bluuebunny/crossref_metadata_2025 huggingface dataset:
A Study of Stray Neutron Field Measurements for the Neutron Scattering Instruments at CSNS
Authors: Zhou Bin , Shen Fei , Hu Zhiliang , Wang Songlin , Ruan Xichao , Liang Tianjiao
Published: May 2022

Stray neutrons might cause several negative impacts. However, it is usually difficult to conduct precise stray neutron simulations using the Monte Carlo method. Therefore, in this study, a measurement technique was proposed to study the stray neutrons experimentally inside the neutron scattering instruments at China Spallation Neutron Source (CSNS). The adopted measurement instruments comprise an extended-range Bonner sphere spectrometer and a commercial neutron ambient-dose-equivalent dosimeter, which enables us to directly measure the neutron spectra and ambient-dose equivalent H*(10) values. Verification experiments were performed inside the BL06 beam line experimental area at CSNS at two exposed locations with different sample conditions. Comparison of the experimentally measured neutron spectra, integral neutron fluence, and H*(10) value with the simulations demonstrated the feasibility of using the proposed method for studying stray neutrons for the neutron instruments.
Time-of-Flight Secondary Ion Mass Spectrometry Analyses of Self-Assembled Monolayers of Octadecyltrimethoxysilane on SiO2 Substrate
Authors: Nie Heng-Yong , Jahangiri-Famenini Hamid-Reza
Published: May 2022

The self-assembled monolayers (SAMs) of organosilanes formed on an oxide substrate are thought to have a polymerized –Si–O–Si– network due to the homocondensation of silanols of hydrolyzed silane headgroups, which is the most significant difference in the SAMs of organosilanes in comparison with those of alkanethoils and organophsosphonic acids. In order to explore the interface chemistry of organosilane SAMs, surface-sensitive time-of-flight secondary ion mass spectrometry (ToF-SIMS) was used to compare ion fragmentation differences between the SAMs of octadecyltrimethoxysilane (OTMS) formed on a SiO2 substrate and free OTMS molecules, as well as oxide substrate. The ability of ToF-SIMS to verify the hydrolysis of the methoxy groups of OTMS molecules and to assess the polymerized –Si–O–Si– network in their SAMs was demonstrated, which shows that ToF-SIMS provides unique information to help us understand the interface chemistry of OTMS SAMs formed on oxides.
Immunoenhancement Effects of the Herbal Formula Hemomine on Cyclophosphamide-Induced Immunosuppression in Mice
Authors: Kim Hyemee , Kim Joo Wan , Kim Yeon-Kye , Ku Sae Kwang , Lee Hae-Jeung
Published: May 2022

Hemomine is an herbal blend comprising Angelicae Gigantis Radix and other herbs known to have immunomodulatory effects. We examined the immunopotentiating effect of this herbal blend on cyclophosphamide (CPA)-induced immunosuppression. Male mice were assigned to one of six groups: the intact control and five CPA treatment groups (one control, one reference (β-glucan), and three with the application of hemomine at different concentrations; 4, 2, or 1 mL/kg; n = 10 per group). Mice were injected with CPA to induce myelosuppression and immunosuppression, after which they received one of the experimental treatments. In immunosuppressed mice, hemomine treatment alleviated the noticeable reductions in body, spleen, and submandibular lymph node weights caused by CPA; caused changes in hematological markers; induced the reduced levels of serum IFN-γ and spleen TNF-α, IL-1β, and IL-10 by CPA; improved natural killer cell activities in the spleen and peritoneal cavity; and also improved lymphoid organ atrophy in a dose-dependent manner. We demonstrate that hemomine, a mixture of six immunomodulatory herbs, is an effective immunomodulatory agent, with the potential to enhance immunity.
An Effect of MHD on Non-Newtonian Fluid Flow over a Porous Stretching/Shrinking Sheet with Heat Transfer
Authors: Vishalakshi Angadi Basettappa , Maranna Thippaiah , Mahabaleshwar Ulavathi Shettar , Laroze David
Published: May 2022

The current article explains the 3-D MHD fluid flow under the impact of a magnetic field with an inclined angle. The porous sheet is embedded in the flow of a fluid to yield the better results of the problem. The governing PDEs are mapped using various transformations to convert in the form of ODEs. The yielded ODEs momentum equation is examined analytically to derive the mass transpiration and then it is used in the energy equation and solved exactly by using various controlling parameters. In the case of multiple solutions, the closed-form exact solutions of highly non-linear differential equations of the flow are presented as viscoelastic fluid, which is classified as two classes, namely the second order liquid and Walters’ liquid B fluid. The results can be obtained by using graphical arrangements. The current work is utilized in many real-life applications, such as automotive cooling systems, microelectronics, heat exchangers, and so on. At the end of the analysis, we concluded that velocity and mass transpiration was more for Chandrasekhar’s number for both the stretching and shrinking case.
Prestress Modal Analysis and Optimization of Cantilever Supported Rotor under the Unbalanced Axis Force and Moving Mass
Authors: Yang Hao , Xu Jian , Wang Guoqiang , Yang Zhen , Li Qiang
Published: May 2022

In order to reduce the x-direction and Y-direction displacement disturbance of the barrel and improve the firing accuracy, based on Bernoulli Euler’s theoretical assumption of beam and taking M134 barrel machine gun as the calculation model, the pre-stress modal analysis and optimization of cantilever supported rotor under unbalanced force and moving mass are carried out in this paper. The main work of this paper is as follows: (1) M134 physical model is established, and the unbalanced force in the motion process of projectile in bore is solved by interior ballistic theory; (2) Based on the unbalanced rotor theory, the barrel vibration model considering the projectile weight and acceleration is established; (3) The critical speed model of high-speed rotating system is established, and the critical speed is determined by finite element modal analysis to determine the rigid/flexible state of barrel components in different speed regions; (4) Based on the above model, take the x-direction and Y-direction displacement of the barrel as the output value, and take the elastic modulus of the barrel, the relative position between the barrel hoop and the fuselage components and the cross-sectional area as the variable values, carry out the optimization design, and verify the firing accuracy before and after optimization through experiments.
High-Expansion Foam: A Risk Control Option to Increase Passenger Ship Safety during Flooding
Authors: Vassalos Dracos , Paterson Donald , Mauro Francesco , Atzampos George , Assinder Peter , Janicek Adam
Published: May 2022

In naval architecture, the standard way adopted to reduce the risk of potential loss of life for passenger ships after an accident is via regulations. In case of flooding, this explicitly implies the introduction of fixed watertight bulkheads, permanently modifying the internal ship’s layout. Damage stability regulations constantly aim at higher safety standards; therefore, the layout reconfiguration of an existing vessel may be essential to meet new requirements, leading to higher costs for retrofitting. Furthermore, increasing fragmentation of the internal layout has a physical limit, neglecting the possibility to elevate standards above a particular upper limit. In this view, innovative solutions give the chance to exceed such a limit. The present work describes the advantages of high-expansion foam application for passive and active protection from flooding events. The possibility to have a material granting sufficient water tightness allows installing fixed or deployable barriers that increase the safety level of the ship. Here, besides the description of the foam characteristics, the application on a reference passenger ship highlights the advantages of passive and active foam barriers to limit flooding and drastically reduce the risk of loss of lives. The changes in the limiting stability margins required by regulations and the analysis of dynamic flooding simulations for specific damage cases demonstrate the benefits of foam installation onboard passenger ships as a risk control option.
Tropical Cyclone Intensity Prediction Using Deep Convolutional Neural Network
Authors: Xu Xiao-Yan , Shao Min , Chen Pu-Long , Wang Qin-Geng
Published: May 2022

In this study, deep convolutional neural network (CNN) models of stimulated tropical cyclone intensity (TCI), minimum central pressure (MCP), and maximum 2 min mean wind speed at near center (MWS) were constructed based on ocean and atmospheric reanalysis, as well Best Track of tropical hurricane data over 2014–2018. In order to explore the interpretability of the model structure, sensitivity experiments were designed with various combinations of predictors. The model test results show that simplified VGG-16 (VGG-16 s) outperforms the other two general models (LeNet-5 and AlexNet). The results of the sensitivity experiments display good consistency with the hypothesis and perceptions, which verifies the validity and reliability of the model. Furthermore, the results also suggest that the importance of predictors varies in different targets. The top three factors that are highly related to TCI are sea surface temperature (SST), temperature at 500 hPa (TEM_500), and the differences in wind speed between 850 hPa and 500 hPa (vertical wind shear speed, VWSS). VWSS, relative humidity (RH), and SST are more significant than MCP. For MWS and SST, TEM_500, and temperature at 850 hPa (TEM_850) outweigh the other variables. This conclusion also implies that deep learning could be an alternative way to conduct intensive and quantitative research.
Effects of Urbanization on Extreme Climate Indices in the Valley of Mexico Basin
Authors: Montero-Martínez Martín José , Andrade-Velázquez Mercedes
Published: May 2022

This study analyzes 50 annual climate change indices related to temperature and precipitation in the Valley of Mexico basin for the period 1951–2010. First, a quality and homogenization analysis of 90 weather stations (categorized as urban, suburban, and rural) in the basin was performed using the Climatol algorithm. The non-parametric Mann–Kendall test and the Sen’s slope method were applied to determine the existence of a trend and to estimate the magnitude of the change in extreme climate indices, respectively. To eliminate the serial correlation problem, the lag-1 method and the Patakamuri tests were used. Statistically significant positive trends were found for SU, TMm, TNm, TNn, TX90p, and WSDI, as well as negative ones for FD, TX10p, TN10p, CSDI, and HDDheat18. The results seem to support an influence of anthropogenic global warming on the study region, rather than local effects of urbanization. However, it is likely that some significant differences in the urban change rate of some indices could be due to local effects, such as the difference in land cover that occurs between urban and rural stations. Not enough statistically significant results were found for the climate change indices related to precipitation in most of the stations. Compared to other studies in the Mexico City area, the main contribution of this study is the analysis of 50 climate indices in a 60-year period working with a quality-controlled and homogenized database.
Comparison of COSMIC and COSMIC-2 Radio Occultation Refractivity and Bending Angle Uncertainties in August 2006 and 2021
Authors: Anthes Richard , Sjoberg Jeremiah , Feng Xuelei , Syndergaard Stig
Published: May 2022

We compare the random error statistics (uncertainties) of COSMIC (Constellation Observing System for Meteorology, Ionosphere and Climate, C1) and COSMIC-2 (C2) radio occultation (RO) bending angles and refractivities for the months of August 2006 and 2021 over the tropics and subtropics using the three-cornered hat method. The uncertainty profiles are similar for the two RO missions in the troposphere. However, a higher percentage of C2 profiles reach close to the surface in the moisture-rich tropics, an advantage of the higher signal-to-noise ratio (SNR) in C2. C2 uses signals from both GPS (Global Positioning System) and GLONASS Global Navigation System Satellites (GNSS). The GPS occultations show smaller uncertainties in the stratosphere and lower mesosphere (30–60 km) than the GLONASS occultations, a result of more accurate GPS clocks. Therefore, C2 (GPS) uncertainties are smaller than C1 uncertainties between 30–60 km while the C2 (GLONASS) uncertainties are larger than those of C1. The uncertainty profiles vary with latitude at all levels. We find that horizontal gradients in temperature and water vapor, and therefore refractivity, are the major cause of uncertainties in the tropopause region and troposphere through the violation of the assumption of spherical symmetry in the retrieval of bending angles and refractivity.
Analysing the Main Standards for Climate-Induced Mechanical Risk in Heritage Wooden Structures: The Case of the Ringebu and Heddal Stave Churches (Norway)
Authors: Califano America , Baiesi Marco , Bertolin Chiara
Published: May 2022

Studying, controlling and extrapolating the indoor microclimate of historical buildings have always been at the forefront among numerous preventive conservation strategies, especially in case of buildings made of organic hygroscopic materials, e.g., wood. The variations and fluctuations of the microclimatic variables, namely temperature (T) and relative humidity (RH), could have a detrimental effect on the mechanical properties of wooden objects, works of art and structures. For this reason, through the years, several guidelines have been provided by standards and protocols about the optimal microclimatic conditions that should be ensured to avoid the decay and the eventual catastrophic failure of heritage objects and buildings. In this work, two historical buildings entirely made of Scots pine wood have been analysed: the Ringebu and Heddal stave churches (Norway). These churches store several wooden medieval statues and paintings that are also susceptible to the effects of the microclimate. For this reason, the timeseries of the indoor relative humidity of the two churches have been analysed, in the framework of the indications provided by the standards. The criticalities of the existing protocols have been pointed out, emphasizing the need for systematically and periodically updated specifications, tailorable to a given case study of concern, without forgetting the ever-present needs of energy- and money-saving approaches.
Dual-Polarization Radar Observations of the Evolution of a Supercell Tornado and Analysis of the Echo Mechanisms
Authors: Wu Bin , Wei Ming , Li Yanfang
Published: May 2022

To gain a deeper understanding of the structural and evolutionary characteristics of supercell tornadoes that occurred in eastern China on 14 May 2021, observations from the S-band dual-polarization radars, soundings and other instruments are used to investigate the evolutionary process of the tornado formation by the mergering and strengthening of supercell storms. The results are described as follows. The updraft by upper divergence and vertical thermal instability induced by the cold source at the tropopause provided the environmental conditions suitable for tornado formation. The tornado event involved three storm merger processes, each of which was associated with an increase in the echo intensity, vertical rising speed, and vertical vorticity of the supercell. Furthermore, during the last merger, the merging of the two vortices resulted in the reduction of the rotation radius of the new vortex, which also provided a favorable condition for tornadogenesis. A schematic was proposed to describe storm mergers. The characteristics of the velocity spectrum width were indicative of the occurrence and evolution of the tornado in this case. During the tornado stage, distinct polarimetric variable signatures (e.g., a tornado debris signature and a differential reflectivity arc) and radial velocity signatures (i.e., a tornadic vortex signature) were observed.
Impact of Climate Change on Water Resources in the Western Route Areas of the South-to-North Water Diversion Project
Authors: Ning Zhongrui , Zhang Jianyun , Yuan Shanshui , Wang Guoqing
Published: May 2022

The South-to-North Water Diversion Project (SNWDP) is a national strategic project for water shortages in northern China. Climate change will affect the availability of water resources in both source and receiving areas. A grid-based RCCC-WBM model based on climate projections from nine Global Climate Models under SSP2-4.5 was used for analyzing the changes in temperature, precipitation, and streamflow in the near future (2025–2045, NF) and far future (2040–2060, FF) relative to the baseline (1956–2000). The results showed that: (1) the temperature of the western route will increase significantly in the NF and FF with an extent of 1.6 °C and 2.0 °C, respectively, (2) precipitation will very likely increase even though Global Climate Model (GCM) projections are quite dispersed and uncertain, and (3) over half of the GCMs projected that streamflow of receiving area will slightly increase with a rate of 1.68% [−8.67%, 12.3%] and 2.78% [−3.30%, 11.0%] in the NF and FF, respectively. Climate change will support the planning of the western route to a certain extent. However, water supply risk induced by the extreme situation of climate change should be paid adequate consideration when the project operates in practice due to the large dispersion and uncertainty of GCM projections.
A Digital Microfluidic Device Integrated with Electrochemical Impedance Spectroscopy for Cell-Based Immunoassay
Authors: Zhang Yuqian , Liu Yuguang
Published: May 2022

The dynamic immune response to various diseases and therapies has been considered a promising indicator of disease status and therapeutic effectiveness. For instance, the human peripheral blood mononuclear cell (PBMC), as a major player in the immune system, is an important index to indicate a patient’s immune function. Therefore, establishing a simple yet sensitive tool that can frequently assess the immune system during the course of disease and treatment is of great importance. This study introduced an integrated system that includes an electrochemical impedance spectroscope (EIS)-based biosensor in a digital microfluidic (DMF) device, to quantify the PBMC abundance with minimally trained hands. Moreover, we exploited the unique droplet manipulation feature of the DMF platform and conducted a dynamic cell capture assay, which enhanced the detection signal by 2.4-fold. This integrated system was able to detect as few as 104 PBMCs per mL, presenting suitable sensitivity to quantify PBMCs. This integrated system is easy-to-operate and sensitive, and therefore holds great potential as a powerful tool to profile immune-mediated therapeutic responses in a timely manner, which can be further evolved as a point-of-care diagnostic device to conduct near-patient tests from blood samples.
A Patient-Ready Wearable Transcutaneous CO2 Sensor
Authors: Cascales Juan Pedro , Li Xiaolei , Roussakis Emmanuel , Evans Conor L.
Published: May 2022

Continuously monitoring transcutaneous CO2 partial pressure is of crucial importance in the diagnosis and treatment of respiratory and cardiac diseases. Despite significant progress in the development of CO2 sensors, their implementation as portable or wearable devices for real-time monitoring remains under-explored. Here, we report on the creation of a wearable prototype device for transcutaneous CO2 monitoring based on quantifying the fluorescence of a highly breathable CO2-sensing film. The developed materials are based on a fluorescent pH indicator (8-hydroxy-1,3,6-pyrenetrisulfonic acid trisodium salt or HPTS) embedded into hydrophobic polymer matrices. The film’s fluorescence is highly sensitive to changes in CO2 partial pressure in the physiological range, as well as photostable and insensitive to humidity. The device and medical-grade films are based on our prior work on transcutaneous oxygen-sensing technology, which has been extensively validated clinically.
Field-Effect Capacitors Decorated with Ligand-Stabilized Gold Nanoparticles: Modeling and Experiments
Authors: Poghossian Arshak , Karschuck Tobias , Wagner Patrick , Schöning Michael J.
Published: May 2022

Nanoparticles are recognized as highly attractive tunable materials for designing field-effect biosensors with enhanced performance. In this work, we present a theoretical model for electrolyte-insulator-semiconductor capacitors (EISCAP) decorated with ligand-stabilized charged gold nanoparticles. The charged AuNPs are taken into account as additional, nanometer-sized local gates. The capacitance-voltage (C–V) curves and constant-capacitance (ConCap) signals of the AuNP-decorated EISCAPs have been simulated. The impact of the AuNP coverage on the shift of the C–V curves and the ConCap signals was also studied experimentally on Al–p-Si–SiO2 EISCAPs decorated with positively charged aminooctanethiol-capped AuNPs. In addition, the surface of the EISCAPs, modified with AuNPs, was characterized by scanning electron microscopy for different immobilization times of the nanoparticles.
Functionalization of Glucose Oxidase in Organic Solvent: Towards Direct Electrical Communication across Enzyme-Electrode Interface
Authors: Dudkaitė Vygailė , Bagdžiūnas Gintautas
Published: May 2022

Enzymatic biosensors based on glucose oxidase has been proven to be one of the effective strategies for the detection of glucose and contributed to health improvements. Therefore, research and debates to date are ongoing in an attempt to find the most effective way to detect this analyte using this enzyme as the recognition center. The 3rd generation biosensors using direct electron transfer (DET) type enzymes are a great way towards practical devices. In this work, we developed a simple method for the functionalization of glucose oxidase with redoxable ferrocene groups in chloroform. The enzyme retained its activity after storage in this organic solvent and after the functionalization procedures. This enzyme functionalization strategy was employed to develop the biosensing monolayer-based platforms for the detection of glucose utilizing the quasi-DET mechanism. As a result of an electrochemical regeneration of the catalytic center, the formation of harmful H2O2 is minimized during enzymatic electrocatalysis.
Assessment of Nanoparticle-Mediated Tumor Oxygen Modulation by Photoacoustic Imaging
Authors: Sivasubramanian Maharajan , Lo Leu-Wei
Published: May 2022

Photoacoustic imaging (PAI) is an invaluable tool in biomedical imaging, as it provides anatomical and functional information in real time. Its ability to image at clinically relevant depths with high spatial resolution using endogenous tissues as contrast agents constitutes its major advantage. One of the most important applications of PAI is to quantify tissue oxygen saturation by measuring the differential absorption characteristics of oxy and deoxy Hb. Consequently, PAI can be utilized to monitor tumor-related hypoxia, which is a crucial factor in tumor microenvironments that has a strong influence on tumor invasiveness. Reactive oxygen species (ROS)-based therapies, such as photodynamic therapy, radiotherapy, and sonodynamic therapy, are oxygen-consuming, and tumor hypoxia is detrimental to their efficacy. Therefore, a persistent demand exists for agents that can supply oxygen to tumors for better ROS-based therapeutic outcomes. Among the various strategies, NP-mediated supplemental tumor oxygenation is especially encouraging due to its physio-chemical, tumor targeting, and theranostic properties. Here, we focus on NP-based tumor oxygenation, which includes NP as oxygen carriers and oxygen-generating strategies to alleviate hypoxia monitored by PAI. The information obtained from quantitative tumor oxygenation by PAI not only supports optimal therapeutic design but also serves as a highly effective tool to predict therapeutic outcomes.
Conception Preferences during COVID-19 Pandemic Lockdowns
Authors: Albeitawi Soha , Al-Alami Zina , Khamaiseh Khaldoun , Al Mehaisen Lama , Khamees Almu’atasim , Hamadneh Jehan
Published: May 2022

Background: The COVID-19 lockdowns imposed new challenges to couples who were planning to conceive. In this research paper, we aimed to study the perceptions of women in Jordan during the pandemic regarding fertility behavior, the desire to use assisted reproductive technology (ART) and the awareness and beliefs of potential risks related to conception. Methods: A validated online-based questionnaire was distributed to women from April–May 2020, Statistical analysis was performed using the statistical software SPSS version 22 and R software (2020); p values ≤ 0.05 were considered statistically significant. Results: The total number of participants was 814 women, with 78.2% of the participants (58.7% fertile and 76.6% infertile) believing that pregnancy during the COVID-19 pandemic could be risky. Among them, 16% and 40%, respectively, were trying to conceive during the pandemic, and 97.4% and 89.9%, respectively, were not willing to use ART if needed during the pandemic. Young, nulliparous women who were married for less than one year were significantly associated with the desire to conceive during the COVID-19 pandemic. Conclusion: This study concluded that the fertility behavior of women in Jordan changed during the pandemic, and their desire for natural conception and for using ART declined, as they believed that there were potential risks related to conceiving during the pandemic. However, the effect was greater among the general fertile population than the infertile.
Software for the Multi-Criteria Design of the External Walls Based on User Priority
Authors: Majer Jiří , Vavřínová Nikola , Stejskalová Kateřina , Pentková Lenka
Published: May 2022

The external walls of buildings account for a substantial part of the financial costs of the entire construction, and there can be a loss of up to 35% of thermal energy through them. By properly optimizing the price for the construction of m2 of the external wall structure and its thermal technical parameters, interesting savings can be achieved. At present, there is no multi-criteria analysis for designing external wall structure compositions involving broader input options according to the user’s technical parameters and priorities. There is a large selection of special software in the Czech and European markets, but the software is focused only on the narrower area of design and ignores the issue of building material prices. The aim of this work is to create an algorithm that reliably finds the composition that best meets the user’s requirements using a wide database of materials and selected mathematical methods. This article presents an algorithm that would design the ideal composition of an external wall. This algorithm has two options for searching. The first is based on eight technical criteria and the prices of materials used in combination with user priorities. The second option is to find the best composition based only on the specified interval of the selected technical parameters. Materials databases and the use of existing computational methods, such as the Saaty method and the WSM—weighted sum method, applied to the algorithm are essential to find the composition. According to the assignment, the structures will be clearly quantified in values from 1 (best) to 0 (worst). The algorithm, which is based on the analysis of data, sources, and theories of multi-criteria decision-making, should, therefore, facilitate the design of the external wall. At the end of this article, there is a verification of the functionality of the algorithm on a case study. We believe that software that uses the proposed algorithm could be very useful for practice.
Experimental Characterization of Raw Earth Properties for Modeling Their Hygrothermal Behavior
Authors: Belarbi Yassine Elias , Sawadogo Mohamed , Poullain Philippe , Issaadi Nabil , Hamami Ameur El Amine , Bonnet Stéphanie , Belarbi Rafik
Published: May 2022

Raw earth is one of the oldest building materials of mankind. Almost a third of the world’s population is living in an earth-based house. However, their use remains low compared to conventional materials such as concrete, steel, and wood. Although these geosourced materials are abundant, recyclable, and have a low environmental footprint, their use is very limited in the construction sector. This can be explained by the lack of data regarding their hygrothermal behavior. In this context, the present work aims to highlight the properties of cob construction material with straw addition. An experimental characterization of hygrothermal and microstructural properties has been carried out. Thermal conductivity, specific heat, sorption isotherms, moisture storage capacity, moisture buffer value (MBV), and water vapor permeability are obtained experimentally. Then, the collected data are used as input parameters of a numerical prediction model to numerically assess the thermal and hygric behavior. Cob is then compared to other more commonly used materials to highlight the benefits of its use within the context of the energetic and environmental transition. Our results will allow better understanding of the behavior of the new geosourced material thanks to experimental and numerical investigation.
Endocrine Therapy-Resistant Breast Cancer Cells Are More Sensitive to Ceramide Kinase Inhibition and Elevated Ceramide Levels Than Therapy-Sensitive Breast Cancer Cells
Authors: Pal Purab , Millner Alec , Semina Svetlana E. , Huggins Rosemary J. , Running Logan , Aga Diana S. , Tonetti Debra A. , Schiff Rachel , Greene Geoffrey L. , Atilla-Gokcumen G. Ekin , Frasor Jonna
Published: May 2022

ET resistance is a critical problem for estrogen receptor-positive (ER+) breast cancer. In this study, we have investigated how alterations in sphingolipids promote cell survival in ET-resistant breast cancer. We have performed LC-MS-based targeted sphingolipidomics of tamoxifen-sensitive and -resistant MCF-7 breast cancer cell lines. Follow-up studies included treatments of cell lines and patient-derived xenograft organoids (PDxO) with small molecule inhibitors; cytometric analyses to measure cell death, proliferation, and apoptosis; siRNA-mediated knockdown; RT-qPCR and Western blot for gene and protein expression; targeted lipid analysis; and lipid addback experiments. We found that tamoxifen-resistant cells have lower levels of ceramides and hexosylceramides compared to their tamoxifen-sensitive counterpart. Upon perturbing the sphingolipid pathway with small molecule inhibitors of key enzymes, we identified that CERK is essential for tamoxifen-resistant breast cancer cell survival, as well as a fulvestrant-resistant PDxO. CERK inhibition induces ceramide-mediated cell death in tamoxifen-resistant cells. Ceramide-1-phosphate (C1P) partially reverses CERK inhibition-induced cell death in tamoxifen-resistant cells, likely through lowering endogenous ceramide levels. Our findings suggest that ET-resistant breast cancer cells maintain lower ceramide levels as an essential pro-survival mechanism. Consequently, ET-resistant breast cancer models have a unique dependence on CERK as its activity can inhibit de novo ceramide production.
Immune Profile of BRAF-Mutated Metastatic Colorectal Tumors with Good Prognosis after Palliative Chemotherapy
Authors: Kim Jeong Eun , Kim Ji-Hun , Kim Sang-Yeob , Cho Hyungwoo , Ryu Yeon-Mi , Hong Yong Sang , Kim Sun Young , Kim Tae Won
Published: May 2022

Background: BRAF-mutated colorectal cancers (BRAF-MT CRCs) are known to have poor prognoses. BRAF-MT CRC was reported to be possibly related to the immune-activated phenotype. Objectives: This study aimed to investigate the association between the immune microenvironment and prognosis of BRAF-MT CRC. Methods: We evaluated clinical outcomes and investigated the immune profile of the BRAF-MT CRC tumors using the multiplex immunohistochemistry of immune-related markers: cytokeratin, programmed death ligand-1 (PD-L1), programmed cell death protein-1 (PD-1), and a cluster of differentiation 8 (CD8). Results: Out of 2313 tumors, 123 were BRAF-MT tumors. Among them, 86 tumors with available tissue were included. Out of 86 patients, 75 patients were non-good responders (GR), whereas 11 patients were GR. Median progression-free survival after first-line chemotherapy (4.6 vs. 12.4 months, p = 0.008) and overall survival (11.8 vs. 45.0 months) were longer in the GR group (p < 0.001). Median CD8+ T cell (254.29 vs. 656.0, p = 0.092), PD-L1+ tumor cell (0.95 vs.15.56, p = 0.050), PD-L1+ stromal cell (3.17 vs. 72.38, p = 0.025), PD-L1+ tumor and stromal cell (5.08 vs. 74.92, p = 0.032), and PD-1+ stromal cell (45.08 vs. 325.40, p = 0.046) counts were greater in the GR group. Conclusion: The clinical outcomes of unselected patients with BRAF-MT CRC were generally similar to those in previous studies. Based on the immune profile analysis, higher PD-L1 expression and CD8-positive cell infiltration were observed in BRAF-MT tumors with a good prognosis.
Factors Associated with Hemorrhage of Melanoma Brain Metastases after Stereotactic Radiosurgery in the Era of Targeted/Immune Checkpoint Inhibitor Therapies
Authors: Zoga Eleni , Wolff Robert , Ackermann Hanns , Meissner Markus , Rödel Claus , Tselis Nikolaos , Chatzikonstantinou Georgios
Published: May 2022

We aimed to evaluate the factors associated with hemorrhage (HA) of melanoma brain metastases (MBM) after Cyberknife stereotactic radiosurgery (SRS) in the modern era of systemic therapy. A total of 55 patients with 279 MBM were treated in 93 fractions. The median age, SRS dose, radiological follow-up, and time to HA were 60.4 years, 20 Gy, 17.7 months, and 10.7 months, respectively. Radiologically evident HA was documented in 47 (16.8%) metastases. Of the 55 patients, 25 (45.4%) suffered an HA. Among those, HA caused grade 3 toxicity in 10 patients (40%) and grade 1 symptoms in 5 patients (20%). Ten patients (40%) with HA experienced no toxicity. Logistic regression revealed the use of anticoagulants and the administration of systemic therapy within 7/15 days from SRS to be predictive for HA. When considering the HA causing grade 3 symptomatology, only the use of anticoagulants was significant, with the delivery of whole brain radiation therapy (WBRT) before the HA narrowly missing statistical significance. Our retrospective analysis showed that the administration of modern systemic therapy within 7/15 days from SRS may contribute to HA of MBM, though it appears safe, at least concerning grade 3 toxicity. The use of anticoagulants by the time of SRS significantly increased the risk of HA.
Molecular Characterization of BRCA1 c.5339T>C Missense Mutation in DNA Damage Response of Triple-Negative Breast Cancer
Authors: Lee Jeong Dong , Ryu Won-Ji , Han Hyun Ju , Kim Tae Yeong , Kim Min Hwan , Sohn Joohyuk
Published: May 2022

BRCA1 L1780P BRCT domain mutation has been recognized as a pathogenic mutation in patients with breast cancer. However, the molecular significance of this mutation has not yet been studied in triple-negative breast cancer (TNBC) cells in vitro. We established MDA-MB 231, HCC1937, and HCC1395 TNBC cell lines expressing BRCA1 L1780P mutant. BRCA1 L1780P mutant TNBC cells showed increased migration and invasion capacity, as well as increased sensitivity to olaparib and carboplatin compared to BRCA1 wild-type cells. BRCA1 L1780P mutant TNBC cells showed decreased RAD51 expression and reduced nuclear RAD51 foci formation following carboplatin and olaparib treatment. The molecular interaction between p-ATM and BRCA1 was abrogated following introduction of BRCA1 L1780P mutant plasmid in TNBC cells, suggesting that the BRCA1 L1780P mutation disrupts the p-ATM-BRCA1 protein–protein interaction. We established an olaparib-resistant BRCA1 L1780P mutant TNBC cell line by chronic drug treatment. Olaparib-resistant cell lines showed upregulation of RAD51 expression upon olaparib treatment, and reduction in RAD51 expression in olaparib-resistant cells restored olaparib sensitivity. Collectively, these results suggest that the BRCA1 L1780P mutation impairs RAD51 recruitment by disrupting p-ATM-BRCA1 interaction, which is a crucial molecular factor in homologous recombination and olaparib sensitivity. Further therapeutic targeting of RAD51 in BRCA1 L1780P mutant breast cancer is warranted.
Cancer Stem Cells (CSCs), Circulating Tumor Cells (CTCs) and Their Interplay with Cancer Associated Fibroblasts (CAFs): A New World of Targets and Treatments
Authors: Aramini Beatrice , Masciale Valentina , Arienti Chiara , Dominici Massimo , Stella Franco , Martinelli Giovanni , Fabbri Francesco
Published: May 2022

The importance of defining new molecules to fight cancer is of significant interest to the scientific community. In particular, it has been shown that cancer stem cells (CSCs) are a small subpopulation of cells within tumors with capabilities of self-renewal, differentiation, and tumorigenicity; on the other side, circulating tumor cells (CTCs) seem to split away from the primary tumor and appear in the circulatory system as singular units or clusters. It is becoming more and more important to discover new biomarkers related to these populations of cells in combination to define the network among them and the tumor microenvironment. In particular, cancer-associated fibroblasts (CAFs) are a key component of the tumor microenvironment with different functions, including matrix deposition and remodeling, extensive reciprocal signaling interactions with cancer cells and crosstalk with immunity. The settings of new markers and the definition of the molecular connections may present new avenues, not only for fighting cancer but also for the definition of more tailored therapies.
Diagnostic Accuracy of High-Grade Intraepithelial Papillary Capillary Loops by Narrow Band Imaging for Early Detection of Oral Malignancy: A Cross-Sectional Clinicopathological Imaging Study
Authors: Ota Airi , Miyamoto Ikuya , Ohashi Yu , Chiba Toshimi , Takeda Yasunori , Yamada Hiroyuki
Published: May 2022

This study aimed to clarify the advantages and disadvantages of conventional visual inspection (CVI), endoscopic white light imaging (WLI), and narrow-band imaging (NBI) and to examine the diagnostic accuracy of intraepithelial papillary capillary loops (IPCL) for the detection of oral squamous cell carcinoma (OSCC). This cross-sectional study included 60 participants with oral mucosal diseases suspected of having oral potentially malignant disorders (OPMDs) or OSCC. The patients underwent CVI, WLI, NBI, and incisional biopsy. Images were evaluated to assess the lesion size, color, texture, and IPCL. Oral lichen planus (OLP) and oral leukoplakia lesions were observed in larger areas with NBI than with WLI; 75.0% were associated with low-grade (Type 0–II) IPCL. Various types of oral leukoplakia were seen; however, all OSCC cases showed high-grade (Type III–IV) IPCL. The diagnostic accuracy of high-grade IPCL for OSCC showed a sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 100%, 80.9%, 59.1%, 100%, and 85.0%, respectively. A non-homogeneous lesion with high-grade IPCL strongly suggested malignancy. Overall, our results indicate that WLI and NBI are powerful tools for detecting precancerous and cancerous lesions using IPCL. However, NBI is influenced by mucosal thickness; therefore, image interpretation is important for accurate diagnosis.
Strengthen Air Oxidation of Refractory Humic Acid Using Reductively Etched Nickel-Cobalt Spinel Catalyst
Authors: Jing Qi , Cai Jiabai , Li Huan
Published: May 2022

Nickel-cobalt spinel catalyst (NCO) is a promising catalyst for air oxidation of humic acid, which is a typical natural refractory organic matter and a precursor of toxic disinfection by-products. In this study, reductive etchers, NaBH4 or Na2SO3, were used to adjust the NCO surface structure to increase the performance. The modified catalyst (NCO-R) was characterized, and the relationship between its intrinsic properties and catalytic paths was discovered. The results of O2-temperature programmed desorption, NH3-temperature programmed desorption, and X-ray photoelectron spectroscopy (XPS) demonstrated that reductant etching introduced oxygen vacancies to the surface of NCO and increased active surface oxygen species and surface acidity. In addition, the modification did not change the raw hollow sphere structure of NCO. The crystallinity and specific surface area of NCO-R increased, and average pore size of NCO-R decreased. XPS results showed that the ratio of Co3+/Co2+ in NCO-R decreased compared with NCO, while the ratio of Ni3+/Ni2+ increased. The results of H2-temperature programmed reduction showed that the H2 reduction ability of NCO-R was stronger. Due to these changes in chemical and physical properties, NCO-R exhibited much better catalytic performance than NCO. In the catalytic air oxidation of humic acid at 25 °C, the total organic carbon (TOC) removal rate increased significantly from 44.4% using NCO to 77.0% using NCO-R. TOC concentration of humic acid decreased by 90.0% after 12 h in the catalytic air oxidation using NCO-R at 90 °C.
Progesterone-Induced Sperm Release from the Oviduct Sperm Reservoir
Authors: Mirihagalle Supipi , Hughes Jennifer Rose , Miller David Joel
Published: May 2022

In mammalian females, after sperm are deposited in the reproductive tract, a fraction of sperm migrates to the lower oviduct (isthmus) and forms a sperm storage site known as the functional sperm reservoir. The interactions between sperm membrane proteins and oviduct epithelial cells facilitate sperm binding to the oviductal epithelium and retention in the reservoir. Sperm are bound by glycans that contain specific motifs present on isthmic epithelial cells. Capacitated sperm are released from the reservoir and travel further in the oviduct to the ampulla where fertilization occurs. For decades, researchers have been studying the molecules and mechanisms of sperm release from the oviductal sperm reservoir. However, it is still not clear if the release of sperm is triggered by changes in sperm, oviduct cells, oviduct fluid, or a combination of these. While there is a possibility that more than one of these events are involved in the release of sperm from the reservoir, one activator of sperm release has the largest accumulation of supporting evidence. This mechanism involves the steroid hormone, progesterone, as a signal that induces the release of sperm from the reservoir. This review gathers and synthesizes evidence for the role of progesterone in inducing sperm release from the oviduct functional sperm reservoir.
Identification of UDP-Glucuronosyltransferase 2B15 (UGT2B15) as a Target for IGF1 and Insulin Action
Authors: Sarfstein Rive , Nagaraj Karthik , Parikh Shivang , Levy Carmit , Laron Zvi , Benayahu Dafna , Werner Haim
Published: May 2022

Normal growth and development in mammals are tightly controlled by numerous genetic factors and metabolic conditions. The growth hormone (GH)-insulin-like growth factor-1 (IGF1) hormonal axis is a key player in the regulation of these processes. Dysregulation of the GH-IGF1 endocrine system is linked to a number of pathologies, ranging from growth deficits to cancer. Laron syndrome (LS) is a type of dwarfism that results from mutation of the GH receptor (GHR) gene, leading to GH resistance and short stature as well as a number of metabolic abnormalities. Of major clinical relevance, epidemiological studies have shown that LS patients do not develop cancer. While the mechanisms associated with cancer protection in LS have not yet been elucidated, genomic analyses have identified a series of metabolic genes that are over-represented in LS patients. We hypothesized that these genes might constitute novel targets for IGF1 action. With a fold-change of 11.09, UDP-glucuronosyltransferase 2B15 (UGT2B15) was the top up-regulated gene in LS. The UGT2B15 gene codes for an enzyme that converts xenobiotic substances into lipophilic compounds and thereby facilitates their clearance from the body. We investigated the regulation of UGT2B15 gene expression by IGF1 and insulin. Both hormones inhibited UGT2B15 mRNA levels in endometrial and breast cancer cell lines. Regulation of UGT2B15 protein levels by IGF1/insulin, however, was more complex and not always correlated with mRNA levels. Furthermore, UGT2B15 expression was dependent on p53 status. Thus, UGT2B15 mRNA levels were higher in cell lines expressing a wild-type p53 compared to cells containing a mutated p53. Animal studies confirmed an inverse correlation between UGT2B15 and p53 levels. In summary, increased UGT2B15 levels in LS might confer upon patient’s protection from genotoxic damage.
Cytochalasin B Modulates Nanomechanical Patterning and Fate in Human Adipose-Derived Stem Cells
Authors: Bianconi Eva , Tassinari Riccardo , Alessandrini Andrea , Ragazzini Gregorio , Cavallini Claudia , Abruzzo Provvidenza Maria , Petrocelli Giovannamaria , Pampanella Luca , Casadei Raffaella , Maioli Margherita , Canaider Silvia , Facchin Federica , Ventura Carlo
Published: May 2022

Cytoskeletal proteins provide architectural and signaling cues within cells. They are able to reorganize themselves in response to mechanical forces, converting the stimuli received into specific cellular responses. Thus, the cytoskeleton influences cell shape, proliferation, and even differentiation. In particular, the cytoskeleton affects the fate of mesenchymal stem cells (MSCs), which are highly attractive candidates for cell therapy approaches due to their capacity for self-renewal and multi-lineage differentiation. Cytochalasin B (CB), a cyto-permeable mycotoxin, is able to inhibit the formation of actin microfilaments, resulting in direct effects on cell biological properties. Here, we investigated for the first time the effects of different concentrations of CB (0.1–10 μM) on human adipose-derived stem cells (hASCs) both after 24 h (h) of CB treatment and 24 h after CB wash-out. CB influenced the metabolism, proliferation, and morphology of hASCs in a dose-dependent manner, in association with progressive disorganization of actin microfilaments. Furthermore, the removal of CB highlighted the ability of cells to restore their cytoskeletal organization. Finally, atomic force microscopy (AFM) revealed that cytoskeletal changes induced by CB modulated the viscoelastic properties of hASCs, influencing their stiffness and viscosity, thereby affecting adipogenic fate.
Toxoplasma gondii Rhoptry Protein 7 (ROP7) Interacts with NLRP3 and Promotes Inflammasome Hyperactivation in THP-1-Derived Macrophages
Authors: Zhu Lijun , Qi Wanjun , Yang Guang , Yang Yurong , Wang Yuwen , Zheng Lulu , Fu Yongfeng , Cheng Xunjia
Published: May 2022

Toxoplasma gondii is a common opportunistic protozoan pathogen that can parasitize the karyocytes of humans and virtually all other warm-blooded animals. In the host’s innate immune response to T. gondii infection, inflammasomes can mediate the maturation of pro-IL-1β and pro-IL-18, which further enhances the immune response. However, how intercellular parasites specifically provoke inflammasome activation remains unclear. In this study, we found that the T. gondii secretory protein, rhoptry protein 7 (ROP7), could interact with the NACHT domain of NLRP3 through liquid chromatography-mass spectrometry analysis and co-immunoprecipitation assays. When expressing ROP7 in differentiated THP-1 cells, there was significant up-regulation in NF-κB and continuous release of IL-1β. This process is pyroptosis-independent and leads to inflammasome hyperactivation through the IL-1β/NF-κB/NLRP3 feedback loop. The loss of ROP7 in tachyzoites did not affect parasite proliferation in host cells but did attenuate parasite-induced inflammatory activity. In conclusion, these findings unveil that a T. gondii-derived protein is able to promote inflammasome activation, and further study of ROP7 will deepen our understanding of host innate immunity to parasites.