Quantitative Estimation Research Articles

Microphysical Characteristics of Precipitation for Four Types of Typical Weather Systems on Hainan Island

The microphysical characteristics of precipitation and their differences among four typical weather systems over Hainan Island were investigated via multi-source observations from 2019 to 2023. We find that the cold fronts (CFs) have the greatest concentration of small raindrops, with a more substantial raindrop condensation process. The subtropical highs (SHs), with primarily deep convection and more prominent evaporation at low levels, lead to greater medium-to-large raindrops (diameters > 1 mm). Tropical cyclones (TCs) are characterized mainly by raindrop condensation and breakup, resulting in high concentrations of small raindrops and low concentrations of large raindrops. The trough of low pressures (TLPs) produces the lowest concentration of small raindrops because of evaporation processes. The convective clusters of the SHs are between maritime-like and continental-like convective clusters, and those of the other three types of weather systems are closer to maritime-like convective clusters. The relationships between the shape parameter (μ) and the slope parameter (Λ), as well as between the reflectivity factors (Z) and the rain rates (R), were established for the four weather systems. These results could improve the accuracy of radar quantitative precipitation estimation and the microphysical parameterizations of numerical models for Hainan Island.

Experimental determination of the coefficient of viscosity of the dry snow

Snow compaction is a natural process in the evolution of any snow cover, and this obviously changes the physical and mechanical properties of a snow thickness. The quantitative estimate of this process is a coefficient of the snow viscosity, which is linearly related to the rate of the snow cover deformation The technique for preparation and testing of samples with the fine-grain snow under condition of uniaxial compression at negative temperatures is described. It was determined that values of the snow viscosity coefficient fall within the range from 0.10 to 0.30 g/cm³ for three temperature intervals. The viscosity coefficient of the fine-grain snow varies from 10⁸ до 10¹⁰ Па. The data obtained made possible to find the limits of variability of this coefficient for winter conditions on the Russian plain. A dependence of the viscosity coefficient on the snow density and temperature is proposed, and it describes the series of the above shown experimental data. It is shown that influence of changes in the viscosity coefficient of fine-grain snow on the snow properties depending on its density are comparable in scale to the influence of the temperature. The result may be useful for modeling the evolution of snow cover.

Hemodynamic analysis on the flow characteristics around abdominal aortic hemorrhage site

The hemodynamic characteristics of blood flow around the site of abdominal aortic hemorrhage can serve as a valuable indicator for identifying the location of hemorrhage. In this research, we conducted numerical simulations to analyze the flow fields in the patient-specific abdominal aorta with and without hemorrhage. We quantitatively compared differences in flow field patterns, blood loss, and branch vessel perfusion between hemorrhagic and non-hemorrhagic cases. Our numerical results demonstrate that there is a distinct hemodynamic characteristic observed around the hemorrhage site, characterized by continuous abnormal high-velocity (>0.7 m/s) and high-Rortex (>200) zone. Additionally, we evaluated the amount of blood loss and time to moderate shock for different cases of abdominal aortic hemorrhage, while statistically analyzing variations in branch vessel perfusion along the abdominal aorta. These findings provide quantitative estimations for blood loss, branch perfusion, and potential indicators to assess rescue time window as well as evaluate the extent of distal tissue damage and organ injury.

Solvent-Based and Matrix-Matched Calibration Methods on Analysis of Ceftiofur Residues in Milk and Pharmaceutical Samples Using a Novel HPLC Method.

The matrix effect is accepted as one of the critical factors that affect trueness, and it is especially important in the analysis of critical compounds, such as drugs, toxins and pesticides, in complex matrices. Ceftiofur (CEF) is a leading drug used in dairy industry for pulmonary infections. Because milk has a complex matrix, which is rich in fats, proteins and many other compounds, the determination of CEF in milk products deals with issues of trueness. On the other hand, pharmaceuticals also have a complex composition as they contain not only the active pharmaceutical ingredient but also many excipients, such as preservatives and pH modifiers. Due to its frequent use, its residues can be found in meat products or exist as an excreted compound in urine, milk and so on. The aim of this study was to investigate the effect of different calibration methods on quantitative estimation of CEF in milk and pharmaceutical samples. CEF was analysed using a new HPLC method, in which separation was achieved on a C18 bonded fused-core silica particle column by using isocratic elution; the method was optimized by testing different chromatographic conditions and validated according to the ICH Q2(R1) and United States Pharmacopeia guidelines. Interestingly, it was found that CEF signals in milk samples were higher than the ones at the same level prepared in calibration solutions with a ratio of 11.28:1. This finding reveals the necessity of matrix-matched calibration for accurate quantitative determination of CEF in milk samples. Moreover, the milk in the market and the most used pharmaceutical formulations were analysed using the current method.

Osteoclast indices in osteogenesis imperfecta: systematic review and meta-analysis.

Osteogenesis imperfecta (OI) is a rare bone fragility disorder caused by mutations in genes encoding collagen type I or that affect its processing. Alterations in osteoclasts were suggested to contribute to OI pathophysiology. We aimed to systematically identify studies reporting measures of osteoclast formation and function in patients and mouse models of OI, to quantify OI-induced changes. The systematic search of Medline, Ovid, and Web of Science identified 798 unique studies. After screening, we included 23 studies for meta-analysis, reporting osteoclast parameters in 310 patients with OI of 9 different types and 16 studies reporting osteoclast parameters in 406 animals of 11 different OI mouse models. The standardized mean difference with 95% confidence interval (CI) was used as the effect size, and random-effects meta-analysis was performed. In patients with OI, collagen degradation markers were significantly higher compared with age-matched controls, with an effect size of 1.23 (CI: 0.36, 2.10]. Collagen degradation markers were the most elevated in the 3- to 7-year-old age group and in patients with more severe forms of OI. Bone histomorphometry demonstrated the trends for higher osteoclast numbers (1.16; CI: -0.22, 2.55) and osteoclast surface (0.43; CI: -0.63, 1.49), and significantly higher eroded surface (3.24; CI: 0.51, 5.96) compared with age-matched controls. In OI mice, meta-analysis demonstrated significant increases in collagen degradation markers (1.59; CI: 1.07, 2.11), in osteoclast numbers (0.94; CI: 0.50, 1.39), osteoclast surface (0.73; CI: 0.22, 1.23), and eroded surface (1.31; CI: 0.54, 2.08). The largest differences were in OI mice with the mutations in Col1a1 and Col1a2 genes. There were no differences between males and females in clinical or animal studies. Quantitative estimates of changes in osteoclast indices and their variance for patients with OI are important for planning future studies. We confirmed that similar changes are observed in mice with OI, supporting their translational utility.

Diurnal Cycles of Cloud Properties and Precipitation Patterns over the Northeastern Tibetan Plateau During Summer

In the context of rising temperatures and increasing humidity in Northwest China, substantial gaps remain in understanding the mechanisms of land–atmosphere cloud–precipitation coupling across the northeastern Tibetan Plateau (TP), Loess Plateau (LP), and Huangshui Valley (HV). This study addresses these gaps by investigating cloud properties and precipitation patterns utilizing the Fengyun-4 Satellite Quantitative Precipitation Estimation Product (FY4A-QPE) and ERA5 datasets. We specifically focus on Lanzhou, a pivotal city within the LP, and Xining, which epitomizes the HV. Our findings reveal that diurnal variations in precipitation are significantly less pronounced in the eastern regions compared to northeastern TP. This discrepancy is attributed to marked diurnal fluctuations in convective available potential energy (CAPE) and wind shear between 200 and 500 hPa. While both cities share similar wind shear patterns and moisture transport directions, Xining benefits from enhanced snowmelt and effective water retention in surrounding mountains, resulting in higher precipitation levels. Conversely, Lanzhou suffers from moisture deficits, with dry, hot winds exacerbating the situation. Notably, precipitation in Xining is strongly correlated with CAPE, influenced by diurnal variability, and intensified by valley and lake–land breezes, which drive afternoon convection. In contrast, Lanzhou’s precipitation exhibits a weak relationship with CAPE, as even elevated values fail to generate significant cloud formation due to insufficient moisture. The ongoing trends of warming and humidification may lead to improved precipitation patterns, especially in the HV, with potential ecological benefits. However, concentrated rainfall during summer afternoons and midnights raises concerns regarding extreme weather events, highlighting the susceptibility of the HV to geological hazards. This research underscores the need to further explore the uncertainties inherent in precipitation dynamics in these regions.

Performance Assessment of Satellite-Based Precipitation Products in the 2023 Summer Extreme Precipitation Events over North China

In the summer of 2023, North China experienced a rare extreme precipitation storm due to Typhoons Doksuri and Khanun, leading to significant secondary disasters and highlighting the urgent need for accurate rainfall forecasting. Satellite-based quantitative precipitation estimation (QPE) products like Integrated Multi-Satellite Retrievals for GPM (IMERG) and Global Satellite Mapping of Precipitation (GSMaP) from the Global Precipitation Measurement (GPM) Mission have great potential for enhancing forecasts, necessitating a quantitative evaluation before deployment. This study uses a dense rain gauge as a benchmark to assess the accuracy and capability of the latest version 7B IMERG and version 8 GSMaP satellite-based QPE products for the 2023 summer extreme precipitation in North China. These satellite-based QPE products include four satellite-only products, namely IMERG early run (IMERG_ER) and IMERG late run (IMERG_LR), GSMaP near-real-time (GSMaP_NRT), and GSMaP microwave-infrared reanalyzed (GSMaP_MVK), along with two gauge-corrected products, namely IMERG final run (IMERG_FR) and GSMaP gauge adjusted (GSMaP_Gauge). The results show that (1) GSMaP_MVK, IMERG_LR, and IMERG_FR effectively capture the space distribution of the extreme rainfall, with relatively high correlation coefficients (CCs) of approximately 0.77, 0.75, and 0.79. The IMERG_ER, GSMaP_NRT, and GSMaP_Gauge products exhibit a less accurate spatial pattern capture (CCs about 0.66, 0.73, and 0.67, respectively). Each of the six QPE products tends to underestimate rainfall (RBs < 0%). (2) The IMERG products surpass the corresponding GSMaP products in serial rainfall measurement. IMERG_LR demonstrates superior performance with the lowest root-mean-square error (RMSE) (about 0.38 mm), the highest CC (0.97), and less underestimation (RB about −6.37%). (3) The IMERG products at rainfall rates ≥ 30 mm/h, GSMaP_NRT and GSMaP_MVK products at rainfall rates ≥ 55 mm/h, and GSMaP_Gauge products at ≥ 40 mm/h showed marked limitations in event detection, with a near-zero probability of detection (POD) and a nearly 100% false alarm ratio (FAR). In this extreme precipitation event, caution is needed when using the IMERG and GSMaP products.

Quantitative estimation and validation of Alectinib hydrochloride drug substance using quantitative nuclear magnetic resonance spectroscopy

Nuclear magnetic resonance spectroscopy has been recently used for quantitative estimation of drug substance which has numerous merits in pharmaceutical applications when compared to traditional methods of chromatography. Present study focuses on method development and validation of quantitative proton nuclear magnetic spectroscopy method for estimation of alectinib hydrochloride drug substance. This method involves use of internal standard in presence of alectinib hydrochloride. For quantitation, 1H NMR signals at 8.4 ppm and 6.7 ppm corresponding to analyte proton of alectinib and ethyl 4-(dimethyl amino) benzoate internal standard respectively were used. Moreover, this method was validated as per ICH guidelines for accuracy, precision, linearity, limit of detection, limit of quantitation, range and robustness. Assay estimation by Q-NMR is facile and time-efficient which does not require reference standard of analyte and yet accurate and precise alternative as compared to estimation by other chromatographic techniques.

Thermodynamic and Kinetic Studies on the Pyrophoricity of Uranium Flakes

The objective of this work was to arrive at quantitative estimates of pyrophoricity of uranium in different geometries. The major source of heat generation was identified to be exothermic chemical reactions of uranium with moist air. Time evolution of temperature was studied for uranium considering 3D conduction and convection heat loss routes using Finite Element Analysis. Auto ignition temperature for uranium flakes was quantified using heat balance equation and was found to be around 500 K. Excess heat generation rates needed to cause auto ignition of uranium flakes at room temperature were also estimated. The major sources of excess heat leading to its ambient ignition could be attributed to friction and other exothermic chemical reactions of process impurities in uranium.

Ethanol-activated microglial exosomes induce MCP1 signaling mediated death of stress-regulatory proopiomelanocortin neurons in the developing hypothalamus

BackgroundMicroglia, a type of resident immune cells within the central nervous system, have been implicated in ethanol-activated neuronal death of the stress regulatory proopiomelanocortin (POMC) neuron-producing β-endorphin peptides in the hypothalamus in a postnatal rat model of fetal alcohol spectrum disorders. We determined if microglial extracellular vesicles (exosomes) are involved in the ethanol-induced neuronal death of the β-endorphin neuron via secreting elevated levels of the chemokine monocyte chemoattractant protein 1 (MCP1), a key regulator of neuroinflammation.MethodsWe employed an in vitro model, consisting of primary culture of hypothalamic microglia prepared from postnatal day 2 (PND2) rat hypothalami and treated with or without 50 mM ethanol for 24 h, and an in vivo animal model in which microglia were obtained from hypothalami of PND6 rats fed daily with 2.5 mg/kg ethanol or control milk formula for five days prior to use. Exosomes were extracted and characterized with nanosight tracking analysis (NTA), transmission electron microscopy and western blot. Chemokine multiplex immunoassay and ELISA were used for quantitative estimation of MCP1 level. Neurotoxic ability of exosome was tested using primary cultures of β-endorphin neurons and employing nucleosome assay and immunocytochemistry. Elevated plus maze, open field and restraint tests were used to assess anxiety-related behaviors.ResultsEthanol elevated MCP1 levels in microglial exosomes both in vitro and in vivo models. Ethanol-activated microglial exosomes when introduced into primary cultures of β-endorphin neurons, increased cellular levels of MCP1 and the chemokine receptor CCR2 related signaling molecules including inflammatory cytokines and apoptotic genes as well as apoptotic death of β-endorphin neurons. These effects of microglial exosomes on β-endorphin neurons were suppressed by a CCR2 antagonist RS504393. Furthermore, RS504393 when injected in postnatal rats prior to feeding with ethanol it reduced alcohol-induced β-endorphin neuronal death in the hypothalamus. RS504393 also suppressed corticosterone response to stress and anxiety-like behaviors in postnatally alcohol-fed rats during adult period.ConclusionThese data suggest that alcohol exposures during the developmental period elevates MCP1 levels in microglial exosomes that promote MCP1/CCR2 signaling to increase the apoptosis of β-endorphin neurons and resulting in hormonal and behavioral stress responses.

In-line spectroscopy for iodine quantification in dynamic contrast-enhanced dedicated breast CT.

In 4D dynamic contrast-enhanced dedicated breast computed tomography (4D DCE-bCT), the functional properties of the breast will be characterized by monitoring the uptake and washout of iodine-based contrast agents over time. This information could be valuable in breast cancer treatment. However, prior to clinical implementation, it is crucial to validate the quantitative estimates of iodine concentrations at each time point during acquisition. To develop an in-line spectroscopy system capable of measuring iodine concentrations in a dynamic x-ray breast phantom in real-time. Potassium iodide served as the contrast agent. The system was set-up at both the entrance and exit of the phantom. It comprises a fiber-coupled green LED and collimator, which together ensure that a parallel beam passes through the sample holder. Transmitted light is captured by a collimator on the opposite side and directed through a fiber optic cable to a photodetector for intensity measurement. The relationship between 13 iodine concentrations (0-6mg I/mL) and light transmission was tested, and the system's repeatability and accuracy were determined. The system exhibited a strong correlation between iodine concentration and transmission values, achieving a root-mean-square error of 0.007. The repeated measurements had relative standard deviations of 0.04% and 0.1% for repeated water measurements at the phantom's entrance and exit, respectively. Furthermore, the accuracy measurements gave a mean error of fitting of 0.008(±0.07) mg I/mL. The in-line spectroscopy system can effectively monitor iodine concentrations in a dynamic breast phantom, providing a reliable method for quantitative validation of 4D DCE-bCT.

Quantitative estimation of optical properties in bilayer media within the subdiffusive regime using tilted fiber-optic probe diffuse reflectance spectroscopy, part 2: probe design, realization, and experimental validation.

Tissues like skin have a layered structure where each layer's optical properties vary significantly. However, traditional diffuse reflectance spectroscopy assumes a homogeneous medium, often leading to estimations that reflects the properties of neither layer. There's a clear need for probes that can precisely measure the optical properties of layered tissues. This paper aims to design a diffuse reflectance probe capable of accurately estimating the optical properties of bilayer tissues in the subdiffusive regime. Using Monte Carlo simulations, we evaluated key geometric factors-fiber placement, tilt angle, diameter, and numerical aperture-on optical property estimation, following the methodology in Part I. A robust design is proposed that balances accurate intrinsic optical property (IOP) calculations with practical experimental constraints. The designed probe, featuring eight illumination and eight detection fibers with varying spacings and tilt angles. The estimation error of the IOP calculation for bilayer phantoms is less than 20% for top layers with thicknesses between 0.2 and 1.0mm. Building on the approach from Part I and using a precise calibration, the probe effectively quantified and distinguished the IOPs of bilayer samples, particularly those relevant to early skin pathology detection and characterization.

Changes of angiography-derived coronary microcirculatory resistance before and after drug-coated balloon treatment

Abstract Background Drug coated balloon (DCB) is a treatment option for a lesion in a small coronary artery. The effect of DCB is proven in mechanistic and clinical outcomes, however, its influence on the microvascular function has not been elucidated. In addition, because there are differences in the types of drugs and coatings among different DCBs, their effects on microvascular function may vary. Angiography-derived microcirculatory resistance (AMR) is a novel angiographic parameter calculated from angiography-derived quantitative flow ratio and flow velocity estimation. AMR is reported to have a good correlation with the wire-based index of microvascular resistance. Purpose To investigate the AMR in coronary vessels treated with sirolimus or paclitaxel coated balloon. Methods This is a subanalysis of the TRANSFORM I (The TReAtmeNt of Small Coronary Vessels: MagicTouch Sirolimus Coated Balloon) trial. TRANSFORM I is a prospective, randomized, multi-center, open-label noninferiority trial conducted in Europe that enrolled 121 patients (126 vessels) with stabilized acute coronary syndrome or chronic coronary syndrome who had at least one de novo coronary artery lesion in a small coronary vessel. Patients were randomized 1:1 to treatment with the sirolimus coated balloon (SCB) or paclitaxel coated balloon (PCB). The SCB is coated with phospholipid encapsulated sirolimus nanocarrier, whereas the PCB is coated with crystalline paclitaxel. In this subanalysis, angiography at baseline and post-procedure were analyzed to calculate the AMR by an imaging core lab. Coronary microvascular dysfunction (CMD) was defined as AMR≧2.5 mmHg*s/cm. Results In the total of 126 vessels, 63 were included in each of the SCB and PCB group. Angiography both at baseline and post-procedure were analyzable for AMR in 59 vessels in SCB and in 59 vessels in PCB group. In SCB group, the median AMR increased significantly after procedure (baseline; 2.03 [1.58-2.42], post-procedure;2.21 [1.78-2.53], p=0.03). However, the proportion of vessels with CMD did not significantly change (baseline; 22.0% [13/59], post-procedure; 32.2% [18/59], p=0.19) (Figure). In the PCB group, the median AMR increased significantly after procedure (baseline; 2.22 [1.66-2.53], post-procedure;2.45 [1.93-2.96], p=0.003). Furthermore, the proportion of vessels with CMD significantly increased (baseline; 27.1% [16/59], post-procedure; 47.5% [28/59], p=0.046) (Figure). The AMR measurement was not significantly different between SCB and PCB at baseline (p=0.53), but it was significantly higher in PCB than in SCB at post-procedure (p=0.04). Conclusion After DCB treatment, AMR significantly increased in both arms. The proportion of the vessel with CMD after procedure did not significantly change in the SCB group but increased in the PCB group. The potential mechanism of increase in AMR after DCB treatment (e.g. embolization of small crystals) may warrant further investigation.Proportion of AMR≥2.5

Results of a 5 year Antimicrobial Stewardship program in a North Italian Hospital

Abstract Issue A National Action Plan (PNCAR) to fight antimicrobial resistance has been launched in Italy in 2017, further revised in 2022. In order to reduce inappropriate exposure to antibiotics and infections from multidrug resistant bacteria, a structured system of surveillance and monitoring according to PNCAR standards has been set up in all Italian regions. In the Hospital of Cittadella (District of Padua, Veneto region), special focus has been given to the reduction of antibiotic consumption, in particular quinolones, third generation cephalosporins, carbapenems and macrolides. Description Multidisciplinary meetings have been monthly organized by the hospital Antimicrobial Stewardship Group, with the aim of coordinating the implementation of specific stewardship actions. A quantitative estimate of antibiotic consumption (defined daily dose - DDD - consumption per 100 days of hospitalization) has been provided by the Regional data warehouse from 2019 to 2023 regarding all classes of antibiotics. Results Between 2019 and 2023 a clear decrease in the consumption of quinolones (from 8 to 5,8 DDD, -28%) and carbapenems (from 2,5 to 1,3 DDD, -48%) was observed but, at the same time, an increase in the consumption of third generation cephalosporins (from 9 to 15,7 DDD, +74%) has been reported. This can be explained as a direct consequence of the correct application of therapy guidelines, which in several cases suggest the use of ceftriaxone instead of meropenem. Finally, after an increase in the consumption of macrolides during the first COVID-19 pandemic wave, the consumption of this class of antibiotics has returned to pre-pandemic level. Lessons Constant monitoring of antimicrobial consumption and the identification of warning situations that may need to implement specific actions are the cornerstone of Antimicrobial Stewardship programs. Targets must be defined analyzing data of bacterial resistance rates and infections from multidrug resistant bacteria. Key messages • In Antimicrobial Stewardship programs it is important to adopt constant monitoring of antimicrobial consumption. • Antimicrobial stewardship programs need to be adapted according to the characteristics of each hospital.

Kinetics of electromigration mass transfer in micro- and nanoelectronics interface elements depending on the strength of thin-film junctions

The theoretical model proposed earlier by the authors, which describes the interrelation of strength and electromigration (diffusion) properties of interfaces formed by joined materials, has been perfected and extended. Within the framework of the developed model, a linear relationship between the values of the work of reversible interface separation Wa and the activation energy of electromigration in the interface HEM was established. The coefficients of the obtained relation are estimated and compared with experimental data on the study of electromigration in a copper conductors covered with protective dielectrics. Using also the model developed earlier by the authors, which describes the dependence of the value on the concentrations of non-equilibrium lattice defects in the volumes of joined materials, a number of effects due to the influence of such defects on the processes caused by electromigration have been predicted and investigated. In the paper we obtained that by introducing non-equilibrium lattice defects in the volumes of bonded materials in the form of atomic impurities of interstition or substitution it is possible to effectively influence the characteristics of electromigration instability of the shape of the interlayer interface. For the introduction impurities, quantitative analytical estimates of the impurity concentration necessary for a significant change (both increase and decrease) in the characteristic rise time of the instability of the shape of the initially flat interface have been obtained.

Comparison of Different Quantitative Precipitation Estimation Methods Based on a Severe Rainfall Event in Tuscany, Italy, November 2023

Accurate quantitative precipitation estimation (QPE) is fundamental for a large number of hydrometeorological applications, especially when addressing extreme rainfall phenomena. This paper presents a comprehensive comparison of various rainfall estimation methods, specifically those relying on weather radar data, rain gauge data, and their fusion. The study evaluates the accuracy and reliability of each method in estimating rainfall for a severe event that occurred in Tuscany, Italy. The results obtained confirm that merging radar and rain gauge data outperforms both individual approaches by reducing errors and improving the overall reliability of precipitation estimates. This study highlights the importance of data fusion in enhancing the accuracy of QPE and also supports its application in operational contexts, providing further evidence for the greater reliability of merging methods.

De novo design of mIDH1 inhibitors by integrating deep learning and molecular modeling

BackgroundMutations in the IDH1 gene have been shown to be an important driver in the development of acute myeloid leukemia, gliomas and certain solid tumors, which is a promising target for cancer therapy.MethodsBidirectional recurrent neural network (BRNN) and scaffold hopping methods were used to generate new compounds, which were evaluated by principal components analysis, quantitative estimate of drug-likeness, synthetic accessibility analysis and molecular docking. ADME prediction, molecular docking and molecular dynamics simulations were used to screen candidate compounds and assess their binding affinity and binding stability with mutant IDH1 (mIDH1).ResultsBRNN and scaffold hopping methods generated 3890 and 3680 new compounds, respectively. The molecules generated by the BRNN performed better in terms of molecular diversity, druggability, synthetic accessibility and docking score. From the 3890 compounds generated by the BRNN model, 10 structurally diverse drug candidates with great docking score were preserved. Molecular dynamics simulations showed that the RMSD of the four systems, M1, M2, M3 and M6, remained stable, with local flexibility and compactness similar to the positive drug. The binding free energy results indicated that compound M1 exhibited the best binding properties in all energy aspects and was the best candidate molecule among the 10 compounds.ConclusionIn present study, compounds M1, M2, M3 and M6 generated by BRNN exhibited optimal binding properties. This study is the first attempt to use deep learning to design mIDH1 inhibitors, which provides theoretical guidance for the design of mIDH1 inhibitors.

Characterization of Extracellular Vesicles by Sulfophosphovanillin Colorimetric Assay and Raman Spectroscopy.

Detailed characterization of extracellular vesicles (EVs) is crucial for their application in medical diagnostics. However, the complexity of their chemical composition and the heterogeneity of EV populations make their characterization challenging. Here we describe two analytical procedures that can help overcome this challenge. Small EVs were isolated from conditioned cell culture media using ultracentrifugation and characterized using nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM). Raman spectroscopy was used to assess the overall composition of the isolated samples and lipids extracted from them. Sulfophosphovanillin (SPV) colorimetric assay was used to quantify the contents of lipid. Six samples of EVs were characterized. The lipid contents measured using SPV assay was in reasonable agreement with the quantitative estimates based on the particle size and concentration measured using NTA. The most peaks observed in the Raman spectra could be attributed to either proteins or lipids, and their origins was confirmed by lipid extraction. The protein-to-lipid ratio was estimated based on the Raman spectra. The experiential procedures described in this study will help to overcome the challenge of quick and highly informative characterization of the EVs.

Testing Visual Function by Assessment of the Optomotor Reflex in Glaucoma.

Optomotor response/reflex (OMR) is a fast and efficient first-in-line visual screening method, especially for rodents. It has the potential to evaluate both the scotopic and photopic visions of nonrestrained animals through tracking head movement, providing a quantitative estimate of visual functions. In restrained animals, optokinetic response (OKR), compensatory eye movements for visual shifts in the surroundings, is utilized. Both OMR and OKR capitalize on an individual's innate reflex to stabilize images for the purpose of capturing clear vision. The two reflexes have similar reliability when evaluating stimulus luminance, contrast, spatial frequency, and velocity. They have emerged as powerful tools to evaluate the efficacy of pharmacological treatments and phenotypes of subjects undergoing study. With OMR and OKR accurately assessing visual acuity (VA) as well as contrast sensitivity (CS), the gold standards for measuring clinical vision, they provide reliable and easily accessible results that further eye and brain research. These methods of sight evaluation have been used in multiple animal models, particularly mice and zebrafish. Through OMR assays, these animal models have been utilized to investigate retinal degenerative diseases, helping researchers differentiate between worsening stages. Alongside tests such as optical coherence tomography (OCT), OMR provides confirmation of visual status, where increased OMR function often correlates with improved visual status. OMR has continued to be used outside of glaucoma in various retinal diseases, such as retinitis pigmentosa (RP), diabetic retinopathy, and age-related macular degeneration.In this chapter, we will introduce the concept and application of visual stimulus-induced head or eye reflex movement in different animal species and experimental models of eye diseases, such as glaucoma and other neurodegenerative disorders, and in patients with glaucoma.

Active, passive and hybrid multilocal living practices - towards a classification

AbstractThe accelerated pace of life, increased mobility and the individualisation of society have yielded a variety of postmodern living and housing environments. The proliferation of multilocal living practices can be understood as part of this change. Research on multilocality often focuses exclusively on those who reside in several places. The sedentary members of the same household, who remain at the primary residence and whose lives are significantly influenced by the rhythmic absence of the mobile members, are largely overlooked. Furthermore, the quantitative estimates of the extent of multilocal practices, based on official data, are currently insufficient. The aim of this study is to classify multi-local lifestyles to capture the diversity and complexity of these living practices, thereby expanding scholarly understanding of multilocality in its numerical entirety. To achieve this, a representative survey using a largely standardized questionnaire was conducted in two major city regions in Germany in the spring of 2023. The data from the study identified specific types of multilocality: active, passive, and hybrid multilocals, each exhibiting distinct characteristics. The integration of these multilocality types into the structure of multilocal households enables a classification that provides a framework for understanding how such households are organized and how they manage their mobility and residential practices. It is argued that all members of a multilocal household are significantly influenced by practises of multilocality, leading to a constant negotiation of their everyday lives.