Line Model Research Articles

Analysis of the Electromagnetic Effects on the Large Floating Roof Oil Tanks by nearby Lightning Strike Based on TLM

Lightning fire is one of the biggest dangers for chemical and petrochemical storage tank farms, particularly in floating roof oil tanks (FROTs). To improve the lightning protection of FROTs, the process of floating roof tanks affected by lightning is analyzed. Lightning inductive effects can result in the undesired operation of the above-ground storage tank equipment and endanger exploitation safety. The time domain finite element analysis based on the transmission line model (TLM) method is regarded as a numerical technique to solve field problems by implementing circuit equivalents. This study aims to analyze lightning strike characteristics using the Heidler current function and simulate electromagnetic field strength (EMFS) distribution and surface current density (SCD). Calculation of minimum possible effective strike distance and shielding effectiveness (SE) is performed. Parametric modeling ensures accurate modeling of the roof's bypass conductor to the shell. By utilizing the Parameter Sweep technique, multiple simulations can be carried out with varying structure parameter values. This approach ensures optimal efficiency and accuracy in the results obtained.

Analysis of heating defects in extension rods of extra-high voltage direct current overhead transmission lines

This paper studies the overheating defect of an extension rod in a ± 800 kV extra-high voltage direct current overhead transmission line, and proposes various factors that affect the overheating of the extension rod. Establish an equivalent model of an extra high voltage DC transmission line based on equipotential point and line parameter analysis, and calculate the model parameters. The proposed model can also be applied to ultra-high voltage DC overhead transmission lines such as ± 500 kV, and has strong universality. Simulation experiments show that if the equivalent resistance value of the split wire side is reduced by 0.01Ω, the power loss on the extension tie rod can be increased to 380.951 W; if the equivalent resistance value of the jumper side is increased by 0.01Ω, the power loss on the extension tie rod can be increased to 273.41 W. Combined with theoretical analysis and simulation verification, it is concluded that the main factor affecting the overheating of the extension rod is the change in the resistance value on the jumper side caused by the increase in contact resistance. A systematic troubleshooting plan for related defect problems is proposed, which has important reference and guidance significance for such line fault problems.

GPR168 functions as a tumor suppressor in mouse melanoma by restraining Akt signaling pathway.

Malignant melanoma (MM) is a malignant tumor associated with high mortality rates and propensity for metastasis. Despite advancement in treatment, the incidence of MM continue to rise globally. GPR168, also known as MrgprF, is a MAS related GPR family member. The low expression of GPR168 has also been reported in many malignant tumors including MM. In the study, the statistical analysis from The Cancer Genome Atlas (TCGA) revealed a significant down regulation of GPR168 in melanoma compared to normal melanocytes, underscoring its importance in MM. The aim of the present study is to investigate the affect of GPR168 overexpression and elucidate its molecular mechanisms in MM cells. In addition, we used mouse melanoma B16-F10 cell line and xenograph tumor model to explore the function of GPR168 in melanoma. Our findings demonstrate that GPR168 overexpression could inhibit B16-F10 cell proliferation, migration, and xenografts tumor growth. Further, mechanistic studies revealed that GPR168 affected B16-F10 progress through Akt signal pathway with the decreased expression of p-Akt, p-GSK-3β, β-catenin, Myc, CyclinD1 and CDK4. In order to validate these findings, a rescue experiment was formulated employing GPR168 polyclonal antibody (Anti-GPR168 pAbs) to block GPR168 functionality. The addition of Anti-GPR168 pAbs into the culture medium restored both cell proliferation and migration. In conclusion, the overexpression of GPR168 in mouse melanoma B16-F10 cells suppressed proliferation and migration through the Akt signaling pathway. These findings collectively propose GPR168 as a promising novel tumor suppressor in MM, suggesting its potential as a therapeutic target in future interventions.

Revealing potential Rab proteins participate in regulation of secretory autophagy machinery.

Autophagy can be classified as degradative and secretory based on distinct functions. The small GTPase proteins Rab8a and Rab37 are responsible for secretory autophagy-mediated exocytosis of IL-1β, insulin, and TIMP1 (tissue inhibitor of 54 metalloproteinase 1). Other Rab family members participating in secretory autophagy are poorly understood. Herein, we identified 26 overlapped Rab proteins in purified autophagosomes of mouse pancreatic β-cell "Min-6" and human lung cancer cell "CL1-5-Q89L" with high secretory autophagy tendency by LC-MS/MS proteomics analysis. Six Rab proteins (Rab8a, Rab11b, Rab27a, Rab35, Rab37, and Rab7a) were detected in autophagosomes of four cell lines, associating them with autophagy-related vesicle trafficking. We used CL1-5-Q89L cell line model to evaluate the levels of Rab proteins colocalization with autophagy LC3 proteins and presence in purified autophagosomes. We found five Rab proteins (Rab8a, Rab11b, Rab27a, Rab35, and Rab37) are highly expressed in the autophagosome compared to the normal control by immunoblotting under active secretion conditions. However, only Rab8a, Rab35, and Rab37 showing high colocalization with LC3 protein by cofocal microscopy. Despite the discrepancy between the image and immunoblotting analysis, our data sustains the speculation that Rab8a, Rab11b, Rab27a, Rab35, and Rab37 are possibly associated with the secretory autophagy machinery. In contrast, Rab7a shows low colocalization with LC3 puncta and low level in the autophagosome, suggesting it regulates different vesicle trafficking machineries. Our findings open a new direction toward exploring the role of Rab proteins in secretory autophagy-related cargo exocytosis and identifying the cargoes and effectors regulated by specific Rab proteins.

Green silver nanoparticles: Prospective nanotools against neurodegenerative cell line model

AbstractNeurodegenerative diseases represent an increasingly burdensome challenge of the past decade, primarily driven by the global aging of the population. Ongoing efforts focus on implementing diverse strategies to mitigate the adverse effects of neurodegeneration, with the goal of decelerating the pathology progression. Notably, in recent years, it has emerged that the use of nanoparticles (NPs), particularly those obtained through green chemical processes, could constitute a promising therapeutic approach. Green NPs, exclusively sourced from phytochemicals, are deemed safer compared to NPs synthetized through conventional chemical route. In this study, the effects of green chemistry‐derived silver NPs (AgNPs) were assessed in neuroblastoma cells, SHSY‐5Y, which are considered a pivotal model for investigating neurodegenerative diseases. Specifically, we used two different concentrations (0.5 and 1 µM) of AgNPs and two time points (24 and 48 h) to evaluate the impact on neuroblastoma cells by observing viability reduction and intracellular calcium production, especially using 1 µM at 48 h. Furthermore, investigation using atomic force microscopy (AFM) unveiled an alteration in Young's modulus due to the reorganization of cortical actin following exposure to green AgNPs. This evidence was further corroborated by confocal microscopy acquisitions as well as coherency and density analyses on actin fibers. Our in vitro findings suggest the potential efficacy of green AgNPs against neurodegeneration; therefore, further in vivo studies are imperative to optimize possible therapeutic protocols.

Mechanical Characteristics of Cracked Lining Reinforced with Steel Plate–UHPC Subjected to Vertical Load

The steel plate reinforcement method is widely used for strengthening damaged linings. Nevertheless, low durability is one of the disadvantages of the steel plate reinforcement method, which uses epoxy resin as the interface binder. To enhance the load-bearing performance and strengthening effect of steel-plate-reinforced structures, this study introduced ultra-high performance concrete (UHPC) as the reinforcing bonding layer and proposed a novel method for steel plate–UHPC reinforcement of cracked linings. A mechanical performance model test was conducted on a 1/5 scale lining model using a loading test device to evaluate the load-bearing performance and stress deformation of both conventional steel plate and steel plate–UHPC reinforced cracked linings. The characteristics, mechanisms of failure, and impacts of strengthening of the steel plate reinforcement method and steel plate–UHPC reinforcement method for cracked linings were compared. A numerical simulation model was developed to investigate the reinforcement effect of cracked linings using steel plate–UHPC reinforcement. The analysis included examining the influence of steel plate thickness, UHPC bonding layer thickness, and reinforcement timing. Model test results show that the overall damage mode of the steel plate–UHPC-reinforced structure had good elastic–plastic behaviour, and the deformation and damage process under the vertical concentrated load can be divided into four typical phases. Compared with the traditional steel plate reinforcement, the ultimate load-carrying capacity and ductility of the steel plate–UHPC-reinforced structure were increased by 53% and 366%, respectively, showing significantly better load-carrying capacity and deformation performance. Numerical simulation results show that the reinforced structure’s load-carrying capacity and stiffness enhancement rate increased non-linearly with the increase in UHPC layer thickness and steel plate thickness. However, reasonable reinforcement timing exists for steel plate-UHPC reinforcement, and too late reinforcement timing leads to a decrease in structural load-carrying capacity and stiffness enhancement rate.

Determination and Engineering of Li‐Ion Tortuosity in Electrode Toward High Performance of Li‐Ion Batteries

AbstractWith the progressively widespread application of lithium‐ion batteries, their energy density and power density are being pursued to the extremely high. However, both cannot be reached simultaneously at present. Tortuosity depicts the relationship in ionic diffusion between bulk electrolyte and the electrolyte in a porous electrode, provides information about channels within electrodes, and correlates the current dilemma between energy density and power capability of the lithium‐ion batteries. It is crucial to upgrade the fast charging and discharging performance of LIBs electrodes without losing volumetric energy density and using tortuosity as a guide is able to achieve this goal fundamentally. Meanwhile, tortuosity can serve as an evaluation parameter for production quality assessment, but this demands a fast, accurate, and cost‐effective measuring method. After the definition and measurement of tortuosity are provided, this article analyzes the structural influencing factors of tortuosity which have impacts on ion transportation and subsequently on tortuosity to facilitate a more systematic and comprehensive picture. Through the discussion of contradictions and influencing factors, a more refined transmission line model (the refined TLM) is perceived as the very first step to drive both aforementioned goals toward success and is discussed in the perspective part.

Ultrafast active plasmonic switch based on the broadband high absorption of monolayer graphene with high modulation depth

Abstract Optical switches based on plasmonic nanostructures are of great interest due to their high speed performance. To improve the broadband switching performance, a plasmonic design based on metal-insulator-metal (MIM) structure and monolayer graphene (as an active layer) is proposed. In this scheme, the light absorption of the monolayer graphene and the optical bandwidth are increased due to magnetic dipole resonance and magnetic coupling effect. The numerical simulation results of the proposed structure reveal that high absorption is achieved at the wavelength of 1.55 ‌µm which is 67% and 93% for the monolayer graphene and the whole structure, respectively. This structure has a high absorption modulation depth which can be reached nearly 100% around the interband transition position in a wide wavelength range from 1 µm to 2.5 ‌‌‌‌‌µm. Also, regarding its short response time of 10 fs, this structure can be used as an ultrafast switch. In addition, the equivalent circuit model of the structure is derived from the transmission line model (TLM) that its results are in a very good agreement with the numerical simulation results.

CTFNet: Coarse-to-Fine Segmented Lane Line Detection in Complex Road Conditions

To maintain robustness in complex and uncontrollable real-world driving scenarios, this paper proposes a new segmentation-based coarse-to-fine lane line model (CTFNet). Which embeds dual-pathway attention (DPA) in the coarse segmentation encoder-decoder architecture to fuse high and low-level features with dual inputs, taking the strengths and complementing the weaknesses, and at the same time being able to capture more spatial detail information. However, the extracted lane line cues are limited in extreme conditions. As a result, a feature localization module (FLM) is proposed which extracts the global contextual information of the occluded region along the vertical and horizontal axes and determines lane line location by predicting the confidence of the lane lines based on the extracted information. Additionally, some regions of the initial feature map of the coarse segmentation network are difficult to distinguish between classes, the uncertain region refinement module (URRM) is designed in the fine stage to gradually refine the uncertain pixels using the relationship between adjacent features. Finally, the model is extensively tested on the tvtLANE data set, and the results show that CTFNet outperforms most state-of-the-art methods with an F1-measure of 91.48%, which not only reduces false detection but also maintains good robustness in extremely difficult scenarios.

Experimental Infection Models and Their Usefulness for White Spot Syndrome Virus (WSSV) Research in Shrimp

White spot syndrome virus (WSSV) is marked as one of the most economically devastating pathogens in shrimp aquaculture worldwide. Infection of cultured shrimp can lead to mass mortality (up to 100%). Although progress has been made, our understanding of WSSV’s infection process and the virus–host–environment interaction is far from complete. This in turn hinders the development of effective mitigation strategies against WSSV. Infection models occupy a crucial first step in the research flow that tries to elucidate the infectious disease process to develop new antiviral treatments. Moreover, since the establishment of continuous shrimp cell lines is a work in progress, the development and use of standardized in vivo infection models that reflect the host–pathogen interaction in shrimp is a necessity. This review critically examines key aspects of in vivo WSSV infection model development that are often overlooked, such as standardization, (post)larval quality, inoculum type and choice of inoculation procedure, housing conditions, and shrimp welfare considerations. Furthermore, the usefulness of experimental infection models for different lines of WSSV research will be discussed with the aim to aid researchers when choosing a suitable model for their research needs.

A New Method for Anti-Interference Measurement of Capacitance Parameters of Long-Distance Transmission Lines Based on Harmonic Components

In the context of strong electromagnetic interference environments, the measurement accuracy of the capacitance parameters of transmission lines under power frequency measurement methods is not high. In this paper, a capacitance parameter anti-interference measurement method for transmission lines based on harmonic components is proposed to overcome the impact of power frequency interference. When applying this method, it is first necessary to open-circuit the end of the line under test. Subsequently, apply voltage to the head end of the tested line through a step-up transformer. Due to the saturation of the transformer during no-load conditions, a large number of harmonics are generated, primarily third harmonic. The third harmonic components of voltage and current on the tested transmission line are extracted using the Fourier transform. The proposed method addresses the influence of line distribution effects by establishing a distributed parameter model for long-distance transmission lines. The relevant transmission matrix for the zero-sequence distributed parameters is obtained by combining Laplace transform and similarity transform to solve the transmission line equations. Using synchronous measurement data from the third harmonic components of voltage and current at both ends of the transmission line, combined with the transmission matrix, this method accurately measures the zero-sequence capacitance parameters. The PSCAD/EMTDC simulation results and field test outcomes have demonstrated the feasibility and accuracy of the proposed method for measuring line capacitance parameters under strong electromagnetic interference.

Abstract PR008: Modulating the PPARγ pathway to augment NECTIN4-targeting chimeric antigen receptor (CAR) T cell therapy

Abstract Background: We present the development of NECTIN4-CAR T cells targeting bladder cancer and evaluate the ability of thiazolidinedione, a class of anti-diabetic drugs, to specifically upregulate NECTIN4 expression and expand the therapeutic window of NECTIN4-CAR T cells. In addition, we assess efficacy of NECTIN4-CAR T cell therapy against a model of bladder cancer with acquired resistance to enfortumab vedotin (EV). Methods: NECTIN4-targeting chimeric antigen receptor (CAR) constructs were designed and cloned into a second-generation EQ-28ζ CAR backbone construct. Human primary T cells were transduced with lentiviral NECTIN4-CAR constructs and co-cultured with a panel of bladder cancer cell lines with a range of NECTIN4 expression and against NECTIN4 knockout cells to assess specificity. Tumor cell count over time was monitored in vitro using an IncuCyte S3. Bladder cancer cell lines (RT112, UMUC-1, HT1197) were treated with PPARγ agonists (rosiglitazone) and antagonists (T0070907), and total and surface NECTIN4 protein levels were assessed. Anti-tumor effects of the NECTIN4-CAR T were evaluated in vitro and in vivo, either with or without rosiglitazone pre-treatment. Finally, RT112 bladder cancer cells were exposed to “cycles” of escalating doses of EV to generate EV-resistant cell line models, and anti-tumor efficacy against EV-resistant lines was evaluated. Results: NECTIN4-targeting CAR T cells displayed potent and NECTIN4-specific cytotoxic activity against bladder cancer cell lines. The efficacy of NECTIN4-CAR T cells was strongly correlated with NECTIN4 expression. Treatment with PPARγ agonists and antagonists was shown to upregulate and downregulate NECTIN4 expression, respectively. Treatment with the PPARγ agonist rosiglitazone induced NECTIN4 expression in a PPARγ-dependent and dose responsive manner. NECTIN4 expression was increased in bladder cancer xenografts established in immunodeficient NSG mice that were treated with systemic rosiglitazone. Priming with rosiglitazone enhanced sensitivity to NECTIN4-CAR T cells in vitro, and the combination of rosiglitazone pre-treatment and NECTIN4-CAR T cell therapy showed enhanced tumor control in bladder cancer xenograft models. We generated RT112 cells that exhibited resistance to EV in vitro and in vivo, which retained NECTIN4 expression. Interestingly, EV-resistant RT112 cells remained sensitive to NECTIN4-CAR T cell therapy both in vitro and in vivo. Conclusions: We engineered a NECTIN4-targeting CAR T cell therapy that is highly antigen-specific and demonstrates antitumor activity against multiple bladder cancer models, including EV resistant cells. Modulating the PPARγ pathway increases NECTIN4 expression, which we leveraged by repurposing an FDA-approved anti-diabetes drug rosiglitazone to increase targeting and anti-tumor efficacy of NECTIN4-CAR T cells. These preclinical results lay the groundwork for CAR T therapy development in bladder cancer and suggest rational drug combinations that can expand the therapeutic window of NECTIN4-targeting therapies. Citation Format: Kevin Chang, Henry M. Delavan, Jun Zhu, Corynn Kasap, Elizabeth Yip, Roshan Lodha, Sheng-You Liao, Sima Porten, Terence Friedlander, Vadim Koshkin, Felix Feng, Arun Wiita, John Lee, Carissa E. Chu, Jonathan Chou. Modulating the PPARγ pathway to augment NECTIN4-targeting chimeric antigen receptor (CAR) T cell therapy [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2024 May 17-20; Charlotte, NC. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(10_Suppl):Abstract nr PR008.

Online Prediction Method of Transmission Line Icing Based on Robust Seasonal Decomposition of Time Series and Bilinear Temporal–Spectral Fusion and Improved Beluga Whale Optimization Algorithm–Least Squares Support Vector Regression

Due to the prevalent challenges of inadequate accuracy, unstandardized parameters, and suboptimal efficiency with regard to icing prediction, this study introduces an innovative online method for icing prediction based on Robust STL–BTSF and IBWO–LSSVR. Firstly, this study adopts the Robust Seasonal Decomposition of Time Series and Bilinear Temporal–Spectral Fusion (Robust STL–BTSF) approach, which is demonstrably effective for short-term and limited sample data preprocessing. Subsequently, injecting a multi-faceted enhancement approach to the Beluga Whale Optimization algorithm (BWO), which integrates a nonlinear balancing factor, a population optimization strategy, a whale fall mechanism, and an ascendant elite learning scheme. Then, using the Improved BWO (IBWO) above to optimize the key hyperparameters of Least Squares Support Vector Regression (LSSVR), a superior offline predictive part is constructed based on this approach. In addition, an Incremental Online Learning algorithm (IOL) is imported. Integrating the two parts, the advanced online icing prediction model for transmission lines is built. Finally, simulations based on actual icing data unequivocally demonstrate that the proposed method markedly enhances both the accuracy and speed of predictions, thereby presenting a sophisticated solution for the icing prediction on the transmission lines.

SRC inhibition enables formation of a growth suppressive MAGI1-PP2A complex in isocitrate dehydrogenase-mutant cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (ICC) is an aggressive bile duct malignancy that frequently exhibits isocitrate dehydrogenase (IDH1/IDH2) mutations. Mutant IDH (IDHm) ICC is dependent on SRC kinase for growth and survival and is hypersensitive to inhibition by dasatinib, but the molecular mechanism underlying this sensitivity is unclear. We found that dasatinib reduced p70 S6 kinase (S6K) and ribosomal protein S6 (S6), leading to substantial reductions in cell size and de novo protein synthesis. Using an unbiased phosphoproteomic screen, we identified membrane-associated guanylate kinase, WW, and PDZ domain containing 1 (MAGI1) as an SRC substrate in IDHm ICC. Biochemical and functional assays further showed that SRC inhibits a latent tumor-suppressing function of the MAGI1-protein phosphatase 2A (PP2A) complex to activate S6K/S6 signaling in IDHm ICC. Inhibiting SRC led to activation and increased access of PP2A to dephosphorylate S6K, resulting in cell death. Evidence from patient tissue and cell line models revealed that both intrinsic and extrinsic resistance to dasatinib is due to increased phospho-S6 (pS6). To block pS6, we paired dasatinib with the S6K/AKT inhibitor M2698, which led to a marked reduction in pS6 in IDHm ICC cell lines and patient-derived organoids in vitro and substantial growth inhibition in ICC patient-derived xenografts in vivo. Together, these results elucidated the mechanism of action of dasatinib in IDHm ICC, revealed a signaling complex regulating S6K phosphorylation independent of mTOR, suggested markers for dasatinib sensitivity, and described a combination therapy for IDHm ICC that may be actionable in the clinic.

PARP inhibitor synthetic lethality in ATM biallelic mutant cancer cell lines is associated with BRCA1/2 and RAD51 downregulation.

Ataxia telangiectasia-mutated (ATM) kinase is a central regulator of the DNA damage response (DDR) signaling pathway, and its function is critical for the maintenance of genomic stability in cells that coordinate a network of cellular processes, including DNA replication, DNA repair, and cell cycle progression. ATM is frequently mutated in human cancers, and approximately 3% of lung cancers have biallelic mutations in ATM, i.e., including 3.5% of lung adenocarcinomas (LUAD) and 1.4% of lung squamous cell carcinomas (LUSC). We investigated the potential of targeting the DDR pathway in lung cancer as a potential therapeutic approach. In this context, we examined whether ATM loss is synthetically lethal with niraparib monotherapy. This exploration involved the use of hATM knockout (KO) isogenic cell lines containing hATM homozygous (-/-) and heterozygous (+/-) generated via CRISPR/Cas9 gene knockout technology in DLD-1, a human colorectal adenocarcinoma cell line. Subsequently, we extended our investigation to non-small cell lung cancer (NSCLC) patient derived xenograft (PDX) models for further validation of poly ADP-ribose polymerase inhibitor (PARPi) synthetic lethality in ATM mutant NSCLC models. Here, we demonstared that biallelic hATM deletion (-/-) in DLD-1 impairs homologous recombination (HR) repair function and sensitizes cells to the PARPi, niraparib. Niraparib also caused significant tumor regression in one-third of the NSCLC PDX models harboring deleterious biallelic ATM mutations. Loss of hATM (-/-) was concomitantly associated with low BRCA1 and BRCA2 protein expression in both the hATM (-/-) DLD-1 cell line and PARPi-sensitive ATM mutant NSCLC PDX models, suggesting a downstream effect on the impairment of HR-mediated DNA checkpoint signaling. Further analysis revealed that loss of ATM led to inhibition of phosphorylation of MRN (Mre11-Rad50-NBS1) complex proteins, which are required for ATM-mediated downstream phosphorylation of p53, BRCA1, and CHK2. Taken together, our findings highlight that the synthetic lethality of niraparib in ATM-deficient tumors can be regulated through a subsequent effect on the modulation of BRCA1/2 expression and its effect on HR function.

Fusion method for digital twin model of a production line

Fusion method for digital twin model of a production line

Efficient prediction of tidal turbine fatigue loading using turbulent onset flow from Large Eddy Simulations

AbstractTo maximise the availability of power extraction from a tidal stream site, tidal turbines need to be able to operate reliably when located within arrays. This requires a thorough understanding of the operating conditions, which include turbulence, velocity shear due to bed proximity and roughness, ocean waves and due to upstream turbine wakes, over the range of flow speeds that contribute to the loading experienced by the devices. High-fidelity models such as Large Eddy Simulation (LES) can be used to represent these complex flow conditions and turbine device models can be embedded to predict loading. However, to inform micro-siting of multiple turbines with an array, the computational cost of performing multiple simulations of this type is impractical. Unsteady onset conditions can be generated from the LES to be used in an offline coupling fashion as input to lower-fidelity load prediction models to enable computationally efficient array design. In this study, an in-house Blade Element Momentum (BEM) method is assessed for prediction of the unsteady loads on the turbines of a floating tidal device with unsteady inflow developed with the in-house LES solver DOFAS. Load predictions are compared to those obtained using the same unsteady inflow to the commercial tool Tidal Bladed and from an Actuator Line Model (ALM) embedded in the LES solver. Estimates of fatigue loads differ by up to 3% for mean thrust and 11% for blade root bending moment for a turbine subject to a turbulent channel flow. When subjected to more complex flows typical of a turbine wake, the predictions of rotor thrust fatigue differ by up to 10%, with loads reduced by the inclusion of a pitch controller.

Protein Signature Differentiating Neutrophils and Myeloid-Derived Suppressor Cells Determined Using a Human Isogenic Cell Line Model and Protein Profiling.

Myeloid-derived suppressor cells (MDSCs) play an essential role in suppressing the antitumor activity of T lymphocytes in solid tumors, thus representing an attractive therapeutic target to enhance the efficacy of immunotherapy. However, the differences in protein expression between MDSCs and their physiological counterparts, particularly polymorphonuclear neutrophils (PMNs), remain inadequately characterized, making the specific identification and targeting of MDSCs difficult. PMNs and PMN-MDSCs share markers such as CD11b+CD14-CD15+/CD66b+, and some MDSC-enriched markers are emerging, such as LOX-1 and CD84. More proteomics studies are needed to identify the signature and markers for MDSCs. Recently, we reported the induced differentiation of isogenic PMNs or MDSCs (referred to as iPMNs and iMDSCs, respectively) from the human promyelocytic cell line HL60. Here, we profiled the global proteomics and membrane proteomics of these cells with quantitative mass spectrometry, which identified a 41-protein signature ("cluster 6") that was upregulated in iMDSCs compared with HL60 and iPMN. We further integrated our cell line-based proteomics data with a published proteomics dataset of normal human primary monocytes and monocyte-derived MDSCs induced by cancer-associated fibroblasts. The analysis identified a 38-protein signature that exhibits an upregulated expression pattern in MDSCs compared with normal monocytes or PMNs. These signatures may provide a hypothesis-generating platform to identify protein biomarkers that phenotypically distinguish MDSCs from their healthy counterparts, as well as potential therapeutic targets that impair MDSCs without harming normal myeloid cells.

The effectiveness of out-of-hours palliative care telephone advice lines: A rapid systematic review.

People with palliative care needs and their carers often rely on out-of-hours services to remain at home. Policymakers have recommended implementing telephone advice lines to ensure 24/7 access to support. However, the impact of these services on patient and carer outcomes, as well as the health care system, remains poorly understood. To evaluate the clinical- and cost-effectiveness of out-of-hours palliative care telephone advice lines, and to identify service characteristics associated with effectiveness. Rapid systematic review (PROSPERO ID: CRD42023400370) with narrative synthesis. Three databases (Medline, EMBASE and CINAHL) were searched in February 2023 for studies of any design reporting on telephone advice lines with at least partial out-of-hours availability. Study quality was assessed using the Mixed Methods Appraisal Tool, and quantitative and qualitative data were synthesised narratively. Twenty-one studies, published 2000-2022, were included. Most studies were observational, none were experimental. While some evidence suggested that telephone advice lines offer guidance and reassurance, supporting care at home and potentially reducing avoidable emergency care use in the last months of life, variability in reporting and poor methodological quality across studies limit our understanding of patient/carer and health care system outcomes. Despite their increasing use, evidence for the clinical- and cost-effectiveness of palliative care telephone advice lines remains limited, primarily due to the lack of robust comparative studies. There is a need for more rigorous evaluations incorporating experimental or quasi-experimental methods and longer follow-up, and standardised reporting of telephone advice line models and outcomes, to guide policy and practice.

Aspartate β-Hydroxylase Is Upregulated in Head and Neck Squamous Cell Carcinoma and Regulates Invasiveness in Cancer Cell Models.

Aspartate β-hydroxylase (ASPH) is a protein associated with malignancy in a wide range of tumors. We hypothesize that inhibition of ASPH activity could have anti-tumor properties in patients with head and neck cancer. In this study, we screened tumor tissues of 155 head and neck squamous cell carcinoma (HNSCC) patients for the expression of ASPH using immunohistochemistry. We used an ASPH inhibitor, MO-I-1151, known to inhibit the catalytic activity of ASPH in the endoplasmic reticulum, to show its inhibitory effect on the migration of SCC35 head and neck cancer cells in cell monolayers and in matrix-embedded spheroid co-cultures with primary cancer-associated fibroblast (CAF) CAF 61137 of head and neck origin. We also studied a combined effect of MO-I-1151 and HfFucCS, an inhibitor of invasion-blocking heparan 6-O-endosulfatase activity. We found ASPH was upregulated in HNSCC tumors compared to the adjacent normal tissues. ASPH was uniformly high in expression, irrespective of tumor stage. High expression of ASPH in tumors led us to consider it as a therapeutic target in cell line models. ASPH inhibitor MO-I-1151 had significant effects on reducing migration and invasion of head and neck cancer cells, both in monolayers and matrix-embedded spheroids. The combination of the two enzyme inhibitors showed an additive effect on restricting invasion in the HNSCC cell monolayers and in the CAF-containing co-culture spheroids. We identify ASPH as an abundant protein in HNSCC tumors. Targeting ASPH with inhibitor MO-I-1151 effectively reduces CAF-mediated cellular invasion in cancer cell models. We propose that the additive effect of MO-I-1151 with HfFucCS, an inhibitor of heparan 6-O-endosulfatases, on HNSCC cells could improve interventions and needs to be further explored.