developed mobile navigation systems to improve the navigation effect for museum ...visitors. However, most of these systems lack efficient content recommendation, indoor positioning, and augmented reality (AR) display functions, and this situation causes difficulty for visitors to have a personalized and efficient navigation experience. This paper presents an augmented reality mobile navigation system that supports indoor positioning and content recommendation services, which aims to provide personalized suggestions corresponding to the user’s context through the analysis of the interest and location information of visitors. Moreover, combined with the developed markerless augmented reality display functions, this system could effectively enrich and improve visitor’s navigation experience.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Sterile filtration is used to remove microorganisms in the processing of most recombinant proteins, but there are significant challenges in applying this technology to large biotherapeutics like ...Live-Attenuated Vaccines (LAV), lipid-nanoparticles, and gene therapy agents. Previous studies have reported highly variable fouling and product retention behavior of different sterile filters in these applications, but there has been no clear understanding of the origin of these differences. This study used fluorescently-labeled 200, 300, and 400 nm polystyrene latex spheres as model particle challenges for eight commercially available, 0.2/0.22 μm pore size sterile filters, all of which were characterized using mercury intrusion porosimetry, bubble point measurements, and scanning electron microscopy. All filters showed significant fouling, causing an increase in particle retention at high throughput. The maximum transmission of the 300 nm particles varied from only 0.01 for the highly asymmetric Millipore Express® to 0.9 for the dual-layer Sartobran® P. The transmission was well correlated with the ratio of the particle diameter to the maximum pore size (determined by bubble point), with even better agreement obtained using the mean pore size evaluated from mercury intrusion porosimetry. These results provide important insights into the effects of pore size and structure on the retention characteristics of sterile filter as well as guidance on how to select the best sterile filters for processing vaccines and viruses that are >100 nm in size.
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•Nanoparticle retention evaluated for range of commercial 0.2 μm sterile filters.•Transmission of 300 nm particles varied between 1% and >90%.•Filters characterized by bubble point and mercury porometry.•Differences in transmission directly related to small differences in pore size.•Particle fouling resulted in decrease in transmission at high throughput.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Fibromyalgia syndrome (FM) is a multifactorial disorder whose pathogenesis and diagnosis are poorly understood. This study investigated differential serum proteome profiles in patients with FM and ...healthy pain-free controls and explored the association between serum proteome and clinical profiles in patients with FM. Twenty patients with FM (according to the American College of Rheumatology criteria, 2010) and 20 healthy pain-free controls were recruited for optimized quantitative serum proteomics analysis. The levels of pain, pressure pain threshold, sleep, anxiety, depression, and functional status were evaluated for patients with FM. We identified 22 proteins differentially expressed in FM when compared with healthy pain-free controls and propose a panel of methyltransferase-like 18 (METTL18), immunoglobulin lambda variable 3-25 (IGLV3-25), interleukin-1 receptor accessory protein (IL1RAP), and IGHV1OR21-1 for differentiating FM from controls by using a decision tree model (accuracy: 0.97). In addition, we noted several proteins involved in coagulation and inflammation pathways with distinct expression patterns in patients with FM. Novel proteins were also observed to be correlated with the levels of pain, depression, and dysautonomia in patients with FM. We suggest that upregulated inflammation can play a major role in the pathomechanism of FM. The differentially expressed proteins identified may serve as useful biomarkers for diagnosis and evaluation of FM in the future.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
In this paper, we propose an effective novel content-aware chroma reconstruction (CACR) method for screen content images (SCIs). After receiving the decoded downsampled YUV image on the client side, ...our fast chroma-copy approach reconstructs the missing chroma pixels in the flat regions of SCI. Then, for non-flat regions, a non-flat region-based winner-first voting (NRWV) strategy is proposed to identify the chroma subsampling scheme used on the server side prior to compression. Further, an effective adaptive hybrid approach is proposed to reconstruct each missing chroma pixel in the non-flat region by fusing the two reconstructed results, one from our modified NRWV-based chroma subsampling-binding and luma-guided chroma reconstruction scheme, which favors the sharp edges in SCI, as well as the other from the bicubic interpolation scheme, which favors blurred and continuous-tone textures. Further, based on the identified chroma subsampling scheme, a geometry alignment-based error compensation approach is proposed to enhance the reconstructed chroma image. Based on typical test SCIs and JCT-VC screen content videos, comprehensive experiments are carried out in HEVC-16.17 to demonstrate that in terms of quality, visual effect, and quality-bitrate tradeoff of the reconstructed SCIs, our CACR method significantly outperforms the existing state-of-the-art methods.
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•Adsorption of protein mixtures follows an irreversible adsorption model.•Mixture adsorption is predicted by the model based on single component data.•Shell resistance in core–shell ...resins is described by a modified Biot number.
The adsorption rates of mixtures of BSA monomer and dimer and of fibronectin and thyroglobulin are measured for core–shell adsorbents and compared with a pore-diffusion limited irreversible binding model. Measurements are conducted for individual particles, batch, and packed columns. The proteins in this work are irreversibly bound but have different binding capacities and effective pore diffusivities resulting in different one-component rates. Consistent with the theoretical model, mixture adsorption results in a single adsorption front within the particles, batch uptake curves with no overshoot in the amount adsorbed, and breakthrough curves without roll-up and with the stronger binding dimer emerging first from the column. Quantitatively, the model accounts for the different capacities and diffusivities and for the inert shell through a modified Biot number. Based on one-component measurements, the model accurately predicts mixture adsorption and is useful for describing flow-through purifications where multiple contaminants are removed from an unbound product.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•Theory of pore-diffusion controlled multi-component irreversible adsorption.•Shrinking core model for multi-component irreversible binding.•Closed-form expressions for batch uptake and column ...breakthrough.•Solutions validated by numerical simulation with the general rate model.
This paper provides a theoretical analysis of the kinetics of two-component irreversible adsorption in porous spherical particles for conditions where pore diffusion is limiting. The two components are assumed to have the same binding capacity without the possibility of displacement of one component by the other but with different effective pore diffusivities. As a result, the amounts of each component adsorbed depend on the relative rates of mass transfer within the particles. Closed-form analytical expressions derived by solving the relevant conservation equations are obtained to describe adsorption from an infinite bath with constant concentrations at the particle surface, batch adsorption in a finite bath, and adsorption in packed columns, both under constant pattern and non-constant pattern conditions. In each case, the expression derived reduces to a single integral. These expressions are in good agreement with the numerical solutions of the corresponding general rate model for conditions where the kinetics of binding is fast and provide a simple means to predict two-component adsorption in many practical cases where strong adsorption conditions prevail. Generalizations to systems with more than two components, to cases where the external mass transfer resistance is important, and to unequal capacities are also provided.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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