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In mountainous regions, high-locality landslides have the characteristics of a latent disaster process with a wide disaster range, which can easily cause large casualties. Therefore, early landslide identification and dynamic stability evaluation are significant. We first used multi-temporal synthetic aperture radar data to detect potential landslides at Yezhi Site Area during the 2015–2020 period, identifying and mapping a total of 18 active landslides. The study area was found to have an average deformation rate between −15 and 10 mm/y during the period. Then, time series and spatiotemporal deformation characteristics of landslides were examined using interferogram stacking and small baseline interferometry techniques. The results show that the majority of the landslide deformations detected exhibit a periodic variation trend, and the study area was in a slow deformation state before 2017. Finally, combined with detection results, Google Earth optical images, and field investigations, it is concluded that the main factors affecting the time series deformation and spatial distribution of landslides in the study area are rainfall, geological factors, and engineering activities. The results of this study provide valuable technical references and support for early identification and dynamic stability evaluation of regional active landslides in complex terrain, especially for high-locality landslides.

The interface between the filling slope and the original slope is inevitable in the process of building a city in the loess area, which will affect the deformation and stability of the filling slope. In this paper, the loess fill slope of mountain excavation and city construction project in Yan’an City, China, is taken as the research object, and, based on field investigation and sampling, the effect of Loess Fill Slope Interface (LFSI) under rainfall is revealed by physical model test. The test samples were taken from a Loess Fill in Qilipu community, Yan’an, and three layers of sensors were arranged at the left and right interfaces of the original slope and the filled slope to monitor the water content, pore water pressure and deformation and failure characteristics during the experiment. The results show that ILFS is a rainfall dominant seepage channel, and the infiltration of rainfall along the interface lags behind. In addition, the variation laws of water content and pore water pressure at the interface between fill slope and original slope under rainfall are obtained. Finally, the failure process of loess fill slope under rainfall is summarized: local mud flow failure at the toe of the slope → erosion in the middle of the slope → crack initiation on the shoulder of the slope → local slip on the slope → crack propagation on the shoulder of the slope → shallow slip on the shoulder of the slope, and the instability mechanism of loess fill slope under rainfall is further revealed. The research results can provide theoretical and experimental reference for the protection of fill slopes in loess areas.

TAR DNA binding protein 43 KD (TDP-43) is an essential gene that regulates gene transcription, mRNA splicing and stability. In amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), two fatal neurodegenerative diseases, TDP-43 is fragmented, generating multiple fragments that include the C-terminal fragment of ∼25 KD. The role of these fragments in the pathogenesis of ALS and FTD is not clear. Here we investigated the aggregation propensity in various polypeptide regions of TDP-43 in mammalian cells and the effect of these fragments on cultured neurons. By expressing the full length and various TDP-43 fragments in motor neuron-derived NSC-34 cells and primary neurons, we found that both N- and C-terminal fragments of TDP-43 are prone to aggregate and the C-terminal end of RRM2 region is required, though not sufficient, for aggregation. The aggregation of the TDP-43 fragments can drive co-aggregation with the full-length TDP-43, consequently reducing the nuclear TDP-43. In addition, the TDP-43 fragments can impair neurite growth during neuronal differentiation. Importantly, overexpression of the full-length TDP-43 rescues the neurite growth phenotype whereas knockdown of the endogenous TDP-43 reproduces this phenotype. These results suggest that TDP-43 fragments, particularly the pathologically relevant C-terminal fragments, can impair neuronal differentiation by dominant-negatively interfering with the function of the full length TDP-43, thus playing a role in pathogenesis in ALS and FTD.

This study examined the everyday experiences of racism among Chinese immigrants in Canada. Data came from nine virtual focus groups comprising 48 participants of diverse genders and ages taking place in December 2021 and January 2022. We conducted our qualitative analysis by drawing on Essed’s conceptualization of everyday racism and Crenshaw’s conceptualization of intersectionality. Thematic and content analysis showed that racism against Chinese immigrants is more pervasive than previously recognized. Three-quarters of the participants disclosed instances of racism across various settings, including workplaces, schools, shops, airports, banks, hotels, restaurants, streets, and online. Some gender and age groups reported more incidents than others. Young men, on average, encountered the greatest number, followed by young and middle-aged women, while older men reported the fewest. Types of racist incidents also varied by age and gender. Young and middle-aged women encountered unsolicited intimate remarks and racism related to gender division of labour, while older adults, both men and women, faced racism associated with service provision. Younger men reported online racism. Some older participants remained unaware of the racist nature of their encounters, and middle-aged and older men tended to deny having experienced racist encounters. Given these findings, we suggest the need to raise awareness, establish empowerment initiatives, and adopt intersectionality approaches to address and combat racism against Chinese immigrants in Canada. [ABSTRACT FROM AUTHOR]

The widespread integration of wind turbines poses voltage stability challenges to power systems. To enhance the ability of wind power systems to actively support grid voltage, grid-forming control techniques are increasingly being employed. However, current research primarily focuses on voltage stability challenges at the point of common coupling in wind power systems, lacking thorough investigation into system voltage response characterization. This paper establishes the voltage response model of a grid-forming wind power system. Based on this model, mathematical derivation and theoretical analysis are conducted, and the effect factors of the voltage at the point of common coupling are investigated. Furthermore, a voltage stabilization method is explored by adjusting the above effect factors. Finally, based on the MATLAB/Simulink platform, the simulation verification of each effect factor is carried out. The results indicate that voltage response characterization obtained by the theoretical analysis and simulation is similar and that the proposed method is valid.

A grid-forming wind generation system exhibits exceptional grid frequency support abilities. The DC capacitor of the grid-forming wind generation system, which is characterized by rapid response and high sensitivity to minor disturbances, can provide short-term inertia support for the power system. This paper proposes the capacitor virtual inertia control for the grid-forming wind generation system, coupling the DC capacitor voltage with the power system frequency, which enables the DC capacitor to participate in the system frequency response process and reduces the rate of change of the system frequency during the disturbance. To analyze the inertia of the wind power generation system, this paper establishes an equivalent Philips–Heffron model for the grid-forming wind generation system and uses the equivalent inertia constant to quantify the inertia of the wind power generation system. The effectiveness of the proposed control strategy and the reasonableness of the inertia assessment method are verified through simulations in the single-turbine system and the IEEE four-machine two-area system.

The global pursuit of low-carbon technologies has led to the rapid development of renewable energy sources (RES), such as wind and solar power. The large-scale integration of RES into power grid systems can change the characteristics and forms of the system inertia. RES-heavy power systems exhibit lower inertia, compromising their frequency stability and rendering traditional inertia response mechanisms and analysis methods insufficient. This review compares the different inertias in traditional and future RES-heavy power systems, details the inertia response mechanisms of various types of devices, identifies deficiencies in the traditional inertia index when quantifying the inertia response capabilities of the equipment, and illustrates the necessity of exploring a generalized inertia index suitable for such systems. Furthermore, the influence mechanism of system inertia on frequency stability is analyzed, and the action mechanism and response time sequence of various types of devices in the system inertia response are described. The challenges in applying the traditional frequency stability analysis method to future RES-heavy power systems are also identified. This review can serve as a guide for developing power grid control systems and analysis methods to accommodate the increasing application of RES.

Abstract Background The introductions of anti‐ human epidermal growth factor receptor‐2 (HER2) agents have significantly improved the treatment outcome of patients with HER2‐positive breast cancer. BAT8001 is a novel antibody‐drug conjugate targeting human epidermal growth factor receptor‐2 (HER2)‐expressing cells composed of a trastuzumab biosimilar linked to the drug‐linker Batansine. This dose‐escalation, phase I study was designed to assess the safety, tolerability, pharmacokinetics, and preliminary anti‐tumor activity of BAT8001 in patients with HER2‐positive locally advanced or metastatic breast cancer. Methods This trial was conducted in subjects with histologically confirmed HER2‐positive breast cancer (having evaluable lesions and an Eastern Cooperative Oncology Group performance status of 0 or 1) using a 3 + 3 design of escalating BAT8001 doses. Patients received BAT8001 intravenously in a 21‐day cycle, with dose escalation in 5 cohorts: 1.2, 2.4, 3.6, 4.8, and 6.0 mg/kg. The primary objective was to evaluate the safety and tolerability of BAT8001. Preliminary activity of BAT8001 was also assessed as a secondary objective. Results Between March 2017 to May 2018, 29 HER2‐positive breast cancer patients were enrolled. The observed dose‐limiting toxicities were grade 4 thrombocytopenia and grade 3 elevated transaminase. The maximum tolerated dose was determined to be 3.6 mg/kg. Grade 3 or greater adverse events (AEs) occurred in 14 (48.3%) of 29 patients, including thrombocytopenia in 12 (41.4%) patients, aspartate aminotransferase increased in 4 (13.8%) patients, γ‐glutamyl transferase increased in 2 (6.9%) patients, alanine aminotransferase increased in 2 (6.9%) patients, diarrhea in 2 (6.9%) patients. Objective response was observed in 12 (41.4%; 95% confidence interval [CI] = 23.5%‐61.1%) and disease control (including patients achieving objective response and stable disease) was observed in 24 (82.8%; 95% CI = 64.2%‐94.2%) patients. Conclusions BAT8001 demonstrated favorable safety profiles, with promising anti‐tumor activity in patients with HER2‐positive locally advanced or metastatic breast cancer. BAT8001 has the potential to provide a new therapeutic option in patients with metastatic HER2‐positive breast cancer.

With the increase of the penetration rate of wind power in the power grid, the high proportion of renewable energy and the high proportion of power electronic equipment in the power system will continuously reduce the inertia of the grid, and the frequency stability of the system will be seriously affected. The inertia of the system is an important parameter for system frequency regulation and stability calculation. For this reason, a virtual inertial control technology based on fuzzy logic control is proposed in this paper, which is used for wind turbines to participate in grid frequency regulation. In this method, based on power tracking, a fuzzy logic controller is designed to adjust the frequency adjustment coefficient adaptively, and fuzzy logic rules are used to optimize the power tracking curve online. Finally, by building a hardware-in-the-loop real-time simulation platform, the effectiveness of this method in providing system frequency support and improving the frequency response of the power grid is verified.

Amyotrophic lateral sclerosis (ALS) is a fatal neurological disease that causes motor neuron degeneration, progressive motor dysfunction, paralysis, and death. Although multiple causes have been identified for this disease, >95% of ALS cases show aggregation of transactive response DNA binding protein (TDP-43) accompanied by its nuclear depletion. Therefore, the TDP-43 pathology may be a converging point in the pathogenesis that originates from various initial triggers. The aggregation is thought to result from TDP-43 misfolding, which could generate cellular toxicity. However, the aggregation as well as the nuclear depletion could also lead to a partial loss of TDP-43 function or TDP-43 dysfunction. To investigate the impact of TDP-43 dysfunction, we generated a transgenic mouse model for a partial loss of TDP-43 function using transgenic RNAi. These mice show ubiquitous transgene expression and TDP-43 knockdown in both the periphery and the central nervous system (CNS). Strikingly, these mice develop progressive neurodegeneration prominently in cortical layer V and spinal ventral horn, motor dysfunction, paralysis, and death. Furthermore, examination of splicing patterns of TDP-43 target genes in human ALS revealed changes consistent with TDP-43 dysfunction. These results suggest that the CNS, particularly motor neurons, possess a heightened vulnerability to TDP-43 dysfunction. Additionally, because TDP-43 knockdown predominantly occur in astrocytes in the spinal cord of these mice, our results suggest that TDP-43 dysfunction in astrocytes is an important driver for motor neuron degeneration and clinical phenotypes of ALS. [ABSTRACT FROM AUTHOR]

This study aims to analyze the groundwater flow changes caused by rainfall and its influence on slope stability. Taking the slope in Dingjiafen, Chuxiong, Yunnan, China as the study area, the study monitored the data of rainfall and drew upon the calculation module of ArcGIS to predict the change of the groundwater flow and water level fluctuation in the soil. In this way, the visual simulation of groundwater flow distribution of the slope was realized; and the influence of groundwater flow distribution caused by rainfall seepage on the slope’s stability was also analyzed. The results indicate that: (1) the rainfall recharge rate is affected by the thickness of the soil layer, the slope, the rainfall intensity, and the initial water content of the soil; (2) the seepage flow of rainfall in per unit time is positively correlated with the soil layer thickness of the slope; (3) the groundwater is repeatedly raised, maintained, and dissipated by periodic rainfall which destroys the structure of the soil; and (4) the rainfall reduces the cohesion and internal friction angle of the soil resulting in the “muddy water softening effect” in the weak zone.

Background: A proline-to-serine substitution at position-56 (P56S) of vesicle-associated membrane protein-associated protein B (VAPB) causes a form of dominantly inherited motor neuron disease (MND), including typical and atypical amyotrophic lateral sclerosis (ALS) and a mild late-onset spinal muscular atrophy (SMA). VAPB is an integral endoplasmic reticulum (ER) protein and has been implicated in various cellular processes, including ER stress, the unfolded protein response (UPR) and Ca2+ homeostasis. However, it is unclear how the P56S mutation leads to neurodegeneration and muscle atrophy in patients. The formation of abnormal VAPB-positive inclusions by mutant VAPB suggests a possible toxic gain of function as an underlying mechanism. Furthermore, the amount of VAPB protein is reported to be reduced in sporadic ALS patients and mutant SOD1G93A mice, leading to the hypothesis that wild type VAPB plays a role in the pathogenesis of ALS without VAPB mutations. Results: To investigate the pathogenic mechanism in vivo, we generated human wild type (wtVAPB) and mutant VAPB (muVAPB) transgenic mice that expressed the transgenes broadly in the CNS. We observed robust VAPB-positive aggregates in the spinal cord of muVAPB transgenic mice. However, we failed to find an impairment of motor function and motor neuron degeneration. We also did not detect any change in the endogenous VAPB level or evidence for induction of the unfolded protein response (UPR) and coaggregation of VAPA with muVAPB. Furthermore, we crossed these VAPB transgenic mice with mice that express mutant SOD1G93A and develop motor neuron degeneration. Overexpression of neither wtVAPB nor muVAPB modulated the protein aggregation and disease progression in the SOD1G93A mice. Conclusion: Overexpression of VAPBP56S mutant to approximately two-fold of the endogenous VAPB in mouse spinal cord produced abundant VAPB aggregates but was not sufficient to cause motor dysfunction or motor neuron degeneration. Furthermore, overexpression of either muVAPB or wtVAPB does not modulate the course of ALS in SOD1G93A mice. These results suggest that changes in wild type VAPB do not play a significant role in ALS cases that are not caused by VAPB mutations. Furthermore, these results suggest that muVAPB aggregates are innocuous and do not cause motor neuron degeneration by a gain-of-toxicity, and therefore, a loss of function may be the underlying mechanism. [ABSTRACT FROM AUTHOR]

The affect of Hz-2V (a.k.a. gonad-specific virus) virus infection on the reproductive physiology and behavior of infected adult Helicoverpa zea (Boddie) (Lepidoptera: Noctuidae) males was examined. Virus-infected males responded and flew to calling healthy and infected females at about the same rate. Although infected males were slower in approaching healthy females and attempting to mate compared with healthy males, infected males did make sexual contacts with females that could serve to transmit virus. Unlike matings with healthy males, which result in the cessation of calling, females that had made sexual contact with infected males continued to exhibit calling behavior and were receptive to mates. Although calling behavior of both healthy and infected females was inhibited by injecting extracts of reproductive tissues from healthy males, extracts of reproductive tissues from infected males inhibited female calling to a lesser degree and for an additional night compared with extracts from healthy males. The results presented here further demonstrate the ability of Hz-2V to alter the physiology and behavior of infected insects in ways that could serve to facilitate virus transmission. [ABSTRACT FROM AUTHOR]