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High-Performance Chromatographic Characterization of Surface Chemical Heterogeneities of Fluorescent Organic–Inorganic Hybrid Core–Shell Silica Nanoparticles
摘要： In contrast to small-molar-mass compounds, detailed structural investigations of inorganic core–organic ligand shell hybrid nanoparticles remain challenging. The assessment of batch-reaction-induced heterogeneities of surface chemical properties and their correlation with particle size has been a particularly long-standing issue. Applying a combination of high-performance liquid chromatography (HPLC) and gel permeation chromatography (GPC) to ultra-small (<10 nm diameter) poly(ethylene glycol)-coated (PEGylated) fluorescent core–shell silica nanoparticles, we elucidate here previously unknown surface heterogeneities resulting from varying dye conjugation to nanoparticle silica cores and surfaces. Heterogeneities are predominantly governed by dye charge, as corroborated by molecular dynamics simulations. We demonstrate that this insight enables the development of synthesis protocols to achieve PEGylated and targeting ligand-functionalized PEGylated silica nanoparticles with dramatically improved surface chemical homogeneity, as evidenced by single-peak HPLC chromatograms. Because surface chemical properties are key to all nanoparticle interactions, we expect these methods and fundamental insights to become relevant to a number of systems for applications, including bioimaging and nanomedicine.
关键词： surface chemistry heterogeneity,high-performance liquid chromatography,nanoparticle characterization,nanoparticle surface functionalization,fluorescence correlation spectroscopy,molecular dynamics,nanoparticle heterogeneity
更新于2025-09-23 15:23:52
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Double-exponential kinetics of binding and redistribution of the fluorescent dyes in cell membranes witness for the existence of lipid microdomains
摘要： New technique of detecting lateral heterogeneity of the plasma membrane of living cells by means of membrane-binding fluorescent dyes is proposed. The kinetics of dye incorporation into the membrane or its lateral diffusion inside the membrane is measured and decomposed into exponential components by means of the Maximum Entropy Method. Two distinct exponential components are obtained consistently in all cases for several fluorescent dyes, two different cell lines and in different types of experiments including spectroscopy, flow cytometry and fluorescence recovery after photobleaching. These components are attributed to the liquid-ordered and disordered phases in the plasma membrane of studied cells in their dynamic equilibrium.
关键词： Kinetics,Maximum Entropy Method,Decomposition,Lipid phases,Plasma membrane heterogeneity
更新于2025-09-23 15:23:52
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Functional Diversity in the Retina Improves the Population Code
摘要： Within a given brain region, individual neurons exhibit a wide variety of different feature selectivities. Here, we investigated the impact of this extensive functional diversity on the population neural code. Our approach was to build optimal decoders to discriminate among stimuli using the spiking output of a real, measured neural population and compare its performance against a matched, homogeneous neural population with the same number of cells and spikes. Analyzing large populations of retinal ganglion cells, we found that the real, heterogeneous population can yield a discrimination error lower than the homogeneous population by several orders of magnitude and consequently can encode much more visual information. This effect increases with population size and with graded degrees of heterogeneity. We complemented these results with an analysis of coding based on the Chernoff distance, as well as derivations of inequalities on coding in certain limits, from which we can conclude that the beneficial effect of heterogeneity occurs over a broad set of conditions. Together, our results indicate that the presence of functional diversity in neural populations can enhance their coding fidelity appreciably. A noteworthy outcome of our study is that this effect can be extremely strong and should be taken into account when investigating design principles for neural circuits.
关键词： retina,neural coding,discrimination error,mutual information,functional diversity,Chernoff distance,population code,heterogeneity
更新于2025-09-23 15:23:52
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The commissioning and validation of Monaco treatment planning system on an Elekta VersaHD linear accelerator
摘要： Accurate beam modeling is essential to help ensure overall accuracy in the radiotherapy process. This study describes our experience with beam model validation of a Monaco treatment planning system on a Versa HD linear accelerator. Data were collected such that Monaco beam models could be generated using three algorithms: collapsed cone (CC) and photon Monte Carlo (MC) for photon beams, and electron Monte Carlo (eMC) for electron beams. Validations are performed on measured percent depth doses (PDDs) and profiles, for open-field point-doses in homogenous and heterogeneous media, and for obliquely incident electron beams. Gamma analysis is used to assess the agreement between calculation and measurement for intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) plans, including volumetric modulated arc therapy for stereotactic body radiation therapy (VMAT SBRT). For all relevant conditions, gamma index values below 1 are obtained when comparing Monaco calculated PDDs and profiles with measured data. Point-doses in a water medium are found to be within 2% agreement of commissioning data in 99.5% and 98.6% of the points computed by MC and CC, respectively. All point-dose calculations for the eMC algorithm in water are within 4% agreement of measurement, and 92% of measurements are within 3%. In heterogeneous media of air and cortical bone, both CC and MC yielded better than 3% agreement with ion chamber measurements. eMC yielded 3% agreement to measurement downstream of air with oblique beams of up to 27°, 5% agreement distal to bone, and within 4% agreement at extended source to surface distance (SSD) for all electron energies except 6 MeV. The 6-MeV point of measurement is on a steep dose gradient which may impact the magnitude of discrepancy measured. The average gamma passing rate for IMRT/VMAT plans is 96.9% (±2.1%) and 98.0% (±1.9%) for VMAT SBRT when evaluated using 3%/2 mm criteria. Monaco beam models for the Versa HD linac were successfully commissioned for clinical use.
关键词： collapsed cone,SBRT,Monte Carlo,VMAT,heterogeneity,Monaco
更新于2025-09-23 15:22:29
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18F?alfatide positron emission tomography may predict anti?angiogenic responses
摘要： As the crucial issue in the development of anti-angiogenic drugs is how to predict which patients will and will not benefit prior to the initiation of therapy, angiogenic 18F-alfatide positron emission computed tomography (PET) was assessed in the present study. Lung adenocarcinoma A549 (high angiogenesis) and prostate PC?3 (low angiogenesis) cell xenografted tumor-bearing mice underwent 18F-alfatide PET at baseline and following treatment with either an anti?angiogenic therapy or vehicle. The evaluation index for the inhibition of tumor growth in the individuals in the treated groups was represented by treatment/control (T/C) ratio (%). Anti?angiogenic responses were denoted by the changes in 18F-alfatide uptake in the same animal. The T/C ratio was lower in high-uptake tumors than in low?uptake tumors (P=0.001). A significant difference in the tumor volumes between the anti?angiogenic therapy group and the control group occurred earlier in the A549 model than in the PC?3 model. 18F-alfatide uptake decreased more for A549 tumors than for PC?3 tumors following anti?angiogenic therapy. In each treatment group, the degree of tumor response to anti?angiogenic therapy was associated well with the tumor uptake prior to treatment (P<0.05). These results indicated that 18F?alfatide PET may be a useful molecular imaging tool for individual selection prior to anti?angiogenic drug therapy.
关键词： 18F?alfatide positron emission tomography,heterogeneity,integrin αvβ3,response prediction,anti?angiogenic therapy
更新于2025-09-23 15:22:29
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High-fidelity probing of the structure and heterogeneity of extracellular vesicles by resonance-enhanced atomic force microscopy infrared spectroscopy
摘要： Extracellular vesicles (EVs) are highly specialized nanoscale assemblies that deliver complex biological cargos to mediate intercellular communication. EVs are heterogeneous, and characterization of this heterogeneity is paramount to understanding EV biogenesis and activity, as well as to associating them with biological responses and pathologies. Traditional approaches to studying EV composition generally lack the resolution and/or sensitivity to characterize individual EVs, and therefore the assessment of EV heterogeneity has remained challenging. We have recently developed an atomic force microscope IR spectroscopy (AFM-IR) approach to probe the structural composition of single EVs with nanoscale resolution. Here, we provide a step-by-step procedure for our approach and show its power to reveal heterogeneity across individual EVs, within the same population of EVs and between different EV populations. Our approach is label free and able to detect lipids, proteins and nucleic acids within individual EVs. After isolation of EVs from cell culture medium, the protocol involves incubation of the EV sample on a suitable substrate, setup of the AFM-IR instrument and collection of nano-IR spectra and nano-IR images. Data acquisition and analyses can be completed within 24 h, and require only a basic knowledge of spectroscopy and chemistry. We anticipate that new understanding of EV composition and structure through AFM-IR will contribute to our biological understanding of EV biology and could find application in disease diagnosis and the development of EV therapies.
关键词： spectroscopy,heterogeneity,nanoscale characterization,AFM-IR,extracellular vesicles
更新于2025-09-23 15:22:29
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[IEEE IGARSS 2018 - 2018 IEEE International Geoscience and Remote Sensing Symposium - Valencia (2018.7.22-2018.7.27)] IGARSS 2018 - 2018 IEEE International Geoscience and Remote Sensing Symposium - A New Model for P-Band Pol-InSAR Based on Gamma Distribution
摘要： This work proposes a forest model based on Gamma distribution to better describe the forest vertical structure for height inversion using P-band polarimetric synthetic aperture radar interferometry (Pol-InSAR) data. The proposed model takes into account the forest vertical heterogeneity and asymmetry, to which volume interferometric coherence is sensitive. The interferometric coherence associated with a volume where the vertical backscattered power varies following a Gamma distribution is derived. The effect of scattering center height standard deviation and mean elevation to the volume interferometric coherence is investigated. Finally, the strategy of multi-baseline on the proposed model for forest height inversion using P-band Pol-InSAR data is proposed.
关键词： P-band Pol-InSAR,forest model,Gamma distribution,vertical heterogeneity
更新于2025-09-23 15:22:29
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Dispersion of Love waves in size-dependent substrate containing finite piezoelectric and viscoelastic layers
摘要： The dispersion properties of Love waves are utilized for the fabrication of sensor devices in the different material environments. This study involves the propagation of Love wave in a double-layered structure consisting of two finite layers of viscoelastic and piezoelectric material lying over the semi-infinite size-dependent micropolar substrate. The bottom substrate of the structure is modeled as, the material with microstructural properties. The real and damping dispersion relations are obtained analytically in closed form expression under both the cases of electrically open and short conditions. The coupling constant and characteristic length that describe the effect of the microstructure of the micropolar substrate, are studied graphically on Love wave propagation. The effects of piezoelectric layer are shown by considering two different materials of a piezoelectric layer, i.e., PZT-5H or BaTiO3, along with the internal friction and heterogeneity parameter associated with a viscoelastic layer. The numerical computation and the graphs are given for aluminium-epoxy (substrate), viscoelastic material and PZT-5H or BaTiO3 (piezoelectric layer). Some of the particular cases are derived from the study by using different relevant conditions.
关键词： Viscoelastic,Piezoelectricity,Dispersion relations,Heterogeneity,Micropolar,Love wave,Characteristic length
更新于2025-09-23 15:22:29
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Diversity of physical properties of bacterial extracellular membrane vesicles revealed through atomic force microscopy phase imaging
摘要： Bacteria release nanometer-scale extracellular membrane vesicles (MVs) to mediate a variety of biological processes. We analyzed individual MVs under physiological conditions by phase imaging of high-speed atomic force microscopy to assess the physiological heterogeneity of MVs isolated from bacterial cultures. Phase imaging makes it possible to map the physical properties of an individual, fragile MV in an isolated MV population containing a broad variety of vesicle diameters, from 20 to 150 nm. We also developed a method for quantitatively comparing the physical properties of MVs among samples. This allowed for the comparison of the physical properties of MVs isolated from different bacterial species. We compared bacterial MVs isolated from four bacterial species and artificially synthesized liposomes. We demonstrate that each bacterial species generates physically heterogeneous types of MVs, unlike the physical homogeneity displayed by liposomes. These results indicate that the physical heterogeneity of bacterial MVs is mainly caused by compositional differences mediated through biological phenomena and could be unique to each species. We provide a new methodology using phase imaging that would pave the way for single-vesicle analysis of extracellular vesicles of a broad size range.
关键词： heterogeneity,atomic force microscopy,physical properties,phase imaging,bacterial extracellular membrane vesicles
更新于2025-09-23 15:21:01
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Pathologic stratification of operable lung adenocarcinoma using radiomics features extracted from dual energy CT images
摘要： Purpose: To evaluate the usefulness of surrogate biomarkers as predictors of histopathologic tumor grade and aggressiveness using radiomics data from dual-energy computed tomography (DECT), with the ultimate goal of accomplishing stratification of early-stage lung adenocarcinoma for optimal treatment. Results: Pathologic grade was divided into grades 1, 2, and 3. Multinomial logistic regression analysis revealed i-uniformity and 97.5th percentile CT attenuation value as independent significant factors to stratify grade 2 or 3 from grade 1. The AUC value calculated from leave-one-out cross-validation procedure for discriminating grades 1, 2, and 3 was 0.9307 (95% CI: 0.8514–1), 0.8610 (95% CI: 0.7547–0.9672), and 0.8394 (95% CI: 0.7045–0.9743), respectively. Materials and Methods: A total of 80 patients with 91 clinically and radiologically suspected stage I or II lung adenocarcinoma were prospectively enrolled. All patients underwent DECT and F-18-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT, followed by surgery. Quantitative CT and PET imaging characteristics were evaluated using a radiomics approach. Significant features for a tumor aggressiveness prediction model were extracted and used to calculate diagnostic performance for predicting all pathologic grades. Conclusions: Quantitative radiomics values from DECT imaging metrics can help predict pathologic aggressiveness of lung adenocarcinoma.
关键词： heterogeneity,dual energy CT,lung adenocarcinoma,radiomics,texture analysis
更新于2025-09-23 15:21:01