Quantitative Analysis Of Distribution Research Articles

Study of drug particle distributions within mini-tablets using synchrotron X-ray microtomography and superpixel image clustering.

Uniform drug distribution within fast disintegrating tablets is a key quality measure to ensure a reliable, steady, and targeted release of the contained active pharmaceutical ingredients. In this work, the drug particle distribution in mini-tablets was studied with synchrotron phase contrast X-ray microtomography. Mini-tablets had a weight of 9.5mg and a drug load from 2.5% to 20%. Moxidectin, a drug used for treatment of parasitic infections, was used as a model compound. Drug content covered a range from 91% to 121% of the target dose. A linear iterative clustering (SLIC) superpixel method was used for segmentation, analysis, and visualization of the spatial distribution of individual tablet components (i.e., pores, excipients, and drug). Results show that the drug was not uniformly distributed within the tablet, revealing an increasing drug load towards the tablets' outer boundaries and thus indicative of a radial displacement of drug particles during compaction. The presented method can be used for the quantitative analysis of drug content and drug distribution within pharmaceutical tablets, allowing for the optimization of fast disintegrating formulations. The results also affirm that that drug loads up to 20% will not lead to segregation for moxidectin.

Global Economic Trends: A Study of Data from the Years 1961–2013

This research focuses on the problem of unequal development of the world economy. Manifestations of some modern global economic inequality are evaluated. Relative frequency and statistical characteristics for countries of the world in terms of GDP per capita from 1961 to 2013 are analyzed on which deep divergences between countries and very low average value of GDP per capita are identified. Analysis of quantitative and percentage distribution of countries of the world by the revenue categories shows that lately the inequality between countries has slightly decreased, although it remains to be deep.

Quantitative analysis of internal flow distribution and pore interconnectivity within asymmetric virus filtration membranes

Several studies have demonstrated that the filtration performance and fouling characteristics of porous membranes can be significantly influenced by the pore interconnectivity. However, there are no available techniques that can quantify the pore connectivity of highly asymmetric membranes with small pore size used in ultrafiltration and virus removal filtration. In this study, a novel approach was developed to measure the pore interconnectivity from SEM images of gold nanoparticles captured within a membrane in which flow through the exit (skin side) was partially blocked by a stainless steel support. The pore interconnectivity parameter was then evaluated by comparison of the observed capture profile with numerical simulations of the flow and particle capture. Results for the Viresolve® Pro membranes showed much greater pore interconnectivity than for the Viresolve® NFP membranes. SEM images of the Ultipor® DV20 membrane showed nanoparticle capture only at regions of the inlet located directly over the open portions of the membrane exit, indicating that there is minimal lateral flow in this membrane. These results provide the first quantitative measurements of the extent of pore interconnectivity within virus filtration membranes having highly asymmetric pore structures.

Imaging of cellular uptake of boron cluster compound by stimulated Raman scattering microscopy

Boron neutron capture therapy (BNCT) is a cancer-selective radiotherapy to treat malignant tumors using a nuclear reaction of boron isotopes in tumor-localizing drug molecules. To evaluate the efficacy of boron drugs for BNCT, it is crucial to measure the distribution of boron drugs in cells. Here, we present the direct imaging of cellular uptake of boron cluster compound by stimulated Raman scattering microscopy. We demonstrate quantitative analysis of spatial distributions of disodium mercaptoundecahydrododecaborate (BSH)-cholesterol in HeLa cells.

Fragmentation of dolomite bed material at elevated temperature in the presence of H2O & CO2: Implications for fluidized bed gasification

With the aims of improving the understanding of the use of dolomite bed materials in a fluidized bed (FB) gasifier, dolomite primary fragmentation behaviors and mechanisms at elevated temperatures were thoroughly investigated by means of quantitative analysis of particles production, size distribution, and particles shape (in terms of HS circularity and convexity). Crystalline Glanshammar and amorphous Sala dolomites of different original particle sizes (300–350 μm, 350–500 μm, and 500–1000 μm) were treated under various conditions, such as temperatures of 650, 750, and 950 °C and gas conditions of N2, N2 & steam, and H2O & CO2. Crystalline Glanshammar dolomite exhibited severe fragmentation, while amorphous Sala dolomite only fragmented slightly. Fragmentation mechanisms were proposed for amorphous and crystalline dolomite. In case of the Glanshammar dolomite, the release of H2O trapped in the crystal lattices and trace level of CO2 at structure defects, contributed to 10% and 55% of the primary fragmentation, respectively. The presence of CO2 can significantly mitigate the fragmentation of crystalline Glanshammar dolomite, which is probably either due to the prevention of CO2− dissociation at the defects or filling of cations by interchanging CO2− with the dolomite, consequently, allowing for a stabilization of dolomite structure. The analysis shows that elutriation in fluidized bed gasifier can be reduced significantly when either using amorphous Sala dolomite as bed material or treatment of the Glanshammar dolomite in the presence of CO2 before its utilization in a fluidized bed.

Image stitching and partitioning algorithms for infrared thermal human-body images

The thermal infrared image of the human body directly reflects the temperature distribution of the human body surface. Based on in-depth analysis, the infrared image can provide intelligent diagnosis assistance for human diseases. This paper proposed two preprocessing algorithms, i.e., upper-lower body image-stitching and body image partitioning, for medical infrared image analysis. In the image stitching stage, the human body is first extracted from the background by local thresholding based on the characteristics of the actual imaging environment. Then the upper and lower body images are aligned and fused using binary and grayscale template matching. In the image partitioning stage, the key points of the part area are determined by the extremum-point analysis of the human contour. The human body is then partitioned into regions including head, trunk, limbs, etc. Experiments show that the proposed preprocessing algorithms produce satisfactory results in image-stitching and portioning, and can effectively support the quantitative and qualitative analysis of human body temperature distribution.

Archaeo-ceramic 2.0: investigating ancient ceramics using modern technological approaches

Since the first attempts to the petrographic analysis on pottery, a multitude of archaeometric studies have been carried out to solve important issues on provenance, production technology, dating, functionality and conservation state of ancient ceramic materials. According to the scientists’ background, the period when the investigations were done, destructive versus non-destructive analyses (also in relation to the unicity of the studied objects), as well as the purpose of the research, numerous analytical methods, typically used in various disciplines such as geology, physics and chemistry, have been applied. This contribution focuses on the use of innovative approaches to solve archaeological issues on pottery provenance, production technology and post-depositional alteration, reporting some examples of new methods applied to perform mineralogical, petrographic and chemical analyses. The traditional microscopic characterisation of ceramic pastes, for instance, can now be easily coupled with quantitative analysis of abundance and size distribution of their textural features, through the application of digital image analysis. This method, applied to images acquired by polarised transmitted light microscope, scanning electron microscope in back-scattered mode and microchemical mapping, can quantitatively and quickly describe production recipes, contributing to the definition of the pottery production choices and changes over time. As for the mineralogical analysis, the possibility of simultaneously processing numerous X-ray diffraction patterns by statistical tools, such as cluster analysis on raw data, is another example of a modern way to analyse ancient pottery and interpreting, with an objective comparison method, possible differences or analogies in the production recipes and/or firing technology of groups of ceramics. Moreover, modern microdiffraction techniques, both using conventional (X-ray tubes) and advanced sources (synchrotron radiation), also coupled with micro-Raman spectroscopy, allow the determination of mineralogical composition of small-sized phases both in ceramic bodies and slips/glazes, supplying important information on the production technology and possible post-deposition processes. As for the provenance issue, especially on fine ware, constraining relationships between far away communities/societies can now be evaluated not only on the basis of conventional bulk chemistry but also by isotope analysis. These new methodological approaches give rise to the new concept of archaeometric analysis on ancient ceramic materials that can be defined as “archaeo-ceramic 2.0”.

Ratiometric Imaging of the in Situ pH Distribution of Biofilms by Use of Fluorescent Mesoporous Silica Nanosensors.

Biofilms are communities of microorganisms enclosed in a self-generated matrix of extracellular polymeric substances. While biofilm recalcitrance and persistence are caused by several factors, a reduction in antimicrobial susceptibility has been closely associated with the generation of pH gradients within the biofilm structure. Cells embedded within the biofilm create a localized acidic microenvironment, which is unaffected by the external pH. Therefore, pH monitoring is a promising approach for understanding the complexities of a three-dimensional heterogeneous biofilm. A fluorescent pH nanosensor was designed through the synthesis of mesoporous silica nanoparticles (47 ± 5 nm diameter) conjugated to a pH-sensitive dye (fluorescein) and a pH-insensitive dye (rhodamine B) as an internal standard (dye-MSNs). The fluorescence intensity of fluorescein (IF) reduced significantly as the pH was decreased from 8.5 to 3.5. In contrast, the fluorescence intensity of rhodamine B (IR) remained constant at any pH. The ratio of IF/IR produced a sigmoidal curve with respect to the pH, in a working pH range between 4.5 and 7.5. Dye-MSNs enabled the measurement of pH gradients within Pseudomonas fluorescens WCS 365 biofilm microcolonies. The biofilms showed spatially distinct low-pH regions that were enclosed into large clusters corresponding to high-cell-density areas. Also present were small low-pH areas that spread indistinctly throughout the microcolony caused by the mass transfer effect. The lowest detected pH within the inner core of the microcolonies was 5.1, gradually increasing to a neutral pH toward the exterior of the microcolonies. The dye-MSNs were able to fully penetrate the biofilm matrix and allowed a quantitative ratiometric analysis of pH gradients and distribution throughout the biofilm, which was independent of the nanoparticle concentration.

Modeling Research Technique of Nonmetallic Inclusions Distribution in Liquid Steel during Its Flow through the Tundish Water Model

This study shows research results of behaviors of nonmetallic inclusions (NMIs) in a tundish represented by water model. The object under investigation is a two‐strand trough‐type continuous casting tundish operating in one of the Polish steel plants. Hollow glass microspheres with diameters ranging from 10 to 140 μm are used for testing, which represents the NMIs. The distribution process of microspheres is investigated; the qualitative analysis (visualization) and quantitative analysis (using a laser particle counter) of microsphere distribution (movement) are performed. Based on the obtained results, it is found that the analyzed tundish is not of optimal design, in terms of removing small NMIs, as they are conducted in a stream of liquid flowing at the bottom of the tundish, moving directly into nozzles of the tundish. Their movement is caused by the shaped liquid‐flow phenomena in the tundish working space. The test results help to validate a numerical model, which can be used in further studies to redesign the working space of the tundish. The positive result of verification facilitates to obtain a tool for implementing flow optimization in terms of receiving high metallurgical purity of slabs.

Increased urinary bladder volume improves the detectability of urinary stones at the ureterovesical junction in non-enhanced computed tomography (NECT).

To evaluate the influence of the urinary bladder volume on the detectability of urolithiasis at the ureterovesical junction (UVJ) using a low-dose CT (LD-CT) with iterative reconstruction (IR) and a standard-dose CT (SD-CT) without IR in a large cohort. Four hundred patients (278 males (69.5%), mean 44.6 ± 14.7years) with urolithiasis at the UVJ were investigated either by an LD-CT with IR (n = 289, 72%) or an SD-CT without IR (n = 111, 28%) protocol. The detectability of distal urolithiasis was assessed by a dichotomous assessment (definite or questionable) by two radiologists in consensus and by a quantitative analysis of the signal density distribution across a line drawn parallel to the distal ureter. Based on the resulting graph, minimum/maximum density values and mean/maximum upslopes and downslopes were derived and calculated automatically. In all patients, the total bladder volume was calculated by a slice-by-slice approach on axial CT images. Patients with definite stones showed significantly higher urinary bladder volumes compared to patients with questionable stones in both LD-CT and SD-CT (p < 0.01). These results were independent of stones' length and patients' BMI values. Using cutoffs of 92ml for LD-CT and 69ml for SD-CT, high positive predictive values/accuracy rates of 96%/85% (LD-CT) and 98%/86% (SD-CT) were observed to identify definite urinary stones. Urinary bladder volume has a significant impact on the detectability of distal urolithiasis. Moderate bladder filling by pre-CT hydration with subsequent CT scan at the time of high urge to void increases the detectability of urinary stones at the UVJ in clinical routine. • Urinary bladder volume significantly affects the detectability of distal urolithiasis • Higher bladder volumes are associated with improved detectability of distal urinary stones • Oral pre-CT hydration for urolithiasis is easily applicable and cost-effective.

Preparation of Newborn Rat Brain Tissue for Ultrastructural Morphometric Analysis of Synaptic Vesicle Distribution at Nerve Terminals.

Our laboratory and many others have exploited the high resolving power of transmission electron microscopy to study the morphology and spatial organization of synaptic vesicles. In order to obtain high-quality electron micrographs that can yield the degree of morphological detail necessary for quantitative analysis of pre-synaptic vesicle distribution, optimal specimen preparation is critical. Chemical fixation is the first step in the process of specimen preparation, and of utmost importance to preserve fine ultrastructure. Vascular fixation with a glutaraldehyde-formaldehyde solution, followed by treatment of vibratome-sectioned specimens with osmium tetroxide, stabilizes the maximum number of molecules, especially proteins and lipids, and results in superior conservation of ultrastructure. Tissue is then processed with counterstaining, sequential dehydration and resin-embedding. En bloc staining with uranyl acetate (i.e., staining of vibratome-sectioned tissue before resin embedding) enhances endogenous contrast and stabilizes cell components against extraction during specimen processing. Contrast can be further increased by applying uranyl acetate as a post-stain on ultrathin sections. Double-staining of ultrathin sections with lead citrate after uranyl acetate treatment also improves image resolution, by intensifying electron-opacity of nucleic acid-containing structures through selective binding of lead to uranyl acetate. Transmission electron microscopy is a powerful tool for characterization of the morphological details of synaptic vesicles and quantification of their size and spatial organization in the terminal bouton. However, because it uses fixed tissue, transmission electron microscopy can only provide indirect information regarding living or evolving processes. Therefore, other techniques should be considered when the main objective is to study dynamic or functional aspects of synaptic vesicle trafficking and exocytosis.

Electrostatic potential and non-covalent interactions analysis for the design of selective 5-HT7 ligands

Despite the significant improvement of methodology in the field of the in silico drug discovery, the search for selective drugs is still far from trivial. This is especially relevant in the case of designing new medicaments for treatment of central nervous system disorders. In this work, we present a new approach based on the molecular docking and the following electronic properties analysis of ligands' binding poses (electrostatic potential distribution analysis and quantitative topological analysis of the electron density distribution). The proposed protocol significantly increases the success rate of the selective 5-HT7R ligands against 5-HT1AR selection from the prepared databases (the rise from 33.3% to 77.8% and from 22.7% to 62.5% for training and testing sets, respectively). The presented approach can be applied as a supportive method in the virtual screening of ligands databases.

Quantitative analysis of the distribution and content of trace metal elements in liquid samples with a three-dimensional confocal x-ray technique.

Three-dimensional (3D) confocal x-ray fluorescence analysis technology is widely used, but the quantitative analysis of elemental spatial distributions of solid samples is complicated. This paper explores a quantitative analysis method that can be applied to solid samples. Fluorescence spectra of liquid samples are obtained on a 3D confocal x-ray fluorescence spectrometer. Curves are plotted showing the relationships between the fluorescence count intensity and the mass percentage of metal ions, and the respective fitting-curve equations are determined according to the curve morphology. Fluorescence intensity as a function of the mass percentage and depth position is derived from the samples for a particular acquisition time. These data play a potential role in the subsequent quantitative analysis of unknown mass percentages of solid samples.

Automated Segmentation of Fluorescence Microscopy Images for 3D Cell Detection in human-derived Cardiospheres

The ‘cardiosphere’ is a 3D cluster of cardiac progenitor cells recapitulating a stem cell niche-like microenvironment with a potential for disease and regeneration modelling of the failing human myocardium. In this multicellular 3D context, it is extremely important to decrypt the spatial distribution of cell markers for dissecting the evolution of cellular phenotypes by direct quantification of fluorescent signals in confocal microscopy. In this study, we present a fully automated method, named CARE (‘CARdiosphere Evaluation’), for the segmentation of membranes and cell nuclei in human-derived cardiospheres. The proposed method is tested on twenty 3D-stacks of cardiospheres, for a total of 1160 images. Automatic results are compared with manual annotations and two open-source software designed for fluorescence microscopy. CARE performance was excellent in cardiospheres membrane segmentation and, in cell nuclei detection, the algorithm achieved the same performance as two expert operators. To the best of our knowledge, CARE is the first fully automated algorithm for segmentation inside in vitro 3D cell spheroids, including cardiospheres. The proposed approach will provide, in the future, automated quantitative analysis of markers distribution within the cardiac niche-like environment, enabling predictive associations between cell mechanical stresses and dynamic phenotypic changes.

Single-particle measurements reveal damage to filamentous influenza virions during laboratory handling

Most laboratory strains of influenza virus produce near-spherical virions, but clinical isolates also produce extended filaments whose biophysical properties are understudied. Most functional studies of filamentous influenza viruses do not include data on the concentration or lengths of the virions, making it hard to interpret their sometimes contradictory results. Furthermore, anecdotal reports suggest that filaments are damaged during routine laboratory handling. Therefore, to understand filament function we require a tool to assess the number and dimensions of filaments in a sample and an assessment of how filaments respond to standard handling procedures. We initially sought to analyse filament populations using negative stain particle counting, but found that this was low-throughput and could not detect particles longer than 10 µm. Instead, we used confocal microscopy with semi-automated image analysis. This allowed a high-throughput, quantitative analysis of length distributions in filament populations. Using this, we assessed the effects of pipetting, vortexing, sonicating, clarification and freezing on filaments. Most procedures did not appreciably alter filament dimensions. Pipetting and vortexing both slightly reduced filament numbers, but their effects were only appreciable after extended treatment. In contrast, freezing substantially reduced the number and median length of filaments, as well as creating ‘kinks’ in filaments which suggest damage to the capsid. We conclude that confocal microscopy can provide the basic measurements needed to interpret functional studies of filamentous strains. Using this approach, we found that freezing filaments causes previously unappreciated damage, which should be considered when planning further research.

Influence of Shock Losses on Air Distribution in Underground Mines

Air resistances are classified depending on their locality in underground mines. Three groups of local resistances are distinguished: shaft and mining horizon intersections; shaft and air channel intersections; stope and ventilation duct intersections in blind drifts. Influence of each group of the local resistances on the mine depression is evaluated as function of geometry and aerodynamics of underground openings. The criteria are proposed for estimating percentage influence of each group on the total mine depression are proposed. The calculation methods are determined for each group to be advisably used in quantitative analysis of air distribution in underground mine ventilation networks under the ventilation mode change.

The Predictive Closed-Loop Averaging Control of MMC Phase-Unit Losses Under Unbalanced Conditions

This paper introduces an averaging control strategy of the phase-unit losses of modular multilevel converters (MMCs). The quantitative analysis of the MMC phase-unit loss distribution under unbalanced ac conditions is carried out by investigating the individual component of the MMC arm currents. It shows that the unbalanced arm currents will result in unbalanced phase-unit losses. To address this issue, this paper proposes a predictive closed-loop-control-based zero-sequence voltage injection method that results in much averaged loss distribution under unbalanced ac conditions. The essence of the new method is that it adjusts the three-phase sinusoidal references so that the unbalanced arm currents are fully utilized to average phase-unit losses. This paper shows the effectiveness of the new approach by electromagnetic transient simulations on PSCAD/EMTDC.

Medium-Carbon Free-Cutting Steel

The paper presents theoretical and experimental studies of the formation processes of boron nitride, aluminium nitride, aluminium oxide and manganese sulphide inclusions in a free-cutting steel. Fact Sage software was used to model the behaviour of non-metallic inclusions. Formation temperatures and the amount of key inclusions in steel were calculated. Formation order of inclusions is as follows: aluminium oxide &gt; boron nitride &gt; manganese sulphide &gt; aluminium nitride. The object of study was the A45AR grade steel in 1.1–1.2 kg ingots. It was melted in an induction furnace, and aluminium, nitrided ferrosilicon and ferroboron were added after deoxidation before tapping. Quality estimation included chemical composition, macro-and microstructure, the character and shape of non-metallic inclusions. The finished metal contained fine and uniformly distributed inclusions of boron nitride. Qualitative and quantitative analysis of boron nitrides distribution in metal matrix showed that they were present both as individual and complex compounds, mostly of spherical shape. The size of BN inclusions varied from 0.18 to 6.52 μm. The amount of boron added to steel did not affect the size of MnS non-metallic inclusions.

Groundwater level response to the Wenchuan earthquake of May 2008

We have comprehensively analysed the co-seismic response of the groundwater levels of 280 wells in mainland China that were associated with the Wenchuan earthquake (Mw 7.9) that occurred on 12 May 2008. The observed co-seismic responses can be classified as step-like changes in 138 wells, variations in 69 wells and non-responses in 73 wells. After a quantitative analysis of spatial distribution, there was no spatially coherent signal found in the step-like changes (positive values indicate a step-like rise, and negative values indicate a step-like fall), even within 300 km of the epicenter. The amplitude and the phase shift of the M2-wave were compared between the pre- and post-earthquake conditions. The phase was forward and was concentrated at , regardless of the proximity of wells to the epicenter; however, the change in amplitude randomly increased or decreased. By computing the post-seismic groundwater recession, the characteristic times of the aquifers were . We concluded that by assuming a first-order approximation, i.e. a one-dimensional aquifer, the causal mechanism of the co-seismic response of the groundwater level was that the seismic waves enhanced rock permeability by clearing the facture-filling materials. The shapes of the co-seismic responses were determined by the well-aquifer system and the proximity of the wells to recharge or discharge areas (). The water level rose if the well was closer to the recharge area, the water level decline if the well was closer to the discharge area, and the water level oscillated if the well was farther from the recharge or discharge areas when the seismic wave was transmitted. The water level remained unchanged if the well did not penetrate any confined aquifer.

Spatial gradient and quantitative attribution of karst soil erosion in Southwest China.

Soil erosion estimation has attracted considerable attention from the scientific community and governments because of its importance to sustainable regional development. In karst areas, the heterogeneous environment and rocky desertification create difficulties in determining the influencing factors and spatial patterns of soil erosion. A quantitative analysis of karst soil erosion distribution was conducted by applying the revised soil loss equation model and the geographical detector method of attribution identification, which was based on spatial variance analysis. The results show that soil erosion was most severe in areas with an elevation of 1200-1800m and intense anthropogenic activity. When the vegetation coverage was below 0.5-0.6, soil erosion showed characteristics of a source-limited regime and increased with the increasing vegetation coverage. When the vegetation coverage was higher than 0.5-0.6, soil erosion followed a transport-limited regime and decreased with the increasing vegetation coverage. The factor detector showed land use to be the dominant factor, explaining 51% of soil erosion distribution. Among various land use types, dry land had the greatest vulnerability to soil erosion. Slope served as a controlling factor at large scales, especially when combined with annual precipitation exceeding 1500mm, and in dry and grassland areas. From the attribution analysis of multiple factors, the combination of land use and slope was the controlling interaction factor explaining 68% of soil erosion distribution. The methods and results of this research could serve as scientific references for decision makers and researchers exploring the characteristics of soil erosion to develop effective measures for its control.